期刊题录 -- 2022 Critical Care Medicine

# 期刊题录 -- 2022 Critical Care Medicine.

Atman 机器翻译，未校对

# Stability of Spo2/Fio2 and Respiratory Rate-Oxygenation Indexes in Critical Respiratory Disorders.

8:e694-e695. DOI:10.1097/CCM.0000000000005559

# 严重呼吸疾病中 Spo2/Fio2 和呼吸频率 - 氧合指数的稳定性。

# Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial., Kula, Roman

8:e693-e694. DOI:10.1097/CCM.0000000000005555

# 治疗性高热与发热危重症脓毒症患者的生存率改善相关：一项初探性随机化试验。

# The authors reply.

8:e691-e693. DOI:10.1097/CCM.0000000000005573

# 作者回复。

# Fragility Index and Trial Sequential Analysis for Randomized Controlled Studies Testing IV Vitamin C in Critically Ill Patients.

8:e690-e691. DOI:10.1097/CCM.0000000000005562

# 在危重病患者中评估 IV 维生素 C 的随机对照研究的脆性指数和试验序列分析。

# The authors reply.

8:e689-e690. DOI:10.1097/CCM.0000000000005574

# 作者回复。

# Cerebral Tissue Oxygenation Monitoring for Guiding RBC Transfusion in Neurocritical Patients.

8:e688-e689. DOI:10.1097/CCM.0000000000005561

# 神经重症患者指导 RBC 输注的脑组织氧合监测。

# The authors reply.

8:e687-e688. DOI:10.1097/CCM.0000000000005576

# 作者回复。

# Hyperbaric Oxygenation Therapy Alone for Carbon Monoxide Poisoning: Time for Reinforcements?

8:e686-e687. DOI:10.1097/CCM.0000000000005553

# 一氧化碳中毒的单独高压氧合治疗：强化时间？

# The authors reply., Rass, Verena

8:e684-e685. DOI:10.1097/CCM.0000000000005577

# 作者回复。

# Factors Associated With Prolonged Mechanical Ventilation in Nontraumatic Subarachnoid Hemorrhage., Siddiqui, Suhail Sarwar

8:e683-e684. DOI:10.1097/CCM.0000000000005541

# 非创伤性蛛网膜下腔出血机械通气延长的相关因素。

# Home-Ward Bound?, Rampon, Garrett

8:1285-1287. DOI:10.1097/CCM.0000000000005560

# 家庭病房界限？

# Is "Set It and Forget It" Bad Medicine for Sedation and Analgesia for Intubated Emergency Department Patients?, Winkle, Julie

8:1283-1285. DOI:10.1097/CCM.0000000000005566

# “设置它，遗忘它” 是否有损急诊插管患者的镇静和镇痛的良药？

# A Call for a Consensus Approach to the Design, Implementation, and Evaluation of Early Warning Systems., Bhavani, Sivasubramanium V.

8:1280-1282. DOI:10.1097/CCM.0000000000005568

# 呼吁对预警系统的设计、实施和评估采取共识方法。

# Sepsis Awareness Is Good, Please Do Not Let It Be Misunderstood.

8:1277-1279. DOI:10.1097/CCM.0000000000005569

# 败血症意识良好，请不要误解。

# Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

8:1175-1186. DOI:10.1097/CCM.0000000000005580

Abstract:

OBJECTIVES: To determine the safety and efficacy of probiotics or synbiotics on morbidity and mortality in critically ill adults and children.

DATA SOURCES: We searched MEDLINE, EMBASE, CENTRAL, and unpublished sources from inception to May 4, 2021.

STUDY SELECTION: We performed a systematic search for randomized controlled trials (RCTs) that compared enteral probiotics or synbiotics to placebo or no treatment in critically ill patients. We screened studies independently and in duplicate.

DATA EXTRACTION: Independent reviewers extracted data in duplicate. A random-effects model was used to pool data. We assessed the overall certainty of evidence for each outcome using the Grading Recommendations Assessment, Development, and Evaluation approach.

DATA SYNTHESIS: Sixty-five RCTs enrolled 8,483 patients. Probiotics may reduce ventilator-associated pneumonia (VAP) (relative risk [RR], 0.72; 95% CI, 0.59 to 0.89 and risk difference [RD], 6.9% reduction; 95% CI, 2.7-10.2% fewer; low certainty), healthcare-associated pneumonia (HAP) (RR, 0.70; 95% CI, 0.55-0.89; RD, 5.5% reduction; 95% CI, 8.2-2.0% fewer; low certainty), ICU length of stay (LOS) (mean difference [MD], 1.38 days fewer; 95% CI, 0.57-2.19 d fewer; low certainty), hospital LOS (MD, 2.21 d fewer; 95% CI, 1.18-3.24 d fewer; low certainty), and duration of invasive mechanical ventilation (MD, 2.53 d fewer; 95% CI, 1.31-3.74 d fewer; low certainty). Probiotics probably have no effect on mortality (RR, 0.95; 95% CI, 0.87-1.04 and RD, 1.1% reduction; 95% CI, 2.8% reduction to 0.8% increase; moderate certainty). Post hoc sensitivity analyses without high risk of bias studies negated the effect of probiotics on VAP, HAP, and hospital LOS.

CONCLUSIONS: Low certainty RCT evidence suggests that probiotics or synbiotics during critical illness may reduce VAP, HAP, ICU and hospital LOS but probably have no effect on mortality.

# 益生菌在危重症中的应用：一项随机对照试验的系统评价和荟萃分析。

摘要：

目的：确定益生菌或合生元对危重成人和儿童发病率和死亡率的安全性和有效性。

数据来源：我们检索了 MEDLINE、EMBASE、CENTRAL 和未发表的数据库，时间范围为从建库至 2021 年 5 月 4 日。

研究选择：我们对比较肠内益生菌或合生元与安慰剂或不治疗重症患者的随机对照试验 (RCT) 进行了系统检索。我们对研究进行了独立和重复筛选。

数据提取：独立审查者重复提取数据。使用随机效应模型汇总数据。我们使用分级推荐评估、开发和评价方法评估了每项结局证据的总体确定性。

数据综合：65 项 RCT 入组了 8483 例患者。益生菌可减少呼吸机相关性肺炎 (VAP)（相对风险 [RR]，0.72；95% CI，0.59-0.89，风险差异 [RD]，减少 6.9%；95% CI，减少 2.7-10.2%；低确定性）、医疗相关性肺炎 (HAP)（RR，0.70；95% CI，0.55-0.89；RD，减少 5.5%；95% CI，减少 8.2-2.0%；低确定性），ICU 住院时间 (LOS)（平均差异 [MD] 少 1.38 天；95% CI 少 0.57-2.19 天；低确定性）、住院 LOS（MD 少 2.21 天；95% CI 少 1.18-3.24 天；低确定性）和有创机械通气持续时间（MD 少 2.53 天；95% CI 少 1.31-3.74 天；低确定性）。益生菌很可能对死亡率没有影响（RR，0.95；95% CI，0.87-1.04；RD，1.1% 下降；95% CI，2.8% 下降至 0.8% 增加；中度确定）。没有高偏倚风险研究的事后敏感性分析否定了益生菌对 VAP、HAP 和医院 LOS 的影响。

结论：低确定性 RCT 证据表明，危重症期间益生菌或合生菌可降低 VAP、HAP、ICU 和医院 LOS，但可能对死亡率无影响。

# Electrical Impedance Tomography in Acute Respiratory Distress Syndrome Management.

8:1210-1223. DOI:10.1097/CCM.0000000000005582

Abstract:

OBJECTIVE: To describe, through a narrative review, the physiologic principles underlying electrical impedance tomography, and its potential applications in managing acute respiratory distress syndrome (ARDS). To address the current evidence supporting its use in different clinical scenarios along the ARDS management continuum.

DATA SOURCES: We performed an online search in Pubmed to review articles. We searched MEDLINE, Cochrane Central Register, and clinicaltrials.gov for controlled trials databases.

STUDY SELECTION: Selected publications included case series, pilot-physiologic studies, observational cohorts, and randomized controlled trials. To describe the rationale underlying physiologic principles, we included experimental studies.

DATA EXTRACTION: Data from relevant publications were reviewed, analyzed, and its content summarized.

DATA SYNTHESIS: Electrical impedance tomography is an imaging technique that has aided in understanding the mechanisms underlying multiple interventions used in ARDS management. It has the potential to monitor and predict the response to prone positioning, aid in the dosage of flow rate in high-flow nasal cannula, and guide the titration of positive-end expiratory pressure during invasive mechanical ventilation. The latter has been demonstrated to improve physiologic and mechanical parameters correlating with lung recruitment. Similarly, its use in detecting pneumothorax and harmful patient-ventilator interactions such as pendelluft has been proven effective. Nonetheless, its impact on clinically meaningful outcomes remains to be determined.

CONCLUSIONS: Electrical impedance tomography is a potential tool for the individualized management of ARDS throughout its different stages. Clinical trials should aim to determine whether a specific approach can improve clinical outcomes in ARDS management.

# 急性呼吸窘迫综合征管理中的电阻抗断层成像。

摘要：目的：通过叙述性回顾，描述电阻抗断层成像的生理学原理及其在管理急性呼吸窘迫综合征 (ARDS) 中的潜在应用。阐述支持其在 ARDS 管理连续体不同临床情况下使用的当前证据。

数据来源：我们在 Pubmed 中进行了在线检索，以对文章进行综述。我们检索了 MEDLINE、Cochrane Central Register 和 clinicaltrials.gov 对照试验数据库。

研究选择：选定的出版物包括病例系列、初步生理学研究、观察性队列和随机对照试验。为了描述潜在的生理学原理，我们纳入了实验性研究。

数据提取：对相关出版物中的数据进行审查、分析，并对其内容进行总结。

数据综合：电阻抗断层扫描是一种成像技术，有助于了解多种干预措施在 ARDS 管理中的作用机制。它可在有创机械通气期间监测和预测对俯卧位的反应，帮助高流量鼻插管的流速剂量，并指导对呼气末正压的滴定。已证实后者可改善与肺复张相关的生理和机械参数。同样，已证实其用于检测气胸和有害的患者 - 呼吸机相互作用（如 pendelluft）有效。尽管如此，其对有临床意义结局的影响仍有待确定。

结论：电阻抗断层扫描是 ARDS 不同阶段个体化管理的潜在工具。临床试验的目的应是确定特定方法是否能改善 ARDS 管理的临床结局。n 死亡率。

# Patient, Public, and Healthcare Professionals' Sepsis Awareness, Knowledge, and Information Seeking Behaviors: A Scoping Review., Fiest, Kirsten M.

8:1187-1197. DOI:10.1097/CCM.0000000000005564

Abstract:

OBJECTIVES: Sepsis awareness and understanding are important aspects of prevention, recognition, and clinical management of sepsis. We conducted a scoping review to identify and map the literature related to sepsis awareness, general knowledge, and information-seeking behaviors with a goal to inform future sepsis research and knowledge translation campaigns.

DESIGN: Scoping review.

SETTING: Using Arksey and O'Malley's methodological framework, we conducted a systematic search on May 3, 2021, across four databases (MEDLINE, EMBASE, CINAHL, and Education Research Complete). Title/abstract and full-text screening was done in duplicate. One researcher extracted the data for each included article, and a second researcher checked data accuracy. The protocol was registered on Open Science Framework ( https://doi.org/10.17605/OSF.IO/YX7AU ).

SUBJECTS: Articles related to sepsis awareness, knowledge, and information seeking behaviors among patients, public, and healthcare professionals.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Of 5,927 unique studies, 80 reported on patient ( n = 13/80;16.3%), public ( n = 15/80;18.8%), or healthcare professional (nurses, physicians, emergency medical technicians) ( n = 48/80; 60%) awareness and knowledge of sepsis. Healthcare professional awareness and knowledge of sepsis is high compared with patients/public. The proportion of patients/public who had heard of the term sepsis ranged from 2% (Japan) to 88.6% (Germany). The proportions of patients/public who correctly identified the definition of sepsis ranged from 4.2% (Singapore) to 92% (Sweden). The results from the included studies appear to suggest that patient/public awareness of sepsis gradually improved over time. We found that the definition of sepsis was inconsistent in the literature and that few studies reported on patient, public, or healthcare professional knowledge of sepsis risk factors. Most patient/public get their sepsis information from the internet, whereas healthcare professionals get it from their role in healthcare through job training or educational training.

CONCLUSIONS: Patient, public, and healthcare professional awareness and knowledge of sepsis vary globally. Future research may benefit from a consistent definition as well as country-specific data to support targeted public awareness campaigns.

# 患者、公众和医疗保健专业人员的败血症意识、知识和寻求信息的行为：一项应对审查。

摘要

目的：败血症认识和理解是败血症预防、识别和临床管理的重要方面。我们进行了一项范围审查，以确定和映射与败血症意识、一般知识和信息寻求行为相关的文献，目的是告知未来的败血症研究和知识转化项目。

设计：范围审查。

设置：使用 Arksey 和 O'Malley 的方法学框架，我们于 2021 年 5 月 3 日在四个数据库（MEDLINE、EMBASE、CINAHL 和 Education Research Complete）中进行了系统检索。重复进行标题 / 摘要和全文筛选。一名研究者从每篇纳入的文章中提取数据，另一名研究者检查数据的准确性。该方案已在 Open Science Framework（https://doi.org/10.17605/OSF.IO/YX7AU ).

受试者：与患者、公众和医疗保健专业人员的败血症意识、知识和信息寻求行为相关的文章。

干预：无。

测量值和主要结果：在 5,927 项独特的研究中，80 项报告了患者 (n = 13/80；16.3%)、公众 (n = 15/80；18.8%) 或医疗保健专业人员（护士、医生、急救医疗技术人员）(n = 48/80；60%) 对败血症的认识和了解。与患者 / 公众相比，医疗保健专业人士对败血症的认识和知识较高。听说过术语 “脓毒症” 的患者 / 公众比例范围是 2%（日本）至 88.6%（德国）。正确识别败血症定义的患者 / 公众比例范围为 4.2%（新加坡）至 92%（瑞典）。纳入的研究结果似乎表明，随着时间的推移，患者 / 公众对败血症的认识逐渐改善。我们发现文献中败血症的定义不一致，且仅有少数研究报告了败血症风险因素的患者、公共或医疗保健专业人士知识。大多数患者 / 公众通过网络获得其败血症信息，而医疗保健专业人员通过工作培训或教育培训从其在医疗保健中的角色获得这些信息。

结论：败血症的患者、公众和医疗保健专业人员意识和知识在全球各不相同。未来的研究可能受益于一致的定义以及特定国家的数据，以支持目标公众意识活动。

# The Impact of Health Information Technology for Early Detection of Patient Deterioration on Mortality and Length of Stay in the Hospital Acute Care Setting: Systematic Review and Meta-Analysis.

8:1198-1209. DOI:10.1097/CCM.0000000000005554

Abstract:

OBJECTIVE: To evaluate the impact of health information technology (HIT) for early detection of patient deterioration on patient mortality and length of stay (LOS) in acute care hospital settings.

DATA SOURCES: We searched MEDLINE and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Scopus from 1990 to January 19, 2021.

STUDY SELECTION: We included studies that enrolled patients hospitalized on the floor, in the ICU, or admitted through the emergency department.

Eligible studies compared HIT for early detection of patient deterioration with usual care and reported at least one end point of interest: hospital or ICU LOS or mortality at any time point.

DATA EXTRACTION: Study data were abstracted by two independent reviewers using a standardized data extraction form.

DATA SYNTHESIS: Random-effects meta-analysis was used to pool data. Among the 30 eligible studies, seven were randomized controlled trials (RCTs) and 23 were pre-post studies. Compared with usual care, HIT for early detection of patient deterioration was not associated with a reduction in hospital mortality or LOS in the meta-analyses of RCTs. In the meta-analyses of pre-post studies, HIT interventions demonstrated a significant association with improved hospital mortality for the entire study cohort (odds ratio, 0.78 [95% CI, 0.70-0.87]) and reduced hospital LOS overall.

CONCLUSIONS: HIT for early detection of patient deterioration in acute care settings was not significantly associated with improved mortality or LOS in the meta-analyses of RCTs. In the meta-analyses of pre-post studies, HIT was associated with improved hospital mortality and LOS; however, these results should be interpreted with caution. The differences in patient outcomes between the findings of the RCTs and pre-post studies may be secondary to confounding caused by unmeasured improvements in practice and workflow over time.

# 早期检测患者病情恶化的健康信息技术对医院急性护理环境中死亡率和住院时间的影响：系统评价和荟萃分析。

摘要：

目的：旨在评价健康信息技术 (HIT) 对患者恶化的早期检测对急诊医院环境中患者死亡率和住院时间 (LOS) 的影响。

数据来源：我们检索了 1990 年至 2021 年 1 月 19 日期间的 MEDLINE 和 Epub Ahead of Print、In-Process&Other Non-Indexed Citations and Daily、Embase、Cochrane Central Register of Controlled Trials、Cochrane Database of Systematic Reviews 和 Scopus。

研究选择：我们纳入的研究入组了在地板上住院、在 ICU 住院或通过急诊科住院的患者。

符合条件的研究比较了 HIT 与常规护理早期检测患者恶化，并报告了至少一个关注终点：医院或 ICU LOS 或任何时间点的死亡率。

数据提取：由两名独立的审查员使用标准化的数据提取表提取研究数据。

数据综合：采用随机效应荟萃分析汇总数据。30 项合格研究中，7 项为随机对照试验 (RCT)，23 项为前后研究。在 RCT 的荟萃分析中，与常规护理相比，HIT 用于早期检测患者恶化与住院死亡率或 LOS 的降低无关。在对治疗前 - 治疗后研究进行的荟萃分析中，HIT 干预与整个研究队列中住院死亡率的改善存在显著相关性（比值比，0.78 [95% CI，0.70-0.87]），并总体上减少了住院 LOS。

结论：在 RCT 的荟萃分析中，HIT 早期检测急症患者恶化与死亡率或 LOS 改善无显著相关性。在治疗前后研究的荟萃分析中，HIT 与住院死亡率和 LOS 改善相关；然而，这些结果应谨慎解释。RCT 结果和治疗前 - 治疗后研究结果之间的患者结局差异可能是继发于实践和工作流程随时间推移的未测改善所造成的混杂。

# The Feasibility of Implementing Targeted SEDation in Mechanically Ventilated Emergency Department Patients: The ED-SED Pilot Trial.

8:1224-1235. DOI:10.1097/CCM.0000000000005558

Abstract:

OBJECTIVES: Deep sedation in the emergency department (ED) is common, increases deep sedation in the ICU, and is negatively associated with outcome. Limiting ED deep sedation may, therefore, be a high-yield intervention to improve outcome. However, the feasibility of conducting an adequately powered ED-based clinical sedation trial is unknown.

Our objectives were to assess trial feasibility in terms of: 1) recruitment, 2) protocol implementation and practice change, and 3) safety. Patient-centered clinical outcomes were assessed to better plan for a future large-scale clinical trial.

DESIGN: Pragmatic, multicenter ( n = 3), prospective before-after pilot and feasibility trial.

SETTING: The ED and ICUs at three medical centers.

PATIENTS: Consecutive, adult mechanically ventilation ED patients.

INTERVENTIONS: An educational initiative aimed at reliable ED sedation depth documentation and reducing the proportion of deeply sedated patients (primary outcome).

MEASUREMENTS AND MAIN RESULTS: Sedation-related data in the ED and the first 48 ICU hours were recorded. Deep sedation was defined as a Richmond Agitation-Sedation Scale of -3 to -5 or a Sedation-Agitation Scale of 1-3. One thousand three hundred fifty-six patients were screened; 415 comprised the final population. Lighter ED sedation was achieved in the intervention group, and the proportion of deeply sedated patients was reduced from 60.2% to 38.8% ( p < 0.01). There were no concerning trends in adverse events (i.e., inadvertent extubation, device removal, and awareness with paralysis). Mortality was 10.0% in the intervention group and 20.4% in the preintervention group ( p < 0.01). Compared with preintervention, the intervention group experienced more ventilator-free days [22.0 (9.0) vs 19.9 (10.6)] and ICU-free days [20.8 (8.7) vs 18.1 (10.4)], p < 0.05 for both.

CONCLUSIONS: This pilot trial confirmed the feasibility of targeting the ED in order to improve sedation practices and reduce deep sedation. These findings justify an appropriately powered clinical trial regarding ED-based sedation to improve clinical outcomes.

# 在机械通气的急诊科患者中实施靶向镇静的可行性：ED-SED 初探性试验。

摘要：

目的：急诊科 (ED) 中深度镇静很常见，增加了 ICU 中的深度镇静，并且与结局呈负相关。因此，限制 ED 深度镇静可能是改善结局的一种高收益干预。但是，尚不清楚进行具有足够效能的基于 ED 的临床镇静试验的可行性。

我们的目的是评估试验在以下方面的可行性：1）招募，2）方案实施和实践变更，以及 3）安全性。评估了以患者为中心的临床结局，以更好地计划未来的大规模临床试验。

设计：实用、多中心 (n = 3)、前瞻性先导后可行性试验。

单位：三家医疗中心的急诊科 (ED) 和重症监护室 (ICU)。

患者：连续的成人机械通气 ED 患者。

干预：一项旨在提供可靠的 ED 镇静深度记录并降低深度镇静患者比例（主要结局）的教育倡议。

测量和主要结果：记录 ED 和前 48 小时 ICU 内的镇静相关数据。深度镇静定义为 Richmond 躁动 - 镇静量表为 - 3 至 - 5 或镇静 - 躁动量表为 1-3。共筛选了 1356 例患者；415 例患者组成最终人群。干预组达到了更轻的 ED 镇静，深度镇静患者的比例从 60.2% 降至 38.8%(p < 0.01)。不良事件（即，意外拔管、器械移除和瘫痪意识）无相关趋势。干预组死亡率为 10.0%，干预前组为 20.4%(p < 0.01)。与干预前相比，干预组出现更多的无呼吸机天数 [22.0 (9.0) vs 19.9 (10.6)] 和无 ICU 天数 [20.8 (8.7) vs 18.1 (10.4)]，两者均为 p < 0.05。

结论：此项初探性试验证实了靶向 ED 以改善镇静实践和减少深度镇静的可行性。这些结果证明了关于基于 ED 镇静以改善临床结局的具有适当把握度的临床试验的合理性。

# Outcomes After Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis., Martin, Claudio M.

8:1256-1264. DOI:10.1097/CCM.0000000000005533

Abstract:

OBJECTIVES: To compare health service use and clinical outcomes for patients with and without direct discharge to home (DDH) from ICUs in Ontario.

DESIGN: Population-based, observational, cohort study using propensity scoring to match patients who were DDH to those not DDH and a preference-based instrumental variable (IV) analysis using ICU-level DDH rate as the IV.

SETTING: ICUs in Ontario.

PATIENTS: Patients discharged home from a hospitalization either directly or within 48 hours of care in an ICU between April 1, 2015, and March 31, 2017.

INTERVENTION: DDH from ICU.

MEASUREMENTS AND MAIN RESULTS: Among 76,737 patients in our cohort, 46,859 (61%) were DDH from the ICU. In the propensity matched cohort, the odds for our primary outcome of hospital readmission or emergency department (ED) visit within 30 days were not significantly different for patients DDH (odds ratio [OR], 1.00; 95% CI, 0.96-1.04), and there was no difference in mortality at 90 days for patients DDH (OR, 1.08; 95% CI, 0.97-1.21). The effect on hospital readmission or ED visits was similar in the subgroup of patients discharged from level 2 (OR, 0.98; 95% CI, 0.92-1.04) and level 3 ICUs (OR, 1.02; 95% CI, 0.96-1.09) and in the subgroups with cardiac conditions (OR, 1.03; 95% CI, 0.96-1.12) and noncardiac conditions (OR, 0.98; 95% CI, 0.94-1.03). Similar results were obtained in the IV analysis (coefficient for hospital readmission or ED visit within 30 d = -0.03 ?± 0.03 ( se ); p = 0.3).

CONCLUSIONS: There was no difference in outcomes for patients DDH compared with ward transfer prior to discharge when two approaches were used to minimize confounding within a large health systemwide observational cohort. We did not evaluate how patients are selected for DDH. Our results suggest that with careful patient selection, this practice might be feasible for routine implementation to ensure efficient and safe use of limited healthcare resources.

# 从重症监护室直接出院回家后的结局：基于人群的队列分析。

摘要：

目的：比较安大略省 ICUs 直接出院患者和未直接出院患者 (DDH) 的卫生服务使用和临床结局。

设计：基于人群的观察性队列研究，使用倾向评分匹配 DDH 患者和非 DDH 患者，使用 ICU 水平 DDH 率作为 IV 的基于偏好的工具变量 (IV) 分析。

设置：安大略省的 ICU。

患者：2015 年 4 月 1 日至 2017 年 3 月 31 日，患者直接出院或在 ICU 监护 48 小时内出院。

干预：ICU 的 DDH。

测量和主要结果：在我们的队列中 76737 例患者中，46859 例 (61%) 为 ICU DDH。在倾向性匹配队列中，患者 DDH 30 天内再次入院或急诊 (ED) 就诊的主要结局的比值比无显著差异（比值比 [or]，1.00；95% CI，0.96-1.04），患者 DDH 90 天死亡率无差异 (or，1.08；95% CI，0.97-1.21)。从 2 级 (or，0.98；95% CI，0.92-1.04) 和 3 级 ICU (or，1.02；95% CI，0.96-1.09) 出院的患者亚组与心脏疾病 (or，1.03；95% CI，0.96-1.12) 和非心脏疾病 (or，0.98；95% CI，0.94-1.03) 亚组对再次入院或 ED 就诊的影响相似。IV 分析（30 d 内再次入院或急诊就诊系数 =-0.03？±0.03 (se)；p = 0.3）。

结论：当在一个大型卫生系统范围观察队列中使用两种方法将混杂最小化时，患者 DDH 的结局与出院前的病房转入无差异。我们未评估如何选择 DDH 患者。我们的研究结果表明，通过谨慎选择患者，这种做法可能适合常规实施，以确保有限医疗资源的有效和安全使用。

# Acquired von Willebrand Syndrome and Desmopressin Resistance During Venovenous Extracorporeal Membrane Oxygenation in Patients With COVID-19: A Prospective Observational Study.

8:1246-1255. DOI:10.1097/CCM.0000000000005467

Abstract:

OBJECTIVES: Although COVID-19 is associated with high von Willebrand factor (vWF) parameters promoting thrombosis, venovenous extracorporeal membrane oxygenation (vvECMO) is associated with the development of acquired von Willebrand syndrome (AVWS) promoting bleeding. This study was designed to assess both the incidence and severity of AVWS in COVID-19 patients undergoing vvECMO, and the benefit of comprehensive vWF analyses.

DESIGN: Prospective observational study.

SETTING: ICU at a tertiary-care center.

PATIENTS: Twenty-seven consecutive COVID-19 patients with acute respiratory distress syndrome (ARDS) requiring vvECMO.

MEASUREMENTS AND MAIN RESULTS: Comprehensive vWF analyses (including sodium dodecyl-sulfate polyacrylamide gel electrophoresis) were performed before, during, and after vvECMO. In a subgroup of 12 patients with AVWS, effectiveness of treatment with desmopressin was assessed. The patients' mean age was 53 years (range, 23-73), 70% were male, and all had various comorbidities. Following markedly elevated vwf antigen (vWF: Ag; mean, 546% ( sd , 282]), vWF collagen binding capacity (mean, 469% [ sd , 271]), vWF activity (vWF:A; mean, 383% [ sd , 132]), and factor VIII activity (mean, 302% [ sd , 106]), and only borderline decreases in high-molecular-weight (HMW) vWF multimers before vvECMO, all of these variables decreased and HMW vWF multimers became undetectable within hours following initiation of vvECMO. All variables fully recovered within 3-38 hours after discontinuation of vvECMO. During vvECMO, decreases in the vWF:A/vWF:Ag ratio correlated with absent HMW vWF multimers. Desmopressin did not affect vWF parameters.

CONCLUSIONS: In patients with COVID-19-associated ARDS, AVWS developed soon after initiation of vvECMO. The vWF:A/vWF:Ag ratio was a suitable screening test for AVWS. As desmopressin was ineffective, bleeding during vvECMO-associated AVWS should preferably be treated with concentrates containing vWF.

# COVID-19 患者静脉 - 静脉体外膜肺氧合期间获得性血管性血友病综合征和去氨加压素抵抗的前瞻性观察研究。

摘要

目的：尽管 COVID-19 与高血管性血友病因子 (vWF) 参数促进血栓形成相关，但是静脉 - 静脉体外膜肺氧合 (vvECMO) 与获得性血管性血友病综合征 (AVWS) 促进出血的发生相关。本研究旨在评估接受 vvECMO 的 COVID-19 患者中 AVWS 的发生率和严重程度，以及综合 vWF 分析的获益。

设计：前瞻性观察性研究。

地点：三级护理中心的 ICU。

患者：连续 27 例需要 vvECMO 的 COVID-19 急性呼吸窘迫综合征 (ARDS) 患者。

测量和主要结果：在 vvECMO 之前、期间和之后进行综合 vWF 分析（包括十二烷基硫酸钠聚丙烯酰胺凝胶电泳）。在 12 例 AVWS 患者的亚组中，评估了去氨加压素治疗的有效性。患者的平均年龄为 53 岁（范围为 23-73 岁），70% 为男性，均有各种合并症。vwf 抗原（vwf:Ag；平均值，546%(sd,282])、vwf 胶原结合能力（平均值，469%[sd,271]）、vwf 活性（vwf:A；平均值，383%[sd,132]）和因子 VIII 活性（平均值，302%[sd,106]）显著升高后，在 vvECMO、在开始 vvECMO 治疗后数小时内，所有这些变量均降低，HMW vWF 多聚体无法检出。在停止 vvECMO 后 3-38 小时内，所有变量完全恢复。在 vvECMO 期间，vWF:A/vWF:Ag 比率的降低与缺少 HMW vWF 多聚体相关。去氨加压素不影响 vWF 参数。

结论：在 COVID-19 相关 ARDS 患者中，AVWS 在开始 vvECMO 治疗后不久发生。vWF:A/vWF:Ag 比值是 AVWS 的适当筛选试验。由于去氨加压素无效，vvECMO 相关性 AVWS 期间的出血最好使用含 vWF 的浓缩液治疗。

# Relative Hypoglycemia and Lower Hemoglobin A1c-Adjusted Time in Band Are Strongly Associated With Increased Mortality in Critically Ill Patients., Krinsley, James S.

8:e664-e673. DOI:10.1097/CCM.0000000000005490

Abstract:

OBJECTIVES: To determine the associations of relative hypoglycemia and hemoglobin A1c-adjusted time in blood glucose (BG) band (HA-TIB) with mortality in critically ill patients.

DESIGN: Retrospective cohort investigation.

SETTING: University-affiliated adult medical-surgical ICU.

PATIENTS: Three thousand six hundred fifty-five patients with at least four BG tests and hemoglobin A1c (HbA1c) level admitted between September 14, 2014, and November 30, 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Patients were stratified for HbA1c bands of <6.5%; 6.5-7.9%; greater than or equal to 8.0% with optimal affiliated glucose target ranges of 70-140, 140-180, and 180-250 mg/dL, respectively. HA-TIB, a new glycemic metric, defined the HbA1c-adjusted time in band. Relative hypoglycemia was defined as BG 70-110 mg/dL for patients with HbA1c ?‰? 8.0%. Further stratification included diabetes status-no diabetes (NO-DM, n = 2,616) and preadmission treatment with or without insulin (DM-INS, n = 352; DM-No-INS, n = 687, respectively). Severity-adjusted mortality was calculated as the observed:expected mortality ratio (O:EMR), using the Acute Physiology and Chronic Health Evaluation IV prediction of mortality. Among NO-DM, mortality and O:EMR, decreased with higher TIB 70-140 mg/dL ( p < 0.0001) and were lowest with TIB 90-100%. O:EMR was lower for HA-TIB greater than or equal to 50% than less than 50% and among all DM-No-INS but for DM-INS only those with HbA1 greater than or equal to 8.0%.Among all patients with hba1c greater than or equal to 8.0% And no bg less than 70 mg/dl, mortality was 18.0% For patients with relative hypoglycemia (bg, 70-110 mg/dl) ( p < 0.0001) And was 0.0%, 12.9%, 13.0%, And 34.8% For patients with 0, 0.1-2.9, 3.0-11.9, And greater than or equal to 12.0 Hours of relative hypoglycemia ( p < 0.0001).

CONCLUSIONS: These findings have considerable bearing on interpretation of previous trials of intensive insulin therapy in the critically ill. Moreover, they suggest that BG values in the 70-110 range may be deleterious for patients with HbA1c greater than or equal to 8.0% and that the appropriate target for BG should be individualized to HbA1c levels. These conclusions need to be tested in randomized trials.

# 在危重患者中，相对低血糖和较低的血红蛋白 A1c - 调整时间与死亡率增加明显相关。

摘要：

目的：确定相对低血糖和经血红蛋白 A1c 校正的血糖 (BG) 带时间 (HA-TIB) 与重症患者死亡率的相关性。

设计：回顾性队列研究。

单位：大学附属成人内科 - 外科 ICU。

患者：2014 年 9 月 14 日至 2019 年 11 月 30 日期间收治的 30655 例至少接受 4 次 BG 检测和血红蛋白 A1c (HbA1c) 水平的患者。

干预：无。

测量值和主要结果：根据 HbA1c 范围 <6.5%、6.5-7.9%、大于或等于 8.0% 以及 70-140、140-180 和 180-250 mg/dL 的最佳附属葡萄糖目标范围对患者进行分层。HA-TIB 是一种新的血糖指标，定义为 HbA1c 校正的时间带。对于 HbA1c 患者，相对低血糖定义为 BG 70-110 mg/dL？‰?8.0%. 进一步分层包括糖尿病状态 - 无糖尿病 (no-DM，n = 2,616) 和使用或不使用胰岛素的入院前治疗（分别为 DM-INS，n = 352；DM-no-INS，n = 687）。严重程度调整的死亡率计算为观察到的：预期死亡率比 (O:EMR)，使用急性生理学和慢性健康状况评估 IV 预测死亡率。在 NO-DM 患者中，死亡率和 O:EMR 随着 TIB 70-140 mg/dL 升高而降低 (p < 0.0001)，TIB 90-100% 时最低。O：在所有 DM-No-INS 中，HA-TIB 大于或等于 50% 的 EMR 低于 50%，但对于 DM-INS，只有 HbA1 大于或等于 8.0% 的患者。在所有 hba1c≥8.0% 且 bg≤70 mg/dL 的患者中，相对低血糖患者 (bg，70-110 mg/dL) 的死亡率为 18.0%(p < 0.0001)，而相对低血糖患者 (bg，0-11.9) 的死亡率分别为 0.0%、12.9%、13.0% 和 34.8%。且发生相对低血糖的时间≥12.0 小时 (p < 0.0001)。

结论：这些结果对之前危重患者胰岛素强化治疗试验的解释有相当大的影响。此外，他们表明，对于 HbA1c 大于或等于 8.0% 的患者，BG 值在 70-110 范围内可能是有害的，应根据 HbA1c 水平个体化设定适当的 BG 目标。这些结论需要在随机试验中进行检验。

# Neurologic Outcomes of Survivors of COVID-19-Associated Acute Respiratory Distress Syndrome Requiring Intubation., Jaquet, Pierre

8:e674-e682. DOI:10.1097/CCM.0000000000005500

Abstract:

OBJECTIVES: To describe 3-6-month neurologic outcomes of survivors of COVID-19-associated acute respiratory distress syndrome, invasively ventilated in the ICU.

DESIGN: A bicentric prospective study during the two first waves of the pandemic (March to May and September to December, 2020).

SETTING: Two academic hospital ICUs, Paris, France.

PATIENTS: Adult COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated in the ICU, were eligible for a neurologic consultation between 3 and 6 months post ICU discharge.

INTERVENTIONS: Follow-up by face-to-face neurologic consultation.

MEASURES AND MAIN RESULTS: The primary endpoint was favorable functional outcome defined by a modified Rankin scale score less than 2, indicating survival with no significant disability. Secondary endpoints included mild cognitive impairment (Montreal Cognitive Assessment score < 26), ICU-acquired weakness (Medical Research Council score < 48), anxiety and depression (Hospital Anxiety and Depression score > 7), and posttraumatic stress disorder (posttraumatic stress disorder checklist for Diagnostic and Statistical Manual of Mental Disorders 5 score > 30). Of 54 eligible survivors, four non-French-speaking patients were excluded, eight patients were lost-to-follow-up, and one died during follow-up. Forty-one patients were included. Time between ICU discharge and neurologic consultation was 3.8 months (3.6-5.9 mo). A favorable functional outcome was observed in 16 patients (39%) and mild cognitive impairment in 17 of 33 patients tested (52%). ICU-acquired weakness, depression or anxiety, and posttraumatic stress disorder were reported in six of 37 cases (16%), eight of 31 cases (26%), and two of 27 cases (7%), respectively. Twenty-nine patients (74%) required rehabilitation (motor, cognitive, or psychologic). ICU and hospital lengths of stay, tracheostomy, and corticosteroids were negatively associated with favorable outcome. By contrast, use of alpha-2 agonists during ICU stay was associated with favorable outcome.

CONCLUSIONS: COVID-19-associated acute respiratory distress syndrome requiring intubation led to slight-to-severe functional disability in about 60% of survivors 4 months after ICU discharge. Cognitive impairment, muscle weakness, and psychologic symptoms were frequent. A large multicenter study is warranted to allow identification of modifiable factors for improving long-term outcome.

# 需要插管的 COVID-19 相关急性呼吸窘迫综合征生存者的神经系统结局。

目的：描述在 ICU 中接受侵入性通气的 COVID-19 相关急性呼吸窘迫综合征生存者的 3 个月神经系统结局。

设计：在前两轮大流行期间（2020 年 3 月至 5 月和 9 月至 12 月）进行的一项双中心前瞻性研究。

单位：法国巴黎，两个学术医院 ICU。

患者：成年 COVID-19 相关急性呼吸窘迫综合征幸存者，在 ICU 侵入性通气，在离开 ICU 后 3-6 个月有资格进行神经学会诊。

干预：面对面神经科会诊进行随访。

测量值和主要结果：主要终点是有利的功能结局，定义为改良 Rankin 量表评分小于 2，表示生存期无显著残疾。次要终点包括轻度认知功能障碍（蒙特利尔认知评估量表评分 <26）、ICU 获得性虚弱（医学研究委员会评分 < 48）、焦虑和抑郁（医院焦虑和抑郁评分> 7），和创伤后应激障碍（精神障碍诊断和统计手册的创伤后应激障碍检查表 5 分 > 30）。在 54 例合格存活者中，排除了 4 例非法语患者，8 例患者失访，1 例在随访期间死亡。纳入 41 例患者。从离开 ICU 到神经科会诊的时间为 3.8 个月（3.6-5.9 个月）。在检测的 33 例患者中，16 例 (39%) 观察到良好的功能结局，17 例 (52%) 观察到轻度认知功能障碍。37 例病例中分别有 6 例 (16%)、31 例病例中有 8 例 (26%) 和 27 例病例中有 2 例 (7%) 报告 ICU 获得性虚弱、抑郁或焦虑和创伤后应激障碍。29 例患者 (74%) 需要康复治疗（运动、认知或心理）。ICU 和住院时间、气管造口术和皮质类固醇与良好结局呈负相关。相比之下，在 ICU 住院期间使用 α-2 激动剂与有利结局相关。

结论：COVID-19 相关的需要插管的急性呼吸窘迫综合征在离开 ICU 4 个月后，导致约 60% 的存活者出现轻至重度功能残疾。认知障碍、肌无力和心理症状常见。有必要进行一项大型多中心研究，以确定改善长期结局的可调整因素。

# Platelet Phenotype and Function Changes With Increasing Duration of Extracorporeal Membrane Oxygenation.

8:1236-1245. DOI:10.1097/CCM.0000000000005435

Abstract:

OBJECTIVES: To investigate platelet pathophysiology associated with pediatric extracorporeal membrane oxygenation (ECMO).

DESIGN: Prospective observational study of neonatal and pediatric ECMO patients from September 1, 2016, to December 31, 2019.

SETTING: The PICU in a large tertiary referral pediatric ECMO center.

PATIENTS: Eighty-seven neonates and children (< 18 yr) supported by ECMO.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Arterial blood samples were collected on days 1, 2, and 5 of ECMO and were analyzed by whole blood flow cytometry. Corresponding clinical data for each patient was also recorded. A total of 87 patients were recruited (median age, 65 d; interquartile range [IQR], 7 d to 4 yr). The median duration of ECMO was 5 days (IQR, 3-8 d) with a median length of stay in PICU and hospital of 18 days (IQR, 10-29 d) and 35 days (IQR, 19-75 d), respectively. Forty-two patients (48%) had at least one major bleed according to a priori determined definitions, and 12 patients (14%) had at least one thrombotic event during ECMO. Platelet fibrinogen receptor expression decreased (median fluorescence intensity [MFI], 29,256 vs 26,544; p = 0.0005), while von Willebrand Factor expression increased (MFI: 7,620 vs 8,829; p = 0.0459) from day 2 to day 5 of ECMO. Platelet response to agonist, Thrombin Receptor Activator Peptide 6, also decreased from day 2 to day 5 of ECMO, as measured by binding with anti-P-selectin, PAC-1 (binds activated GPIIb/IIIa), and anti-CD63 monoclonal antibodies (P-selectin area under the curve [AUC]: 63.46 vs 42.82, respectively, p = 0.0022; PAC-1 AUC: 93.75 vs 74.46, p = 0.0191; CD63 AUC: 55.69 vs 41.76, p = 0.0020).

CONCLUSIONS: The loss of platelet response over time may contribute to bleeding during ECMO. These novel insights may be useful in understanding mechanisms of bleeding in pediatric ECMO and monitoring platelet markers clinically could allow for prediction or early detection of bleeding and thrombosis.

# 血小板表型和功能随着体外膜氧合持续时间的增加而变化。

摘要：

目的：研究儿科体外膜肺氧合 (ECMO) 相关血小板病理生理学。

设计：2016 年 9 月 1 日 - 2019 年 12 月 31 日新生儿及儿童 ECMO 患者前瞻性观察研究。

设置：大型三级转诊儿科 ECMO 中心的 PICU。

患者：87 名接受 ECMO 支持的新生儿和儿童（< 18 岁）。

干预：无。

测定和主要结果：在 ECMO 第 1、2 和 5 天采集动脉血样，并采用全血流式细胞术进行分析。还记录了每例患者的相应临床数据。共招募 87 例患者（中位年龄 65 天；四分位距 [IQR] 7 天至 4 岁）。ECMO 的中位持续时间为 5 天（IQR，3-8 天），PICU 和住院的中位住院时间分别为 18 天（IQR，10-29 天）和 35 天（IQR，19-75 天）。根据先前确定的定义，42 例患者 (48%) 至少发生一次大出血，12 例患者 (14%) 在 ECMO 期间至少发生一次血栓事件。ECMO 第 2 天至第 5 天，血小板纤维蛋白原受体表达下降（中位荧光强度 [MFI]，29,256 vs 26,544；p = 0.0005），而血管性血友病因子表达增加 (MFI：7,620 vs 8,829；p = 0.0459)。通过与抗 P - 选择素、PAC-1（与活化的 GPIIb/IIIa 结合）和抗 CD63 单克隆抗体（P - 选择素曲线下面积 [AUC]：分别为 63.46 vs 42.82，P = 0.0022；PAC-1 AUC：分别为 93.75 vs 74.46，p = 0.0191；CD63 AUC：55.69 vs 41.76，p = 0.0020）。

结论：ECMO 期间，血小板反应随时间的损失可能会导致出血。这些新见解可能有助于了解儿科 ECMO 的出血机制，临床监测血小板标志物可以预测或早期检测出血和血栓形成。

# Does Interrupting Self-Induced Lung Injury and Respiratory Drive Expedite Early Spontaneous Breathing in the Setting of Early Severe Diffuse Acute Respiratory Distress Syndrome?, Petitjeans, Fabrice

8:1272-1276. DOI:10.1097/CCM.0000000000005288

# 在早期重度弥漫性急性呼吸系统疾病背景下，阻断自身诱发的肺损伤和呼吸驱动是否会加速早期自主呼吸窘迫综合征？

# Can We Always Trust the Wisdom of the Body?, Marini, John J.

8:1268-1271. DOI:10.1097/CCM.0000000000005022

# 我们能否始终相信身体的智慧？

# Emergency Department ICUs Add Value.

8:1265-1267. DOI:10.1097/CCM.0000000000004708

# 急诊科 ICU 附加值。

# Incidence and Outcomes of Cardiopulmonary Resuscitation in ICUs: Retrospective Cohort Analysis.

DOI:10.1097/CCM.0000000000005624

Abstract:

OBJECTIVES: We aim to describe incidence and outcomes of cardiopulmonary resuscitation (CPR) efforts and their outcomes in ICUs and their changes over time.

DESIGN: Retrospective cohort analysis.

SETTING: Patient data documented in the Austrian Center for Documentation and Quality Assurance in Intensive Care database.

PATIENTS: Adult patients (age ?‰? 18 yr) admitted to Austrian ICUs between 2005 and 2019.

INTERVENTIONS: None.

MEASUREMENTS ANDN MAIN RESULTS: Information on CPR was deduced from the Therapeutic Intervention Scoring System. End points were overall occurrence rate of CPR in the ICU and CPR for unexpected cardiac arrest after the first day of ICU stay as well as survival to discharge from the ICU and the hospital. Incidence and outcomes of ICU-CPR were compared between 2005 and 2009, 2010 and 2014, and 2015 and 2019 using chi-square test. A total of 525,518 first admissions and readmissions to ICU of 494,555 individual patients were included; of these, 72,585 patients (14.7%) died in hospital. ICU-CPR was performed in 20,668 (3.9%) admissions at least once; first events occurred on the first day of ICU admission in 15,266 cases (73.9%). ICU-CPR was first performed later during ICU stay in 5,402 admissions (1.0%). The incidence of ICU-CPR decreased slightly from 4.4% between 2005 and 2009, 3.9% between 2010 and 2014, and 3.7% between 2015 and 2019 (p < 0.001). A total of 7,078 (34.5%) of 20,499 patients who received ICU-CPR survived until hospital discharge. Survival rates varied slightly over the observation period; 59,164 (12.0%) of all patients died during hospital stay without ever receiving CPR in the ICU.

CONCLUSIONS: The incidence of ICU-CPR is approximately 40 in 1,000 admissions overall and approximately 10 in 1,000 admissions after the day of ICU admission. Short-term survival is approximately four out of 10 patients who receive ICU-CPR.

# ICU 中心肺复苏的发生率和结局：回顾性队列分析。

摘要：

目的：我们旨在描述心肺复苏术 (CPR) 的发生率和结局及其在 ICU 中的结局，以及随时间的变化。

设计：回顾性队列分析。

设置：奥地利文档和质量保证中心重症监护数据库中记录的患者数据。

患者：成年患者（年龄？‰？18 岁），2005 年至 2019 年间入住奥地利 ICU。

干预：无。

测量和主要结果：CPR 信息根据治疗干预评分系统推导得出。终点是入住 ICU 第 1 天后在 ICU CPR 和非预期心脏骤停 CPR 的总体发生率以及从 ICU 和医院出院的生存率。使用卡方检验比较 2005 年和 2009 年、2010 年和 2014 年、2015 年和 2019 年之间的 ICU-CPR 发生率和结局。共纳入 494,555 例个体患者的 525,518 例首次入院和再次入院至 ICU；其中 72,585 例患者 (14.7%) 在医院死亡。在 20668 例 (3.9%) 至少一次入院的病例中进行了 ICU CPR；在 15266 例 (73.9%) 病例中首起事件发生在 ICU 入院的第一天。随后，在 5402 例入院患者 (1.0%) 的 ICU 住院期间首次进行了 ICU-CPR。ICU-CPR 的发生率从 2005 年至 2009 年的 4.4% 略微下降，2010 年至 2014 年的 3.9%，2015 年至 2019 年的 3.7%(p < 0.001)。20499 例接受 ICU-CPR 的患者中共 7078 例 (34.5%) 存活至出院。观察期间的生存率略有不同；所有患者中有 59164 例 (12.0%) 在住院期间死亡，从未在 ICU 接受过 CPR。

结论：总体 ICU CPR 的发生率约为 40/1,000 次入院，ICU 入院后的发生率约为 10/1,000 次入院。在接受 ICU-CPR 的 10 例患者中，短期存活率约为 4 例。

# Persistent But Not Transient Acute Kidney Injury Was Associated With Lower Transplant-Free Survival in Patients With Acute Liver Failure: A Multicenter Cohort Study., Cardoso, Filipe S.

7:e661-e662e. DOI:10.1097/CCM.0000000000005563

Abstract:

OBJECTIVES: Acute liver failure (ALF) is an orphan disease often complicated by acute kidney injury (AKI). We assessed the impact of transient versus persistent AKI on survival in patients with ALF.

DESIGN: International multicenter retrospective cohort.

SETTING: U.S. ALF Study Group prospective registry.

PATIENTS: Patients with greater than or equal to 18 years and ALF in the registry from 1998 to 2016 were included. Patients with less than 3 days of follow-up, without kidney function evaluation on day 3, or with cirrhosis were excluded.

INTERVENTIONS: AKI was defined by Kidney Disease Improving Global Outcomes guidelines on day 1. Kidney recovery was defined on day 3 as transient AKI, by a return to no-AKI within 48 hours or persistent AKI if no such recovery or renal replacement therapy (RRT) was observed. Primary outcome was transplant-free survival (TFS) at 21 days.

MEASUREMENTS AND MAIN RESULTS: Among 1,071 patients with ALF, 339 (31.7%) were males, and median (interquartile range) age was 39 years (29-51 yr). Acetaminophen-related ALF was found in 497 patients (46.4%). On day 1, 485 of 1,071 patients (45.3%) had grade 3-4 hepatic encephalopathy (HE), 500 of 1,070 (46.7%) required invasive mechanical ventilation (IMV), 197 of 1,070 (18.4%) were on vasopressors, and 221 of 1,071 (20.6%) received RRT. On day 1, 673 of 1,071 patients (62.8%) had AKI. On day 3, 72 of 1,071 patients (6.7%) had transient AKI, 601 of 1,071 (56.1%) had persistent AKI, 71 of 1,071 (6.6%) had late onset AKI, and 327 of 1,071 (30.5%) remained without AKI. Following adjustment for confounders (age, sex, race, etiology, HE grade, use of IMV and vasopressors, international normalized ratio, and year), although persistent acute kidney injury (adjusted odds ratio [aOR] [95% CI] 0.62 [0.44-0.88]) or late onset AKI (aOR [95% CI] 0.48 [0.26-0.89]) was associated with lower TFS, transient AKI was not (aOR [95% CI] 1.89 [0.99-3.64]).

CONCLUSIONS: In a multicenter cohort of patients with ALF, persistent but not transient AKI was independently associated with lower short-term TFS.

# 急性肝衰竭患者中持续性但非一过性急性肾损伤与无移植生存率降低相关：一项多中心研究队列研究。

摘要

目的：急性肝衰竭 (ALF) 是一种孤儿病，通常会并发急性肾损伤 (AKI)。我们评估了一过性与持续性 AKI 对 ALF 患者生存率的影响。

设计：国际多中心回顾性队列研究。

设置：美国 ALF 研究组前瞻性登记研究。

患者：纳入 1998 年至 2016 年登记研究中年龄≥18 岁的 ALF 患者。随访小于 3 天、第 3 天未进行肾功能评价或患有肝硬化的患者被排除。

干预：AKI 根据第 1 天改善全球肾脏病预后组织指南定义。肾脏恢复第 3 天定义为短暂性 AKI，即 48 小时内恢复至无 AKI 水平，或如果未观察到这种恢复或肾脏替代治疗 (RRT) 则定义为持续性 AKI。主要结局为 21 天的无移植生存率 (TFS)。

测量和主要结果：在 1,071 例 ALF 患者中，339 例 (31.7%) 为男性，中位（四分位距）年龄为 39 岁（29-51 岁）。497 例患者 (46.4%) 发现对乙酰氨基酚相关 ALF。第 1 天，1,071 例患者中有 485 例 (45.3%) 发生 3-4 级肝性脑病 (HE)，1,070 例患者中有 500 例 (46.7%) 需要侵入性机械通气 (IMV)，1,070 例患者中有 197 例 (18.4%) 正在接受血管加压药，1,071 例患者中有 221 例 (20.6%) 接受 RRT。第 1 天，1,071 例患者中有 673 例 (62.8%) 发生 AKI。在第 3 天，1,071 例患者中有 72 例 (6.7%) 发生一过性 AKI，1,071 例患者中有 601 例 (56.1%) 发生持续性 AKI，1,071 例患者中有 71 例 (6.6%) 发生迟发性 AKI，1,071 例患者中有 327 例 (30.5%) 保持无 AKI。在校正混杂因素（年龄、性别、人种、病因、HE 分级、IMV 和血管加压药的使用、国际标准化比值比和年份）后，尽管持续性急性肾损伤（校正比值比 [aOR][95% CI] 0.62 [0.44-0.88]）或迟发性 AKI (aOR [95% CI] 0.48 [0.26-0.89]) 与较低的 TFS 相关，一过性 AKI 不是 (aOR [95% CI] 1.89 [0.99-3.64])。

结论：在 ALF 患者的多中心队列中，持续性但非一过性 AKI 与较低的短期 TFS 独立相关。

# The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis.

Abstract:

OBJECTIVE: Hepatorenal syndrome (HRS) is associated with high rates of morbidity and mortality. Evidence examining commonly used drug treatments remains uncertain. We assessed the comparative effectiveness of inpatient treatments for HRS by performing a network meta-analysis of randomized clinical trials (RCTs).

DATA SOURCES: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Medline In-Process & Other Non-Indexed Citations, Scopus, and Web of Science from inception.

STUDY SELECTION AND DATA EXTRACTION: Pairs of reviewers independently identified eligible RCTs that enrolled patients with type 1 or 2 HRS. Pairs of reviewers independently extracted data.

DATA SYNTHESIS: We assessed risk of bias using the Cochrane tool for RCTs and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach. Our main outcomes are all-cause mortality, HRS reversal, and serious adverse events. Of 3,079 citations, we included 26 RCTs examining 1,736 patients. Based on pooled analysis, terlipressin increases HRS reversal compared with placebo (142 reversals per 1,000 [95% CI, >87.7 to >210.9]; high certainty). Norepinephrine (112.7 reversals per 1,000 [95% CI, 52.6 to >192.3]) may increase HRS reversal compared with placebo (low certainty). The effect of midodrine+octreotide (67.8 reversals per 1,000 [95% CI, <2.8 to >177.4]; very low) on HRS reversal is uncertain. Terlipressin may reduce mortality compared with placebo (93.7 fewer deaths [95% CI, 168.7 to <12.5]; low certainty). Terlipressin probably increases the risk of serious adverse events compared with placebo (20.4 more events per 1,000 [95% CI, <5.1 to >51]; moderate certainty).

CONCLUSIONS: Terlipressin increases HRS reversal compared with placebo. Terlipressin may reduce mortality. Until access to terlipressin improves, initial norepinephrine administration may be more appropriate than initial trial with midodrine+octreotide. Our review has the potential to inform future guideline and practice in the treatment of HRS.

DOI: 10.1097/CCM.0000000000005595

# 血管活性药物治疗肝肾综合征的有效性比较：一项系统评价和网络荟萃分析。

摘要：

目的：肝肾综合征 (HRS) 与高发病率和死亡率相关。检查常用药物治疗的证据仍不确定。我们通过对随机临床试验 (RCT) 进行网络荟萃分析，评估了 HRS 住院治疗的比较有效性。

数据来源：我们从一开始就检索了 MEDLINE、Embase、Cochrane 对照试验中心注册数据库、MEDLINE In-Process&Other Non-Indexed Citations、Scopus 和 Web of Science。

研究选择和数据提取：由成对的审查员独立确定入选 1 型或 2 型 HRS 患者的合格 RCT。成对审查员独立提取数据。

数据综合：我们使用 RCT 的 Cochrane 工具评估了偏倚风险，使用推荐、评估、开发和评价方法分级评估了证据的确定性。我们的主要结局是全因死亡率、HRS 逆转和严重不良事件。在 3,079 篇引文中，我们纳入了 26 项 RCT，检查了 1,736 例患者。基于汇总分析，与安慰剂相比，特利加压素增加 HRS 逆转（142 次逆转 / 1,000 [95% CI，> 87.7 至 > 210.9]；高度确定性）。与安慰剂相比，去甲肾上腺素（112.7 次逆转 / 1,000 [95% CI，52.6 至 > 192.3]）可增加 HRS 逆转（低确定性）。米多君 + 奥曲肽（67.8 次逆转 / 1000 [95% CI，<2.8 至 > 177.4]；极低）对 HRS 逆转的影响尚不确定。特利加压素与安慰剂相比可降低死亡率（死亡减少 93.7 [95% CI，168.7 至 < 12.5]；确定性较低）。特利加压素与安慰剂相比很可能增加严重不良事件的风险（每 1000 人中 20.4 起事件增加 [95% CI，<5.1 至 > 51]；中度确定性）。

结论：与安慰剂相比，特利加压素增加 HRS 逆转。特利加压素可能降低死亡率。在特利加压素使用改善之前，初始去甲肾上腺素给药可能比初始米多君 + 奥曲肽试验更合适。我们的审查有可能为未来 HRS 治疗指南和实践提供信息。

# The authors reply., Kleinpell, Ruth M.

7:e662-e663. DOI:10.1097/CCM.0000000000005545

# 作者回复。

# Omission of Dietitian as Integral Member of Critical Care Team.

7:e661-e662e. DOI: 10.1097/CCM.0000000000005536

# 遗漏营养师作为重症监护团队的成员。

Keyword: Humans; Critical Care; *Nutritionists; Patient Care Team

# The Role of Registered Dietitian Nutritionists on the Critical Care Interdisciplinary Team., Sauer, Kevin L.

7:e659-e660. DOI:10.1097/CCM.0000000000005532

# 注册营养师在重症监护跨学科团队中的作用。

Keyword: Humans; Critical Care; *Nutritionists; Clinical Competence

# Dietitians' Role in Critical Care Interdisciplinary Team Needs Better Recognition.

7:e658-e659. DOI:10.1097/CCM.0000000000005508

# 营养师在重症监护跨学科团队中的角色需要得到更好的认可。

Keyword: Humans; Critical Care; Health Knowledge, Attitudes, Practice; Surveys and Questionnaires; *Nutritionists; Patient Care Team

# The authors reply.

7:e656-e657e. DOI:10.1097/CCM.0000000000005543

# 作者回复。

# "RAISE"ing a Score to Predict Prolonged Mechanical Ventilation Following Subarachnoid Hemorrhage.

7:e655-e656e. DOI:10.1097/CCM.0000000000005507

# 预测蛛网膜下腔出血后机械通气延长的 “RAISE” 评分。

Keyword: Humans; Respiration, Artificial; Retrospective Studies; *Subarachnoid Hemorrhage/complications/therapy

# The authors reply., Shanahan, Kristen H.

7:e654-e655e. DOI:10.1097/CCM.0000000000005552

# 作者回复。

# Abandon Noninvasive Ventilation in Bronchiolitis? How Unrecognized Bias Can Lead to Problematic Conclusions., Keim, Garrett

7:e653-e654e. DOI:10.1097/CCM.0000000000005531

Keyword: Humans; Respiration, Artificial; Infant; *Bronchiolitis/therapy; *Noninvasive Ventilation

# The authors reply., Seeliger, Benjamin

7:e651-e652. DOI:10.1097/CCM.0000000000005546

# 作者回复。

# Symptomatic and Asymptomatic Intracranial Hemorrhage in Patients Receiving Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Are We Missing an Opportunity for Early Intervention?, Clarke, Jonathan

7:e650-e651. DOI:10.1097/CCM.0000000000005527

# 接受静脉 - 静脉体外膜肺氧合治疗急性呼吸窘迫的患者的症状性和无症状性颅内出血综合征：我们是否错过了早期干预的机会？

Keyword: Humans; Intensive Care Units; Retrospective Studies; *Extracorporeal Membrane Oxygenation/adverse effects; *Respiratory Distress Syndrome/therapy; Intracranial Hemorrhages/therapy

# The authors reply.

7:e649-e650. DOI:10.1097/CCM.0000000000005547

# 作者回复。

# Oversight in Executive Summary of Sepsis Guidelines 2021.

7:e649. DOI:10.1097/CCM.0000000000005522

# 败血症指导原则 2021 执行摘要的监督。

Keyword: Humans; Critical Care; *Sepsis/therapy

# Catch Me If You Can-How Herpes Simplex Virus Tries to Evade Diagnosis in Viral Encephalitis.

7:1170-1173. DOI:10.1097/CCM.0000000000005501

# 病毒性脑炎单纯疱疹病毒如何逃避诊断请抓住我。

Keyword: Humans; *Encephalitis, Viral/diagnosis; *Herpes Simplex/diagnosis; Simplexvirus

# Lung Ultrasound and Electrical Impedance as Long-Term Monitoring Tools for Acute Respiratory Failure: Sometimes No Numbers Are Better Than Bad (or Confusing) Numbers.

7:1167-1170. DOI:10.1097/CCM.0000000000005540

# 肺部超声和电阻抗作为急性呼吸衰竭的长期监测工具：有时没有数字比好（或令人困惑）编号。

Keyword: Humans; Tomography; *Respiratory Distress Syndrome/diagnostic imaging/therapy; *Respiratory Insufficiency/therapy; Electric Impedance; Lung/diagnostic imaging

# Should We Intubate Pediatric Hematopoietic Cell Transplant Patients With Respiratory Failure Sooner?

7:1163-1167. DOI:10.1097/CCM.0000000000005548

# 对有呼吸衰竭的儿童造血细胞移植患者，我们应该更快地插管吗？

Keyword: Humans; Respiration, Artificial; Child; *Hematopoietic Stem Cell Transplantation; *Respiratory Insufficiency/therapy

# Leveraging Robust Mixed Methodologies to Advance Implementation Research and Practice.

7:1159-1161. DOI:10.1097/CCM.0000000000005551

# 利用稳健混合方法推进实施研究和实践。

# REDOX REDUX? Glutamine, Catabolism, and the Urea-to-Creatinine Ratio as a Novel Nutritional Metric.

7:1156-1159. DOI:10.1097/CCM.0000000000005520

# 还原？谷氨酰胺、分解代谢和尿素 / 肌酐比值作为一种新型营养指标。

Keyword: Liver/metabolism; *Glutamine; *Urea; Creatinine/metabolism; Oxidation-Reduction

# Hey, Community-Acquired Pneumonia Is Back on the Map!

7:1153-1155. DOI:10.1097/CCM.0000000000005525

# 嘿，社区获得性肺炎又回来了！

Keyword: Humans; *Community-Acquired Infections; *Pneumonia

# Predictive Algorithms for a Crisis., Sotillo, Claudia L.

7:1150-1153. DOI:10.1097/CCM.0000000000005550.

# 危机的预测算法。

Keyword: *Algorithms

# A Palace With a Common Tongue or a Multivariate Tower of Babel?

7:1148-1149. DOI:10.1097/CCM.0000000000005549

# 有普通舌头的宫殿还是多变量的巴别塔？

# Society of Critical Care Medicine Presidential Address-51st Annual Congress, April 2022.

7:1035-1039. DOI:10.1097/CCM.0000000000005584.

# 重症监护医学学会主席致辞 - 第 51 届年会，2022 年 4 月。

Keyword: Humans; *Critical Care; *Societies, Medical

# Temperature Management in the ICU., Drewry, Anne

Abstract:

OBJECTIVE: Temperature abnormalities are recognized as a marker of human disease, and the therapeutic value of temperature is an attractive treatment target. The objective of this synthetic review is to summarize and critically appraise evidence for active temperature management in critically ill patients.

DATA SOURCES: We searched MEDLINE for publications relevant to body temperature management (including targeted temperature management and antipyretic therapy) in cardiac arrest, acute ischemic and hemorrhagic stroke, traumatic brain injury, and sepsis. Bibliographies of included articles were also searched to identify additional relevant studies.

STUDY SELECTION: English-language systematic reviews, meta-analyses, randomized trials, observational studies, and nonhuman data were reviewed, with a focus on the most recent randomized control trial evidence.

DATA EXTRACTION: Data regarding study methodology, patient population, temperature management strategy, and clinical outcomes were qualitatively assessed.

DATA SYNTHESIS: Temperature management is common in critically ill patients, and multiple large trials have been conducted to elucidate temperature targets, management strategies, and timing. The strongest data concerning the use of therapeutic hypothermia exist in comatose survivors of cardiac arrest, and recent trials suggest that appropriate postarrest temperature targets between 33?°C and 37.5?°C are reasonable. Targeted temperature management in other critical illnesses, including acute stroke, traumatic brain injury, and sepsis, has not shown benefit in large clinical trials. Likewise, trials of pharmacologic antipyretic therapy have not demonstrated improved outcomes, although national guidelines do recommend treatment of fever in patients with stroke and traumatic brain injury based on observational evidence associating fever with worse outcomes.

CONCLUSIONS: Body temperature management in critically ill patients remains an appealing therapy for several illnesses, and additional studies are needed to clarify management strategies and therapeutic pathways.

7:1138-1147: DOI:10.1097/CCM.0000000000005556

# ICU 的温度管理。

目的：温度异常被公认为是人类疾病的标志，温度的治疗价值是一个有吸引力的治疗目标。本综合综述的目的是总结和批判性评价重症患者主动温度管理的证据。

数据来源：我们在 MEDLINE 中检索了与体温管理（包括针对性温度管理和退热治疗）在心脏骤停、急性缺血性和出血性卒中、创伤性脑损伤和败血症中相关的出版物。还检索了纳入文献的参考书目，以识别其他相关研究。

研究选择：对英文系统综述、荟萃分析、随机试验、观察性研究和非人类数据进行综述，重点关注最新的随机对照试验证据。

数据提取：定性评估关于研究方法、患者人群、温度管理策略和临床结局的数据。

数据综合：温度管理在危重患者中很常见，已经进行了多项大型试验来阐明温度目标、管理策略和时间。关于心脏骤停昏迷幸存者使用治疗性低温的最强数据存在，最近的试验表明，适当的骤停后温度目标在 33℃-37.5℃是合理的。其他危重疾病（包括急性卒中、创伤性脑损伤和败血症）的靶向温度管理在大型临床试验中未显示获益。同样，药物退热治疗的试验也未显示结局改善，但根据发热与较差结局相关的观察性证据，国家指南确实建议治疗卒中和创伤性脑损伤患者的发热。

结论：重症患者的体温管理仍然是几种疾病的一种有吸引力的疗法，需要额外的研究来阐明管理策略和治疗途径。

Keyword: Humans; *Intensive Care Units; *Temperature

# Early Neuromuscular Electrical Stimulation in Addition to Early Mobilization Improves Functional Status and Decreases Hospitalization Days of Critically Ill Patients.

7:1116-1126. DOI:10.1097/CCM.0000000000005557.

Abstract:

OBJECTIVES: To evaluate the impact of the additional use of early neuromuscular electrical stimulation (NMES) on an early mobilization (EM) protocol.

DESIGN: Randomized controlled trial.

SETTING: ICU of the Clinical Hospital of Ribeirão Preto, University of São Paulo, Brazil.

PATIENTS: One hundred and thirty-nine consecutive mechanically ventilated patients were included in the first 48 hours of ICU admission.

INTERVENTIONS: The patients were divided into two groups: EM and EM+NMES. Both groups received EM daily. In the EM+NMES group, patients additionally received NMES 5 days a week, for 60 minutes, starting in the first 48 hours of ICU admission until ICU discharge.

MEASUREMENTS AND MAIN RESULTS: Functional status, muscle strength, ICU and hospital length of stay (LOS), frequency of delirium, days on mechanical ventilation, mortality, and quality of life were assessed. Patients in the EM+NMES group presented a significant higher score of functional status measured by the Functional Status Score for the ICU scale when compared with the EM group in the first day awake: 22 (15-26) versus 12 (8-22) (p = 0.019); at ICU discharge: 28 (21-33) versus 18 (11-26) (p = 0.004); and hospital discharge: 33 (27-35) versus 25 (17-33) (p = 0.014), respectively. They also had better functional status measured by the Physical Function Test in the ICU scale, took less days to stand up during the ICU stay, and had a significant shorter hospital LOS, lower frequency of ICU-acquired weakness, and better global muscle strength.

CONCLUSIONS: The additional application of early NMES promoted better functional status outcomes on the first day awake and at ICU and hospital discharge. The patients in the EM+NMES group also took fewer days to stand up and had shorter hospital LOS, lower frequency of ICU-acquired weakness, and better muscle strength. Future studies are still necessary to clarify the effects of therapies associated with EM, especially to assess long-term outcomes.

# 早期神经肌肉电刺激联合早期活动可改善危重患者的功能状态并减少住院天数。

目的：评价额外使用早期神经肌肉电刺激 (NMES) 对早期活动 (EM) 方案的影响。

设计：随机对照试验。

设置：巴西圣保罗大学里贝朗普雷托临床医院 ICU。

患者：在进入 ICU 的前 48 小时内，连续纳入 139 例机械通气患者。

干预：将患者分为两组：EM 和 EM + NMES。两组均每日接受 EM。在 EM + NMES 组，患者额外接受 NMES，每周 5 天，持续 60 min，从进入 ICU 的前 48 小时开始，直至离开 ICU。

测量和主要结果：评估功能状态、肌力、ICU 和住院时间 (LOS)、谵妄频率、机械通气天数、死亡率和生活质量。在第 1 天清醒时，与 EM 组相比，EM + NMES 组患者通过 ICU 量表的功能状态评分测量的功能状态评分显著较高：22 (15-26) vs 12 (8-22)(p = 0.019)；在离开 ICU 时：28 (21-33) vs 18 (11-26)(p = 0.004)；和出院：分别为 33 例 (27-35) 和 25 例 (17-33)(p = 0.014)。通过 ICU 量表身体功能试验测得他们的功能状态更好，在 ICU 住院期间站立的天数更少，住院 LOS 显著更短，ICU 获得性虚弱的频率更低，且整体肌肉力量更好。

结论：早期 NMES 的额外应用在第一天清醒时以及 ICU 和出院时促进更好的功能状态结局。EM + NMES 组的患者站立的天数更少，住院 LOS 更短，ICU 获得性无力的频率更低，肌肉力量更好。未来的研究仍有必要阐明 EM 相关治疗的作用，尤其是评估长期结局。

Keyword: Humans; Intensive Care Units; Length of Stay; Respiration, Artificial; Quality of Life; Electric Stimulation; *Critical Illness/therapy; *Early Ambulation; Functional Status

# The Global Open Source Severity of Illness Score (GOSSIS).

Abstract:

OBJECTIVES: To develop and demonstrate the feasibility of a Global Open Source Severity of Illness Score (GOSSIS)-1 for critical care patients, which generalizes across healthcare systems and countries.

DESIGN: A merger of several critical care multicenter cohorts derived from registry and electronic health record data. Data were split into training (70%) and test (30%) sets, using each set exclusively for development and evaluation, respectively. Missing data were imputed when not available. SETTING/PATIENTS: Two large multicenter datasets from Australia and New Zealand (Australian and New Zealand Intensive Care Society Adult Patient Database [ANZICS-APD]) and the United States (eICU Collaborative Research Database [eICU-CRD]) representing 249,229 and 131,051 patients, respectively. ANZICS-APD and eICU-CRD contributed data from 162 and 204 hospitals, respectively. The cohort included all ICU admissions discharged in 2014-2015, excluding patients less than 16 years old, admissions less than 6 hours, and those with a previous ICU stay.

INTERVENTIONS: Not applicable.

MEASUREMENTS AND MAIN RESULTS: GOSSIS-1 uses data collected during the ICU stay's first 24 hours, including extrema values for vital signs and laboratory results, admission diagnosis, the Glasgow Coma Scale, chronic comorbidities, and admission/demographic variables. The datasets showed significant variation in admission-related variables, case-mix, and average physiologic state. Despite this heterogeneity, test set discrimination of GOSSIS-1 was high (area under the receiver operator characteristic curve [AUROC], 0.918; 95% CI, 0.915-0.921) and calibration was excellent (standardized mortality ratio [SMR], 0.986; 95% CI, 0.966-1.005; Brier score, 0.050). Performance was held within ANZICS-APD (AUROC, 0.925; SMR, 0.982; Brier score, 0.047) and eICU-CRD (AUROC, 0.904; SMR, 0.992; Brier score, 0.055). Compared with GOSSIS-1, Acute Physiology and Chronic Health Evaluation (APACHE)-IIIj (ANZICS-APD) and APACHE-IVa (eICU-CRD), had worse discrimination with AUROCs of 0.904 and 0.869, and poorer calibration with SMRs of 0.594 and 0.770, and Brier scores of 0.059 and 0.063, respectively.

CONCLUSIONS: GOSSIS-1 is a modern, free, open-source inhospital mortality prediction algorithm for critical care patients, achieving excellent discrimination and calibration across three countries.

7:1040-1050. DOI:10.1097/CCM.0000000000005518

# 全球开源疾病严重程度评分 (GOSSIS)。

目的：开发和证明重症监护患者的全球开源疾病严重程度评分 (GOSSIS)-1 的可行性，该评分在整个卫生保健系统和国家均适用。

设计：从登记研究和电子健康记录数据中得出的几个重症监护多中心队列的合并。将数据分为培训 (70%) 和测试 (30%) 集，分别使用每个集专门用于开发和评价。缺失数据在不可用时进行插补。设置 / 患者：来自澳大利亚和新西兰（澳大利亚和新西兰重症监护协会成人患者数据库 [ANZICS-APD]）和美国（eICU 合作研究数据库 [eICU-CRD]）的两个大型多中心数据集，分别代表 249,229 例患者和 131,051 例患者。ANZICS-APD 和 eICU-CRD 分别提供了 162 家医院和 204 家医院的数据。该队列纳入了 2014-2015 年所有 ICU 出院患者，不包括小于 16 岁的患者、住院小于 6 小时的患者和既往留住 ICU 的患者。

干预：不适用。

测量和主要结果：GOSSIS-1 使用在 ICU 停留的最初 24 小时收集的数据，包括生命体征和实验室结果的极值、入院诊断、格拉斯哥昏迷量表、慢性合并症和入院 / 人口统计学变量。数据集显示入院相关变量、病例混合和平均生理状态有显著变化。尽管存在这种异质性，但 GOSSIS-1 的试验集区分度较高（受试者工作特征曲线下面积 [AUROC]，0.918；95% CI，0.915-0.921），并且校准良好（标准化死亡率 [SMR]，0.986；95% CI，0.966-1.005；Brier 评分，0.050）。性能在 ANZICS-APD（AUROC，0.925；SMR，0.982；Brier 评分，0.047）和 eICU-CRD（AUROC，0.904；SMR，0.992；Brier 评分，0.055）范围内。与 GOSSIS-1 相比，急性生理学和慢性健康状况评分 (APACHE)-IIIj (ANZICS-APD) 和 APACHE?IVa (eICU-CRD)，AUROCs 为 0.904 和 0.869 时的辨别较差，SMR 为 0.594 和 0.770 时的校准较差，Brier 评分分别为 0.059 和 0.063。

结论：GOSSIS-1 是一种现代、免费、开源的危重患者住院死亡率预测算法，在三个国家实现了极好的区分和校准。

Keyword: Humans; APACHE; Adult; Adolescent; Australia; Hospital Mortality; *Intensive Care Units; *Critical Care

# Preintubation Sequential Organ Failure Assessment Score for Predicting COVID-19 Mortality: External Validation Using Electronic Health Record From 86 U.S. Healthcare Systems to Appraise Current Ventilator Triage Algorithms., Keller, Michael B.

7:1051-1062. DOI:10.1097/CCM.0000000000005534.

Abstract:

OBJECTIVES: Prior research has hypothesized the Sequential Organ Failure Assessment (SOFA) score to be a poor predictor of mortality in mechanically ventilated patients with COVID-19. Yet, several U.S. states have proposed SOFA-based algorithms for ventilator triage during crisis standards of care. Using a large cohort of mechanically ventilated patients with COVID-19, we externally validated the predictive capacity of the preintubation SOFA score for mortality prediction with and without other commonly used algorithm elements.

DESIGN: Multicenter, retrospective cohort study using electronic health record data.

SETTING: Eighty-six U.S. health systems.

PATIENTS: Patients with COVID-19 hospitalized between January 1, 2020, and February 14, 2021, and subsequently initiated on mechanical ventilation.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Among 15,122 mechanically ventilated patients with COVID-19, SOFA score alone demonstrated poor discriminant accuracy for inhospital mortality in mechanically ventilated patients using the validation cohort (area under the receiver operating characteristic curve [AUC], 0.66; 95% CI, 0.65-0.67). Discriminant accuracy was even poorer using SOFA score categories (AUC, 0.54; 95% CI, 0.54-0.55). Age alone demonstrated greater discriminant accuracy for inhospital mortality than SOFA score (AUC, 0.71; 95% CI, 0.69-0.72). Discriminant accuracy for mortality improved upon addition of age to the continuous SOFA score (AUC, 0.74; 95% CI, 0.73-0.76) and categorized SOFA score (AUC, 0.72; 95% CI, 0.71-0.73) models, respectively. The addition of comorbidities did not substantially increase model discrimination. Of 36 U.S. states with crisis standards of care guidelines containing ventilator triage algorithms, 31 (86%) feature the SOFA score. Of these, 25 (81%) rely heavily on the SOFA score (12 exclusively propose SOFA; 13 place highest weight on SOFA or propose SOFA with one other variable).

CONCLUSIONS: In a U.S. cohort of over 15,000 ventilated patients with COVID-19, the SOFA score displayed poor predictive accuracy for short-term mortality. Our findings warrant reappraisal of the SOFA score's implementation and weightage in existing ventilator triage pathways in current U.S. crisis standards of care guidelines.

# 插管前序贯器官功能衰竭评分预测 COVID-19 死亡率：使用美国 86 家医疗保健系统的电子健康记录评估当前呼吸机分类算法的外部验证。

目的：既往研究假设序贯器官衰竭评估 (SOFA) 评分是 COVID-19 机械通气患者死亡率的较差预测因子。但是，几个美国各州已经提出了在危象标准治疗期间基于 SOFA 的算法来进行呼吸机分类。使用一个大型队列的 COVID-19 机械通气患者，我们外部验证了插管前 SOFA 评分对死亡率预测的预测能力，使用和不使用其他常用的算法元素。

设计：采用电子健康记录数据的多中心、回顾性队列研究。

单位：86 个美国卫生系统。

患者：COVID-19 患者于 2020 年 1 月 1 日至 2021 年 2 月 14 日住院，随后开始机械通气。

干预：无。

测量值和主要结果：在 15,122 例具有 COVID-19 的机械通气患者中，使用验证队列（接受者操作特征曲线下面积 [AUC]，0.66；95% CI，0.65-0.67），仅 SOFA 评分对机械通气患者住院死亡率的鉴别准确性较差。使用 SOFA 评分类别 (AUC，0.54；95% CI，0.54-0.55) 判别准确性更差。单独年龄对住院死亡率的判别准确性大于 SOFA 评分 (AUC，0.71；95% CI，0.69-0.72)。在连续 SOFA 评分 (AUC，0.74；95% CI，0.73-0.76) 和分类 SOFA 评分 (AUC，0.72；95% CI，0.71-0.73) 模型中添加年龄后，死亡率的判别准确性得到改善。增加合并症并未显著增加模型鉴别。在 36 个美国州的危象标准护理指南中包含呼吸机分类算法，31 个州 (86%) 具有 SOFA 评分。其中，25 例 (81%) 严重依赖于 SOFA 评分（12 例专门提出 SOFA；13 例在 SOFA 上放置最高权重或提出 SOFA 与另一个变量）。

结论：在英国在超过 15000 例 COVID-19 通气患者的美国队列中，SOFA 评分对短期死亡率的预测准确性较差。我们的研究结果需要重新评估 SOFA 评分的实施情况和当前美国危象护理标准指南中现有呼吸机分类途径的权重。

Keyword: Humans; Prognosis; Intensive Care Units; Retrospective Studies; Hospital Mortality; ROC Curve; *COVID-19; Algorithms; *Organ Dysfunction Scores; Delivery of Health Care; Electronic Health Records; Triage; Ventilators, Mechanical

# Can Early Electroencephalography Findings Predict Survival and Functional Outcome in Patients With Severe COVID-19 Infection?, Bermeo-Ovalle, Adriana

# 早期脑电图结果能否预测重度 COVID-19 感染患者的生存和功能结局？

Keyword: Humans; Brain; *COVID-19; Electroencephalography

# The Use and Duration of Preintubation Respiratory Support Is Associated With Increased Mortality in Immunocompromised Children With Acute Respiratory Failure., Lindell, Robert B.

7:1127-1137. DOI:10.1097/CCM.0000000000005535

Abstract:

OBJECTIVES: To determine the association between preintubation respiratory support and outcomes in patients with acute respiratory failure and to determine the impact of immunocompromised (IC) diagnoses on outcomes after adjustment for illness severity.

DESIGN: Retrospective multicenter cohort study.

SETTING: Eighty-two centers in the Virtual Pediatric Systems database.

PATIENTS: Children 1 month to 17 years old intubated in the PICU who received invasive mechanical ventilation (IMV) for greater than or equal to 24 hours.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: High-flow nasal cannula (HFNC) or noninvasive positive-pressure ventilation (NIPPV) or both were used prior to intubation in 1,825 (34%) of 5,348 PICU intubations across 82 centers. When stratified by IC status, 50% of patients had no IC diagnosis, whereas 41% were IC without prior hematopoietic cell transplant (HCT) and 9% had prior HCT. Compared with patients intubated without prior support, preintubation exposure to HFNC (adjusted odds ratio [aOR], 1.33; 95% CI, 1.10-1.62) or NIPPV (aOR, 1.44; 95% CI, 1.20-1.74) was associated with increased odds of PICU mortality. Within subgroups of IC status, preintubation respiratory support was associated with increased odds of PICU mortality in IC patients (HFNC: aOR, 1.50; 95% CI, 1.11-2.03; NIPPV: aOR, 1.76; 95% CI, 1.31-2.35) and HCT patients (HFNC: aOR, 1.75; 95% CI, 1.07-2.86; NIPPV: aOR, 1.85; 95% CI, 1.12-3.02) compared with IC/HCT patients intubated without prior respiratory support. Preintubation exposure to HFNC/NIPPV was not associated with mortality in patients without an IC diagnosis. Duration of HFNC/NIPPV greater than 6 hours was associated with increased mortality in IC HCT patients (HFNC: aOR, 2.41; 95% CI, 1.05-5.55; NIPPV: aOR, 2.53; 95% CI, 1.04-6.15) and patients compared HCT patients with less than 6-hour HFNC/NIPPV exposure. After adjustment for patient and center characteristics, both preintubation HFNC/NIPPV use (median, 15%; range, 0-63%) and PICU mortality varied by center.

CONCLUSIONS: In IC pediatric patients, preintubation exposure to HFNC and/or NIPPV is associated with increased odds of PICU mortality, independent of illness severity. Longer duration of exposure to HFNC/NIPPV prior to IMV is associated with increased mortality in HCT patients.

# 插管前呼吸支持的使用和持续时间与免疫力受损的急性呼吸衰竭儿童中死亡率增加相关。

目的：确定急性呼吸衰竭患者中插管前呼吸支持与结局之间的相关性，并确定校正疾病严重程度后免疫功能低下 (IC) 诊断对结局的影响。

设计：回顾性多中心队列研究。

设置：Virtual Pediatric Systems 数据库中的 82 家中心。

患者：在 PICU 接受插管，接受有创机械通气 (IMV)≥24 小时的 1 个月 - 17 岁儿童。

干预：无。

测量和主要结果：在 82 家中心的 5348 次 PICU 插管中，1825 次 (34%) 在插管前采用了高流量鼻插管 (HFNC) 或非侵入性正压通气 (NIPPV) 或两者。当按 IC 状态分层时，50% 的患者无 IC 诊断，而 41% 为 IC 而既往未接受造血细胞移植 (HCT)，9% 为既往 HCT。与既往未接受支持治疗的插管患者相比，插管前暴露于 HFNC（调整后优势比 [aOR]，1.33；95% CI，1.10-1.62）或 NIPPV (aOR，1.44；95% CI，1.20-1.74) 与 PICU 死亡率优势增加相关。IC 状态亚组内，插管前呼吸支持与 IC 患者 (HFNC：aOR，1.50；95% CI，1.11-2.03；NIPPV：aOR，1.76；95% CI，1.31-2.35) 和 HCT 患者（HFNC：aOR，1.75；95% CI，1.07-2.86；NIPPV：aOR，1.85；95% CI，1.12-3.02），比较既往未接受呼吸支持的插管 IC/HCT 患者。插管前暴露于 HFNC/NIPPV 与无 IC 诊断的患者的死亡率无关。HFNC/NIPPV 持续时间大于 6 小时与 IC HCT 患者死亡率增加相关 (HFNC：aOR，2.41；95% CI，1.05-5.55；NIPPV：aOR，2.53；95% CI，1.04-6.15)，患者比较 HFNC/NIPPV 暴露小于 6 小时的 HCT 患者。调整患者和中心特征后，插管前 HFNC/NIPPV 使用（中位数，15%；范围，0-63%）和 PICU 死亡率随中心而变化。

结论：在 IC 儿科患者中，插管前暴露于 HFNC 和 / 或 NIPPV 与 PICU 死亡率增加相关，与疾病严重程度无关。在 IMV 之前暴露于 HFNC/NIPPV 的时间较长与 HCT 患者的死亡率增加相关。

Keyword: Humans; Cohort Studies; Retrospective Studies; Child; Oxygen Inhalation Therapy; *Hematopoietic Stem Cell Transplantation; *Noninvasive Ventilation; *Respiratory Distress Syndrome; *Respiratory Insufficiency; Cannula; Intubation, Intratracheal/adverse effects

# Patient Harm and Institutional Avoidability of Out-of-Hours Discharge From Intensive Care: An Analysis Using Mixed Methods.

7:1083-1092. DOI:10.1097/CCM.0000000000005514

Abstract:

OBJECTIVES: Out-of-hours discharge from ICU to the ward is associated with increased in-hospital mortality and ICU readmission. Little is known about why this occurs. We map the discharge process and describe the consequences of out-of-hours discharge to inform practice changes to reduce the impact of discharge at night.

DESIGN: This study was part of the REcovery FoLlowing intensive CarE Treatment mixed methods study. We defined out-of-hours discharge as 16:00 to 07:59 hours. We undertook 20 in-depth case record reviews where in-hospital death after ICU discharge had been judged "probably avoidable" in previous retrospective structured judgment reviews, and 20 where patients survived. We conducted semistructured interviews with 55 patients, family members, and staff with experience of ICU discharge processes. These, along with a stakeholder focus group, informed ICU discharge process mapping using the human factors-based functional analysis resonance method.

SETTING: Three U.K. National Health Service hospitals, chosen to represent different hospital settings.

SUBJECTS: Patients discharged from ICU, their families, and staff involved in their care.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Out-of-hours discharge was common. Patients and staff described out-of-hours discharge as unsafe due to a reduction in staffing and skill mix at night. Patients discharged out-of-hours were commonly discharged prematurely, had inadequate handover, were physiologically unstable, and did not have deterioration recognized or escalated appropriately.

We identified five interdependent function keys to facilitating timely ICU discharge: multidisciplinary team decision for discharge, patient prepared for discharge, bed meeting, bed manager allocation of beds, and ward bed made available.

CONCLUSIONS: We identified significant limitations in out-of-hours care provision following overnight discharge from ICU. Transfer to the ward before 16:00 should be facilitated where possible. Our work highlights changes to help make day time discharge more likely. Where discharge after 16:00 is unavoidable, support systems should be implemented to ensure the safety of patients discharged from ICU at night.

# 从重症监护中出院的患者损害和机构可避免性：使用混合方法的分析。

目的：离开 ICU 离开 ICU 的时间延长与住院死亡率和再次入住 ICU 相关。目前尚不清楚这种情况的原因。我们绘制了放电过程图，并描述了非工作时间放电的后果，以通知实践变化，减少夜间放电的影响。

设计：本研究是 REcovery FoLlowing 强化 CarE 治疗混合方法研究的一部分。我们将非工作时间出院定义为 16:00 至 07:59 小时。我们进行了 20 项深度病例记录审查，其中在既往回顾性结构化判断审查中，ICU 出院后的院内死亡被判定为 “很可能可以避免”，20 例患者存活。我们对 55 例有 ICU 出院过程经验的患者、家属和工作人员进行了半结构式访谈。这些人员与利益攸关方小组一起，使用基于人为因素的功能分析共振法绘制知情 ICU 出院过程图。

背景：选择 3 家英国国家卫生服务医院代表不同的医院环境。

受试者：从 ICU 出院的患者及其家属和参与其护理的工作人员。

干预：无。

测量和主要结果：通常在非工作时间出院。由于夜间人员配备和技术组合减少，患者和工作人员描述非工作时间出院不安全。非工作时间出院的患者通常提前出院、交接不充分、生理不稳定，且未发现恶化或适当升级。我们确定了 5 个相互依赖的功能关键，以促进 ICU 及时出院：多学科团队决定出院、患者准备出院、床位会议、床位管理者分配床位和提供病床。

结论：我们确定了从 ICU 过夜出院后非工作时间护理的显著局限性。尽可能在 16:00 之前转移到病房。我们的工作重点是做出改变，使您更有可能在白天出院。16:00 以后不可避免出院的，应实施支持系统，保证夜间离开 ICU 患者的安全。

Keyword: Humans; Intensive Care Units; Retrospective Studies; Hospital Mortality; Critical Care/methods; *After-Hours Care; *Patient Harm; Patient Discharge; State Medicine

# Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial.

7:1072-1082. DOI:10.1097/CCM.0000000000005499

Abstract:

OBJECTIVES: Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay.

DESIGN: Reanalysis of multicenter randomized trial of glutamine supplementation in critical illness (REducing Deaths due to OXidative Stress [REDOXS]).

SETTING: Multiple adult ICUs.

PATIENTS: Adult patients admitted to ICU with two or more organ failures related to their acute illness and surviving to day 7.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The association between time-varying urea-to-creatinine ratio and 30-day mortality was tested using Bayesian joint models adjusted for prespecified-covariates (age, kidney replacement therapy, baseline Sequential Organ Failure Assessment, dietary protein [g/kg/d], kidney dysfunction, and glutamine-randomization). From 1,021 patients surviving to day 7, 166 (16.3%) died by day 30. After adjustment in a joint model, a higher time-varying urea-to-creatinine ratio was associated with increased mortality (hazard ratio [HR], 2.15; 95% credible interval, 1.66-2.82, for a two-fold greater urea-to-creatinine ratio). This association persisted throughout the 30-day follow-up. Mediation analysis was performed to explore urea-to-creatinine ratio as a mediator-variable for the increased risk of death reported in REDOXS when randomized to glutamine, an exogenous nitrogen load. Urea-to-creatinine ratio closest to day 7 was estimated to mediate the risk of death associated with randomization to glutamine supplementation (HR, 1.20; 95% CI, 1.04-1.38; p = 0.014), with no evidence of a direct effect of glutamine (HR, 0.90; 95% CI, 0.62-1.30; p = 0.566).

CONCLUSIONS: The catabolic phenotype measured by increased urea-to-creatinine ratio is associated with increased risk of death during prolonged ICU stay and signals the deleterious effects of glutamine administration in the REDOXS study. Urea-to-creatinine ratio is a promising catabolic signature and potential interventional target.

# 危重症患者中的分解代谢：氧化性应激 (REDOXS) 试验所致死亡减少的再分析。

目的：持续的死亡风险和不良功能结局是长期危重疾病的重要后果。描述长期危重疾病的分解代谢表型特征可促进生物学过程，并为减弱分解代谢的策略提供信息。我们旨在检查作为长期危重疾病分解代谢标志的尿素肌酐比是否与 ICU 住院第一周后的死亡率相关。

设计：危重病患者补充谷氨酰胺的多中心随机试验再分析（减少氧化应激导致的死亡 [REDOXS]）。

设置：多个成人 ICU。

患者：因急性疾病相关的两次或多次器官衰竭入住 ICU 并存活至第 7 天的成人患者。

干预：无。

测量值和主要结果：使用 Bayesian 关节模型检验了经预先指定协变量（年龄、肾脏替代治疗、基线序贯器官衰竭评估、饮食蛋白质 [g/kg/d]、肾功能不全和谷氨酰胺随机分组）校正的随时间变化的尿素 - 肌酐比与 30 天死亡率之间的相关性。在存活至第 7 天的 1,021 例患者中，166 例 (16.3%) 在第 30 天死亡。在联合模型中校正后，较高的随时间变化的尿素 - 肌酐比值与死亡率升高相关（风险比 [HR]，2.15；95% 置信区间，1.66-2.82，尿素 - 肌酐比值升高 2 倍）。30 天随访期间，这种相关性持续存在。进行了介导分析，以探索当随机分配至谷氨酰胺（外源性氮负荷）时，尿素 / 肌酐比值作为 REDOXS 中报告的死亡风险增加的介导变量。估计最接近第 7 天的尿素 / 肌酐比值介导了与随机分配至补充谷氨酰胺相关的死亡风险 (HR，1.20；95% CI，1.04-1.38；p = 0.014)，没有证据表明谷氨酰胺的直接效应 (HR，0.90；95% CI，0.62-1.30；p = 0.566)。

结论：通过尿素与肌酐比值升高测定的分解代谢表型与延长 ICU 住院期间的死亡风险增加相关，并在 REDOXS 研究中信号了谷氨酰胺给药的有害作用。尿素肌酐比是一种有前景的分解代谢特征和潜在的干预性靶标。

Keyword: Humans; Oxidative Stress; *Critical Illness/therapy; *Glutamine; Bayes Theorem; Creatinine; Urea

# Lung-Dependent Areas Collapse, Monitored by Electrical Impedance Tomography, May Predict the Oxygenation Response to Prone Ventilation in COVID-19 Acute Respiratory Distress Syndrome., Cardinale, Michael

7:1093-1102. DOI:10.1097/CCM.0000000000005487

Abstract:

OBJECTIVES: ICUs have had to deal with a large number of patients with acute respiratory distress syndrome COVID-19, a significant number of whom received prone ventilation, which is a substantial consumer of care time. The selection of patients that we have to ventilate in prone position seems interesting. We evaluate the correlation between the percentage of collapsed dependent lung areas in the supine position, monitoring by electrical impedance tomography and the oxygenation response (change in Pao2/Fio2 ratio) to prone position.

DESIGN: An observational prospective study.

SETTING: From October 21, 2020, to 30 March 30, 2021. At the Sainte Anne military teaching Hospital and the Timone University Hospital.

PATIENTS: Fifty consecutive patients admitted in our ICUs, with COVID-19 acute respiratory distress syndrome and required mechanical, were included. Twenty-four (48%) received prone ventilation. Fifty-eight prone sessions were investigated.

INTERVENTIONS: An electrical impedance tomography recording was made in supine position, daily and repeated just before and just after the prone session. The daily dependent area collapse was calculated in relation to the previous electrical impedance tomography recording. Prone ventilation response was defined as a Pao2/Fio2 ratio improvement greater than 20%.

MEASUREMENT AND MAIN RESULTS: The main outcome was the correlation between dependent area collapse and the oxygenation response to prone ventilation. Dependent area collapse was correlated with oxygenation response to prone ventilation (R2 = 0.49) and had a satisfactory prediction accuracy of prone response with an area under the curve of 0.94 (95% CI, 0.87-1.00; p < 0.001). Best Youden index was obtained for a dependent area collapse greater than 13.5 %. Sensitivity of 92% (95% CI, 78-97), a specificity of 91% (95% CI, 72-97), a positive predictive value of 94% (95% CI, 88-100), a negative predictive value of 87% (95% CI, 78-96), and a diagnostic accuracy of 91% (95% CI, 84-98).

CONCLUSIONS: Dependent lung areas collapse (> 13.5%), monitored by electrical impedance tomography, has an excellent positive predictive value (94%) of improved oxygenation during prone ventilation.

# 肺依赖区域塌陷，通过电阻抗断层扫描监测，可预测 COVID-19 急性呼吸窘迫综合征中对俯卧位通气的氧合反应。

目的：ICU 必须处理大量急性呼吸窘迫综合征 COVID-19 患者，其中相当数量的患者接受俯卧位通气，这是大量的护理时间消耗。选择必须在俯卧位通气的患者似乎很有趣。我们评估了仰卧位时塌陷依赖性肺区的百分比、电阻抗断层扫描监测与俯卧位时氧合反应（Pao2/Fio2 比值变化）之间的相关性。

设计：观察性前瞻性研究。

地点：2020 年 10 月 21 日至 2021 年 3 月 30 日。在 Sainte Anne 军事教学医院和 Timone 大学医院。

患者：连续纳入 50 例在我们 ICU 住院的 COVID-19 急性呼吸窘迫综合征且需要机械通气的患者。24 例患者 (48%) 接受俯卧位通气。研究了 58 次俯卧位治疗。

干预：每天在仰卧位进行电阻抗断层扫描记录，并在俯卧位前后重复。相对于之前的电阻抗断层扫描记录，计算每日依赖区域萎缩。俯卧位通气反应定义为 Pao2/Fio2 比值改善大于 20%。

测量和主要结果：主要结局是依赖区塌陷和俯卧位通气的氧合反应之间的相关性。依赖面积萎缩与俯卧位通气的氧合反应相关 (R2 = 0.49)，俯卧位反应的预测准确性令人满意，曲线下面积为 0.94 (95% CI，0.87-1.00；p < 0.001)。当依赖区塌陷大于 13.5% 时，约登指数最佳。灵敏度为 92%(95% CI，78-97)，特异性为 91%(95% CI，72-97)，阳性预测值为 94%(95% CI，88-100)，阴性预测值为 87%(95% CI，78-96)，诊断准确性为 91%(95% CI，84-98)。

结论：依赖性肺区萎缩 (> 13.5%)，通过电阻抗断层扫描监测，在俯卧位通气中氧合作用改善具有极好的阳性预测值 (94%)。

Keyword: Humans; Prospective Studies; Tomography, X-Ray Computed; Prone Position; *COVID-19/therapy; *Respiratory Distress Syndrome/therapy; Electric Impedance; Lung/diagnostic imaging; *Shock

# Etiology, Treatments, and Outcomes of Patients With Severe Community-Acquired Pneumonia in a Large U.S. Sample., Haessler, Sarah

7:1063-1071. DOI:10.1097/CCM.0000000000005498

Abstract:

OBJECTIVES: Compare the clinical practice and outcomes in severe community-acquired pneumonia (sCAP) patients to those in non-sCAP patients using guideline-defined criteria for sCAP.

DESIGN: Retrospective observational cohort study.

SETTING: One hundred seventy-seven U.S. hospitals within the Premier Healthcare Database.

PATIENTS: Hospitalized adult (?‰? 18 yr old) patients with pneumonia.

MEASUREMENTS AND MAIN RESULTS: Adult patients (?‰? 18 yr old) with a principal diagnosis of pneumonia or a secondary diagnosis of pneumonia paired with a principal diagnosis of sepsis or respiratory failure were included. Patients with at least one guideline-defined major criterion for severe pneumonia were compared with patients with nonsevere disease. Among 154,799 patients with pneumonia, 21,805 (14.1%) met criteria for sCAP. They had higher organ failure scores (1.9 vs 0.63; p < 0.001) and inpatient mortality (22.0 vs 5.0%; p < 0.001), longer lengths of stay (8 vs 5 d; p < 0.001), and higher costs ($20,046 vs $7,543; p < 0.001) than those with nonsevere disease. Patients with sCAP had twice the rate of positive blood cultures (10.0% vs 4.5%; p < 0.001) and respiratory cultures (34.2 vs 21.1%; p < 0.001) and more often had isolates resistant to first-line community-acquired pneumonia antibiotics (10% of severe vs 3.1% of nonsevere; p < 0.001). Regardless of disease severity, Streptococcus pneumoniae was the most common pathogen recovered from blood cultures and Staphylococcus aureus and Pseudomonas species were the most common pathogens recovered from the respiratory tract. Although few patients with sCAP had cultures positive for a resistant organism, 65% received vancomycin and 42.8% received piperacillin-tazobactam.

CONCLUSIONS: sCAP patients had worse outcomes and twice the rate of culture positivity. S. aureus and S. pneumoniae were the most common organisms in respiratory and blood specimens, respectively. Although only recommended for sCAP patients, nearly all pneumonia patients received blood cultures, a quarter of nonsevere patients received sputum cultures, and treatment with broad-spectrum agents was widespread, indicating fertile ground for antimicrobial and diagnostic stewardship programs.

# 一项大型美国样本研究中严重社区获得性肺炎患者的病因、治疗和结局。

目的：使用指南定义的 sCAP 标准，比较重度社区获得性肺炎 (sCAP) 患者与非 sCAP 患者的临床实践和结果。

设计：回顾性观察性队列研究。

设置：Premier Healthcare 数据库中的 177 家美国医院。

患者：肺炎成年住院患者（ ≥ 18 岁）。

测量值和主要结果：主要诊断为肺炎或次要诊断为肺炎同时主要诊断为败血症或呼吸衰竭的成人患者（ ≥ 18 岁）被纳入。将具有至少一项指南定义的重度肺炎主要标准的患者与非重度疾病患者进行比较。在 154,799 例肺炎患者中，21,805 例 (14.1%) 符合 sCAP 标准。与非重度疾病患者相比，重度疾病患者的器官衰竭评分 (1.9 vs 0.63；p < 0.001) 和住院死亡率 (22.0 vs 5.0%；p < 0.001) 更高，住院时间更长（8 vs 5 天；p < 0.001），费用更高（20,046 美元 vs 7,543 美元；p < 0.001）。sCAP 患者的血培养 (10.0% vs 4.5%；p < 0.001) 和呼吸道培养 (34.2 vs 21.1%；p < 0.001) 的阳性率是普通患者的 2 倍，更常见的分离株对一线社区获得性肺炎抗生素耐药（10% 重症 vs 3.1% 非重症；p < 0.001）。无论疾病的严重程度如何，从血培养中回收的最常见病原体为肺炎链球菌，从呼吸道回收的最常见病原体为金黄色葡萄球菌和假单胞菌属。虽然少数 sCAP 患者的耐药微生物培养呈阳性，但 65% 的患者接受万古霉素，42.8% 的患者接受哌拉西林 - 他唑巴坦。

结论：sCAP 患者预后更差，培养阳性率是普通人群的 2 倍。金黄色葡萄球菌和肺炎链球菌分别是呼吸道和血液样本中最常见的微生物。虽然只推荐 sCAP 患者使用，但是几乎所有的肺炎患者都接受了血培养，四分之一的非重症患者接受了痰培养，并且广谱抗菌药的治疗也很广泛，这表明抗菌和诊断管理方案是有利的。

Keyword: Humans; Adult; Retrospective Studies; Anti-Bacterial Agents/therapeutic use; *Community-Acquired Infections/drug therapy; *Pneumonia/drug therapy/epidemiology/etiology; Staphylococcus aureus

# Herpes Simplex Virus Encephalitis With Initial Negative Polymerase Chain Reaction in the Cerebrospinal Fluid: Prevalence, Associated Factors, and Clinical Impact., de Montmollin, Etienne

7:e643-e648. DOI:10.1097/CCM.0000000000005485

Abstract:

OBJECTIVES: To describe the prevalence, associated factors, and clinical impact of an initial negative herpes simplex virus (HSV) polymerase chain reaction (PCR) in critically ill patients with PCR-proven HSV encephalitis.

DESIGN: Retrospective multicenter study from 2007 to 2017.

SETTING: Forty-seven French ICUs.

PATIENTS: Critically ill patients admitted to the ICU with possible/probable acute encephalitis and a positive cerebrospinal fluid (CSF) PCR for HSV.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We included 273 patients with a median Glasgow Coma Scale score of 9 (6-12) at ICU admission. CSF HSV PCR was negative in 11 cases (4%), exclusively in lumbar punctures (LPs) performed less than 4 days after symptoms onset. Patients with an initial negative PCR presented with more frequent focal neurologic signs (4/11 [36.4%] vs 35/256 [13.7%]; p = 0.04) and lower CSF leukocytosis (4 cells/mm3 [3-25 cells/mm3] vs 52 cells/mm3 [12-160 cells/mm3]; p < 0.01). An initial negative PCR was associated with an increased delay between LP and acyclovir treatment (3 d [2-7 ] vs 0 d [0-0 d]; p < 0.01) and was independently associated with a poor neurologic outcome at hospital discharge (modified Rankin Scale score ?‰? 4) (adjusted odds ratio, 9.89; 95% CI, 1.18-82.78).

CONCLUSIONS: In severe herpes simplex encephalitis, initial negative CSF HSV PCR occurred in 4% of cases and was independently associated with worse neurologic outcome at hospital discharge. In these patients, a systematic multimodal diagnostic approach including early brain MRI and EEG will help clinicians avoid delayed acyclovir initiation or early inappropriate discontinuation.

# 脑脊液中聚合酶链反应初始阴性的单纯疱疹病毒性脑炎：患病率、相关因素和临床影响。

目的：描述初次单纯疱疹病毒 (HSV) 聚合酶链反应 (PCR) 阴性的重症患者中经 PCR 证实的 HSV 脑炎的患病率、相关因素和临床影响。

设计：回顾性多中心研究，2007-2017 年。

设置：47 个法国 ICU。

患者：ICU 收治的可能 / 很可能患有急性脑炎且脑脊液 (CSF) PCR 检测 HSV 呈阳性的重症患者。

干预：无。

测量和主要结果：我们纳入了 273 例入住 ICU 时中位格拉斯哥昏迷量表评分为 9 (6-12) 的患者。11 例病例 (4%) 的 CSF HSV PCR 为阴性，仅见于症状发作后不到 4 天进行的腰椎穿刺 (LP)。初始 PCR 阴性的患者表现出更常见的局灶性神经病学体征 (4/11 [36.4%] vs 35/256 [13.7%]；p = 0.04) 和更低的 CSF 白细胞增多（4 个细胞 /mm3 [3-25 个细胞 /mm3] vs 52 个细胞 /mm3 [12-160 个细胞 /mm3]；p < 0.01）。初始阴性 PCR 与 LP 和阿昔洛韦治疗之间延迟增加相关（3 天 [2-7] vs 0 天 [0-0 天]；p < 0.01），并与出院时较差的神经系统结局独立相关（改良 Rankin 量表评分 ≥ 4）（调整比值比，9.89；95% CI，1.18-82.78）。

结论：在重度单纯疱疹性脑炎中，4% 的病例初始 CSF HSV PCR 阴性，并且与出院时较差的神经系统结局独立相关。在这些患者中，一种包括早期脑部 MRI 和 EEG 的系统性多模式诊断方法将帮助临床医生避免延迟阿昔洛韦开始或早期不当停药。

Keyword: Humans; Critical Illness; Prevalence; Polymerase Chain Reaction; *Encephalitis, Herpes Simplex/diagnosis/drug therapy/epidemiology; Acyclovir/therapeutic use; Cerebrospinal Fluid; Simplexvirus/genetics

# Early Clinical and Electrophysiological Brain Dysfunction Is Associated With ICU Outcomes in COVID-19 Critically Ill Patients With Acute Respiratory Distress Syndrome: A Prospective Bicentric Observational Study.

7:1103-1115. DOI:10.1097/CCM.0000000000005491

Abstract:

OBJECTIVES: Describe the prevalence of acute cerebral dysfunction and assess the prognostic value of an early clinical and electroencephalography (EEG) assessment in ICU COVID-19 patients.

DESIGN: Prospective observational study.

SETTING: Two tertiary critical care units in Paris, France, between April and December 2020.

PATIENTS: Adult critically ill patients with COVID-19 acute respiratory distress syndrome.

INTERVENTIONS: Neurologic examination and EEG at two time points during the ICU stay, first under sedation and second 4-7 days after sedation discontinuation.

MEASUREMENTS AND MAIN RESULTS: Association of EEG abnormalities (background reactivity, continuity, dominant frequency, and presence of paroxystic discharges) with day-28 mortality and neurologic outcomes (coma and delirium recovery). Fifty-two patients were included, mostly male (81%), median (interquartile range) age 68 years (56-74 yr). Delayed awakening was present in 68% of patients (median awakening time of 5 d [2-16 d]) and delirium in 74% of patients who awoke from coma (62% of mixed delirium, median duration of 5 d [3-8 d]). First, EEG background was slowed in the theta-delta range in 48 (93%) patients, discontinuous in 25 patients (48%), and nonreactive in 17 patients (33%). Bifrontal slow waves were observed in 17 patients (33%). Early nonreactive EEG was associated with lower day-28 ventilator-free days (0 vs 16; p = 0.025), coma-free days (6 vs 22; p = 0.006), delirium-free days (0 vs 17; p = 0.006), and higher mortality (41% vs 11%; p = 0.027), whereas discontinuous background was associated with lower ventilator-free days (0 vs 17; p = 0.010), coma-free days (1 vs 22; p < 0.001), delirium-free days (0 vs 17; p = 0.001), and higher mortality (40% vs 4%; p = 0.001), independently of sedation and analgesia.

CONCLUSIONS: Clinical and neurophysiologic cerebral dysfunction is frequent in COVID-19 ARDS patients. Early severe EEG abnormalities with nonreactive and/or discontinuous background activity are associated with delayed awakening, delirium, and day-28 mortality.

# COVID-19 急性呼吸窘迫综合征危重病患者的早期临床和电生理脑功能障碍与 ICU 预后相关：一项前瞻性双中心观察性研究。

目的：描述急性脑功能障碍的患病率，并评估早期临床和脑电图 (EEG) 评估在 ICU COVID-19 患者中的预后价值。

设计：前瞻性观察性研究。

设置：2020 年 4 月至 12 月，法国巴黎的两个三级重症监护室。

患者：COVID-19 急性呼吸窘迫综合征的成年重症患者。

干预：在 ICU 住院期间的两个时间点进行神经系统检查和 EEG 检查，第一次是在镇静状态下，第二次是在镇静停止后 4-7 天。

测量和主要结果：EEG 异常（背景反应性、连续性、显性频率和存在阵发性放电）与第 28 天死亡率和神经系统结局（昏迷和谵妄恢复）的相关性。纳入了 52 例患者，大多数为男性 (81%)，中位（四分位距）年龄为 68 岁（56-74 岁）。68% 的患者存在觉醒延迟（中位觉醒时间为 5 天 [2-16 天]），74% 从昏迷中觉醒的患者存在谵妄（62% 为混合型谵妄，中位持续时间为 5 天 [3-8 天]）。首先，48 例患者 (93%) 的 EEG 背景在 θ-δ 范围内减慢，25 例患者 (48%) 不连续，17 例患者 (33%) 无反应。17 例患者 (33%) 观察到双额慢波。早期无反应性 EEG 与较低第 28 天无呼吸机天数 (0 vs 16；p = 0.025)、无昏迷天数 (6 vs 22；p = 0.006)、无谵妄天数 (0 vs 17；p = 0.006) 和较高的死亡率 (41% vs 11%；p = 0.027) 相关，而不连续背景与较低的无呼吸机天数 (0 vs 17；p = 0.010) 相关，无昏迷天数 (1 vs 22；p < 0.001)、无谵妄天数 (0 vs 17；p = 0.001) 和更高的死亡率 (40% vs 4%；p = 0.001)，与镇静和镇痛无关。

结论：COVID-19 ARDS 患者临床和神经生理性脑功能障碍常见。早期重度 EEG 异常伴无反应性和 / 或不连续背景活动与觉醒延迟、谵妄和第 28 天死亡率相关。

Keyword: Humans; Female; Male; Prospective Studies; Aged; Critical Illness; Intensive Care Units; Adult; Brain; *Brain Diseases/etiology; *COVID-19/complications; *Delirium/diagnosis/epidemiology/etiology; *Respiratory Distress Syndrome/epidemiology/therapy; Coma/diagnosis/etiology; Respiration, Artificial/adverse effects

# Lung Ultrasound and Electrical Impedance Tomography During Ventilator-Induced Lung Injury.

7:e630-e637. DOI:10.1097/CCM.0000000000005479

Abstract:

OBJECTIVES: Lung damage during mechanical ventilation involves lung volume and alveolar water content, and lung ultrasound (LUS) and electrical impedance tomography changes are related to these variables. We investigated whether these techniques may detect any signal modification during the development of ventilator-induced lung injury (VILI).

DESIGN: Experimental animal study.

SETTING: Experimental Department of a University Hospital.

SUBJECTS: Forty-two female pigs (24.2 ?± 2.0 kg).

INTERVENTIONS: The animals were randomized into three groups (n = 14): high tidal volume (TV) (mean TV, 803.0 ?± 121.7 mL), high respiratory rate (RR) (mean RR, 40.3 ?± 1.1 beats/min), and high positive-end-expiratory pressure (PEEP) (mean PEEP, 24.0 ?± 1.1 cm H2O). The study lasted 48 hours. At baseline and at 30 minutes, and subsequently every 6 hours, we recorded extravascular lung water, end-expiratory lung volume, lung strain, respiratory mechanics, hemodynamics, and gas exchange. At the same time-point, end-expiratory impedance was recorded relatively to the baseline. LUS was assessed every 12 hours in 12 fields, each scoring from 0 (presence of A-lines) to 3 (consolidation).

MEASUREMENTS AND MAIN RESULTS: In a multiple regression model, the ratio between extravascular lung water and end-expiratory lung volume was significantly associated with the LUS total score (p < 0.002; adjusted R2, 0.21). The variables independently associated with the end-expiratory difference in lung impedance were lung strain (p < 0.001; adjusted R2, 0.18) and extravascular lung water (p < 0.001; adjusted R2, 0.11).

CONCLUSIONS: Data suggest as follows. First, what determines the LUS score is the ratio between water and gas and not water alone. Therefore, caution is needed when an improvement of LUS score follows a variation of the lung gas content, as after a PEEP increase. Second, what determines the end-expiratory difference in lung impedance is the strain level that may disrupt the intercellular junction, therefore altering lung impedance. In addition, the increase in extravascular lung water during VILI development contributed to the observed decrease in impedance.

# 呼吸机诱导肺损伤期间的肺部超声和电阻抗断层扫描。

目的：机械通气期间的肺损伤涉及肺容量和肺泡水含量，肺超声 (LUS) 和电阻抗断层扫描变化与这些变量相关。我们研究了这些技术是否可以检测到呼吸机诱导肺损伤 (VILI) 发展过程中的任何信号改变。

设计：实验动物研究。

单位：某大学医院试验科。

受试者：42 头雌性猪 (24.2 μm±2.0 kg)。

干预：将动物随机分为 3 组 (n = 14)：高潮气量 (TV)（平均 TV，803.0?±121.7 mL）、高呼吸频率 (RR)（平均 RR，40.3?±1.1 次 /min）和高呼气末正压 (PEEP)（平均 PEEP，24.0?±1.1 cm H2O）。研究持续 48 小时。在基线和 30 min 以及随后每 6 小时，我们记录了血管外肺水、呼气末肺容量、肺应变、呼吸力学、血液动力学和气体交换。在相同时间点，相对于基线记录呼气末阻抗。每 12 小时在 12 个区域中评估 LUS，每次评分从 0（存在 A 线）至 3（巩固）。

测量值和主要结果：在多元回归模型中，血管外肺水和呼气末肺容量的比值与 LUS 总分显著相关（p < 0.002；校正的 R2，0.21）。与肺阻抗的呼气末差异独立相关的变量为肺应变（p < 0.001；校正的 R2，0.18）和血管外肺水（p < 0.001；校正的 R2，0.11）。

结论：数据提示如下。首先，决定 LUS 评分的因素是水和气的比例，而不是水本身。因此，LUS 评分的改善伴随肺气体含量的变化时需要谨慎，如 PEEP 增加后。其次，决定肺阻抗呼气末差异的是可能破坏细胞间连接，从而改变肺阻抗的应变水平。此外，VILI 开发过程中血管外肺水增加导致观察到的阻抗降低。

Keyword: Humans; Female; Animals; Swine; Tomography, X-Ray Computed; Tidal Volume; Electric Impedance; Lung/diagnostic imaging; *Lung Injury/diagnostic imaging/etiology; *Ventilator-Induced Lung Injury/diagnostic imaging; Positive-Pressure Respiration/methods

7:e638-e642. DOI:10.1097/CCM.0000000000005474

Abstract:

OBJECTIVES: The respiratory rate-oxygenation (ROX) index is a fraction of oxygen saturation, Fio2, and respiratory rate that has been validated to predict receipt of invasive mechanical ventilation in patients receiving high-flow nasal cannula (HFNC). This study aimed to validate ROX in a cohort of inpatients with COVID-19-related respiratory failure.

DESIGN: Retrospective validation of the ROX index. We calculated sensitivity, specificity, positive predictive value, negative predictive value, and 95% CIs of ROX for invasive mechanical ventilation any time during hospitalization.

SETTING: Twenty-one hospitals of Kaiser Permanente Northern California, an integrated healthcare delivery system.

PATIENTS: We identified adults with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test within 3 weeks of, or during, hospitalization between February 1, 2020, and December 31, 2020. We calculated ROX at 12 hours after HFNC initiation. We grouped patients as low (?‰? 4.88), intermediate (< 4.88 and ?‰? 3.85), or high (< 3.85) risk using previously published thresholds.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We identified 1,847 patients who had no limitation of life support. Of these, 525 (31.7%) received invasive mechanical ventilation any time during hospitalization and 511 died (27.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of 12-hour ROX threshold (< 3.85) predicting invasive mechanical ventilation were 32.3% (95% CI, 28.5-36.3%), 89.8% (95% CI, 88.0-91.4%), 59.4% (95% CI, 53.8-64.9%), and 74.1% (95% CI, 71.8-76.3%), respectively.

CONCLUSIONS: The 12-hour ROX index has a positive predictive value (59.4%) using threshold of less than 3.85 for COVID-19 patients needing invasive mechanical ventilation. Our health system has embedded ROX into the electronic health record to prioritize rounding during periods of inpatient surge.

# 在 COVID-19 相关呼吸衰竭患者中验证呼吸频率 - 氧合指数。

目的：呼吸频率 - 氧合 (ROX) 指数是氧饱和度、Fio2 和呼吸频率的分数，已经过验证，可以预测接收在接受高流量鼻插管的患者中进行有创机械通气 (HFNC). 本研究的目的是在住院患者队列中验证 ROX COVID-19 相关的呼吸衰竭。

设计：ROX 的回顾性验证指数。我们计算了敏感性、特异性、阳性预测值，有创机械通气 ROX 的阴性预测值和 95% CI 住院期间的任何时间。

单位：Kaiser 的 21 家医院 Permanente Northern California，一个综合医疗保健服务系统。

患者：我们确定了重度急性呼吸综合征阳性的成人患者冠状病毒 2 聚合酶链反应检测， 2020 年 2 月 1 日至 2020 年 12 月 31 日期间住院。我们计算开始 HFNC 后 12 小时 ROX。我们按低风险 (≥ 4.88) 对患者进行分组，既往使用，中等（< 4.88 和 ≥ 3.85）或高 (< 3.85) 风险公布的阈值。

干预：无。

测量和主要结果：我们确定了 1847 例生命支持不受限的患者。其中，525 (31.7%) 在住院期间的任何时间接受了有创机械通气 511 例死亡 (27.7%)。灵敏度、特异性、阳性预测值，和 12 小时 ROX 阈值 (< 3.85) 预测的阴性预测值有创机械通气分别为 32.3%(95% CI，28.5-36.3%)，89.8%（95% CI， 88.0-91.4%）、59.4%(95% CI，53.8-64.9%) 和 74.1%(95% CI，71.8-76.3%)，分别为。

结论：12 小时 ROX 指数具有阳性预测值 (59.4%) 对 COVID-19 需要侵入性治疗的患者采用小于 3.85 的阈值机械通气。我们的卫生系统将 ROX 嵌入电子在住院患者激增期间优先对健康记录进行四舍五入。

Keyword: Humans; Adult; Retrospective Studies; Oxygen Inhalation Therapy; *COVID-19/therapy; *Noninvasive Ventilation; Cannula; *Respiratory Insufficiency/etiology/therapy; Blood Gas Analysis; Respiratory Rate

# The Effect of Clusters of Double Triggering and Ineffective Efforts in Critically Ill Patients., Magrans, Rudys

7:e619-e629. DOI:10.1097/CCM.0000000000005471

Abstract:

OBJECTIVES: To characterize clusters of double triggering and ineffective inspiratory efforts throughout mechanical ventilation and investigate their associations with mortality and duration of ICU stay and mechanical ventilation.

DESIGN: Registry-based, real-world study.

BACKGROUND: Asynchronies during invasive mechanical ventilation can occur as isolated events or in clusters and might be related to clinical outcomes.

SUBJECTS: Adults requiring mechanical ventilation greater than 24 hours for whom greater than or equal to 70% of ventilator waveforms were available.

INTERVENTIONS: We identified clusters of double triggering and ineffective inspiratory efforts and determined their power and duration. We used Fine-Gray's competing risk model to analyze their effects on mortality and generalized linear models to analyze their effects on duration of mechanical ventilation and ICU stay.

MEASUREMENTS AND MAIN RESULTS: We analyzed 58,625,796 breaths from 180 patients. All patients had clusters (mean/d, 8.2 [5.4-10.6]; mean power, 54.5 [29.6-111.4]; mean duration, 20.3 min [12.2-34.9 min]). Clusters were less frequent during the first 48 hours (5.5 [2.5-10] vs 7.6 [4.4-9.9] in the remaining period [p = 0.027]). Total number of clusters/d was positively associated with the probability of being discharged alive considering the total period of mechanical ventilation (p = 0.001). Power and duration were similar in the two periods. Power was associated with the probability of being discharged dead (p = 0.03), longer mechanical ventilation (p < 0.001), and longer ICU stay (p = 0.035); cluster duration was associated with longer ICU stay (p = 0.027).

CONCLUSIONS: Clusters of double triggering and ineffective inspiratory efforts are common. Although higher numbers of clusters might indicate better chances of survival, clusters with greater power and duration indicate a risk of worse clinical outcomes.

# 危重患者中双重触发和无效努力集群的影响。

目的：描述整个机械通气期间双重触发和无效吸气努力的集群特征，并研究其与死亡率、ICU 停留时间和机械通气的相关性。

设计：基于注册的现实世界研究。

背景：治疗期间不同步有创机械通气可能作为孤立事件或聚集性事件发生，并且可能与临床结局相关。

受试者：需要机械辅助治疗的成人通气大于 24 小时，大于或等于 70% 呼吸机波形可用。

干预：我们确定了以下事件的集群双触发和无效的吸气努力并确定其力量和持续时间。我们使用 Fine-Gray 竞争风险模型分析了它们的影响死亡率和广义线性模型，以分析其对持续时间的影响机械通气和留住 ICU。

测量和主要结果：我们分析了 180 例患者的 58,625,796 次呼吸。所有患者均有聚集现象（平均 /d， 8.2 [5.4-10.6]；平均功率，54.5 [29.6-111.4]；平均持续时间，20.3 min [12.2-34.9] min]）。前 48 小时内，群集发生率较低（5.5 [2.5-10] vs 7.6 [4.4-9.9]）。集群总数 /d 为与出院存活概率正相关，考虑机械通气的总周期 (p = 0.001)。把握度和持续时间为两个阶段相似。

把握度与以下概率相关：出院时死亡 (p = 0.03)、机械通气时间更长 (p < 0.001) 和时间更长 ICU 停留时间 (p = 0.035)；集群持续时间与更长的 ICU 停留时间相关（p = 0.027). 结论：双触发和无效吸气的集群努力是很常见的。尽管聚集数量越多可能表明越好存活率，把握度和持续时间更高的群组表明存在以下风险临床结局较差。

Keyword: Humans; Adult; Respiration, Artificial; *Critical Illness/therapy; *Ventilators, Mechanical

# Clinical Benefits of Early Concurrent Use of Cryoprecipitate and Plasma Compared With Plasma Only in Bleeding Trauma Patients.

DOI:10.1097/CCM.0000000000005596

Abstract:

OBJECTIVES: The effectiveness of cryoprecipitate (Cryo) in trauma has not been well established; the benefits of Cryo might have been overestimated in previous studies since the difference in the total amount of administered clotting factors was not considered. We aimed to evaluate the benefits of the concurrent use of Cryo in combination with fresh frozen plasma (FFP) for bleeding trauma patients.

DESIGN: Retrospective cohort study.

SETTING: The American College of Surgeons Trauma Quality Improvement Program database between 2015 and 2019.

PATIENTS: Patients who received greater than or equal to 5 units of packed RBCs and at least 1 unit of FFP within the first 4 hours after arrival to a hospital were included and dichotomized according to whether Cryo was used within the first 4 hours of hospital arrival.

INTERVENTION: None.

MEASUREMENTS AND MAIN RESULTS: The outcomes of patients treated with Cryo and FFP were compared with those treated with FFP only using propensity score-matching analysis. The dose of administered clotting factors in each group was balanced. The primary outcome was inhospital mortality, and the secondary outcome was the occurrence rate of adverse events. A total of 24,002 patients (Cryo+FFP group: 6,018; FFP only group: 17,984) were eligible for analysis, of whom 4,852 propensity score-matched pairs were generated. Significantly lower inhospital mortality (1,959 patients [40.4%] in the Cryo+FFP group vs 2,142 patients [44.1%] in the FFP only group; odds ratio [OR], 0.86; 95% CI, 0.79-0.93) was observed in the Cryo+FFP group; no significant difference was observed in the occurrence rate of adverse events (1,857 [38.3%] vs 1,875 [38.6%]; OR, 1.02; 95% CI, 0.94-1.10). Several sensitivity analyses showed similar results.

CONCLUSIONS: Cryo use combined with FFP was significantly associated with reduced mortality in bleeding trauma patients. Future randomized controlled trials are warranted to confirm these results.

# 早期联合使用冷沉淀和血浆与仅使用血浆相比在出血性创伤患者中的临床获益。

目的：尚未充分确立冷沉淀 (Cryo) 在创伤中的有效性；之前可能高估了 Cryo 的获益由于给予的凝血因子总量差异的研究未考虑。我们旨在评价同时使用冷冻联合新鲜冰冻血浆 (FFP) 用于创伤出血患者。

设计：回顾性队列研究。

单位：美国外科医师学会 2015 年至 2019 年期间的创伤质量改进项目数据库。

患者：接受≥5 个单位浓缩 RBC 的患者到达医院后前 4 小时内至少 1 个单位的 FFP 根据是否在前 4 个月内使用 Cryo 纳入并进行二分类医院到达的小时数。

干预：无。

测量和主要结果：将接受冷冻和 FFP 治疗的患者与接受治疗的患者的结局进行比较 FFP 仅使用倾向评分匹配分析。给药剂量各组的凝血因子平衡。主要结局是住院死亡率，次要结局是不良事件的发生率。A 共 24002 例患者（Cryo + FFP 组：6018 例；仅 FFP 组：17984 例）符合分析资格，其中 4852 个倾向评分匹配对生成。住院死亡率显著降低（1,959 例患者 [40.4%] Cryo + FFP 组 vs 仅 FFP 组的 2,142 例患者 [44.1%]；比值比 [OR]，0.86；95% CI，0.79-0.93），在 Cryo + FFP 组中观察到；无显著观察到不良事件发生率存在差异 (1,857)[38.3%] vs 1,875 [38.6%]；或者，1.02; 95% CI, 0.94-1.10). 多项敏感性分析显示相似的结果。

结论：冷冻联合 FFP 使用显著与出血性创伤患者的死亡率降低相关。未来随机化有必要进行对照试验来证实这些结果。

# Reexamining the Role of Postoperative ICU Admission for Patients Undergoing Elective Craniotomy: A Systematic Review.

DOI:10.1097/CCM.0000000000005588

Abstract:

OBJECTIVES: The standard-of-care for postoperative care following elective craniotomy has historically been ICU admission. However, recent literature interrogating complications and interventions during this postoperative ICU stay suggests that all patients may not require this level of care. Thus, hospitals began implementing non-ICU postoperative care pathways for elective craniotomy. This systematic review aims to summarize and evaluate the existing literature regarding outcomes and costs for patients receiving non-ICU care after elective craniotomy.

DATA SOURCES: A systematic review of the PubMed database was performed following PRISMA guidelines from database inception to August 2021.

STUDY SELECTION: Included studies were published in peer-reviewed journals, in English, and described outcomes for patients undergoing elective craniotomies without postoperative ICU care.

DATA EXTRACTION: Data regarding study design, patient characteristics, and postoperative care pathways were extracted independently by two authors. Quality and risk of bias were evaluated using the Oxford Centre for Evidence-Based Medicine Levels of Evidence tool and Risk Of Bias In Non-Randomized Studies-of Interventions tool, respectively.

DATA SYNTHESIS: In total, 1,131 unique articles were identified through the database search, with 27 meeting inclusion criteria. Included articles were published from 2001 to 2021 and included non-ICU inpatient care and same-day discharge pathways. Overall, the studies demonstrated that postoperative non-ICU care for elective craniotomies led to length of stay reduction ranging from 6 hours to 4 days and notable cost reductions. Across 13 studies, 53 of the 2,469 patients (2.1%) intended for postoperative management in a non-ICU setting required subsequent care escalation.

CONCLUSIONS: Overall, these studies suggest that non-ICU care pathways for appropriately selected postcraniotomy patients may represent a meaningful opportunity to improve care value. However, included studies varied greatly in patient selection, postoperative care protocol, and outcomes reporting. Standardization and multi-institutional collaboration are needed to draw definitive conclusions regarding non-ICU postoperative care for elective craniotomy.

DOI: 10.1097/CCM.0000000000005588

# 系统回顾：对择期开颅手术患者术后 ICU 住院的作用。

目的：既往择期开颅术后护理的标准治疗是 ICU 入院。但近期文献询问术后留住 ICU 期间的并发症和干预措施提示所有患者可能不需要该水平的治疗。因此，医院开始实施非 ICU 择期开颅手术术后护理路径。本系统综述旨在总结和评价现有文献关于择期手术后接受非 ICU 护理患者的结局和费用开颅手术。

数据来源：对 PubMed 数据库进行了系统回顾。从数据库建立至 2021 年 8 月，遵循 PRISMA 指南进行。

研究选择：纳入的研究发表在同行评议期刊上，英文，并描述了接受择期开颅手术的患者的结局无术后 ICU 监护。

数据提取：关于研究设计的数据，提取患者特征和术后护理路径由两名作者独立完成。使用牛津循证医学中心证据分级工具和风险分别为非随机化研究 - 干预工具中的偏倚。数据综合：通过数据库总共确定了 1,131 篇独特的文章检索，其中 27 例符合入选标准。纳入的文章发表于 2001 年至 2021 年，包括非 ICU 住院护理和当天出院途径。总体而言，研究表明择期手术的术后非 ICU 护理开颅术导致住院时间缩短，范围从 6 小时至 4 天，和显著的成本降低。在 13 项研究中，2,469 例患者中的 53 例 (2.1%) 计划在后续需要的非 ICU 环境中进行术后管理护理升级。

结论：总体而言，这些研究表明非 ICU 护理适当选择的开颅术后患者的路径可能代表有意义的机会提高护理价值。然而，纳入的研究各不相同在患者选择、术后护理方案和结局方面发挥了重要作用报告。需要标准化和多机构合作来得出关于非 ICU 择期术后护理的明确结论开颅手术。

# Right-to-Left Shunts Occur During Cardiopulmonary Resuscitation: Echocardiographic Observations.

Abstract:

OBJECTIVES: A significant proportion of the population has a patent foramen ovale (PFO). The intracardiac pressure during cardiopulmonary resuscitation (CPR) may differ from that of normal circulation, which may result in a right-to-left shunt in the presence of a PFO. In this study, transesophageal echocardiography (TEE) was conducted to evaluate whether CPR carried out in patients after cardiac arrest causes right-to-left shunt.

DESIGN: A retrospective observational study.

SETTING: One academic medical center from January 2017 to April 2020.

PATIENTS: Patients older than 20 years who suffered from nontraumatic out-of-hospital cardiac arrest (OHCA) and underwent intra-arrest TEE.

MEASUREMENT AND MAIN RESULTS: Patients who had microbubbles resulting from fluid injection in the right atrium, as indicated on TEE imaging, were included in the analysis. The presence of right-to-left shunt was defined as the appearance of microbubbles in the systemic circulation, including the left atrium, left ventricle, or aorta. A total of 97 patients were included in the final analysis. A right-to-left shunt was observed in 21 patients (21.6%), and no shunt was found in 76 patients (78.4%). The degree of the right-to-left shunt, determined by the number of microbubbles, was mild in 11 patients (52.4%), moderate in eight (38.0%), and severe in two (9.6%). Multivariate analysis showed that no factors were associated with the presence of right-to-left shunt during CPR.

CONCLUSIONS: Right-to-left shunts can be appreciated during CPR in patients who experience OHCA. Further studies are needed to verify its clinical significance.

DOI: 10.1097/CCM.0000000000005593

# 心肺复苏期间右向左分流：超声心动图观察。

目的：相当大比例的人群有卵圆孔未闭 (PFO)。心肺复苏过程中的心内压可能与正常循环不同，可能导致右向左分流存在 PFO。本研究中，经食管超声心动图 (TEE) 评价患者在心脏术后是否进行 CPR 心脏停搏引起右向左分流。

设计：回顾性观察性研究。

单位：2017 年 1 月至 2020 年 4 月，学术医学中心 1 家。

患者： 20 岁以上非创伤性院外患者心脏停搏 (OHCA) 并接受了停搏内 TEE。测量和主要结果：患者体内液体注射产生微气泡分析中包括 TEE 成像所示的右心房。事件存在右向左分流定义为存在微气泡体循环，包括左心房、左心室或主动脉。A 最终分析共纳入 97 例患者。右向左分流 21 例 (21.6%) 观察到分流，76 例未发现分流 (78.4%). 右向左分流的程度，由以下数量决定微气泡，11 例患者 (52.4%) 为轻度，8 例患者 (38.0%) 为中度，以及 2 例 (9.6%) 为重度。多变量分析显示无因素与 CPR 期间出现右向左分流相关。

结论：在经历 CPR 的患者中，可以识别右向左分流 OHCA. 还需要进一步的研究来验证其临床意义。

# Impact of Pharmacists to Improve Patient Care in the Critically Ill: A Large Multicenter Analysis Using Meaningful Metrics With the Medication Regimen Complexity-ICU (MRC-ICU)., Sikora, Andrea

Abstract:

OBJECTIVES: Despite the established role of the critical care pharmacist on the ICU multiprofessional team, critical care pharmacist workloads are likely not optimized in the ICU. Medication regimen complexity (as measured by the Medication Regimen Complexity-ICU [MRC-ICU] scoring tool) has been proposed as a potential metric to optimize critical care pharmacist workload but has lacked robust external validation. The purpose of this study was to test the hypothesis that MRC-ICU is related to both patient outcomes and pharmacist interventions in a diverse ICU population.

DESIGN: This was a multicenter, observational cohort study.

SETTING: Twenty-eight ICUs in the United States.

PATIENTS: Adult ICU patients.

INTERVENTIONS: Critical care pharmacist interventions (quantity and type) on the medication regimens of critically ill patients over a 4-week period were prospectively captured. MRC-ICU and patient outcomes (i.e., mortality and length of stay [LOS]) were recorded retrospectively.

MEASUREMENTS AND MAIN RESULTS: A total of 3,908 patients at 28 centers were included. Following analysis of variance, MRC-ICU was significantly associated with mortality (odds ratio, 1.09; 95% CI, 1.08-1.11; p < 0.01), ICU LOS (?? coefficient, 0.41; 95% CI, 00.37-0.45; p < 0.01), total pharmacist interventions (?? coefficient, 0.07; 95% CI, 0.04-0.09; p < 0.01), and a composite intensity score of pharmacist interventions (?? coefficient, 0.19; 95% CI, 0.11-0.28; p < 0.01). In multivariable regression analysis, increased patient: pharmacist ratio (indicating more patients per clinician) was significantly associated with increased ICU LOS (?? coefficient, 0.02; 0.00-0.04; p = 0.02) and reduced quantity (?? coefficient, -0.03; 95% CI, -0.04 to -0.02; p < 0.01) and intensity of interventions (?? coefficient, -0.05; 95% CI, -0.09 to -0.01).

CONCLUSIONS: Increased medication regimen complexity, defined by the MRC-ICU, is associated with increased mortality, LOS, intervention quantity, and intervention intensity. Further, these results suggest that increased pharmacist workload is associated with decreased care provided and worsened patient outcomes, which warrants further exploration into staffing models and patient outcomes.

DOI: 10.1097/CCM.0000000000005585

# 药剂师对改善危重病患者治疗的影响：一项使用有意义的指标及给药方案的大型多中心分析复杂性 - ICU (MRC-ICU)。

目的：尽管重症监护药剂师在 ICU 多专业团队中的作用已经明确，但是重症监护药剂师的工作量可能不会在 ICU 优化。用药方案复杂性（根据给药方案复杂性 - ICU [MRC-ICU] 评分工具）被提议作为优化重症监护药剂师工作负荷的潜在指标，但缺乏稳健的外部验证。本研究的目的是检验假设 MRC-ICU 与患者结局和药剂师干预均相关不同的 ICU 人群。

设计：多中心、观察性队列研究。

设置：美国 28 间 ICU。

患者：成人 ICU 患者。

干预：重症监护药剂师干预（数量和类型），为期 4 周的重症患者用药方案前瞻性采集。MRC-ICU 和患者结局（即，死亡率和住院时间 [LOS]）进行回顾性记录。测量和主要结果：共纳入 28 家研究中心的 3,908 例患者。方差分析后发现，MRC-ICU 与死亡率（比值比，1.09；95% CI，1.08-1.11；p < 0.01）、ICU LOS（β 系数，0.41；95% CI，00.37-0.45；p < 0.01）、总药剂师干预（β 系数，0.07；95% CI，0.04-0.09；p < 0.01）、和药剂师干预措施的复合强度评分（β 系数，0.19；95% CI，0.11-0.28；p < 0.01）。在多变量回归分析中，患者：药剂师比率增加（表明每名临床医生有更多患者）与 ICU LOS 增加（β 系数，0.02；0.00-0.04；p = 0.02）、数量减少（β 系数，-0.03；95% CI，-0.04 至 - 0.02；p < 0.01）和干预强度（β 系数，-0.05；95% CI，-0.09 to -0.01)。

结论： MRC-ICU 定义的用药方案复杂性增加与死亡率、LOS、干预量和干预强度增加。此外，这些结果表明增加的药剂师工作量与提供的护理减少，患者结局变差，需要进一步探索人员配备模式和患者结局。

# Accuracy of the Initial Rhythm to Predict a Short No-Flow Time in Out-of-Hospital Cardiac Arrest.

Abstract:

OBJECTIVES: The no-flow time (NFT) can help establish prognosis in out-of-hospital cardiac arrest (OHCA) patients. It is often used as a selection criterion for extracorporeal resuscitation. In patients with an unwitnessed OHCA for whom the NFT is unknown, the initial rhythm has been proposed to identify those more likely to have had a short NFT. Our objective was to determine the predictive accuracy of an initial shockable rhythm for an NFT of 5 minutes or less (NFT ?‰¤ 5).

DESIGN: Retrospective analysis of prospectively collected data.

SETTING: Prehospital OHCA in eight U.S. and three Canadian sites.

PATIENTS: A total of 28,139 adult patients with a witnessed nontraumatic OHCA were included, of whom 11,228 (39.9%) experienced an emergency medical service-witnessed OHCA (NFT = 0), 695 (2.7%) had a bystander-witnessed OHCA, and an NFT less than or equal to 5, and 16,216 (57.6%) with a bystander-witnessed OHCA and an NFT greater than 5.

INTERVENTIONS: Sensitivity, specificity, and likelihood ratios of an initial shockable rhythm to identify patients with an NFT less than or equal to 5 minutes.

MEASUREMENTS AND MAIN RESULTS: The sensitivity of an initial shockable rhythm to identify patients with an NFT less than or equal to 5 was poor (25% [95% CI, 25-26]), but specificity was moderate (70% [95% CI, 69-71]). The positive and likelihood ratios were inverted (negative accuracy) (positive likelihood ratio, 0.76 [95% CI, 0.74-0.79]; negative likelihood ratio, 1.12 [95% CI, 1.10-1.12]). Including only patients with a bystander-witnessed OHCA improved the sensitivity to 48% (95% CI, 45-52), the positive likelihood ratio to 1.45 (95% CI, 1.33-1.58), and the negative likelihood ratio to 0.77 (95% CI, 0.72-0.83), while slightly lowering the specificity to 67% (95% CI, 66-67).

CONCLUSIONS: Our analysis demonstrated that the presence of a shockable rhythm at the time of initial assessment was poorly sensitive and only moderately specific for OHCA patients with a short NFT. The initial rhythm, therefore, should not be used as a surrogate for NFT in clinical decision-making.

ONLINE. DOI: 10.1097/CCM.0000000000005594

# 院外心脏骤停中初始节律预测短无流量时间的准确性。

目的：无流量时间 (NFT) 可帮助建立院外心脏骤停 (OHCA) 患者的预后。常用作选择体外复苏标准。在无目击者的 OHCA 患者中对于 NFT 未知的患者，已提出初始节律来确定更有可能发生短暂 NFT 的患者。我们的目的是确定 5 min NFT 的初始可电击节律的预测准确度或小于 (NFT?‰?5)。

设计：回顾性分析前瞻性收集的数据。

设置：8 个美国和 3 个加拿大研究中心的院前 OHCA。

患者：A 共纳入 28139 例有证据的非创伤性 OHCA 成年患者，其中 11228 例 (39.9%) 经历了紧急医疗服务见证的 OHCA (NFT = 0)，695 例 (2.7%) 有旁观者察觉的 OHCA，且 NFT 小于或等于 5 和 16，216 例 (57.6%) 旁观者察觉的 OHCA 和更高的 NFT > 5. 干预：一种干预的敏感性、特异性和似然比识别 NFT≤5 患者的初始可电击节律分钟。

测量和主要结果：初始可电击的灵敏度识别 NFT≤5 患者的节律较差 (25%) [95% CI，25-26]），但特异性为中等 (70%[95% CI，69-71])。事件阳性和似然比倒置（阴性准确性）（阳性似然比，0.76 [95% CI，0.74-0.79]；阴性似然比，1.12 [95% CI, 1.10-1.12]). 仅包括旁观者见证的 OHCA 改善的患者敏感性为 48%(95% CI，45-52)，阳性似然比为 1.45 (95% CI，1.33-1.58)，阴性似然比 0.77（95% CI， 0.72-0.83），同时特异性略微降低至 67%(95% CI，66-67)。

结论：我们的分析证明，存在可电击心律初始评估的时间敏感性较差，仅具有中度特异性对于 NFT 较短的 OHCA 患者。因此，初始节律不应该是在临床决策中用作 NFT 的替代指标。

# Immune Profiling Demonstrates a Common Immune Signature of Delayed Acquired Immunodeficiency in Patients With Various Etiologies of Severe Injury: Erratum.

6:e618. DOI:10.1097/CCM.0000000000005565

# The Fundamentals of Hysteresis and Lung Recruitment in Patients With Acute Respiratory Distress Syndrome.

6:e616-e617. doi: 10.1097/CCM.0000000000005473

Keyword: Humans; Lung; *Respiratory Distress Syndrome/therapy

# Sepsis and Resuscitation: The Importance of Time., Feichtinger, Stuart

# 败血症和复苏：时间的重要性。

6:e615-e616. DOI:10.1097/CCM.0000000000005494

Keyword: Humans; Resuscitation; Fluid Therapy; *Sepsis/therapy; *Shock, Septic

# Effects of Moderate Hypothermia on Diastolic Functions of Heart.

6:e613-e614. DOI:10.1097/CCM.0000000000005497

# 中度低温对心脏舒张功能的影响。

Keyword: Humans; Heart; *Hypothermia; *Hypothermia, Induced; Diastole

# The authors reply.

6:e612-e613. DOI:10.1097/CCM.0000000000005544

# 作者回复。

# Wacker et al, Who Conclude That Vitamin C Monotherapy Failed to Significantly Reduce Mortality in Septic Shock Patients: Beware of Potential Confounding Factors!, Honore, Patrick M.

6:e611-e612. DOI:10.1097/CCM.0000000000005516

# Wacker 等人的结论是维生素 C 单药治疗未能显著降低感染性休克患者的死亡率：需注意潜在的混杂因素因素！

Keyword: Humans; *Sepsis; *Shock, Septic/drug therapy; Ascorbic Acid/therapeutic use; Vitamins

# The authors reply.

6:e610-e611. DOI:10.1097/CCM.0000000000005528

# 作者回复。

# Benzodiazepine-Based Sedation Did Not Add an Independent Risk of Delirium?, Cai, Xingwei

6:e608-e609. DOI:10.1097/CCM.0000000000005515

# 基于苯二氮卓类的镇静未增加谵妄的独立风险？

Keyword: Humans; Intensive Care Units; *Benzodiazepines/adverse effects; *Delirium/drug therapy; Hypnotics and Sedatives/adverse effects

# The authors reply., Massart, Nicolas

6:e607-e608. DOI:10.1097/CCM.0000000000005542

# 作者回复。

# A Hypothesis-Generating Clinical Study We Should Be Concerned About., Nadeem, Rashid

6:e606-e607. DOI:10.1097/CCM.0000000000005510

# 我们应该关注的假设生成性临床研究。

# The authors reply.

6:e604-e606. DOI:10.1097/CCM.0000000000005529

# 作者回复。

# Further Retractions of Articles by Joachim Boldt., Wiedermann, Christian J.

6:e601-e603. DOI:10.1097/CCM.0000000000005506

# Joachim Boldt 进一步撤回文章。

Keyword: Humans; *Biomedical Research; Dyspnea

# The authors reply.

6:e600-e601. DOI:10.1097/CCM.0000000000005521

# 作者回复。

# Is Early Vasopressor Safe in Septic Shock?

6:e599-e600. DOI:10.1097/CCM.0000000000005505

# 感染性休克早期使用血管加压药是否安全？

Keyword: Humans; Retrospective Studies; *Shock, Septic/drug therapy; Vasoconstrictor Agents/adverse effects

# The authors reply., Grim, Chloe C. A.

6:e598-e599. DOI:10.1097/CCM.0000000000005526

# 作者回复。

# What Is the Abnormal Serum Sodium to Be Associated With Mortality in Critically Ill?

6:e596-e597. DOI:10.1097/CCM.0000000000005496

# 危重患者中异常血清钠与死亡率的相关性是什么？

关键词：Humans; *Intensive Care Units; *Critical Illness; Sodium

# The authors reply., L'Her, Erwan

6:e595-e596. DOI:10.1097/CCM.0000000000005523

# 作者回复。

# Noninvasive Method of Measuring of Tidal Volume: A Promising Novel Tool?

6:e594-e595. DOI:10.1097/CCM.0000000000005489

# 潮气量无创测量方法：一种有前景的新型工具？

关键词：Tidal Volume; *Noninvasive Ventilation

# The authors reply., Taran, Shaurya

6:e590. DOI:10.1097/CCM.0000000000005511

# 作者回复。

# Concordance Between Outcomes Associated With Withholding Extubation and Extubation Failure After Successful Spontaneous Breathing Trial.

6:e589. DOI:10.1097/CCM.0000000000005481

# 自主呼吸试验成功后拔管失败和拔管失败相关结局的一致性。

关键词：Respiration, Artificial; *Airway Extubation; *Ventilator Weaning

# Seventeen Years Is Too Long to Move From the ICU to the Emergency Department., Danboise, Brook

6:1032-1034. DOI:10.1097/CCM.0000000000005472

# 从 ICU 转移到急诊科已是 17 年之久。

关键词：Retrospective Studies; *Intensive Care Units; *Emergency Service, Hospital

# After a Heart Attack, Who Should Care?

6:1030-1032. DOI:10.1097/CCM.0000000000005477

# 心脏病发作后，谁应该关心？

关键词：Humans; Health Knowledge, Attitudes, Practice; *Myocardial Infarction/therapy

# Metformin: An Intriguing Protective Agent in Hospitalized Diabetic Patients With Sepsis.

6:1018-1020. DOI:10.1097/CCM.0000000000005480

# 二甲双胍：糖尿病脓毒症住院患者的无效保护剂。

关键词：Humans; *Diabetes Mellitus; *Metformin/therapeutic use; *Sepsis/drug therapy; Hypoglycemic Agents/therapeutic use; Protective Agents

# From Syphilis to Sepsis: Pilot Studies and the Importance of Staying Grounded.

6:1015-1018. DOI:10.1097/CCM.0000000000005539

# 从梅毒到败血症：初探性研究和保持接地的重要性。

关键词：Humans; Pilot Projects; *Sepsis; *Syphilis/drug therapy

# A Tale of Two ICUs: One for Women and One for Men?

6:1012-1015. DOI:10.1097/CCM.0000000000005538

# 两个 ICU 的故事：一个是女性，一个是男性？

关键词：Humans; Female; Male; *Intensive Care Units

# MEDucation: Healthcare Providers, Educators, and Families Partnering to Address the Educational Challenges of Children After Recovery From Critical Illness.

6:1010-1012. DOI:10.1097/CCM.0000000000005478

# 医疗服务：医疗保健提供者、教育者和家庭合作，解决儿童从危重病康复后面临的教育挑战。

关键词：Humans; Child; *Critical Illness/therapy; *Health Personnel; Educational Status; Parents

# The authors reply.

6:e592-e594. DOI:10.1097/CCM.0000000000005530

# 作者回复。

# Sleep and Circadian Health of Critical COVID-19 Survivors 3 Months After Hospital Discharge.

6:945-954. DOI:10.1097/CCM.0000000000005476

Abstract:

OBJECTIVES: To evaluate the sleep and circadian rest-activity pattern of critical COVID-19 survivors 3 months after hospital discharge.

DESIGN: Observational, prospective study.

SETTING: Single-center study.

PATIENTS: One hundred seventy-two consecutive COVID-19 survivors admitted to the ICU with acute respiratory distress syndrome.

INTERVENTIONS: Seven days of actigraphy for sleep and circadian rest-activity pattern assessment; validated questionnaires; respiratory tests at the 3-month follow-up.

MEASUREMENTS AND MAIN RESULTS: The cohort included 172 patients, mostly males (67.4%) with a median (25th-75th percentile) age of 61.0 years (52.8-67.0 yr). The median number of days at the ICU was 11.0 (6.00-24.0), and 51.7% of the patients received invasive mechanical ventilation (IMV). According to the Pittsburgh Sleep Quality Index (PSQI), 60.5% presented poor sleep quality 3 months after hospital discharge, which was further confirmed by actigraphy. Female sex was associated with an increased score in the PSQI (p < 0.05) and IMV during ICU stay was able to predict a higher fragmentation of the rest-activity rhythm at the 3-month follow-up (p < 0.001). Furthermore, compromised mental health measured by the Hospital Anxiety and Depression Scale was associated with poor sleep quality (p < 0.001).

CONCLUSIONS: Our findings highlight the importance of considering sleep and circadian health after hospital discharge. Within this context, IMV during the ICU stay could aid in predicting an increased fragmentation of the rest-activity rhythm at the 3-month follow-up. Furthermore, compromised mental health could be a marker for sleep disruption at the post-COVID period.

# COVID-19 危重存活者出院后 3 个月的睡眠和昼夜节律健康。

目的：评价关键 COVID-19 存活者出院后 3 个月的睡眠和昼夜节律静息 - 活动模式。

设计：观察性，前瞻性研究。

设置：单中心研究。

患者：100 例 72 例连续 COVID-19 存活者因急性呼吸窘迫综合征。

干预：7 天睡眠活动描记和昼夜节律静息 - 活动模式评估；经验证的问卷； 3 个月随访时的呼吸试验。

测量和主要结果：队列包括 172 例患者，大部分是男性 (67.4%)，中位数（第 25-75 百分位数）百分位数）年龄为 61.0 岁（52.8-67.0 岁）。以下时间点的中位天数 ICU 为 11.0 (6.00-24.0)，51.7% 的患者接受了侵入性机械治疗通气 (IMV)。根据匹兹堡睡眠质量指数 (PSQI),60.5% 在出院后 3 个月表现睡眠质量差，进一步通过活动描记术证实。

女性与以下方面的评分增加相关： PSQI (p < 0.05) 和 ICU 住院期间 IMV 能够预测更高的 3 个月随访时的静息 - 活动节律破碎 (p < 0.001)。此外，根据医院焦虑和抑郁量表与睡眠质量差相关 (p < 0.001)。

结论：我们的发现强调了考虑睡眠和昼夜节律健康的重要性出院后。在这种情况下，在 ICU 住院期间使用 IMV 可能有助于预测静息 - 活动节律碎裂增加 3 个月随访。此外，受损的心理健康可能是 COVID 后期间睡眠中断。关键词：Humans; Female; Male; Middle Aged; Prospective Studies; Intensive Care Units; *COVID-19; Survivors; Hospitals; *Patient Discharge; Sleep

# Systematic Review and Comparison of Publicly Available ICU Data Sets-A Decision Guide for Clinicians and Data Scientists., Sauer, Christopher M.

6:e581-e588. DOI:10.1097/CCM.0000000000005517

Abstract:

OBJECTIVE: As data science and artificial intelligence continue to rapidly gain traction, the publication of freely available ICU datasets has become invaluable to propel data-driven clinical research. In this guide for clinicians and researchers, we aim to: 1) systematically search and identify all publicly available adult clinical ICU datasets, 2) compare their characteristics, data quality, and richness and critically appraise their strengths and weaknesses, and 3) provide researchers with suggestions, which datasets are appropriate for answering their clinical question.

DATA SOURCES: A systematic search was performed in Pubmed, ArXiv, MedRxiv, and BioRxiv.

STUDY SELECTION: We selected all studies that reported on publicly available adult patient-level intensive care datasets.

DATA EXTRACTION: A total of four publicly available, adult, critical care, patient-level databases were included (Amsterdam University Medical Center data base [AmsterdamUMCdb], eICU Collaborative Research Database eICU CRD], High time-resolution intensive care unit dataset [HiRID], and Medical Information Mart for Intensive Care-IV). Databases were compared using a priori defined categories, including demographics, patient characteristics, and data richness. The study protocol and search strategy were prospectively registered.

DATA SYNTHESIS: Four ICU databases fulfilled all criteria for inclusion and were queried using SQL (PostgreSQL version 12; PostgreSQL Global Development Group) and analyzed using R (R Foundation for Statistical Computing, Vienna, Austria). The number of unique patient admissions varied between 23,106 (AmsterdamUMCdb) and 200,859 (eICU-CRD). Frequency of laboratory values and vital signs was highest in HiRID, for example, 5.2 (?±3.4) lactate values per day and 29.7 (?±10.2) systolic blood pressure values per hour. Treatment intensity varied with vasopressor and ventilatory support in 69.0% and 83.0% of patients in AmsterdamUMCdb versus 12.0% and 21.0% in eICU-CRD, respectively. ICU mortality ranged from 5.5% in eICU-CRD to 9.9% in AmsterdamUMCdb.

CONCLUSIONS: We identified four publicly available adult clinical ICU datasets. Sample size, severity of illness, treatment intensity, and frequency of reported parameters differ markedly between the databases. This should guide clinicians and researchers which databases to best answer their clinical questions.

# 可公开发表的 ICU 数据集的系统回顾和比较 - 临床医生和数据科学家的决策指南。

目的：随着数据科学和人工智能持续快速获得吸引力，免费提供的 ICU 数据集的发表对于推动数据驱动的临床研究变得非常宝贵。在本临床医生和研究人员指南中，我们的目的是：1）系统检索和识别所有公开的成人临床 ICU 数据集，2）比较其特征、数据质量和丰富度，并严格评价其优势和劣势，3）向研究人员提供建议，哪些数据集适合回答其临床问题。

数据来源：在 Pubmed、ArXiv、MedRxiv 和 BioRxiv 中进行了系统的检索。

研究选择：我们选择了报告公开的成人患者级重症监护数据集的所有研究。

数据提取：共纳入 4 个公开的成人重症监护患者级别数据库（阿姆斯特丹大学医学中心数据库 [AmsterdamUMCdb]、eICU 合作研究数据库 eICU CRD]、高时间分辨率重症监护室数据集 [HiRID] 和重症监护医学信息市场 IV）。使用事先定义的类别比较数据库，包括人口统计学、患者特征和数据丰富度。前瞻性登记研究方案和检索策略。

数据综合：四个 ICU 数据库符合所有入选标准，使用 SQL（PostgreSQL 第 12 版；PostgreSQL 全球开发组）进行查询，并使用 R (R Foundation for Statistical Computing,Vienna,Austria) 进行分析。独特患者入院的数量在 23,106 (AmsterdamUMCdb) 和 200,859 (eICU-CRD) 之间。HiRID 中实验室值和生命体征的频率最高，例如，5.2 (?±3.4) 个乳酸盐值 / 天和 29.7 (?±10.2) 个收缩压值 / 小时。AmsterdamUMCdb 组 69.0% 和 83.0% 的患者治疗强度随血管加压药和通气支持的不同而不同 vs 12.0% eICU-CRD 中为 21.0%。ICU 死亡率范围从 eICU-CRD 的 5.5% 至 AmsterdamUMCdb 的 9.9%。

结论：我们确定了 4 个可公开获取的成人临床 ICU 数据集。数据库之间的样本量、疾病严重程度、治疗强度和报告参数的频率存在显著差异。这将指导临床医生和研究人员使用哪些数据库来最佳地回答他们的临床问题。关键词：Humans; Adult; Critical Care; *Intensive Care Units; Systematic Reviews as Topic; *Artificial Intelligence; Data Accuracy; Databases, Factual

# COVID-19, Critical Illness, and Sleep., Chatterjee, Arjun Bijoy

6:1021-1023. DOI:10.1097/CCM.0000000000005519

# COVID-19，危重病和睡眠。

关键词：Humans; Critical Illness; *COVID-19; SARS-CoV-2; Sleep

# Is This the Beginning of the End of Cytokine Adsorption?

6:1026-1029. DOI:10.1097/CCM.0000000000005509

# 这是否是细胞因子吸附结束的开始？

关键词：*Cytokines; *Extracorporeal Membrane Oxygenation; Adsorption

# Does Unprecedented ICU Capacity Strain, As Experienced During the COVID-19 Pandemic, Impact Patient Outcome?

6:e548-e556. DOI:10.1097/CCM.0000000000005464

Abstract:

OBJECTIVES: To determine whether patients admitted to an ICU during times of unprecedented ICU capacity strain, during the COVID-19 pandemic in the United Kingdom, experienced a higher risk of death.

DESIGN: Multicenter, observational cohort study using routine clinical audit data.

SETTING: Adult general ICUs participating the Intensive Care National Audit & Research Centre Case Mix Programme in England, Wales, and Northern Ireland.

PATIENTS: One-hundred thirty-thousand six-hundred eighty-nine patients admitted to 210 adult general ICUs in 207 hospitals.

INTERVENTIONS: Multilevel, mixed effects, logistic regression models were used to examine the relationship between levels of ICU capacity strain on the day of admission (typical low, typical, typical high, pandemic high, and pandemic extreme) and risk-adjusted hospital mortality.

MEASUREMENTS AND MAIN RESULTS: In adjusted analyses, compared with patients admitted during periods of typical ICU capacity strain, we found that COVID-19 patients admitted during periods of pandemic high or pandemic extreme ICU capacity strain during the first wave had no difference in hospital mortality, whereas those admitted during the pandemic high or pandemic extreme ICU capacity strain in the second wave had a 17% (odds ratio [OR], 1.17; 95% CI, 1.05-1.30) and 15% (OR, 1.15; 95% CI, 1.00-1.31) higher odds of hospital mortality, respectively. For non-COVID-19 patients, there was little difference in trend between waves, with those admitted during periods of pandemic high and pandemic extreme ICU capacity strain having 16% (OR, 1.16; 95% CI, 1.08-1.25) and 30% (OR, 1.30; 95% CI, 1.14-1.48) higher overall odds of acute hospital mortality, respectively.

CONCLUSIONS: For patients admitted to ICU during the pandemic, unprecedented levels of ICU capacity strain were significantly associated with higher acute hospital mortality, after accounting for differences in baseline characteristics. Further study into possible differences in the provision of care and outcome for COVID-19 and non-COVID-19 patients is needed.

# 既往 ICU 容量负荷（如 COVID-19 期间发生的流行病）是否会影响患者结局？

目的：确定在英国 COVID-19 大流行期间，在 ICU 容量菌株前所未有的时期入住 ICU 的患者是否经历更高的死亡风险。

设计：采用常规临床稽查数据的多中心、观察性队列研究。

设置：在英格兰、威尔士和北爱尔兰参加重症监护国家稽查和研究中心病例混合项目的成人普通 ICU。

患者：207 家医院 210 间成人普通 ICU 的 130689 例患者。

干预：使用多水平、混合效应、logistic 回归模型检查入院当天 ICU 能力菌株水平（典型低、典型、典型高、流行高和流行极端）与经风险调整的住院死亡率之间的关系。

测量和主要结果：在调整后的分析中，与典型 ICU 能力菌株期间入院的患者相比，我们发现 COVID-19 患者在第一波大流行期间高或大流行期间极端 ICU 能力菌株期间入院，住院死亡率无差异，而在第二波大流行期间高流行或大流行极端 ICU 能力菌株期间入院的患者住院死亡率的比值比分别高 17%（比值比 [or]，1.17；95% CI，1.05-1.30）和 15%(or，1.15；95% CI，1.00-1.31)。对于非 COVID-19 患者，波之间的趋势几乎没有差异，在大流行期间高流行和大流行极端 ICU 能力菌株期间入院的患者急性住院死亡率的总体比值比分别高 16%(OR，1.16；95% CI，1.08-1.25) 和 30%(OR，1.30；95% CI，1.14-1.48)。

结论：考虑基线特征的差异后，对于大流行期间入住 ICU 的患者，史无前例的 ICU 能力菌株水平与较高的急性医院死亡率显著相关。需要进一步研究 COVID-19 和非 COVID-19 患者在护理提供和结局方面的可能差异。关键词：Humans; Intensive Care Units; Adult; Critical Care; Retrospective Studies; Pandemics; Hospital Mortality; *COVID-19/epidemiology

# Educational Outcomes of Childhood Survivors of Critical Illness-A Population-Based Linkage Study.

6:901-912. DOI:10.1097/CCM.0000000000005461

Abstract:

OBJECTIVES: Major postintensive care sequelae affect up to one in three adult survivors of critical illness. Large cohorts on educational outcomes after pediatric intensive care are lacking. We assessed primary school educational outcomes in a statewide cohort of children who survived PICU during childhood.

DESIGN: Multicenter population-based study on children less than 5 years admitted to PICU. Using the National Assessment Program-Literacy and Numeracy database, the primary outcome was educational achievement below the National Minimum Standard (NMS) in year 3 of primary school. Cases were compared with controls matched for calendar year, grade, birth cohort, sex, socioeconomic status, Aboriginal and Torres Strait Islander status, and school. Multivariable logistic regression models to predict educational outcomes were derived.

SETTING: Tertiary PICUs and mixed ICUs in Queensland, Australia.

PATIENTS: Children less than 5 years admitted to PICU between 1998 and 2016.

INTERVENTIONS: Not applicable.

MEASUREMENTS AND MAIN RESULTS: Year 3 primary school data were available for 5,017 PICU survivors (median age, 8.0 mo at first PICU admission; interquartile range, 1.9-25.2). PICU survivors scored significantly lower than controls across each domain (p < 0.001); 14.03% of PICU survivors did not meet the NMS compared with 8.96% of matched controls (p < 0.001). In multivariate analyses, socioeconomic status (odds ratio, 2.14; 95% CI, 1.67-2.74), weight (0.94; 0.90-0.97), logit of Pediatric Index of Mortality-2 score (1.11; 1.03-1.19), presence of a syndrome (11.58; 8.87-15.11), prematurity (1.54; 1.09-2.19), chronic neurologic conditions (4.38; 3.27-5.87), chronic respiratory conditions (1.65; 1.24-2.19), and continuous renal replacement therapy (4.20; 1.40-12.55) were independently associated with a higher risk of not meeting the NMS.

CONCLUSIONS: In this population-based study of childhood PICU survivors, 14.03% did not meet NMSs in the standardized primary school assessment. Socioeconomic status, underlying diseases, and severity on presentation allow risk-stratification to identify children most likely to benefit from individual follow-up and support.

# 危重病儿童期幸存者的教育结局 - 基于人群的连锁研究。

目的：重大重症监护后后遗症影响了多达三分之一危重疾病成人幸存者。缺乏儿科重症监护后教育结局的大型队列。我们在全州儿童队列中评估了儿童期 PICU 存活的儿童的小学教育结局。

设计：对 5 岁以下入住 PICU 的儿童进行多中心人群研究。使用国家评估项目 - 识字和数字数据库，主要结局是小学 3 年时的教育成就低于国家最低标准 (NMS)。将病例与日历年、等级、出生队列、性别、社会经济地位、土著和托雷斯海峡岛民地位和学校匹配的对照进行比较。推导出了预测教育结局的多变量 logistic 回归模型。

设置：澳大利亚昆士兰第三 PICU 和混合 ICU。

患者：1998 年至 2016 年，小于 5 岁的儿童入住 PICU。

干预：不适用。

测量和主要结果：5,017 名 PICU 存活者的 3 年小学数据可用（中位年龄，首次入住 PICU 时 8.0 个月；四分位距，1.9-25.2）。在每个领域，PICU 存活者的评分均显著低于对照组 (p < 0.001)；14.03% 的 PICU 存活者不符合 NMS，而匹配对照组为 8.96%(p < 0.001)。在多变量分析中，社会经济地位（比值比，2.14；95% CI，1.67-2.74）、体重 (0.94；0.90-0.97)、儿科死亡率指数 - 2 评分的 logit (1.11；1.03-1.19)、存在综合征 (11.58；8.87-15.11)、早产 (1.54；1.09-2.19)、慢性神经系统疾病 (4.38；3.27-5.87)、慢性呼吸系统疾病 (1.65；1.24-2.19)，和连续肾脏替代治疗 (4.20；1.40-12.55) 与不满足 NMS 的风险升高独立相关。

结论：在这项儿童期 PICU 存活者人群研究中，14.03% 在标准化小学评估中未达到 NMS。社会经济状况、基础疾病和表现的严重程度允许进行风险分层，以确定最有可能从个体随访和支持中获益的儿童。关键词：Humans; Length of Stay; Retrospective Studies; Child; Infant; Chronic Disease; Survivors; *Critical Illness; Educational Status; *Intensive Care Units, Pediatric

# Aberrant Fibrin Clot Structure Visualized Ex Vivo in Critically Ill Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Infection.

6:e557-e568. DOI:10.1097/CCM.0000000000005465

Abstract:

OBJECTIVES: Disseminated fibrin-rich microthrombi have been reported in patients who died from COVID-19. Our objective is to determine whether the fibrin clot structure and function differ between critically ill patients with or without COVID-19 and to correlate the structure with clinical coagulation biomarkers.

DESIGN: A cross-sectional observational study. Platelet poor plasma was used to analyze fibrin clot structure; the functional implications were determined by quantifying clot turbidity and porosity.

SETTING: ICU at an academic medical center and an academic laboratory.

PATIENTS: Patients admitted from July 1 to August 1, 2020, to the ICU with severe acute respiratory syndrome coronavirus 2 infection confirmed by reverse transcription-polymerase chain reaction or patients admitted to the ICU with sepsis.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Blood was collected from 36 patients including 26 ICU patients with COVID-19 and 10 ICU patients with sepsis but without COVID-19 at a median of 11 days after ICU admission (interquartile range, 3-16). The cohorts were similar in age, gender, body mass index, comorbidities, Sequential Organ Failure Assessment (SOFA) score, and mortality. More patients with COVID-19 (100% vs 70%; p = 0.003) required anticoagulation. Ex vivo fibrin clots formed from patients with COVID-19 appeared to be denser and to have smaller pores than those from patients with sepsis but without COVID-19 (percent area of fluorescent fibrin 48.1% [SD, 16%] vs 24.9% [SD, 18.8%]; p = 0.049). The turbidity and flow-through assays corroborated these data; fibrin clots had a higher maximum turbidity in patients with COVID-19 compared with patients without COVID-19 (0.168 vs 0.089 OD units; p = 0.003), and it took longer for buffer to flow through these clots (216 vs 103 min; p = 0.003). In patients with COVID-19, d-dimer levels were positively correlated with percent area of fluorescent fibrin (ρ = 0.714, p = 0.047). Denser clots (assessed by turbidity and thromboelastography) and higher SOFA scores were independently associated with delayed clot lysis.

CONCLUSIONS: We found aberrant fibrin clot structure and function in critically ill patients with COVID-19. These findings may contribute to the poor outcomes observed in COVID-19 patients with widespread fibrin deposition.

# 严重急性呼吸综合征冠状病毒 2 感染的危重患者中离体可视化的异常纤维蛋白凝块结构。

目的：COVID-19 死亡的患者报告了弥散性富含纤维蛋白的微血栓。我们的目的是确定有或无 COVID-19 的重症患者之间纤维蛋白凝块结构和功能是否存在差异，并将该结构与临床凝血生物标志物相关联。

设计：横断面观察性研究。使用弱血小板血浆分析纤维蛋白凝块结构；通过量化凝块浊度和孔隙度测定其功能意义。

地点：ICU，学术医学中心和学术实验室。

患者：2020 年 7 月 1 日至 8 月 1 日入住 ICU，经逆转录聚合酶链反应证实有严重急性呼吸综合征冠状病毒 2 型感染或伴有败血症的患者。

干预：无。

测量和主要结果：在入住 ICU 后平均 11 天（四分位距，3-16），从 36 名患者中采集血液，包括 26 名有 COVID-19 的 ICU 患者和 10 名有败血症但无 COVID-19 的 ICU 患者。队列在年龄、性别、体重指数、合并症、序贯器官衰竭评估 (SOFA) 评分和死亡率方面相似。更多的 COVID-19 患者（100% 对比 70%；p = 0.003）需要抗凝治疗。与没有 COVID-19 的脓毒症患者相比，COVID-19 患者形成的离体纤维蛋白凝块更致密，孔更小（荧光纤维蛋白面积百分比 48.1%[SD，16%] vs 24.9%[SD，18.8%]；p = 0.049）。浊度和流过试验证实了这些数据；与无 COVID-19 的患者相比，使用 COVID-19 的患者中纤维蛋白凝块的最大浊度更高（0.168 vs 0.089 OD 单位；p = 0.003），缓冲液流过这些凝块的时间更长 (216 vs 103 min；p = 0.003)。在 COVID-19 患者中，d - 二聚体水平与荧光纤维蛋白面积百分比呈正相关 (ρ=0.714，p=0.047)。更致密的凝块（通过浊度和血栓弹性成像评估）和更高的 SOFA 评分与延迟凝块溶解独立相关。

结论：我们在 COVID-19 重症患者中发现了异常的纤维蛋白凝块结构和功能。这些发现可能导致在广泛纤维蛋白沉积的 COVID-19 患者中观察到的不良结局。关键词：Humans; Critical Illness; Cross-Sectional Studies; *COVID-19; Fibrinolysis; *Sepsis; *Thromboembolism; *Thrombosis; Fibrin

# Longitudinal Trends in Bleeding Complications on Extracorporeal Life Support Over the Past Two Decades-Extracorporeal Life Support Organization Registry Analysis., Willers, Anne

6:e569-e580. DOI:10.1097/CCM.0000000000005466

Abstract:

OBJECTIVES: Data about inhospital outcomes in bleeding complications during extracorporeal life support (ECLS) have been poorly investigated.

DESIGN: Retrospective observational study.

SETTING: Patients reported in Extracorporeal Life Support Organization Registry.

PATIENTS: Data of 53.644 adult patients (greater than or equal to 18 yr old) mean age 51.4 ?± 15.9 years, 33.859 (64.5%) male supported with single ECLS run between 01.01.2000 and 31.03.2020, and 19.748 cannulated for venovenous (V-V) ECLS and 30.696 for venoarterial (V-A) ECLS.

INTERVENTIONS: Trends in bleeding complications, bleeding risk factors, and mortality.

MEASUREMENT AND MAIN RESULTS: Bleeding complications were reported in 14.786 patients (27.6%), more often in V-A ECLS compared with V-V (30.0% vs 21.9%; p < 0.001). Hospital survival in those who developed bleeding complications was lower in both V-V ECLS (49.6% vs 66.6%; p < 0.001) and V-A ECLS (33.9 vs 44.9%; p < 0.001). Steady decrease in bleeding complications in V-V and V-A ECLS was observed over the past 20 years (coef., -1.124; p < 0.001 and -1.661; p < 0.001). No change in mortality rates was reported over time in V-V or V-A ECLS (coef., -0.147; p = 0.442 and coef., -0.195; p = 0.139).Multivariate regression revealed advanced age, ecls duration, surgical cannulation, renal replacement therapy, prone positioning as independent bleeding predictors in v-v ecls and female gender, ecls duration, pre-ecls arrest or bridge to transplant, therapeutic hypothermia, and surgical cannulation in v-a ecls.

CONCLUSIONS: A steady decrease in bleeding over the last 20 years, mostly attributable to surgical and cannula-site-related bleeding has been found in this large cohort of patients receiving ECLS support. However, there is not enough data to attribute the decreasing trends in bleeding to technological refinements alone. Especially reduction in cannulation site bleeding is also due to changes in timing, patient selection, and ultrasound guided percutaneous cannulation. Other types of bleeding, such as CNS, have remained stable, and overall bleeding remains associated with a persistent increase in mortality.

# 过去二十年期间体外生活支持出血并发症的纵向趋势 - 体外生活支持组织注册分析。

目的：关于体外生命支持 (ECLS) 期间出血并发症的住院结局数据的研究很少。

设计：回顾性观察性研究。

设置：体外生命支持组织登记研究中报告的患者。

患者：53.644 例成人患者（≥18 岁）的数据平均年龄为 51.4±15.9 岁，33.859 例 (64.5%) 男性支持在 2000 年 1 月 1 日至 2020 年 3 月 31 日期间进行单次 ECLS，19.748 例静脉 - 静脉 (V-V) ECLS 插管，30.696 例静脉 - 动脉 (V-A) ECLS 插管。

干预：出血并发症、出血风险因素和死亡率的趋势。

测量和主要结果：14.786 例患者 (27.6%) 报告了出血并发症，V-A ECLS 比 V-V 更常见 (30.0% vs 21.9%；p < 0.001)。V-V ECLS (49.6% vs 66.6%；p < 0.001) 和 V-A ECLS (33.9% vs 44.9%；p < 0.001) 发生出血并发症的患者的住院生存率较低。在过去 20 年中，观察到 V-V 和 V-A ECLS 的出血并发症稳定减少（系数，-1.124；p < 0.001 和 - 1.661；p < 0.001）。V-V 或 V-A ECLS 中未报告死亡率随时间的变化（系数，-0.147；p = 0.442 和系数，-0.195；p = 0.139）。多变量回归分析显示高龄、ecls 持续时间、手术插管、肾脏替代治疗、俯卧位作为 v-v ecls 独立出血预测因素和女性性别、ecls 持续时间、ecls 前停搏或移植桥接、治疗性低温和 v-a ecls 手术插管。

结论：在接受 ECLS 支持的大型患者队列中发现，过去 20 年的出血稳步减少，主要归因于手术和插管部位相关出血。然而，没有足够的数据将出血减少的趋势仅归因于技术改进。尤其是减少插管部位出血也是由于时间、患者选择和超声引导下经皮插管的变化。其他类型的出血（例如 CNS）保持稳定，总体出血与死亡率的持续增加相关。关键词：Humans; Female; Male; Middle Aged; Aged; Adult; Cohort Studies; Retrospective Studies; Registries; *Extracorporeal Membrane Oxygenation/adverse effects; Catheterization/adverse effects

# Sex Differences in Treatment of Adult Intensive Care Patients: A Systematic Review and Meta-Analysis., Modra, Lucy J.

6:913-923. DOI:10.1097/CCM.0000000000005469

Abstract:

OBJECTIVES: To evaluate and synthesize the available literature on sex differences in the treatment of adult ICU patients.

DATA SOURCES: MEDLINE and EMBASE.

STUDY SELECTION: Two reviewers independently screened publications to identify observational studies of adult ICU patients that explicitly examined the association between sex and ICU treatment-specifically, mechanical ventilation, renal replacement therapy, and length of stay.

DATA EXTRACTION: We extracted data independently and in duplicate: mean age, illness severity, use of mechanical ventilation and renal replacement therapy, and length of stay in ICU and hospital. We assessed risk of bias using the Newcastle-Ottawa Scale. We used a DerSimonian-Laird random-effects model to calculate pooled odds ratios (ORs) and mean differences between women and men.

DATA SYNTHESIS: We screened 4,098 publications, identifying 21 eligible studies with 545,538 participants (42.7% women). The study populations ranged from 246 to 261,255 participants (median 4,420). Most studies (76.2%) were at high risk of bias in at least one domain, most commonly representativeness or comparability. Women were less likely than men to receive invasive mechanical ventilation (OR, 0.83; 95% CI, 0.77-0.89; I2 = 90.4%) or renal replacement therapy (OR, 0.79; 95% CI, 0.70-0.90; I2 = 76.2%). ICU length of stay was shorter in women than men (mean difference, -0.24 d; 95% CI, -0.37 to -0.12; I2 = 89.9%). These findings persisted in meta-analysis of data adjusted for illness severity and other confounders and also in sensitivity analysis excluding studies at high risk of bias. There was no significant sex difference in duration of mechanical ventilation or hospital length of stay.

CONCLUSIONS: Women were less likely than men to receive mechanical ventilation or renal replacement therapy and had shorter ICU length of stay than men. There is substantial heterogeneity and risk of bias in the literature; however, these findings persisted in sensitivity analyses.

# 成人重症监护患者治疗中的性别差异：一项系统回顾和荟萃分析。

目的：评价和整合关于成人 ICU 患者治疗中性别差异的现有文献。

数据来源：MEDLINE 和 EMBASE。

研究选择：两名评审员独立筛选了出版物，以识别 ICU 成人患者的观察性研究，该研究明确了性别与 ICU 治疗（尤其是机械通气、肾脏替代治疗）和住院时间之间的相关性。

数据提取：我们独立和重复提取数据：平均年龄、疾病严重程度、机械通气和肾脏替代治疗的使用以及 ICU 和医院住院时间。我们使用 Newcastle-Ottawa 量表评估了偏倚风险。我们使用 DerSimonian-Laird 随机效应模型计算合并比值比 (OR) 和女性与男性之间的平均差异。

数据综合：我们筛选了 4098 篇发表文献，确定了 21 项合格研究，545538 例受试者（42.7% 为女性）。研究人群范围为 246 ~ 261,255 例受试者（中位数 4,420 例）。大多数研究 (76.2%) 至少在一个领域存在较高的偏倚风险，最常见的是代表性或可比性。女性接受有创机械通气 (OR，0.83；95% CI，0.77-0.89；I2 = 90.4%) 或肾脏替代治疗 (OR，0.79；95% CI，0.70-0.90；I2 = 76.2%) 的可能性低于男性。女性 ICU 住院时间短于男性（平均差异，-0.24 d；95% CI，-0.37 至 - 0.12；I2 = 89.9%）。这些结果在针对疾病严重程度和其他混杂因素调整的数据荟萃分析以及排除偏倚高风险研究的敏感性分析中持续存在。机械通气时间或住院时间无显著性别差异。

结论：女性接受机械通气或肾脏替代治疗的可能性低于男性，ICU 住院时间短于男性。文献中存在显著的异质性和偏倚风险；但是，敏感性分析中仍存在这些结果。关键词：Humans; Female; Male; Time Factors; Length of Stay; Adult; Critical Care; Respiration, Artificial; *Intensive Care Units; *Critical Illness/therapy; Sex Characteristics

# CytoSorb Rescue for COVID-19 Patients With Vasoplegic Shock and Multiple Organ Failure: A Prospective, Open-Label, Randomized Controlled Pilot Study., Stockmann, Helena

6:964-976. DOI:10.1097/CCM.0000000000005493

Abstract:

OBJECTIVES: To investigate the effect of extracorporeal cytokine reduction by CytoSorb (CytoSorbents, Monmouth Junction, NJ) on COVID-19-associated vasoplegic shock.

DESIGN: Prospective, randomized controlled pilot study.

SETTING: Eight ICUs at three sites of the tertiary-care university hospital Charit??-Universit?¤tsmedizin Berlin.

PATIENTS: COVID-19 patients with vasoplegic shock requiring norepinephrine greater than 0.2 ??g/kg/min, C-reactive protein greater than 100 mg/L, and indication for hemodialysis.

INTERVENTIONS: Randomization of 1:1 to receive CytoSorb for 3-7 days or standard therapy. To account for inadvertent removal of antibiotics, patients in the treatment group received an additional dose at each adsorber change.

MEASUREMENTS AND MAIN RESULTS: The primary endpoint was time until resolution of vasoplegic shock, estimated by Cox-regression. Secondary endpoints included mortality, interleukin-6 concentrations, and catecholamine requirements. The study was registered in the German Registry of Clinical Trials (DRKS00021447). From November 2020 to March 2021, 50 patients were enrolled. Twenty-three patients were randomized to receive CytoSorb and 26 patients to receive standard of care. One patient randomized to cytokine adsorption was excluded due to withdrawal of informed consent. Resolution of vasoplegic shock was observed in 13 of 23 patients (56.5%) in the CytoSorb and 12 of 26 patients (46.2%) in the control group after a median of 5 days (interquartile range [IQR], 4-5 d) and 4 days (IQR, 3-5 d). The hazard ratio (HR) for the primary endpoint, adjusted for the predefined variables age, gender, extracorporeal membrane oxygenation-therapy, or time from shock onset to study inclusion was HR, 1.23 (95% CI, 0.54-2.79); p = 0.63. The mortality rate was 78% in the CytoSorb and 73% in the control group (unadjusted HR, 1.17 [95% CI, 0.61-2.23]; p = 0.64). The effects on inflammatory markers, catecholamine requirements, and the type and rates of adverse events were similar between the groups.

CONCLUSIONS: In severely ill COVID-19 patients, CytoSorb did not improve resolution of vasoplegic shock or predefined secondary endpoints.

# COVID-19 血管痉挛性休克和多器官功能衰竭患者的 CytoSorb 抢救：一项前瞻性、开放标签、随机对照初探性研究。

目的：研究 CytoSorb (CytoSorbents,Monmouth Junction,NJ) 减少体外细胞因子对 COVID-19 血管麻痹性休克的影响。

设计：前瞻性、随机对照初探性研究。

设置：柏林夏里特医学院三级大学医院三个研究中心的 8 个 ICU。

患者：需要去甲肾上腺素大于 0.2 ?g/kg/min、C 反应蛋白大于 100 mg/L 和血液透析指征的血管麻痹性休克 COVID-19 患者。

干预措施：以 1:1 的比例随机接受 CytoSorb 治疗 3-7 天或标准治疗。为了解释意外去除抗生素，治疗组患者在每次更换吸附器时接受了额外剂量。

测量和主要结果：主要终点是通过 Cox 回归估计的至血管麻痹性休克消退的时间。次要终点包括死亡率、白细胞介素 - 6 浓度和儿茶酚胺需要量。本研究在德国临床试验注册中心注册 (DRKS00021447)。2020 年 11 月至 2021 年 3 月，入组 50 例。23 例患者随机接受 CytoSorb 治疗，26 例患者接受标准治疗。1 例随机接受细胞因子吸附的患者因撤回知情同意而被排除。在中位 5 天（四分位距 [IQR]，4-5 天）和 4 天（IQR，3-5 天）后，观察到 CytoSorb 组 23 例患者中的 13 例 (56.5%) 和对照组 26 例患者中的 12 例 (46.2%) 血管麻痹性休克消退。针对预先定义的变量年龄、性别、体外膜肺氧合治疗或从休克发作到研究入选的时间进行调整后，主要终点的风险比 (HR) 为 HR，1.23 (95% CI，0.54-2.79)；p = 0.63。CytoSorb 组的死亡率为 78%，对照组为 73%（未校正 HR，1.17 [95% CI，0.61-2.23]；p = 0.64）。两组之间对炎症标志物、儿茶酚胺需求以及不良事件类型和发生率的影响相似。

结论：在重症 COVID-19 患者中，CytoSorb 不能改善血管麻痹性休克的缓解或预定的次要终点。关键词：Humans; Treatment Outcome; Prospective Studies; Pilot Projects; Norepinephrine; Cytokines; Research Design; *COVID-19/therapy; *Shock; Multiple Organ Failure/therapy

# Frailty and Disability: Predictors or Outcomes or Both in Post COVID-19.

6:1023-1025. DOI:10.1097/CCM.0000000000005502

# 虚弱和残疾：COVID-19 后的预测因素或结局或两者兼而有之。

关键词：Humans; Aged; *COVID-19; Frail Elderly; *Disabled Persons; *Frailty/epidemiology

# Factors Associated With Brain Tissue Oxygenation Changes After RBC Transfusion in Acute Brain Injury Patients., Gouv??a Bogossian, Elisa

6:e539-e547. DOI:10.1097/CCM.0000000000005460

Abstract:

OBJECTIVES: Anemia is common after acute brain injury and can be associated with brain tissue hypoxia. RBC transfusion (RBCT) can improve brain oxygenation; however, predictors of such improvement remain unknown. We aimed to identify the factors associated with PbtO2 increase (greater than 20% from baseline value) after RBCT, using a generalized mixed model.

DESIGN: This is a multicentric retrospective cohort study (2012-2020).

SETTING: This study was conducted in three European ICUs of University Hospitals located in Belgium, Switzerland, and Austria.

PATIENTS: All patients with acute brain injury who were monitored with brain tissue oxygenation (PbtO2) catheters and received at least one RBCT.

INTERVENTION: Patients received at least one RBCT. PbtO2 was recorded before, 1 hour, and 2 hours after RBCT.

MEASUREMENTS AND MAIN RESULTS: We included 69 patients receiving a total of 109 RBCTs after a median of 9 days (5-13 d) after injury. Baseline hemoglobin (Hb) and PbtO2 were 7.9 g/dL [7.3-8.7 g/dL] and 21 mm Hg (16-26 mm Hg), respectively; 2 hours after RBCT, the median absolute Hb and PbtO2 increases from baseline were 1.2 g/dL [0.8-1.8 g/dL] (p = 0.001) and 3 mm Hg (0-6 mm Hg) (p = 0.001). A 20% increase in PbtO2 after RBCT was observed in 45 transfusions (41%). High heart rate (HR) and low PbtO2 at baseline were independently associated with a 20% increase in PbtO2 after RBCT. Baseline PbtO2 had an area under receiver operator characteristic of 0.73 (95% CI, 0.64-0.83) to predict PbtO2 increase; a PbtO2 of 20 mm Hg had a sensitivity of 58% and a specificity of 73% to predict PbtO2 increase after RBCT.

CONCLUSIONS: Lower PbtO2 values and high HR at baseline could predict a significant increase in brain oxygenation after RBCT.

# 急性脑损伤患者输注 RBC 后脑组织氧合变化的相关因素。

目的：贫血在急性脑损伤后很常见，可能与脑组织缺氧有关。RBC 输注 (RBCT) 可改善脑氧合；然而，这种改善的预测因素仍不清楚。我们的目的是使用广义混合模型确定 RBCT 后 PbtO2 升高（较基线值大于 20%）的相关因素。

设计：这是一项多中心回顾性队列研究 (2012-2020)。

单位：本研究在位于比利时、瑞士和奥地利的大学医院的三个欧洲 ICU 进行。

患者：所有使用脑组织氧合 (PbtO2) 导管监测并接受至少一次 RBCT 的急性脑损伤患者。

干预：患者接受至少一次 RBCT。记录 RBCT 前、RBCT 后 1 h、2 h 的 PbtO2。

测量和主要结果：我们纳入了 69 例患者，在受伤后中位 9 天（5-13 天）接受了总计 109 次 RBCT。基线血红蛋白 (Hb) 和 PbtO2 分别为 7.9 g/dL [7.3-8.7 g/dL] 和 21 mmHg (16-26 mmHg)；RBCT 后 2 小时，中位绝对 Hb 和 PbtO2 相对于基线的增加分别为 1.2 g/dL [0.8-1.8 g/dL](p = 0.001) 和 3 mmHg (0-6 mmHg)(p = 0.001)。在 45 例输血 (41%) 中观察到 RBCT 后 PbtO2 增加 20%。基线时高心率 (HR) 和低 PbtO2 与 RBCT 后 PbtO2 增加 20% 独立相关。基线 PbtO2 预测 PbtO2 增加的受试者工作特征下面积为 0.73 (95% CI，0.64-0.83)；20 mmHg 的 PbtO2 预测 RBCT 后 PbtO2 增加的敏感性为 58%，特异性为 73%。

结论：基线时较低的 PbtO2 值和较高的 HR 可以预测 RBCT 后脑氧合的显著增加。关键词：Humans; Brain; Oxygen; Retrospective Studies; *Brain Injuries/complications/therapy; Erythrocyte Transfusion; Erythrocytes

# High-Flow Nasal Cannula in COVID-19 Pneumonia: Practical Issues.

6:e591-e592. DOI:10.1097/CCM.0000000000005483

# 高流量鼻导管在 COVID-19 肺炎中的应用：实际问题。

关键词：Humans; Oxygen Inhalation Therapy; *COVID-19; SARS-CoV-2; *Noninvasive Ventilation; *Respiratory Insufficiency/therapy; Cannula

# Low Tidal Volume Ventilation for Emergency Department Patients: A Systematic Review and Meta-Analysis on Practice Patterns and Clinical Impact.

6:986-998. DOI:10.1097/CCM.0000000000005459

Abstract:

OBJECTIVES: Data suggest that low tidal volume ventilation (LTVV) initiated in the emergency department (ED) has a positive impact on outcome. This systematic review and meta-analysis quantify the impact of ED-based LTVV on outcomes and ventilator settings in the ED and ICU.

DATA SOURCES: We systematically reviewed MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, references, conferences, and ClinicalTrials.gov.

STUDY SELECTION: Randomized and nonrandomized studies of mechanically ventilated ED adults were eligible.

DATA EXTRACTION: Two reviewers independently screened abstracts. The primary outcome was mortality. Secondary outcomes included ventilation duration, lengths of stay, and occurrence rate of acute respiratory distress syndrome (ARDS). We assessed impact of ED LTVV interventions on ED and ICU tidal volumes.

DATA SYNTHESIS: The search identified 1,023 studies. Eleven studies (n = 12,912) provided outcome data and were meta-analyzed; 10 additional studies (n = 1,863) provided descriptive ED tidal volume data. Overall quality of evidence was low. Random effect meta-analytic models revealed that ED LTVV was associated with lower mortality (26.5%) versus non-LTVV (31.1%) (odds ratio, 0.80 [0.72-0.88]). ED LTVV was associated with shorter ICU (mean difference, -1.0; 95% CI, -1.7 to -0.3) and hospital (mean difference, -1.2; 95% CI, -2.3 to -0.1) lengths of stay, more ventilator-free days (mean difference, 1.4; 95% CI, 0.4-2.4), and lower occurrence rate (4.5% vs 8.3%) of ARDS (odds ratio, 0.57 [0.44-0.75]). ED LTVV interventions were associated with reductions in ED (-1.5-mL/kg predicted body weight [PBW] [-1.9 to -1.0]; p < 0.001) and ICU (-1.0-mL/kg PBW [-1.8 to -0.2]; p = 0.01) tidal volume.

CONCLUSIONS: The use of LTVV in the ED is associated with improved clinical outcomes and increased use of lung protection, recognizing low quality of evidence in this domain. Interventions aimed at implementing and sustaining LTVV in the ED should be explored.

# 急诊科患者的低潮气量通气：实践模式和临床影响的系统综述和荟萃分析。

目的：数据表明，在急诊科 (ED) 开始的低潮气量通气 (LTVV) 对结局有积极影响。该系统综述和荟萃分析量化了基于 ED 的 LTVV 对 ED 和 ICU 结局和呼吸机设置的影响。

数据来源：我们系统回顾了 MEDLINE,EMBASE,Scopus,Cochrane Central Register of Controlled Trials,Cochrane Database of Systematic Reviews,references,conferences,andClinicalTrials.gov. 研究选择：机械通气 ED 成人的随机和非随机研究均合格。

数据提取：两名评审员独立筛选摘要。主要结局是死亡率。次要结局包括通气持续时间、住院时间和急性呼吸窘迫综合征 (ARDS) 的发生率。我们评估了 ED LTVV 干预对 ED 和 ICU 潮气量的影响。

数据综合：检索识别出 1,023 项研究。11 项研究 (n = 12,912) 提供了结局数据并进行了荟萃分析；另外 10 项研究 (n = 1,863) 提供了描述性 ED 潮气量数据。证据的总体质量较低。随机效应荟萃分析模型显示，与非 LTVV (31.1%) 相比，ED LTVV 与较低的死亡率 (26.5%) 相关（比值比，0.80 [0.72-0.88]）。ED LTVV 与 ICU（平均差异，-1.0；95% CI，-1.7 至 - 0.3）和住院（平均差异，-1.2；95% CI，-2.3 至 - 0.1）时间更短、无呼吸机天数更多（平均差异，1.4；95% CI，0.4-2.4）和 ARDS 发生率更低 (4.5% vs 8.3%) 相关（比值比，0.57 [0.44-0.75]）。ED LTVV 干预与 ED（-1.5 mL/kg 预测体重 [PBW][-1.9 至 - 1.0]；p < 0.001）和 ICU（-1.0 mL/kg PBW [-1.8 至 - 0.2]；p = 0.01）潮气量减少相关。

结论：在 ED 中使用 LTVV 与临床结局改善和肺保护的使用增加相关，认识到该领域的证据质量较低。应探讨旨在在 ED 实施和维持 LTVV 的干预措施。关键词：Humans; Intensive Care Units; Adult; Emergency Service, Hospital; Randomized Controlled Trials as Topic; Lung; Tidal Volume; *Respiratory Distress Syndrome/therapy; *Respiration, Artificial

# Association of Metformin Use During Hospitalization and Mortality in Critically Ill Adults With Type 2 Diabetes Mellitus and Sepsis.

6:935-944. DOI:10.1097/CCM.0000000000005468

Abstract:

OBJECTIVES: Whether metformin exposure is associated with improved outcomes in patients with type 2 diabetes mellitus and sepsis.

DESIGN: Retrospective cohort study.

SETTING: Patients admitted to ICUs in 16 hospitals in Pennsylvania from October 2008 to December 2014.

PATIENTS: Adult critical ill patients with type 2 diabetes mellitus and sepsis.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective cohort study to compare 90-day mortality in diabetic patients with sepsis with and without exposure to metformin during hospitalization. Data were obtained from the electronic health record of a large healthcare system in Pennsylvania from October 2008 to December 2014, on patients admitted to the ICU at any of the 16 hospitals within the system. The primary outcome was mortality at 90 days. The absolute and adjusted odds ratio (OR) with 95% CI were calculated in a propensity score-matched cohort. Among 14,847 patients with type 2 diabetes mellitus and sepsis, 682 patients (4.6%) were exposed to metformin during hospitalization and 14,165 (95.4%) were not. Within a total of 2,691 patients subjected to propensity score-matching at a 1:4 ratio, exposure to metformin (n = 599) was associated with decreased 90-day mortality (71/599, 11.9% vs 475/2,092, 22.7%; OR, 0.46; 95% CI, 0.35-0.60), reduced severe acute kidney injury (50% vs 57%; OR, 0.75; 95% CI, 0.62-0.90), less Major Adverse Kidney Events at 1 year (OR, 0.27; 95% CI, 0.22-0.68), and increased renal recovery (95% vs 86%; OR, 6.43; 95% CI, 3.42-12.1).

CONCLUSIONS: Metformin exposure during hospitalization is associated with a decrease in 90-day mortality in patients with type 2 diabetes mellitus and sepsis.

# 住院期间使用二甲双胍与 2 型糖尿病和败血症危重成人患者死亡率的相关性。

目的：二甲双胍暴露是否与 2 型糖尿病和败血症患者结局改善相关。

设计：回顾性队列研究。

地点：2008 年 10 月至 2014 年 12 月宾夕法尼亚州 16 家医院 ICU 收治的患者。

患者：2 型糖尿病和败血症成人重症患者。

干预：无。

测量和主要结果：我们进行了一项回顾性队列研究，以比较住院期间暴露于和未暴露于二甲双胍的伴有败血症的糖尿病患者的 90 天死亡率。数据来自 2008 年 10 月至 2014 年 12 月宾夕法尼亚州一家大型医疗系统的电子健康记录，关于系统内 16 家医院中任何一家入住 ICU 的患者。主要结局为 90 天时的死亡率。在倾向评分匹配队列中计算绝对和校正比值比 (OR) 及 95% CI。在 14,847 例 2 型糖尿病和败血症患者中，682 例患者 (4.6%) 在住院期间暴露于二甲双胍，14,165 例患者 (95.4%) 未暴露于二甲双胍。在总计 2,691 例以 1:4 比例进行倾向评分匹配的患者中，暴露于二甲双胍 (n = 599) 与 90 天死亡率降低 (71/599，11.9% vs 475/2,092，22.7%；OR，0.46；95% CI，0.35-0.60)、重度急性肾损伤降低 (50% vs 57%；OR，0.75；95% CI，0.62-0.90) 相关，1 年时主要肾脏不良事件减少 (OR，0.27；95% CI，0.22-0.68)，肾脏恢复增加 (95% vs 86%；OR，6.43；95% CI，3.42-12.1)。

结论：住院期间二甲双胍暴露与 2 型糖尿病和败血症患者 90 天死亡率降低相关。关键词：Humans; Critical Illness; Adult; Retrospective Studies; Hospitalization; *Metformin/therapeutic use; *Diabetes Mellitus, Type 2/complications/drug therapy; *Sepsis/complications/drug therapy

# Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial., Drewry, Anne M.

6:924-934. DOI:10.1097/CCM.0000000000005470

Abstract:

OBJECTIVES: To test the hypothesis that forced-air warming of critically ill afebrile sepsis patients improves immune function compared to standard temperature management.

DESIGN: Single-center, prospective, open-label, randomized controlled trial.

SETTING: One thousand two hundred-bed academic medical center.

PATIENTS: Eligible patients were mechanically ventilated septic adults with: 1) a diagnosis of sepsis within 48 hours of enrollment; 2) anticipated need for mechanical ventilation of greater than 48 hours; and 3) a maximum temperature less than 38.3?°C within the 24 hours prior to enrollment.

Primary exclusion criteria included: immunologic diseases, immune-suppressing medications, and any existing condition sensitive to therapeutic hyperthermia (e.g., brain injury). The primary outcome was monocyte human leukocyte antigen (HLA)-DR expression, with secondary outcomes of CD3/CD28-induced interferon gamma (IFN-??) production, mortality, and 28-day hospital-free days.

INTERVENTIONS: External warming using a forced-air warming blanket for 48 hours, with a goal temperature 1.5?°C above the lowest temperature documented in the previous 24 hours.

MEASUREMENTS AND MAIN RESULTS: We enrolled 56 participants in the study. No differences were observed between the groups in HLA-DR expression (692 vs 2,002; p = 0.396) or IFN-?? production (31 vs 69; p = 0.678). Participants allocated to external warming had lower 28-day mortality (18% vs 43%; absolute risk reduction, 25%; 95% CI, 2-48%) and more 28-day hospital-free days (difference, 2.6 d; 95% CI, 0-11.6).

CONCLUSIONS: Participants randomized to external forced-air warming did not have a difference in HLA-DR expression or IFN-?? production. In this pilot study, however, 28-day mortality was lower in the intervention group. Future research should seek to better elucidate the impact of temperature modulation on immune and nonimmune organ failure pathways in sepsis.

# 治疗性高热与发热危重症脓毒症患者的生存率改善相关：一项初探性随机化试验。

目的：检验与标准温度管理相比，强制空气加温重症无热败血症患者改善免疫功能的假设。

设计：单中心、前瞻性、开放标签、随机对照试验。

单位：一千二百张床位的学术医学中心。

患者：合格患者为机械通气的脓毒症成人患者：1）入组前 48 小时内诊断为脓毒症；2）预期需要机械通气超过 48 小时；和 3）入组前 24 小时内最高体温低于 38.3℃。

主要排除标准包括：免疫性疾病、免疫抑制药物和对治疗性体温过高敏感的任何现有疾病（例如，脑损伤）。主要结局是单核细胞人类白细胞抗原 (HLA)-DR 表达，次要结局是 CD3/CD28 诱导的干扰素 γ (IFN-ō?) 产生、死亡率和 28 天无住院天数。

干预：使用强制空气加温毯进行外部加温 48 小时，目标温度比之前 24 小时内记录的最低温度高 1.5℃。

测量和主要结果：我们入组了 56 例受试者。两组之间的 HLA-DR 表达 (692 vs 2,002;p = 0.396) 或 IFN-ō? 产生 (31 vs 69;p = 0.678) 没有差异。分配到外部加温组的受试者 28 天死亡率较低（18% vs 43%；绝对风险降低，25%；95% CI，2-48%），28 天无住院天数较多（差异，2.6 天；95% CI，0-11.6）。

结论：随机接受外部强制空气加温的参与者在 HLA-DR 表达或 IFN-ō? 产生方面没有差异。然而，在这项初探性研究中，干预组的 28 天死亡率较低。未来的研究应该寻求更好地阐明温度调节对脓毒症免疫和非免疫器官衰竭途径的影响。关键词：Humans; Prospective Studies; Adult; Pilot Projects; *COVID-19; SARS-CoV-2; Critical Illness/therapy; *Sepsis/therapy; *Hyperthermia, Induced; HLA-DR Antigens

# Intravascular Versus Surface Cooling in Patients Resuscitated From Cardiac Arrest: A Systematic Review and Network Meta-Analysis With Focus on Temperature Feedback., Ramadanov, Nikolai

6:999-1009. DOI:10.1097/CCM.0000000000005463

Abstract:

OBJECTIVE: The aim of the study was to compare the effect of intravascular cooling (IC), surface cooling with temperature feedback (SCF), and surface cooling without temperature feedback (SCnoF) on neurologic outcome and survival in patients successfully resuscitated from cardiac arrest (CA) and treated with targeted temperature management (TTM) at 32-34?°C.

DATA SOURCES: We performed a systematic review on Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, MEDLINE, SCOPUS, CINAHL, Web of Science, and Clinical Trials up to June 30, 2021.

STUDY SELECTION: We included randomized and nonrandomized studies on IC, SCF, and SCnoF in adult humans resuscitated from CA undergoing TTM, reporting neurologic outcome or survival.

DATA EXTRACTION: We performed a network meta-analysis to assess the comparative effects of IC, SCF, and SCnoF. The overall effect between two cooling methods included the effect of direct and indirect comparisons. Results are given as odds ratios (OR) and 95% CIs. Rankograms estimated the probability of TTM methods being ranked first, second, and third best interventions.

DATA SYNTHESIS: A total of 14 studies involving 4,062 patients met the inclusion criteria. Four studies were randomized controlled studies, and 10 studies were nonrandomized observational studies. IC compared with SCnoF was significantly associated with better neurologic outcome (OR, 0.6; 95% CI, 0.49-0.74) and survival (OR, 0.8; 95% CI, 0.66-0.96). IC compared with SCF, and SCF compared with SCnoF did not show significant differences in neurologic outcome and survival. The rankogram showed that IC had the highest probability to be the most beneficial cooling method, followed by SCF and SCnoF.

CONCLUSIONS: Our results suggest that in patients resuscitated from CA and treated with TTM at 32-34?°C, IC has the highest probability of being the most beneficial cooling method for survival and neurologic outcome.

# 心脏骤停复苏患者的血管内与表面冷却比较：一项关注温度反馈的系统综述和网络荟萃分析。

目的：本研究的目的是比较血管内冷却 (IC)、表面冷却与温度反馈 (SCF)、以及无温度反馈的表面冷却 (SCnoF) 对心脏骤停 (CA) 成功复苏并在 32-34℃下接受靶向温度管理 (TTM) 治疗的患者的神经系统结局和存活率的影响。

数据来源：我们对 Cochrane 临床对照试验中心注册数据库进行了系统综述，Cochrane 系统综述数据库、MEDLINE、SCOPUS、CINAHL、Web of Science 和截至 2021 年 06 月 30 日的临床试验。

研究选择：我们纳入了在接受 TTM 的 CA 复苏的成人中进行 IC、SCF 和 SCnoF 的随机和非随机研究，报告了神经系统结局或生存期。

数据提取：我们进行了一项网络荟萃分析，以评估 IC、SCF 和 SCnoF 的比较效应。两种冷却方法之间的总体效果包括直接和间接比较的效果。结果表示为比值比 (OR) 和 95% CI。等级图估计了 TTM 方法排在第一、第二和第三最佳干预措施的概率。

数据综合：共有 14 项研究（涉及 4062 例患者）符合入选标准。4 项研究为随机对照研究，10 项研究为非随机观察性研究。与 SCnoF 相比，IC 与更好的神经系统结局 (OR，0.6；95% CI，0.49-0.74) 和生存率 (OR，0.8；95% CI，0.66-0.96) 显著相关。IC 与 SCF 相比，SCF 与 SCnoF 相比，在神经系统结局和生存率方面未显示出显著差异。等级图显示，IC 是最有益的冷却方法的概率最高，其次是 SCF 和 SCnoF。

结论：我们的结果表明，在从 CA 复苏并用 TTM 在 32-34℃治疗的患者中，IC 是对生存和神经系统结局最有益的冷却方法的概率最高。关键词：Humans; Adult; Feedback; *Cardiopulmonary Resuscitation/methods; *Heart Arrest/complications; *Hypothermia, Induced/methods; Network Meta-Analysis; Temperature

# Patient-Centered Outcomes Following COVID-19: Frailty and Disability Transitions in Critical Care Survivors.

6:955-963. DOI:10.1097/CCM.0000000000005488

Abstract:

OBJECTIVES: As the pandemic advances, the interest in the long-lasting consequences of COVID-19 increases. However, a few studies have explored patient-centered outcomes in critical care survivors. We aimed to investigate frailty and disability transitions in COVID-19 patients admitted to ICUs.

DESIGN: Prospective cohort study.

SETTING: University hospital in Sao Paulo.

PATIENTS: Survivors of COVID-19 ICU admissions.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We assessed frailty using the Clinical Frailty Scale (CFS). We also evaluated 15 basic, instrumental, and mobility activities. Baseline frailty and disability were defined by clinical conditions 2-4 weeks before COVID-19, and post-COVID-19 was characterized 90 days (day 90) after hospital discharge. We used alluvial flow diagrams to visualize transitions in frailty status, Venn diagrams to describe the overlap between frailty and disabilities in activities of daily living, and linear mixed models to explore the occurrence of new disabilities following critical care in COVID-19. We included 428 participants with a mean age of 64 years, 57% males, and a median Simplified Acute Physiology Score-3 score of 59. Overall, 14% were frail at baseline. We found that 124/394 participants (31%) were frail at day 90, 70% of whom were previously non-frail. The number of disabilities also increased (mean difference, 2.46; 95% CI, 2.06-2.86), mainly in participants who were non-frail before COVID-19. Higher pre-COVID-19 CFS scores were independently associated with new-onset disabilities. At day 90, 135 patients (34%) were either frail or disabled.

CONCLUSIONS: Frailty and disability were more frequent 90 days after hospital discharge compared with baseline in COVID-19 patients admitted to the ICU. Our results show that most COVID-19 critical care survivors transition to poorer health status, highlighting the importance of long-term medical follow-up for this population.

# COVID-19 后以患者为中心的结局：重症监护幸存者的虚弱和残疾转变。

目的：随着大流行的进展，人们对 COVID-19 长期后果的兴趣增加。然而，一些研究探索了重症监护幸存者以患者为中心的结局。我们的目的是调查入住 ICU 的 COVID-19 患者的虚弱和残疾转变。

设计：前瞻性队列研究。

单位：圣保罗大学医院。

患者：入住 COVID-19 ICU 的幸存者。

干预：无。

测量和主要结果：我们使用临床虚弱量表 (CFS) 评估虚弱。我们还评估了 15 项基本、工具和活动。基线虚弱和残疾定义为 COVID-19 前 2-4 周的临床状况，COVID-19 后在出院后 90 天（第 90 天）进行表征。我们使用冲积流图来可视化虚弱状态的转变，使用维恩图来描述日常生活活动中虚弱和残疾之间的重叠，使用线性混合模型来探索 COVID-19 重症监护后新发残疾的发生。我们纳入了 428 例受试者，平均年龄为 64 岁，57% 为男性，简化急性生理学评分 - 3 分的中位数为 59 分。总体而言，14% 的患者在基线时虚弱。我们发现 124/394 的参与者 (31%) 在第 90 天虚弱，其中 70% 以前不虚弱。致残人数也增加（平均差异，2.46；95% CI，2.06-2.86），主要发生在 COVID-19 前非虚弱的参与者中。较高的 COVID-19 前 CFS 评分与新发残疾独立相关。在第 90 天，135 例患者 (34%) 虚弱或残疾。

结论：在入住 ICU 的 COVID-19 患者中，与基线相比，出院后 90 天虚弱和残疾更常见。我们的结果显示，大多数 COVID-19 重症监护幸存者向较差的健康状况过渡，突出了对该人群进行长期医学随访的重要性。关键词：Humans; Female; Male; Middle Aged; Prospective Studies; Critical Care; Activities of Daily Living; *COVID-19; Survivors; *Frailty/epidemiology; *Fatigue Syndrome, Chronic; Brazil; Critical Illness/epidemiology; Patient-Centered Care

# Drp1/Fis1-Dependent Pathologic Fission and Associated Damaged Extracellular Mitochondria Contribute to Macrophage Dysfunction in Endotoxin Tolerance., Mukherjee, Riddhita

6:e504-e515. DOI:10.1097/CCM.0000000000005437

Abstract:

OBJECTIVES: Recent publications have shown that mitochondrial dynamics can govern the quality and quantity of extracellular mitochondria subsequently impacting immune phenotypes. This study aims to determine if pathologic mitochondrial fission mediated by Drp1/Fis1 interaction impacts extracellular mitochondrial content and macrophage function in sepsis-induced immunoparalysis.

DESIGN: Laboratory investigation.

SETTING: University laboratory.

SUBJECTS: C57BL/6 and BALB/C mice.

INTERVENTIONS: Using in vitro and murine models of endotoxin tolerance (ET), we evaluated changes in Drp1/Fis1-dependent pathologic fission and simultaneously measured the quantity and quality of extracellular mitochondria. Next, by priming mouse macrophages with isolated healthy mitochondria (MC) and damaged mitochondria, we determined if damaged extracellular mitochondria are capable of inducing tolerance to subsequent endotoxin challenge. Finally, we determined if inhibition of Drp1/Fis1-mediated pathologic fission abrogates release of damaged extracellular mitochondria and improves macrophage response to subsequent endotoxin challenge.

MEASUREMENTS AND MAIN RESULTS: When compared with na??ve macrophages (NMs), endotoxin-tolerant macrophages (ETM) demonstrated Drp1/Fis1-dependent mitochondrial dysfunction and higher levels of damaged extracellular mitochondria (Mitotracker-Green + events/50 ??L: ETM = 2.42 ?? 106 ?± 4,391 vs NM = 5.69 ?? 105 ?± 2,478; p < 0.001). Exposure of NMs to damaged extracellular mitochondria (MH) induced cross-tolerance to subsequent endotoxin challenge, whereas MC had minimal effect (tumor necrosis factor [TNF]-?± [pg/mL]: NM = 668 ?± 3, NM + MH = 221 ?± 15, and NM + Mc = 881 ?± 15; p < 0.0001). Inhibiting Drp1/Fis1-dependent mitochondrial fission using heptapeptide (P110), a selective inhibitor of Drp1/Fis1 interaction, improved extracellular mitochondrial function (extracellular mitochondrial membrane potential, JC-1 [R/G] ETM = 7 ?± 0.5 vs ETM + P110 = 19 ?± 2.0; p < 0.001) and subsequently improved immune response in ETMs (TNF-?± [pg/mL]; ETM = 149 ?± 1 vs ETM + P110 = 1,150 ?± 4; p < 0.0001). Similarly, P110-treated endotoxin tolerant mice had lower amounts of damaged extracellular mitochondria in plasma (represented by higher extracellular mitochondrial membrane potential, TMRM/MT-G: endotoxin tolerant [ET] = 0.04 ?± 0.02 vs ET + P110 = 0.21 ?± 0.02; p = 0.03) and improved immune response to subsequent endotoxin treatment as well as cecal ligation and puncture.

CONCLUSIONS: Inhibition of Drp1/Fis1-dependent mitochondrial fragmentation improved macrophage function and immune response in both in vitro and in vivo models of ET. This benefit is mediated, at least in part, by decreasing the release of damaged extracellular mitochondria, which contributes to endotoxin cross-tolerance. Altogether, these data suggest that alterations in mitochondrial dynamics may play an important role in sepsis-induced immunoparalysis.

# Drp1/Fis1 - 依赖性病理性裂变和相关的细胞外线粒体损伤促进内毒素耐受中的巨噬细胞功能障碍。

目的：近期发表的文献表明，线粒体动力学可控制随后影响细胞外线粒体质量和数量免疫表型。本研究旨在确定病理性线粒体 Drp1/Fis1 相互作用介导的裂变对胞外线粒体的影响败血症诱导的免疫麻痹中的含量和巨噬细胞功能。

设计：实验室检查。

单位：大学实验室。

受试者：C57BL/6 和 BALB/C 小鼠。

干预：使用内毒素的体外和小鼠模型耐受 (ET)，我们评估了 Drp1/Fis1 依赖性病理性裂变的变化同时测定细胞外线粒体。接下来，用分离的健康小鼠巨噬细胞启动小鼠巨噬细胞线粒体 (MC) 和受损线粒体，我们确定是否受损胞外线粒体能够诱导对后续内毒素挑战。最后，我们确定是否抑制 Drp1/Fis1 - 介导的病理性裂变消除了受损细胞外线粒体的释放，以及改善巨噬细胞对后续内毒素激发的反应。测量值和主要结果：与天然巨噬细胞 (NM) 相比，内毒素耐受巨噬细胞 (ETM) 表现出 Drp1/Fis1 - 依赖性线粒体功能障碍和受损的胞外线粒体水平较高（Mitotracker-Green + 事件 / 50μ?L：ETM = 2.42μ-106 μm±4,391 对比 NM = 5.69 μm-105 μm±2,478；p < 0.001）。NM 暴露于损伤的细胞外线粒体 (MH) 诱导对后续内毒素激发的交叉耐受，而 MC 的影响极小（肿瘤坏死因子 [TNF]-β±[pg/mL]：NM = 668 μm±3，NM + MH = 221 μm±15，和 NM + Mc = 881?±15；p < 0.0001）。抑制 Drp1/Fis1 依赖性线粒体使用七肽 (P110) 裂解，Drp1/Fis1 的选择性抑制剂相互作用，改善细胞外线粒体功能（细胞外线粒体膜电位，JC-1 [R/G] ETM = 7 μm±0.5 对比 ETM + P110 = 19Μ±2.0；p < 0.001），随后改善了 ETM 中的免疫应答 (TNF-Μ±2.0)。 [pg/mL]；ETM = 149?±1 vs ETM + P110 = 1,150?4；P < 0.0001）。同样， P110 处理的内毒素耐受小鼠细胞外的损伤量较低血浆中的线粒体（由较高的胞外线粒体代表）膜电位，TMRM/MT-G：内毒素耐受性 [ET]= 0.04 μm±0.02 vs ET + P110 = 0.21 ?± 0.02;p = 0.03），并改善了对随后内毒素的免疫应答治疗以及盲肠结扎和穿刺。

结论：抑制 Drp1/Fis1 - 依赖性线粒体碎片化改善巨噬细胞功能和 ET 体外和体内模型中的免疫应答。该获益为至少部分通过减少受损细胞外信号的释放介导线粒体，有助于内毒素交叉耐受。总之，这些数据表明，线粒体动力学的改变可能起着重要作用在败血症诱导的免疫麻痹中的作用。关键词：Humans; Animals; Mice, Inbred C57BL; Mice; Mice, Inbred BALB C; *Sepsis/pathology; Dynamins/genetics/*metabolism/pharmacology; Endotoxin Tolerance; Endotoxins; Macrophages; Membrane Proteins/genetics; Mitochondria; Mitochondrial Dynamics/physiology; Mitochondrial Proteins

# Intracranial Hemorrhages on Extracorporeal Membrane Oxygenation: Differences Between COVID-19 and Other Viral Acute Respiratory Distress Syndrome., Seeliger, Benjamin

6:e526-e538. DOI:10.1097/CCM.0000000000005441

Abstract:

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) is a potentially lifesaving procedure in acute respiratory distress syndrome (ARDS) due to COVID-19. Previous studies have shown a high prevalence of clinically silent cerebral microbleeds in patients with COVID-19. Based on this fact, together with the hemotrauma and the requirement of therapeutic anticoagulation on ECMO support, we hypothesized an increased risk of intracranial hemorrhages (ICHs). We analyzed ICH occurrence rate, circumstances and clinical outcome in patients that received ECMO support due to COVID-19-induced ARDS in comparison to viral non-COVID-19-induced ARDS intracerebral hemorrhage.

DESIGN: Multicenter, retrospective analysis between January 2010 and May 2021.

SETTING: Three tertiary care ECMO centers in Germany and Switzerland.

PATIENTS: Two-hundred ten ARDS patients on ECMO support (COVID-19, n = 142 vs viral non-COVID, n = 68).

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Evaluation of ICH occurrence rate, parameters of coagulation and anticoagulation strategies, inflammation, and ICU survival. COVID-19 and non-COVID-19 ARDS patients showed comparable disease severity regarding Sequential Organ Failure Assessment score, while the oxygenation index before ECMO cannulation was higher in the COVID group (82 vs 65 mm Hg). Overall, ICH of any severity occurred in 29 of 142 COVID-19 patients (20%) versus four of 68 patients in the control ECMO group (6%). Fifteen of those 29 ICH events in the COVID-19 group were classified as major (52%) including nine fatal cases (9/29, 31%). In the control group, there was only one major ICH event (1/4, 25%). The adjusted subhazard ratio for the occurrence of an ICH in the COVID-19 group was 5.82 (97.5% CI, 1.9-17.8; p = 0.002). The overall ICU mortality in the presence of ICH of any severity was 88%.

CONCLUSIONS: This retrospective multicenter analysis showed a six-fold increased adjusted risk for ICH and a 3.5-fold increased incidence of ICH in COVID-19 patients on ECMO. Prospective studies are needed to confirm this observation and to determine whether the bleeding risk can be reduced by adjusting anticoagulation strategies.

# 体外膜式氧合的颅内出血：COVID-19 与其他病毒性急性呼吸窘迫综合征的差异。

目的：体外膜肺氧合 (ECMO) 是急性呼吸窘迫综合征 (ARDS) 患者的潜在救命手术，原因如下副本 - 19。既往研究表明，临床无症状的患病率较高 COVID-19 患者的脑微出血。基于这一事实，与 ECMO 时的血伤和抗凝治疗的需求因此，我们假设颅内出血 (ICH) 的风险增加。We 分析了患者的 ICH 发生率、情况和临床结局由于与病毒相比，COVID-19 诱导的 ARDS，接受 ECMO 支持非 - COVID-19 诱导的 ARDS 脑出血。

设计：多中心， 2010 年 1 月至 2021 年 5 月的回顾性分析。

设置：三级德国和瑞士的 ECMO 治疗中心。

患者：210 例 ARDS ECMO 支持的患者（COVID-19，n = 142 vs 病毒性非 COVID，n = 68）。

干预：无。

测量和主要结果：ICH 发生率评价速率、凝血参数和抗凝策略、炎症，以及 ICU 存活率。COVID-19 和非 COVID-19 ARDS 患者显示了相当的疾病严重程度关于序贯器官衰竭评估评分，而 COVID 组 ECMO 插管前的氧合指数更高（82 vs 65 mmHg）。总体而言，142 例 COVID-19 患者中的 29 例发生任何严重程度的 ICH (20%) 对比对照 ECMO 组 68 例患者中的 4 例 (6%)。其中 15 例 COVID-19 组的 29 起 ICH 事件归类为重大 (52%)，包括 9 起致死性病例 (9/29，31%)。在对照组中，仅有一起重大 ICH 事件 (1/4, 25%). 以下患者中 ICH 发生率的校正亚风险比 COVID-19 组为 5.82 (97.5% CI，1.9-17.8；p = 0.002)。整个 ICU 存在任何严重程度的 ICH 时，死亡率为 88%。

结论：这回顾性多中心分析显示校正后风险增加 6 倍 ICH 和 3.5 倍在接受 ECMO 的 COVID-19 患者中 ICH 发生率增加。需要前瞻性研究来证实该观察结果并确定是否可以通过调整抗凝策略来降低出血风险。关键词：Humans; Retrospective Studies; *Respiratory Distress Syndrome/epidemiology/therapy; *COVID-19/complications/therapy; *Extracorporeal Membrane Oxygenation/adverse effects/methods; Anticoagulants/therapeutic use; Intracranial Hemorrhages/drug therapy/epidemiology/etiology

# ICU Versus High-Dependency Care Unit for Patients With Acute Myocardial Infarction: A Nationwide Propensity Score-Matched Cohort Study., Ohbe, Hiroyuki

6:977-985. DOI:10.1097/CCM.0000000000005440

Abstract:

OBJECTIVES: To compare the outcomes of patients with acute myocardial infarction who were treated in ICUs versus high-dependency care units (HDUs).

DESIGN: A nationwide, propensity score-matched, retrospective cohort study of a national administrative inpatient database in Japan from July 2010 to March 2018.

SETTING: Six hundred sixty-six acute-care hospitals with ICU and/or HDU beds covering about 75% of all ICU beds and 70% of all HDU beds in Japan.

PATIENTS: Adult patients who were hospitalized for acute myocardial infarction and admitted to the ICU or HDU on the day of hospital admission. Propensity score-matching analysis was performed to compare the inhospital mortality between patients treated in the ICU and HDU on the day of hospital admission.

INTERVENTIONS: ICU or HDU admission on the day of hospital admission.

MEASUREMENTS AND MAIN RESULTS: Of 135,142 eligible patients, 89,382 (66%) were admitted to the ICU and 45,760 (34%) were admitted to the HDU on the day of admission. After propensity score matching, there was no statistically significant difference in inhospital mortality between the ICU and HDU groups (5.0% vs 5.5%; difference, -0.5%; 95% CI, -1.0% to 0.1%). In the subgroup analyses, inhospital mortality was significantly lower in the ICU group than that in the HDU group among patients with Killip class IV (25.6% vs 28.4%; difference, -2.9%; 95% CI, -5.4% to -0.3%), patients who underwent intubation (40.0% vs 46.6%; difference, -6.6%; 95% CI, -10.6% to -2.7%), and patients who received mechanical circulatory support (21.8% vs 24.7%; difference, -2.8%; 95% CI, -5.5% to -0.2%).

CONCLUSIONS: Critical care in the ICU compared with that in the HDU was not associated with reduced inhospital mortality among the entire cohort of patients with acute myocardial infarction but was associated with reduced inhospital mortality among the subsets of patients with Killip class IV, intubation, or mechanical circulatory support.

# 急性心肌梗死患者 ICU 与高依赖性监护病房的比较：全国倾向评分匹配队列研究。

目的：比较在 ICU 与高依赖性监护病房 (HDU) 接受治疗的急性心肌梗死患者的结局。

设计：A 国家、倾向评分匹配的回顾性队列研究 2010 年 7 月至 2018 年 3 月日本住院患者管理数据库。

设置： 666 家急症医院，ICU 和 / 或 HDU 床位覆盖日本约 75% 的 ICU 床位和 70% 的 HDU 床位。

患者：成人因急性心肌梗死而住院的患者入院当天的 ICU 或 HDU。倾向评分匹配分析比较患者之间的住院死亡率入院当天在 ICU 和 HDU 接受治疗。

干预措施：ICU 或在入院当天入住 HDU。

测量和主要结果：在 135,142 例合格患者中，89,382 例 (66%) 进入 ICU，45,760 例 (34%) 在入院当天进入 HDU。倾向评分后匹配，住院时间无统计学显著差异 ICU 和 HDU 组之间的死亡率（5.0% vs 5.5%；差异，-0.5%；95%） CI，-1.0% 至 0.1%）。在亚组分析中，住院死亡率为 ICU 组患者显著低于 HDU 组 Killip IV 级（25.6% vs 28.4%；差异，-2.9%；95% CI，-5.4% 至 - 0.3%），接受插管的患者（40.0% vs 46.6%；差异，-6.6%；95% CI， -10.6% to -2.7%), 和接受机械循环支持的患者（21.8% vs 24.7%；差异，-2.8%；95% CI，-5.5% 至 - 0.2%）。

结论：重症监护 ICU 与 HDU 相比，与减少急性心肌梗死患者整个队列的住院死亡率梗死，但与亚组中住院死亡率降低相关 Killip IV 级插管患者，或机械循环支持。关键词：Humans; Adult; Cohort Studies; Propensity Score; Retrospective Studies; Hospital Mortality; *Intensive Care Units; *Myocardial Infarction/therapy

# Brain Biopsy for Neurological Diseases of Unknown Etiology in Critically Ill Patients: Feasibility, Safety, and Diagnostic Yield.

6:e516-e525. DOI:10.1097/CCM.0000000000005439

Abstract:

OBJECTIVES: Brain biopsy is a useful surgical procedure in the management of patients with suspected neoplastic lesions. Its role in neurologic diseases of unknown etiology remains controversial, especially in ICU patients. This study was undertaken to determine the feasibility, safety, and the diagnostic yield of brain biopsy in critically ill patients with neurologic diseases of unknown etiology. We also aimed to compare these endpoints to those of non-ICU patients who underwent a brain biopsy in the same clinical context.

DESIGN: Monocenter, retrospective, observational cohort study.

SETTING: A French tertiary center.

PATIENTS: All adult patients with neurologic diseases of unknown etiology under mechanical ventilation undergoing in-ICU brain biopsy between January 2008 and October 2020 were compared with a cohort of non-ICU patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Among the 2,207 brain-biopsied patients during the study period, 234 biopsies were performed for neurologic diseases of unknown etiology, including 29 who were mechanically ventilated and 205 who were not ICU patients. Specific histological diagnosis and final diagnosis rates were 62.1% and 75.9%, respectively, leading to therapeutic management modification in 62.1% of cases. Meningitis on prebiopsy cerebrospinal fluid analysis was the sole predictor of obtaining a final diagnosis (2.3 [1.4-3.8]; p = 0.02). ICU patients who experienced therapeutic management modification after the biopsy had longer survival (p = 0.03). The grade 1 to 4 (mild to severe) complication rates were: 24.1%, 3.5%, 0%, and 6.9%, respectively. Biopsy-related mortality was significantly higher in ICU patients compared with non-ICU patients (6.9% vs 0%; p = 0.02). Hematological malignancy was associated with biopsy-related mortality (1.5 [1.01-2.6]; p = 0.04).

CONCLUSIONS: Brain biopsy in critically ill patients with neurologic disease of unknown etiology is associated with high diagnostic yield, therapeutic modifications and postbiopsy survival advantage. Safety profile seems acceptable in most patients. The benefit/risk ratio of brain biopsy in this population should be carefully weighted.

# 危重患者病因不明的神经系统疾病的脑活检：可行性、安全性和诊断率。

目的：脑活检是管理疑似肿瘤病变患者的有用外科手术。它在下列神经系统疾病中的作用病因不明仍有争议，尤其在 ICU 患者中。本研究旨在确定以下研究的可行性、安全性和诊断率伴有未知神经系统疾病的重症患者的脑活检病因。我们还旨在将这些终点与非 ICU 患者的终点进行比较在相同临床背景下接受脑活检。

设计：单中心，回顾性、观察性队列研究。

地点：法国第三中心。

患者：所有病因不明的神经系统疾病成年患者 2008 年 1 月至 2008 年 1 月接受机械通气的 ICU 脑活组织检查 2020 年 10 月与一个非 ICU 患者队列进行比较。

干预：无。

测量和主要结果：在 2207 例脑活检患者中在研究期间，在以下患者中进行了 234 次活检，以诊断神经系统疾病病因不明，包括 29 例机械通气患者和 205 例不是 ICU 患者。特异性组织学诊断和最终确诊率为分别为 62.1% 和 75.9%，导致 62.1% 的病例。活检前脑脊液分析脑膜炎是唯一获得最终诊断的预测因子 (2.3 [1.4-3.8]；p = 0.02)。ICU 患者在活检更长时间后经历治疗管理改变的患者生存期 (p = 0.03)。1-4 级（轻度至重度）并发症发生率为：分别为 24.1%、3.5%、0% 和 6.9%。活检相关死亡率为与非 ICU 患者相比，ICU 患者显著更高（6.9% vs 0%； p = 0.02). 血液恶性肿瘤与活检相关死亡率相关 (1.5 [1.01-2.6]; p = 0.04). 结论：重症患者的脑活检病因不明的神经系统疾病与高诊断性相关缓解率、治疗调整和活检后生存优势。安全性在大多数患者中似乎可接受。脑活检获益 / 风险比应仔细权衡该人群。关键词：Humans; Adult; Brain; Respiration, Artificial; Retrospective Studies; Feasibility Studies; *Critical Illness/therapy; *Nervous System Diseases/diagnosis/etiology; Biopsy/adverse effects/methods

# Daily Written Care Summaries for Families of Critically Ill Patients: A Randomized Controlled Trial., Greenberg, Jared A.

5:e502-e503. DOI:10.1097/CCM.0000000000005583

Abstract:

OBJECTIVES: To determine the effect of daily written updates on the satisfaction and psychologic symptoms of families of ICU patients.

DESIGN: Randomized controlled trial.

SETTING: Single, urban academic medical center.

SUBJECTS: Surrogates of nondecisional, critically ill adults with high risk of mortality (n = 252) enrolled from June 2019 to January 2021.

INTERVENTIONS: Usual communication with the medical team with or without written communication detailing the suspected cause and management approach of each ICU problem, updated each day.

MEASUREMENTS AND MAIN RESULTS: Participants completed surveys at three time points during the ICU stay: enrollment (n = 252), 1 week (n = 229), and 2 weeks (n = 109) after enrollment. Satisfaction with care was measured using the Critical Care Family Needs Inventory (CCFNI). The presence of anxiety, depression, and acute stress were assessed using the Hospital Anxiety and Depression Scale (HADS) and Impact of Events Scale Revised (IES-R). CCFNI, HADS, and IES-R scores were similar among participants assigned to the intervention group and control group upon enrollment and during the first week after enrollment (p > 0.05). From enrollment to the second week after enrollment, there was an improvement in CCFNI and HADS scores among participants assigned to the intervention group versus the control group. At week 2, CCFNI scores were significantly lower among participants in the intervention group versus the control group, indicating greater satisfaction with care: 15.1 (95% CI, 14.2-16.0) versus 16.4, (95% CI, 15.5-17.3); p = 0.04. In addition, 2 weeks after enrollment, the odds of symptoms of anxiety, depression, and acute stress among participants assigned to the intervention versus control group were 0.16 (95% CI, 0.03-0.82; p = 0.03); 0.15 (95% CI, 0.01-1.87; p = 0.14); and 0.27 (95% CI, 0.06-1.27; p = 0.10), respectively.

CONCLUSIONS: Written communication improved satisfaction and the emotional well-being of families of critically ill patients, supporting its use as a supplement to traditional communication approaches.

# 危重患者家庭的每日书面护理总结：一项随机化对照试验。

目的：确定每日书面更新对 ICU 患者家庭满意度和心理症状的影响。

设计：随机对照试验。

单位：单所、城市学术医学中心。

受试者：具有高死亡风险的非决定性重症成人的替代物（n = 252）。

干预措施：通常与医疗团队进行沟通（有或无书面沟通）详细说明了每个 ICU 问题的可疑原因和处理方法，每天更新。

测量和主要结果：受试者完成调查在 ICU 住院期间的 3 个时间点：入组 (n = 252)，1 周 (n = 229)，入组后 2 周 (n = 109)。使用以下量表测量护理满意度重症监护家庭需求量表 (CCFNI)。存在焦虑，使用医院焦虑和抑郁量表 (HADS) 和事件影响量表修订版 (IES-R)。CCFNI、HADS、且分配到干预组的受试者 IES-R 评分相似入组时和入组后第 1 周的对照组入组 (p > 0.05)。从入组至入组后第 2 周，有 CCFNI 和 HADS 评分在分配至干预组与对照组。第 2 周时，CCFNI 评分为与对照组相比，干预组受试者的对照组，表示护理满意度更高：15.1（95% CI， 14.2-16.0）；16.4 (95% CI，15.5-17.3)；p = 0.04。此外，2 周后入组，受试者出现焦虑、抑郁和急性应激症状的几率与对照组相比，分配至干预组的受试者为 0.16（95% CI， 0.03-0.82；p = 0.03）；0.15 (95% CI，0.01-1.87；p = 0.14)；0.27（95% CI， 0.06-1.27；p = 0.10）。

结论：书面沟通改善重症患者家属的满意度和情感幸福感，支持将其用作传统沟通方法的补充。

# Renin-Angiotensin System Pathway Therapeutics Associated With Improved Outcomes in Males Hospitalized With COVID-19.

5:e500-e502. DOI:10.1097/CCM.0000000000005404

Abstract:

OBJECTIVES: To determine whether angiotensin receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors are associated with improved outcomes in hospitalized patients with COVID-19 according to sex and to report sex-related differences in renin-angiotensin system (RAS) components.

DESIGN: Prospective observational cohort study comparing the effects of ARB or ACE inhibitors versus no ARBs or ACE inhibitors in males versus females. Severe acute respiratory syndrome coronavirus 2 downregulates ACE-2, potentially increasing angiotensin II (a pro-inflammatory vasoconstrictor). Sex-based differences in RAS dysregulation may explain sex-based differences in responses to ARBs because the ACE2 gene is on the X chromosome. We recorded baseline characteristics, comorbidities, prehospital ARBs or ACE inhibitor treatment, use of organ support and mortality, and measured RAS components at admission and days 2, 4, 7, and 14 in a subgroup (n = 46), recorded d-dimer (n = 967), comparing males with females.

SETTING: ARBs CORONA I is a multicenter Canadian observational cohort of patients hospitalized with acute COVID-19. This analysis includes patients admitted to 10 large urban hospitals across the four most populated provinces.

PATIENTS: One-thousand six-hundred eighty-six patients with polymerase chain reaction-confirmed COVID-19 (February 2020 to March 2021) for acute COVID-19 illness were included.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Males on ARBs before admission had decreased use of ventilation (adjusted odds ratio [aOR] = 0.52; p = 0.007) and vasopressors (aOR = 0.55; p = 0.011) compared with males not on ARBs or ACE inhibitors. No significant effects were observed in females for these outcomes. The test for interaction was significant for use of ventilation (p = 0.006) and vasopressors (p = 0.044) indicating significantly different responses to ARBs according to sex. Males had significantly higher plasma ACE-1 at baseline and angiotensin II at day 7 and 14 than females.

CONCLUSIONS: ARBs use was associated with less ventilation and vasopressors in males but not females. Sex-based differences in RAS dysregulation may contribute to sex-based differences in outcomes and responses to ARBs in COVID-19.

DOI: 10.1097/CCM.0000000000005589

# 与 COVID-19 住院男性患者预后改善相关的肾素 - 血管紧张素系统通路治疗。

目的：确定血管紧张素受体阻滞剂 (ARB) 或血管紧张素转换酶 (ACE) 抑制剂是否与改善根据性别和报告的 COVID-19 住院患者的结局肾素 - 血管紧张素系统 (RAS) 组分的性别相关差异。

设计：比较 ARB 或 ACE 效应的前瞻性观察性队列研究男性 vs 女性中的抑制剂 vs 无 ARB 或 ACE 抑制剂。重度急性呼吸综合征冠状病毒 2 下调 ACE-2，可能增加血管紧张素 II（一种促炎性血管收缩剂）。RAS 中基于性别的差异调节异常可能解释 ARB 应答的性别差异，因为 ACE2 基因位于 X 染色体上。我们记录了基线特征，合并症，院前 ARB 或 ACE 抑制剂治疗，使用器官支持和死亡率，并在入院时和第 2、4、7、14 天测量 RAS 组分亚组中 (n = 46)，记录 d - 二聚体 (n = 967)，比较男性和女性。

背景：ARB CORONA I 是加拿大患者的多中心观察性队列因急性 COVID-19 住院。该分析包括 10 位住院患者四个人口最多的省份的大城市医院。

患者： 1686 例聚合酶链患者反应确认的急性 COVID-19（2020 年 2 月至 2021 年 3 月）疾病包括在内。

干预：无。

测量和主要结果：雄性入院前使用 ARB 的患者通气减少（调整后比值比 [aOR]= 0.52；p = 0.007）和血管加压药 (aOR = 0.55；p = 0.011) 与未接受 ARB 或 ACE 抑制剂的男性。在这些结局的女性。相互作用检验对于通气量 (p = 0.006) 和血管加压素 (p = 0.044) 显著不同性别对 ARB 的不同反应。男性显著更高基线时血浆 ACE-1 和第 7 天和第 14 天血管紧张素 II 高于雌性。

结论：ARB 使用与通气和血管加压素减少相关男性而非女性。RAS 失调中基于性别的差异可能导致 COVID-19 中 ARB 结局和反应的性别差异。

# A Randomized Double-Blinded Placebo Controlled Trial of Clazakizumab for the Treatment of COVID-19 Pneumonia With Hyperinflammation.

Abstract:

OBJECTIVES: We designed this study to test whether clazakizumab, a direct interleukin-6 inhibitor, benefits patients hospitalized with severe or critical COVID-19 disease accompanied by hyperinflammation.

DESIGN: Multicenter, randomized, double-blinded, placebo-controlled, seamless phase II/III trial.

SETTING: Five U.S. medical centers.

PATIENTS: Adults inpatients with severe COVID-19 disease and hyperinflammation.

INTERVENTIONS: Eighty-one patients enrolled in phase II, randomized 1:1:1 to low-dose (12.5 mg) or high-dose (25 mg) clazakizumab or placebo. Ninety-seven patients enrolled in phase III, randomized 1:1 to high-dose clazakizumab or placebo.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was 28-day ventilator-free survival. Secondary outcomes included overall survival ,frequency and duration of intubation, and frequency and duration of ICU admission. Per Data Safety and Monitoring Board recommendations, additional secondary outcomes describing clinical status and status changes, as measured by an ordinal scale, were added. Bayesian cumulative proportional odds, logistic, and Poisson regression models were used. The low-dose arm was dropped when the phase II study suggested superiority of the high-dose arm. We report on 152 patients, 74 randomized to placebo and 78 to high-dose clazakizumab. Patients receiving clazakizumab had greater odds of 28-day ventilator-free survival (odds ratio [OR] = 3.84; p [OR > 1] 99.9%), as well as overall survival at 28 and 60 days (OR = 1.75; p [OR > 1] 86.5% and OR = 2.53; p [OR > 1] 97.7%). Clazakizumab was associated with lower odds of intubation (OR = 0.2; p [OR] < 1; 99.9%) and ICU admission (OR = 0.26; p [OR < 1] 99.6%); shorter durations of ventilation and ICU stay (risk ratio [RR] < 0.75; p [RR < 1] > 99% for both); and greater odds of improved clinical status at 14, 28, and 60 days (OR = 2.32, p [OR > 1] 98.1%; OR = 3.36, p [OR > 1] 99.6%; and OR = 3.52, p [OR > 1] 99.8%, respectively).

CONCLUSIONS: Clazakizumab significantly improved 28-day ventilator-free survival, 28- and 60-day overall survival, as well as clinical outcomes in hospitalized patients with COVID-19 and hyperinflammation.

DOI: 10.1097/CCM.0000000000005591

# Clazakizumab 治疗 COVID-19 肺炎伴高炎症状态的随机、双盲、安慰剂对照试验。

目的：我们设计本研究旨在检测克拉珠单抗（一种直接白细胞介素 - 6 抑制剂）是否对重度或危重住院患者有益 COVID-19 疾病伴炎症反应。

设计：多中心，随机、双盲、安慰剂对照、无缝 II/III 期试验。

单位：美国 5 家医学中心。

患者：重度住院患者 COVID-19 疾病和炎症。

干预：81 例患者入组 II 期研究，以 1:1:1 的比例随机分配至低剂量组 (12.5 mg) 或高剂量组 (25 mg) clazakizumab 或安慰剂。97 例患者入组 III 期研究，随机化 1:1 至高剂量 clazakizumab 或安慰剂。

测量和主要结果：主要结局为 28 天无呼吸机生存。次要结局包括总生存期，插管频率和持续时间，以及频率和 ICU 住院时间。根据数据安全性监查委员会的建议，描述临床状态和状态变化的其他次要结局，如增加了序数标尺测量结果。Bayesian 累积比例优势比，使用 logistic 和泊松回归模型。去掉低剂量组 II 期研究表明高剂量组具有优效性。我们报告 152 例患者，74 例随机接受安慰剂，78 例接受高剂量 clazakizumab。患者接受 clazakizumab 的患者 28 天无呼吸机生存的几率更大（比值 [OR]= 3.84；p [OR > 1] 99.9%），以及 28 和 60 时的总生存期天（OR = 1.75；p [OR > 1] 86.5% 和 OR = 2.53；p [OR > 1] 97.7%）。克拉珠单抗插管率较低 (OR = 0.2；p [OR]< 1；99.9%) 且入住 ICU (OR = 0.26；p [OR < 1] 99.6%)；通气时间更短，留住 ICU（两者的风险比 [RR]<0.75；p [RR<1]>99%）；第 14、28 天临床状态改善，和 60 天（OR = 2.32，p [OR > 1] 98.1%；OR = 3.36，p [OR > 1] 99.6%；OR = 3.52，p [OR > 1] 99.8%）。

结论：Clazakizumab 显著改善了 28 天无呼吸机生存，住院患者的 28 天和 60 天总生存期以及临床结局伴有 COVID-19 和过度炎症的患者。

# Tracheostomy Practices and Outcomes in Patients With COVID-19 Supported by Extracorporeal Membrane Oxygenation: An Analysis of the Extracorporeal Life Support Organization Registry., Kohne, Joseph G.

Abstract:

OBJECTIVES: The use of extracorporeal membrane oxygenation (ECMO) in patients with COVID-19 has been supported by major healthcare organizations, yet the role of specific management strategies during ECMO requires further study. We sought to characterize tracheostomy practices, complications, and outcomes in ECMO-supported patients with acute respiratory failure related to COVID-19.

DESIGN: Retrospective cohort study.

SETTING: ECMO centers contributing to the Extracorporeal Life Support Organization Registry.

PATIENTS: Patients 16 years or older receiving venovenous ECMO for respiratory support for: 1) COVID-19 in 2020 and 2021 (through October 2021) and 2) pre-COVID-19 viral pneumonia in 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We identified 7,047 patients who received ECMO support for acute respiratory failure related to COVID-19. A total of 32% of patients were recorded as having a tracheostomy procedure during ECMO, and 51% had a tracheostomy at some point during hospitalization. The frequency of tracheostomy was similar in pre-COVID-19 viral pneumonia, but tracheostomies were performed 3 days earlier compared with patients with COVID-19 (median 6.7 d [interquartile range [IQR], 3.0-12.0 d] vs 10.0 d [IQR, 5.0-16.5 d]; p < 0.001). More patients were mobilized with pre-COVID-19 viral pneumonia, but receipt of a tracheostomy during ECMO was associated with increased mobilization in both cohorts. More bleeding complications occurred in patients who received a tracheostomy, with 9% of patients with COVID-19 who received a tracheostomy reported as having surgical site bleeding.

CONCLUSIONS: Tracheostomies are performed in COVID-19 patients receiving ECMO at rates similar to practices in pre-COVID-19 viral pneumonia, although later during the course of ECMO. Receipt of a tracheostomy was associated with increased patient mobilization. Overall mortality was similar between those who did and did not receive a tracheostomy.

DOI: 10.1097/CCM.0000000000005579

# 体外膜肺氧合支持下 COVID-19 患者的气管造口术实践和结局：体外生活分析支持组织注册。

目的：主要医疗保健组织支持在 COVID-19 患者中使用体外膜肺氧合 (ECMO)，但其作用 ECMO 期间的具体管理策略还需要进一步研究。我们寻求表征气管造口术操作、并发症和结局 ECMO 支持的与 COVID-19 相关的急性呼吸衰竭患者。

设计：回顾性队列研究。

设置：ECMO 中心参与体外生命支持组织注册。

患者：患者 16 岁或接受静脉 - 静脉 ECMO 支持呼吸的老年患者：1）2020 年 COVID-19 和 2021（至 2021 年 10 月）和 2）2019 年 COVID-19 前病毒性肺炎。

干预：无。

测量和主要结果：我们确定了 7,047 例患者接受 ECMO 支持治疗与 COVID-19 相关的急性呼吸衰竭。A 总计 32% 的患者记录为在 ECMO，51% 在住院期间的某个时间点进行了气管造口术。事件 COVID-19 前病毒性肺炎的气管造口术频率相似，但与 COVID-19 患者相比，气管造口术提前 3 天进行（中位数 6.7 天 [四分位距 [IQR]，3.0-12.0 天] vs 10.0 天 [IQR，5.0-16.5 天]） d]; p < 0.001). 动员更多的 pre-COVID-19 病毒性肺炎患者，但在 ECMO 期间接受气管造口术与增加两个队列中的活动。患者发生的出血并发症更多接受气管造口术的患者，9% 的 COVID-19 患者接受气管造口术报告手术部位出血。

结论：在接受 ECMO 的 COVID-19 患者中以相似的速率进行了气管造口术在前 COVID-19 病毒性肺炎实践中，尽管在病程的后期 ECMO. 接受气管造口术与患者增加相关活动。有和无死亡率的患者总体死亡率相似接受气管造口术。

# The authors reply., Barichello, Tatiana

DOI: 10.1097/CCM.0000000000005484

# 作者回复。

# Key Role of Gut Microbiota in Neuroinflammation of Septic Patients.

# 肠道菌群在脓毒症患者神经炎症中的关键作用。

关键词：Humans; *Gastrointestinal Microbiome; *Sepsis; Neuroinflammatory Diseases

# The author replies.

5:e499-e500. DOI:10.1097/CCM.0000000000005482

# 作者回复。

# Refractory Anaphylaxis Needing Emergency Intubation Supported by Expert Opinion and Published Guidelines: Could We Use Off-Label Drugs to Avoid It?, Honore, Patrick M.

5:e498-e499. DOI:10.1097/CCM.0000000000005399

# 专家意见和已发表指南支持难治性过敏性反应需要紧急插管：我们可以使用标签外药物来避免吗？

关键词：Humans; Off-Label Use; Expert Testimony; *Anaphylaxis/drug therapy/prevention & control; Drug Labeling; Intubation, Intratracheal

# Phase 2 Vitamin C Sepsis Trials: Another Brick in the (Evidence) Wall?, Agarwal, Ankita

5:897-899. DOI:10.1097/CCM.0000000000005432

# 2 期维生素 C 败血症试验：（证据）墙中的另一块砖？

关键词：Humans; Vitamins; *Sepsis/drug therapy; *Ascorbic Acid/therapeutic use

# Falling for It: Of Falls, Families, and Delirium.

5:889-891. DOI:10.1097/CCM.0000000000005431

# 跌倒：跌倒、家庭和谵妄。

关键词：Humans; *Accidental Falls; *Delirium/epidemiology/etiology; Fear

# Heterogeneity in Clinical Presentations of Sepsis: Challenges and Implications for "One-Size-Fits-All" Time-to-Antibiotic Measures.

5:886-889. DOI:10.1097/CCM.0000000000005430

# 败血症临床表现的异质性：“一刀切” 的抗生素测量时间的挑战和影响。

关键词：Humans; Emergency Service, Hospital; *Sepsis/drug therapy; *Anti-Bacterial Agents/therapeutic use

# Moving Forward: Frailty and Adverse Sepsis Outcomes.

5:880-882. DOI:10.1097/CCM.0000000000005377

# 下一步：虚弱和不良败血症结局。

关键词：Humans; Aged; Geriatric Assessment; *Sepsis; Frail Elderly; *Frailty

# Death and Dying in the ICU., Mols, Georg

5:878-880. DOI:10.1097/CCM.0000000000005380

# ICU 中死亡和濒死。

关键词：Humans; Intensive Care Units; *Attitude to Death; *Terminal Care

# What Socioeconomic Disadvantage Means for Critical Illness Recovery, Clinical Care, and Research.

5:876-878. DOI:10.1097/CCM.0000000000005414

# 危重疾病康复、临床护理和研究的社会经济劣势意味着什么。

关键词：Humans; Risk Factors; Socioeconomic Factors; *Critical Illness/therapy

# The Child With Severe Chronic Illness in the ICU: A Concise Review.

5:848-859. DOI:10.1097/CCM.0000000000005512

Abstract:

OBJECTIVES: Children with severe chronic illness are a prevalent, impactful, vulnerable group in PICUs, whose needs are insufficiently met by transitory care models and a narrow focus on acute care needs. Thus, we sought to provide a concise synthetic review of published literature relevant to them and a compilation of strategies to address their distinctive needs.

DATA SOURCES: English language articles were identified in MEDLINE using a variety of phrases related to children with chronic conditions, prolonged admissions, resource utilization, mortality, morbidity, continuity of care, palliative care, and other critical care topics. Bibliographies were also reviewed.

STUDY SELECTION: Original articles, review articles, and commentaries were considered.

DATA EXTRACTION: Data from relevant articles were reviewed, summarized, and integrated into a narrative synthetic review.

DATA SYNTHESIS: Children with serious chronic conditions are a heterogeneous group who are growing in numbers and complexity, partly due to successes of critical care. Because of their prevalence, prolonged stays, readmissions, and other resource use, they disproportionately impact PICUs. Often more than other patients, critical illness can substantially negatively affect these children and their families, physically and psychosocially. Critical care approaches narrowly focused on acute care and transitory/rotating care models exacerbate these problems and contribute to ineffective communication and information sharing, impaired relationships, subpar and untimely decision-making, patient/family dissatisfaction, and moral distress in providers. Strategies to mitigate these effects and address these patients' distinctive needs include improving continuity and communication, primary and secondary palliative care, and involvement of families. However, there are limited outcome data for most of these strategies and little consensus on which outcomes should be measured.

CONCLUSIONS: The future of pediatric critical care medicine is intertwined with that of children with serious chronic illness. More concerted efforts are needed to address their distinctive needs and study the effectiveness of strategies to do so.

# ICU 中的重度慢性疾病儿童：一项简要审查。

目的：在 PICU 中，重度慢性疾病儿童是一个普遍、有影响力的弱势群体，其需求无法通过过渡性护理充分满足模型和狭义的急性护理需求重点。因此，我们试图提供对与其相关的已发表文献进行的简要综合审查，以及编写策略以满足其独特需求。

数据来源：在 MEDLINE 中使用各种短语识别英语文章与慢性疾病儿童、长期住院、资源治疗的利用、死亡率、发病率、治疗的连续性、姑息治疗和其他重症监护主题。还对参考书目进行了审查。

研究选择：考虑了原始文章、综述文章和评论。数据摘录：对相关文章中的数据进行审核、总结和整合纳入叙述性合成综述。

资料综合：严重慢性疾病是一个在数量和复杂性上不断增长的异质性群体，部分原因是重症监护成功。由于其患病率，延长住院、再次入院和其他资源使用，它们的影响不成比例 PICU。危重病患者通常多于其他患者对这些儿童及其家庭、身体和精神心理性。重症监护方法狭义地侧重于急性护理和一过性 / 轮换护理模型加剧了这些问题，并导致沟通和信息共享无效、人际关系受损、低于标准决策不及时、患者 / 家庭不满和道德困扰在提供者中。减轻这些影响并解决这些患者的策略独特的需求包括改善连续性和沟通，主要和次要姑息治疗和家庭参与。然而，有大多数这些策略的结局数据有限，几乎没有达成共识应测量结局。

结论：儿科重症监护的未来药物与严重慢性疾病儿童的药物交织在一起。更多需要协调一致的努力来解决其独特的需求，并研究策略的有效性。关键词：Humans; Intensive Care Units; Child; Palliative Care; Chronic Disease; *Critical Illness/therapy; *Family

# Do Tracheostomy and Gastrostomy Confer Immortality in COVID-19?

5:891-893. DOI:10.1097/CCM.0000000000005504

# COVID-19 中气管造口术和胃造口术是否能带来永生？

关键词：Humans; Respiration, Artificial; Retrospective Studies; *COVID-19; *Tracheostomy; Gastrostomy

# Effects of Prone Position on Lung Recruitment and Ventilation-Perfusion Matching in Patients With COVID-19 Acute Respiratory Distress Syndrome: A Combined CT Scan/Electrical Impedance Tomography Study.

5:723-732. DOI:10.1097/CCM.0000000000005450

Abstract:

OBJECTIVES: Prone positioning allows to improve oxygenation and decrease mortality rate in COVID-19-associated acute respiratory distress syndrome (C-ARDS). However, the mechanisms leading to these effects are not fully understood. The aim of this study is to assess the physiologic effects of pronation by the means of CT scan and electrical impedance tomography (EIT).

DESIGN: Experimental, physiologic study.

SETTING: Patients were enrolled from October 2020 to March 2021 in an Italian dedicated COVID-19 ICU.

PATIENTS: Twenty-one intubated patients with moderate or severe C-ARDS.

INTERVENTIONS: First, patients were transported to the CT scan facility, and image acquisition was performed in prone, then supine position. Back to the ICU, gas exchange, respiratory mechanics, and ventilation and perfusion EIT-based analysis were provided toward the end of two 30 minutes steps (e.g., in supine, then prone position).

MEASUREMENTS AND MAIN RESULTS: Prone position induced recruitment in the dorsal part of the lungs (12.5% ?± 8.0%; p < 0.001 from baseline) and derecruitment in the ventral regions (-6.9% ?± 5.2%; p < 0.001). These changes led to a global increase in recruitment (6.0% ?± 6.7%; p < 0.001). Respiratory system compliance did not change with prone position (45 ?± 15 vs 45 ?± 18 mL/cm H2O in supine and prone position, respectively; p = 0.957) suggesting a decrease in atelectrauma. This hypothesis was supported by the decrease of a time-impedance curve concavity index designed as a surrogate for atelectrauma (1.41 ?± 0.16 vs 1.30 ?± 0.16; p = 0.001). Dead space measured by EIT was reduced in the ventral regions of the lungs, and the dead-space/shunt ratio decreased significantly (5.1 [2.3-23.4] vs 4.3 [0.7-6.8]; p = 0.035), showing an improvement in ventilation-perfusion matching.

CONCLUSIONS: Several changes are associated with prone position in C-ARDS: increased lung recruitment, decreased atelectrauma, and improved ventilation-perfusion matching. These physiologic effects may be associated with more protective ventilation.

# 仰卧位对 COVID-19 急性呼吸窘迫综合征患者肺复张和通气灌注匹配的影响：联合 CT 扫描 / 电阻抗断层成像研究。

目的：俯卧位可改善 COVID-19 相关急性呼吸窘迫综合征的氧合，降低死亡率 (C-ARDS)。然而，导致这些效应的机制并不完全理解。本研究的目的是评估通过 CT 扫描和电阻抗断层成像 (EIT) 旋前。

设计：实验性、生理学研究。

设置：患者从 2020 年 10 月至 2021 年 3 月，在意大利专用 COVID-19 ICU。

患者： 21 例中度或重度 C-ARDS 插管患者。

干预：首先，将患者运送至 CT 扫描机构，并进行图像采集患者取俯卧位，然后仰卧位。回到 ICU，进行气体交换，呼吸力学、基于 EIT 的通气和灌注分析准备两个 30 min 的步骤结束（例如，仰卧位，然后俯卧）位置）。

测量和主要结果：俯卧位诱导的肺复张肺背侧部分（12.5%?±8.0%；p <0.001，较基线）和腹侧区皮肤脱落（分别为 - 6.9% 和 ±5.2%；p < 0.001）。这些变更导致全球招募数量增加 (6.0%τ±6.7%；p < 0.001)。呼吸系统俯卧位时依从性没有变化（45?±15 vs 45?±18 mL/cm H2O，仰卧位和俯卧位；p = 0.957），提示创伤性休克。时间 - 阻抗降低支持该假设作为非创伤性替代指标的曲线凹度指数（分别为 1.41±0.16vs 1.30 ?± 0.16; p = 0.001). 腹侧通过 EIT 测量的死腔减少肺脏区域，以及死腔 / 分流比显著下降（5.1 [2.3-23.4] vs 4.3 [0.7-6.8]；p = 0.035），显示了通气 - 灌注匹配。

结论：一些变化与 C-ARDS 俯卧位：增加肺复张，减少肺不张创伤，和改善通气 - 灌注匹配。这些生理效应可能是与更多的保护性通气相关。关键词：Humans; Perfusion; Tomography, X-Ray Computed; *COVID-19; Prone Position; *Respiratory Distress Syndrome/diagnostic imaging/therapy; Electric Impedance; Lung/diagnostic imaging; Positive-Pressure Respiration/methods

# A Retrospective Observational Study Exploring 30- and 90-Day Outcomes for Patients With COVID-19 After Percutaneous Tracheostomy and Gastrostomy Placement., Kiser, Stephanie B.

5:819-824. DOI:10.1097/CCM.0000000000005451

Abstract:

OBJECTIVES: To determine the 30- and 90-day outcomes of COVID-19 patients receiving tracheostomy and percutaneous endoscopic gastrostomy (PEG).

DESIGN: Retrospective observational study.

SETTING: Multisite, inpatient.

PATIENTS: Hospitalized COVID-19 patients who received tracheostomy and PEG at four Boston hospitals.

INTERVENTIONS: Tracheostomy and PEG placement.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was mortality at 30 and 90 days post-procedure. Secondary outcomes included continued device presence, place of residence, complications, and rehospitalizations. Eighty-one COVID-19 patients with tracheostomy and PEG placement were included. At 90 days post-device placement, the mortality rate was 9.9%, 2.7% still had the tracheostomy, 32.9% still had the PEG, and 58.9% were at home.

CONCLUSIONS: More than nine-in-10 patients in our population of COVID-19 patients who underwent tracheostomy and PEG were alive 90 days later and most were living at home. This study provides new information regarding the outcomes of this patient population that may serve as a step in guiding clinicians, patients, and families when making decisions regarding these devices.

# 一项探讨 COVID-19 患者接受经皮气管造口术和胃造口术后 30 天和 90 天结局的回顾性观察性研究。

目的：确定接受气管造口术和经皮内镜下胃造瘘术 (PEG) 的 COVID-19 患者的 30 天和 90 天结局。

设计：回顾性观察性研究。

设置：多家研究中心，住院患者。

患者：住院 COVID-19 在 4 个波士顿接受气管造口术和 PEG 的患者医院。

干预：气管造口术和 PEG 置入。测量和主要结果：主要结局是术后 30 天和 90 天的死亡率。次要结局包括继续使用器械、居住地、并发症和再次住院。81 例 COVID-19 患者发生包括气管造口术和 PEG 置入。器械置入后 90 天，死亡率 9.9%，2.7% 仍行气管造口术，32.9% 仍行气管切开术。 PEG，58.9% 在家。

结论：我们的研究中有超过 9/10 的患者接受气管造口术和 PEG 的 COVID-19 患者人群存活 90 几天后，大多数患者仍在家中。本研究提供了新信息关于该患者人群的结局，可能作为指导临床医生、患者和家属做出这些决定器械。关键词：Humans; Retrospective Studies; *COVID-19; *Gastrostomy; Boston; Tracheostomy

# Ventilator-Associated Lower Respiratory Tract Bacterial Infections in COVID-19 Compared With Non-COVID-19 Patients.

5:825-836. DOI:10.1097/CCM.0000000000005462

Abstract:

OBJECTIVES: Ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with prolonged length of stay and increased mortality. We aimed to investigate the occurrence of bacterial VA-LRTI among mechanically ventilated COVID-19 patients and compare these findings to non-COVID-19 cohorts throughout the first and second wave of the pandemic.

DESIGN: Retrospective cohort study.

SETTING: Karolinska University Hospital, Stockholm, Sweden.

PATIENTS: All patients greater than or equal to 18 years treated with mechanical ventilation between January 1, 2011, and December 31, 2020.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The cohort consisted of 20,223 ICU episodes (479 COVID-19), with a VA-LRTI incidence proportion of 30% (129/426) in COVID-19 and 18% (1,081/5,907) in non-COVID-19 among patients ventilated greater than or equal to 48 hours. The median length of ventilator treatment for COVID-19 patients was 10 days (interquartile range, 5-18 d), which was significantly longer than for all other investigated specific diagnoses. The VA-LRTI incidence rate per 1,000 ventilator days at risk was 31 (95% CI, 26-37) for COVID-19 and 34 (95% CI, 32-36) for non-COVID-19. With COVID-19 as reference, adjusted subdistribution hazard ratios for VA-LRTI was 0.29-0.50 (95% CI, < 1) for influenza, bacterial pneumonia, acute respiratory distress syndrome, and severe sepsis, but 1.38 (95% CI, 1.15-1.65) for specific noninfectious diagnoses. Compared with COVID-19 in the first wave of the pandemic, COVID-19 in the second wave had adjusted subdistribution hazard ratio of 1.85 (95% CI, 1.14-2.99). In early VA-LRTI Staphylococcus aureus was more common and Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli less common in COVID-19 patients, while Serratia species was more often identified in late VA-LRTI.

CONCLUSIONS: COVID-19 is associated with exceptionally long durations of mechanical ventilation treatment and high VA-LRTI occurrence proportions. The incidence rate of VA-LRTI was compared with the pooled non-COVID-19 cohort, however, not increased in COVID-19. Significant differences in the incidence of VA-LRTI occurred between the first and second wave of the COVID-19 pandemic.

# COVID-19 与非 COVID-19 患者的呼吸机相关下呼吸道细菌感染的比较。

目的：呼吸机相关下呼吸道感染 (VA-LRTI) 与住院时间延长和死亡率增加相关。我们的目标是调查机械通气患者中细菌性 VA-LRTI 的发生情况整个研究期间，COVID-19 患者将这些结果与非 COVID-19 队列进行比较第一波和第二波大流行。

设计：回顾性队列研究。

单位：Karolinska University Hospital,Stockholm,Sweden。

患者：全部接受机械通气治疗的≥18 岁患者 2011 年 1 月 1 日至 2020 年 12 月 31 日。

干预：无。测量主要结果：队列包括 20223 例 ICU 发作（479 例 COVID-19）， COVID-19 中 VA-LRTI 发生率比例为 30%(129/426)，18% (1,081/5,907)，非 - COVID-19 中，通气≥ 48 小时。COVID-19 患者呼吸机治疗的中位时长为 10 天（四分位距，5-18 天），显著长于所有其他研究的特定诊断。每 1,000 人中 VA-LRTI 的发生率 COVID-19 的通气风险天数为 31 (95% CI，26-37)，COVID-19 为 34（95% CI， 32-36）。以 COVID-19 为参照，调整亚分布细菌性流感的 VA-LRTI 风险比为 0.29-0.50 (95% CI，< 1) 肺炎、急性呼吸窘迫综合征和重度败血症，但 1.38 (95%) CI，1.15-1.65）。与 COVID-19 相比在第一波大流行，第二波的 COVID-19 已经调整亚分布风险比为 1.85 (95% CI，1.14-2.99)。早期 VA-LRTI 金黄色葡萄球菌多见，肺炎链球菌、嗜血杆菌流感和大肠杆菌在 COVID-19 患者中不常见，而沙雷菌属在晚期 VA-LRTI 中更常识别种属。

结论：COVID-19 是与长期机械通气治疗相关和高 VA-LRTI 发生率比例。VA-LRTI 的发生率为但是，与非 COVID-19 队列相比，COVID-19 队列没有增加。VA-LRTI 发生率的显著差异发生在第二波 COVID-19 大流行。关键词：Humans; Retrospective Studies; Pandemics; Respiratory System; Ventilators, Mechanical; *COVID-19/epidemiology/therapy; *Pneumonia, Ventilator-Associated/epidemiology; *Respiratory Tract Infections/epidemiology; *Staphylococcal Infections/epidemiology

# The Puzzles of Ventilator-Associated Pneumonia and COVID-19: Absolute Knowns and Relative Unknowns.

5:894-896. DOI:10.1097/CCM.0000000000005475

# 呼吸机相关性肺炎和 COVID-19 的困惑：绝对未知和相对未知。

关键词：Humans; *COVID-19; SARS-CoV-2; *Pneumonia, Ventilator-Associated/epidemiology

# Prone Position and COVID-19: Mechanisms and Effects.

5:873-875. DOI:10.1097/CCM.0000000000005486

# 俯卧位和 COVID-19：机制和效应。

关键词：Humans; *COVID-19; SARS-CoV-2; Prone Position; Patient Positioning

# A Minimally Invasive and Highly Effective Extracorporeal CO2 Removal Device Combined With a Continuous Renal Replacement Therapy., Zanella, Alberto

5:e468-e476. DOI:10.1097/CCM.0000000000005428

Abstract:

OBJECTIVES: Extracorporeal carbon dioxide removal is used to treat patients suffering from acute respiratory failure. However, the procedure is hampered by the high blood flow required to achieve a significant CO2 clearance. We aimed to develop an ultralow blood flow device to effectively remove CO2 combined with continuous renal replacement therapy (CRRT).

DESIGN: Preclinical, proof-of-concept study.

SETTING: An extracorporeal circuit where 200 mL/min of blood flowed through a hemofilter connected to a closed-loop dialysate circuit. An ion-exchange resin acidified the dialysate upstream, a membrane lung to increase Pco2 and promote CO2 removal.

PATIENTS: Six, 38.7 ?± 2.0-kg female pigs.

INTERVENTIONS: Different levels of acidification were tested (from 0 to 5 mEq/min). Two l/hr of postdilution CRRT were performed continuously. The respiratory rate was modified at each step to maintain arterial Pco2 at 50 mm Hg.

MEASUREMENTS AND MAIN RESULTS: Increasing acidification enhanced CO2 removal efficiency of the membrane lung from 30 ?± 5 (0 mEq/min) up to 145 ?± 8 mL/min (5 mEq/min), with a 483% increase, representing the 73% ?± 7% of the total body CO2 production. Minute ventilation decreased accordingly from 6.5 ?± 0.7 to 1.7 ?± 0.5 L/min. No major side effects occurred, except for transient tachycardia episodes. As expected from the alveolar gas equation, the natural lung Pao2 dropped at increasing acidification steps, given the high dissociation between the oxygenation and CO2 removal capability of the device, thus Pao2 decreased.

CONCLUSIONS: This new extracorporeal ion-exchange resin-based multiple-organ support device proved extremely high efficiency in CO2 removal and continuous renal support in a preclinical setting. Further studies are required before clinical implementation.

# 微创和高效体外 CO2 清除装置联合连续肾脏替代治疗。

目的：体外二氧化碳清除用于治疗急性呼吸衰竭患者。但是，该程序受到以下因素的限制实现显著 CO2 清除所需的高血流量。我们的目标是开发超低血流量装置，有效去除 CO2 结合连续性肾脏替代治疗 (CRRT)。

设计：临床前，概念验证研究。

设置：体外循环回路，200 mL/min 血液流经连接闭环透析液回路的血液滤器。将上游透析液酸化的离子交换树脂，膜肺增加 Pco2，促进 CO2 清除。

患者：6 头 38.7 μm±2.0 kg 的雌性猪。

干预：检测不同酸化水平 (0-5) mEq/min）。连续进行 2 l/hr 后稀释 CRRT。事件在每个步骤调整呼吸速率，将动脉 Pco2 维持在 50 mmHg。

测量和主要结果：增加酸化增强了 CO2 去除膜肺的效率从 30 μm±5 (0 mEq/min) 至 145 μm±8 mL/min (5 μm) mEq/min），增加 483%，表示体内 CO2 总量的 73%±7% 生产。分钟通气量相应地从 6.5?±0.7 下降至 1.7?± 0.5 L / 分钟。除一过性心动过速外，未发生重大副作用发作。正如根据肺泡气体方程所预期的，自然肺 Pao2 在增加酸化步骤时下降，因为该装置的氧合和 CO2 清除能力，Pao2 降低。

结论：这种新型体外离子交换树脂基多器官证明支撑装置具有非常高的 CO2 去除效率和持续性临床前背景中的肾脏支持。之前还需要进一步的研究临床实施。关键词：Humans; Female; Oxygen; Animals; Swine; *Continuous Renal Replacement Therapy; Carbon Dioxide; Dialysis Solutions; Respiration, Artificial/methods

# Early Neuromuscular Blockade in Moderate-to-Severe Pediatric Acute Respiratory Distress Syndrome., Rudolph, Michelle W.

5:e445-e457. DOI:10.1097/CCM.0000000000005426

Abstract:

OBJECTIVES: The use of neuromuscular blocking agents (NMBAs) in pediatric acute respiratory distress syndrome (PARDS) is common but unsupported by efficacy data. We sought to compare the outcomes between patients with moderate-to-severe PARDS receiving continuous NMBA during the first 48 hours of endotracheal intubation (early NMBA) and those without.

DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure (RESTORE) clinical trial, a pediatric multicenter cluster randomized trial of sedation.

SETTING: Thirty-one PICUs in the United States.

PATIENTS: Children 2 weeks to 17 years receiving invasive mechanical ventilation (MV) for moderate-to-severe PARDS (i.e., oxygenation index ?‰? 8 and bilateral infiltrates on chest radiograph on days 0-1 of endotracheal intubation).

INTERVENTIONS: NMBA for the entire duration of days 1 and 2 after intubation.

MEASUREMENTS AND MAIN RESULTS: Among 1,182 RESTORE patients with moderate-to-severe PARDS, 196 (17%) received early NMBA for a median of 50.0% ventilator days (interquartile range, 33.3-60.7%). The propensity score model predicting the probability of receiving early NMBA included high-frequency oscillatory ventilation on days 0-2 (odds ratio [OR], 7.61; 95% CI, 4.75-12.21) and severe PARDS on days 0-1 (OR, 2.16; 95% CI, 1.50-3.12). After adjusting for risk category, early use of NMBA was associated with a longer duration of MV (hazard ratio, 0.57; 95% CI, 0.48-0.68; p < 0.0001), but not with mortality (OR, 1.62; 95% CI, 0.92-2.85; p = 0.096) compared with no early use of NMBA. Other outcomes including cognitive, functional, and physical impairment at 6 months post-PICU discharge were similar. Outcomes did not differ when comparing high versus low NMBA usage sites or when patients were stratified by baseline Pao2/Fio2 less than 150.

CONCLUSIONS: Early NMBA use was associated with a longer duration of MV. This propensity score analysis underscores the need for a randomized controlled trial in pediatrics.

# 中重度儿科急性呼吸窘迫综合征的早期神经肌肉阻滞。

目的：神经肌肉阻滞剂 (NMBA) 在儿科急性呼吸窘迫综合征 (PARDS) 中的使用很常见，但未得到疗效数据的支持。我们试图比较中度至重度 PARDS 患者之间的结局在气管插管的前 48 小时内持续接受 NMBA （早期 NMBA）和无。

设计：对呼吸衰竭镇静滴定的随机评估 (RESTORE) 镇静的儿科多中心集群随机临床试验。

环境：美国 31 家 PICU。

患者：2 周至 17 岁的儿童接受有创机械通气 (MV) 治疗中重度 PARDS 的年数（即氧合指数 ≥ 8 和胸部 x 光片双侧浸润气管插管的第 0-1 天）。

干预：在整个研究期间给予 NMBA 插管后第 1 天和第 2 天。

测量和主要结果：1,182 名受试者中 RESTORE 中 - 重度 PARDS 患者，196 例 (17%) 接受早期 NMBA 治疗呼吸机使用天数中位数为 50.0%（四分位距，33.3-60.7%）。事件倾向评分模型预测接受早期 NMBA 的概率包括第 0-2 天的高频振荡通气（比值比 [OR]， 7.61；95% CI，4.75-12.21）和第 0-1 天重度 PARDS（OR，2.16；95% CI， 1.50-3.12). 校正风险类别后，早期使用 NMBA 与 MV 持续时间更长（风险比，0.57；95% CI，0.48-0.68；p < 0.0001），但与无死亡相比，无死亡 (OR，1.62；95% CI，0.92-2.85；p = 0.096) 早期使用 NMBA。其他结局，包括认知、功能和身体 PICU 出院后 6 个月的损害相似。结局无差异比较高、低 NMBA 使用率的研究中心或对患者进行分层时按基线 Pao2/Fio2 < 150。

结论：早期使用 NMBA 与 MV 持续时间更长。该倾向评分分析强调了需求儿科随机对照试验。关键词：Humans; Propensity Score; Respiration, Artificial; Child; *Respiratory Distress Syndrome/therapy; *Anesthetics; *High-Frequency Ventilation; *Neuromuscular Blockade; *Neuromuscular Diseases; *Pediatrics

# Monitoring Spinal Cord Tissue Oxygen in Patients With Acute, Severe Traumatic Spinal Cord Injuries., Visagan, Ravindran

5:e477-e486. DOI:10.1097/CCM.0000000000005433

Abstract:

OBJECTIVES: To determine the feasibility of monitoring tissue oxygen tension from the injury site (pscto2) in patients with acute, severe traumatic spinal cord injuries.

DESIGN: We inserted at the injury site a pressure probe, a microdialysis catheter, and an oxygen electrode to monitor for up to a week intraspinal pressure (ISP), spinal cord perfusion pressure (SCPP), tissue glucose, lactate/pyruvate ratio (LPR), and pscto2. We analyzed 2,213 hours of such data. Follow-up was 6-28 months postinjury.

SETTING: Single-center neurosurgical and neurocritical care units.

SUBJECTS: Twenty-six patients with traumatic spinal cord injuries, American spinal injury association Impairment Scale A-C. Probes were inserted within 72 hours of injury.

INTERVENTIONS: Insertion of subarachnoid oxygen electrode (Licox; Integra LifeSciences, Sophia-Antipolis, France), pressure probe, and microdialysis catheter.

MEASUREMENTS AND MAIN RESULTS: pscto2 was significantly influenced by ISP (pscto2 26.7 ?± 0.3 mm Hg at ISP > 10 mmHg vs pscto2 22.7 ?± 0.8 mm Hg at ISP ?‰¤ 10 mm Hg), SCPP (pscto2 26.8 ?± 0.3 mm Hg at SCPP < 90 mm Hg vs pscto2 32.1 ?± 0.7 mm Hg at SCPP ?‰? 90 mm Hg), tissue glucose (pscto2 26.8 ?± 0.4 mm Hg at glucose < 6 mM vs 32.9 ?± 0.5 mm Hg at glucose ?‰? 6 mM), tissue LPR (pscto2 25.3 ?± 0.4 mm Hg at LPR > 30 vs pscto2 31.3 ?± 0.3 mm Hg at LPR ?‰¤ 30), and fever (pscto2 28.8 ?± 0.5 mm Hg at cord temperature 37-38?°C vs pscto2 28.7 ?± 0.8 mm Hg at cord temperature ?‰? 39?°C). Tissue hypoxia also occurred independent of these factors. Increasing the Fio2 by 0.48 increases pscto2 by 71.8% above baseline within 8.4 minutes. In patients with motor-incomplete injuries, fluctuations in pscto2 correlated with fluctuations in limb motor score. The injured cord spent 11% (39%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-complete outcomes, compared with 1% (30%) hours at pscto2 less than 5 mm Hg (< 20 mm Hg) in patients with motor-incomplete outcomes. Complications were cerebrospinal fluid leak (5/26) and wound infection (1/26).

CONCLUSIONS: This study lays the foundation for measuring and altering spinal cord oxygen at the injury site. Future studies are required to investigate whether this is an effective new therapy.

# 急性、重度创伤性脊髓损伤患者的脊髓组织氧监测。

目的：确定在急性重度创伤性脊髓患者中监测损伤部位 (pscto2) 组织氧张力的可行性损伤。

设计：我们在损伤部位插入一个压力探头，一个微透析导管和氧气电极，用于长达一周的监测椎管内压 (ISP)、脊髓灌注压 (SCPP)、组织葡萄糖、乳酸 / 丙酮酸比值 (LPR) 和 pscto2。我们分析了 2,213 小时的此类数据。伤后随访 6-28 个月。

设置：单中心神经外科和神经重症监护室。

受试者：26 例患者创伤性脊髓损伤，美国脊髓损伤协会损伤损伤 72 小时内插入探针。

干预：插入蛛网膜下氧电极（Licox;Integra LifeSciences, Sophia-Antipolis，法国），压力探头和微透析导管。

测量值和主要结果：ISP 对 pscto2 有显著影响（pscto2 inr 26.7±0.3 mmHg，ISP > 10 mmHg；inr 22.7±0.8 mmHg，ISP?‰?10 mmHg）， SCPP（在 SCPP <90 mmHg 时 pscto2 26.8 μm Hg vs 在 SCPP < 90 mmHg 时 pscto2 32.1 μm Hg vs 在 SCPP < 90 mmHg 时 pscto2 32.1 μm Hg vs 0.7 mmHg） SCPP ≥ 90 mmHg），组织葡萄糖（pscto2 26.8?±0.4 mmHg，葡萄糖 < 6 mm vs 血糖 ≥ 6 mm 时为 32.9±0.5 mmHg，组织 LPR（LPR> 时为 pscto2 25.3?±0.4 mmHg） 30 vs. pscto2（在 LPR??‰30 时为 31.3±0.3 mmHg），发热 (pscto2 28.8 μm Hg±0.5 mmHg) 脐带温度 37-38?°C 对比 pscto2 28.7±0.8 mmHg，脐带温度 ≥ 39?°C）。组织缺氧的发生也与这些因素无关。Fio2 增加幅度 8.4 min 内 pscto2 升高 0.48%，高于基线值 71.8%。患者伴有运动不全损伤，pscto2 波动与肢体运动评分波动。受损的脐带在以下时间花费 11%(39%) 小时具有运动完全结局的患者的 pscto2 小于 5 mmHg (< 20 mmHg)，相比 1%(30%) 小时，pscto2 < 5 mmHg (< 20 mmHg) 的患者伴电机不完整结局。并发症为脑脊液漏 (5/26) 和伤口感染 (1/26)。

结论：本研究为用于测量和改变损伤部位的脊髓氧含量。未来研究需要研究这是否是一种有效的新疗法。关键词：Humans; Oxygen; *Spinal Cord Injuries; *Cerebrospinal Fluid Pressure; Glucose; Spinal Cord

# A Multicenter Cohort Study of Falls Among Patients Admitted to the ICU.

5:810-818. DOI:10.1097/CCM.0000000000005423

Abstract:

OBJECTIVES: To determine the incidence of falls, risk factors, and adverse outcomes, among patients admitted to the ICU.

DESIGN: Retrospective cohort study.

SETTING: Seventeen ICUs in Alberta, Canada.

PATIENTS: Seventy-three thousand four hundred ninety-five consecutive adult patient admissions between January 1, 2014, and December 31, 2019.

MEASUREMENTS AND MAIN RESULTS: A mixed-effects negative binomial regression model was used to examine risk factors associated with falls. Linear and logistic regression models were used to evaluate adverse outcomes. Six hundred forty patients experienced 710 falls over 398,223 patient days (incidence rate of 1.78 falls per 1,000 patient days [95% CI, 1.65-1.91]). The daily incidence of falls increased during the ICU stay (e.g., day 1 vs day 7; 0.51 vs 2.43 falls per 1,000 patient days) and varied significantly between ICUs (range, 0.37-4.64 falls per 1,000 patient days). Male sex (incidence rate ratio [IRR], 1.37; 95% CI, 1.15-1.63), previous invasive mechanical ventilation (IRR, 1.82; 95% CI, 1.40-2.38), previous sedative and analgesic medication infusions (IRR, 1.60; 95% CI, 1.15-2.24), delirium (IRR, 3.85; 95% CI, 3.23-4.58), and patient mobilization (IRR, 1.26; 95% CI, 1.21-1.30) were risk factors for falling. Falls were associated with longer ICU (ratio of means [RM], 3.10; 95% CI, 2.86-3.36) and hospital (RM, 2.21; 95% CI, 2.01-2.42) stays, but lower odds of death in the ICU (odds ratio [OR], 0.09; 95% CI, 0.05-0.17) and hospital (OR, 0.21; 95% CI, 0.14-0.30).

CONCLUSIONS: We observed that among ICU patients, falls occur frequently, vary substantially between ICUs, and are associated with modifiable risk factors, longer ICU and hospital stays, and lower risk of death. Our study suggests that fall prevention strategies should be considered for critically ill patients admitted to ICU.

# 一项入 ICU 患者跌倒的多中心队列研究。

目的：确定入住 ICU 的患者中跌倒的发生率、风险因素和不良结局。

设计：回顾性队列研究。

设置：加拿大艾伯塔省 17 间 ICU。

患者：73004 195 名连续成年患者于 2014 年 1 月 1 日住院， 2019 年 12 月 31 日。

测量和主要结果：混合效应的负面影响使用二项式回归模型检查与跌倒相关的风险因素。线性和 logistic 回归模型用于评价不良结局。6 名 398，223 患者日内，140 例患者发生了 710 次跌倒（发生率发生率为 1.78 次跌倒 / 1,000 患者日 [95% CI，1.65-1.91]）。每日在 ICU 住院期间跌倒的发生率增加（例如，第 1 天与第 7 天；0.51vs 2.43 次跌倒 / 1000 患者天），在 ICU 之间差异显著（范围， 0.37-4.64 次跌倒 / 1000 患者天）。男性（发生率比 [IRR]， 1.37；95% CI，1.15-1.63），既往有创机械通气（IRR，1.82； 95% CI，1.40-2.38），既往镇静和镇痛药物输注（IRR， 1.60；95% CI，1.15-2.24），谵妄 (IRR，3.85；95% CI，3.23-4.58) 和患者动员（IRR，1.26；95% CI，1.21-1.30）是跌倒的风险因素。跌倒与 ICU 时间较长相关（均值比 [RM]，3.10；95% CI，2.86-3.36）和住院 (RM，2.21；95% CI，2.01-2.42)，但在 ICU（比值比 [OR]，0.09；95% CI，0.05-0.17）和医院（OR，0.21；95% CI， 0.14-0.30). 结论：我们观察到在 ICU 患者中，跌倒发生通常情况下，ICU 之间存在显著差异，并与可修改的危险因素，ICU 和住院时间较长，死亡风险较低。我们的研究提示危重患者应考虑预防跌倒策略 ICU 患者。关键词：Humans; Male; Adult; Cohort Studies; Retrospective Studies; *Intensive Care Units; *Accidental Falls; Alberta/epidemiology

# Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study From a New England Health Care Network.

5:e434-e444. DOI:10.1097/CCM.0000000000005425

Abstract:

OBJECTIVES: To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU.

DESIGN: Retrospective cohort study.

SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA).

PATIENTS: Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to -3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients who received a high proportion of deep sedation using benzodiazepine compared with propofol-based sedation (adjusted absolute difference, -1.17 d; 95% CI, -0.64 to -1.69; p < 0.001). This differential effect was magnified in elderly patients (age > 65) and in patients with liver or kidney failure (p-for-interaction < 0.001) but not observed in patients who received a low proportion of deep sedation (p = 0.95). GABAergic-induced deep sedation days during mechanical ventilation was a better predictor of post-extubation delirium than the GABAergic daily average effective dose (area under the curve 0.76 vs 0.69; p < 0.001).

CONCLUSIONS: Deep sedation during mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.

# ICU 中 γ- 氨基丁酸能镇静剂对拔管后谵妄风险的不同影响：一项新的回顾性队列研究英国医疗保健网络。

目的：评价不同 γ- 氨基丁酸 (GABAergic) 镇静剂（如丙泊酚和苯二氮卓类）是否存在差异 ICU 中拔管后谵妄的风险。

设计：回顾性队列研究。

设置：学术医院网络中的 7 间 ICU，Beth Israel Deaconess 医学中心（马萨诸塞州波士顿）。

患者：一万五百一成人机械通气超过 24 小时的患者。

干预：无。

测量值和主要结果：我们检验了苯二氮卓类与基于丙泊酚的镇静相比，丙泊酚可以缩短术后无谵妄的天数拔管后 14 天。此外，我们假设测得的镇静 gaba 能药物诱发的水平是比药物更好的谵妄预测因子给药剂量。gaba 能药物诱导的深度镇静的比例为定义为平均 Richmond 躁动 - 镇静量表评分为机械通气期间低于或等于 - 3。多变量回归使用了效应调整分析。无谵妄天数较短使用苯二氮卓类药物接受较高比例深度镇静的患者与丙泊酚镇静相比（校正的绝对差异，-1.17 d；95%） CI，-0.64 至 - 1.69；p <0.001）。这种差异效应在老年人中被放大患者（年龄> 65 岁）和肝衰竭或肾衰竭患者（相互作用 p 值 < 0.001），但在接受低剂量深度镇静的比例 (p = 0.95)。GABAergic - 诱导的深度镇静天数机械通气期间是拔管后谵妄的更好预测因素高于 gaba 能每日平均有效剂量（曲线下面积 0.76 vs 0.69; p < 0.001). 结论：机械通气期间深度镇静与丙泊酚相比，苯二氮卓类药物与下列风险增加相关拔管后谵妄。我们的数据不支持以下观点在 ICU 中，以苯二氮卓类为基础的镇静与以丙泊酚为基础的镇静相比是一种谵妄的独立风险因素，只要可以避免深度镇静这些患者。关键词：Humans; Aged; Intensive Care Units; Adult; Retrospective Studies; Delivery of Health Care; Respiration, Artificial/adverse effects; Hypnotics and Sedatives/adverse effects; *Delirium/chemically induced/etiology; *Propofol/adverse effects; Airway Extubation; Benzodiazepines/adverse effects

# Evaluating Vitamin C in Septic Shock: A Randomized Controlled Trial of Vitamin C Monotherapy., Wacker, David A.

5:e458-e467. DOI:10.1097/CCM.0000000000005427

Abstract:

OBJECTIVES: To determine whether IV vitamin C therapy reduces 28-day mortality in patients with septic shock.

DESIGN: Multicenter, double-blinded, randomized controlled trial.

SETTING: One academic medical ICU and four community ICUs.

PATIENTS: Of 167 adult patients within 24 hours of vasopressor initiation for septic shock, 126 consented to participation, and 124 received study drug and were included in analysis.

INTERVENTIONS: IV vitamin C (10 mg/mL in normal saline) administered as a 1,000-mg bolus over 30 minutes followed by continuous infusion of 250 mg/hr for 96 hours or placebo of equal volumes of normal saline.

MEASUREMENTS AND MAIN RESULTS: Of 124 subjects receiving study drug and included in analysis, 60 received vitamin C and 64 placebo. The primary outcome of all-cause 28-day mortality (vitamin C, 26.7%; placebo, 40.6%; p = 0.10) was lower in the vitamin C arm but did not reach statistical significance. Initiation of renal replacement therapy was higher in the vitamin C arm (vitamin C, 16.7%; placebo, 3.3%; p = 0.015), as was volume of fluid administration within 6 hours of study drug initiation (vitamin C, 1.07 L; placebo, 0.76 L; p = 0.03). There were no statistically significant differences in other secondary outcomes. In post hoc subgroup analysis, there was a decrease in 28-day mortality in the vitamin C arm among patients requiring positive-pressure ventilation at the time of enrollment (vitamin C, 36.3%; placebo, 60.0%; p = 0.05). This trial is registered at clinicaltrials.gov under identifier NCT03338569.

CONCLUSIONS: Vitamin C monotherapy failed to significantly reduce mortality in septic shock patients as hypothesized. Our findings do not support its routine clinical use for this purpose.

# 评价维生素 C 在感染性休克中的作用：一项维生素 C 单药治疗的随机对照试验。

目的：确定 IV 维生素 C 治疗是否可降低感染性休克患者的 28 天死亡率。

设计：多中心、双盲、随机对照试验。

单位：1 个学术型内科 ICU 和 4 个社区 ICU。

患者：在 167 例血管加压素开始治疗 24 小时内的成人患者中脓毒性休克，126 例同意参加研究，124 例接受研究药物和纳入分析。

干预：静脉注射维生素 C（正常情况下为 10 mg/mL）生理盐水），以 1000 mg 推注 30 min，然后连续给药以 250 mg/h 的速率输注 96 小时或等体积生理盐水安慰剂。

测量和主要结果：在 124 名接受研究药物的受试者中，包括分析中，60 名患者接受维生素 C 治疗，64 名患者接受安慰剂治疗。主要结局全因 28 天死亡率（维生素 C，26.7%；安慰剂，40.6%；p = 0.10）较低维生素 C 组未达到统计学显著性。开始维生素 C 组的肾脏替代疗法较高（维生素 C，16.7%；安慰剂，3.3%；p = 0.015），6 小时内的输液量也是如此的治疗开始（维生素 C，1.07 L；安慰剂，0.76 L；p = 0.03）。有其他次要结局无统计学显著差异。In 事后亚组分析显示，治疗组 28 天死亡率降低在当时需要正压通气的患者中的维生素 C 组的受试者数量（维生素 C，36.3%；安慰剂，60.0%；p = 0.05）。本试验为在临床试验中注册。标识 NCT03338569 下的 gov。

结论：维生素 C 单药治疗未能显著降低感染性休克的死亡率假设患者。我们的结果不支持其常规临床应用出于此目的。关键词：Humans; Double-Blind Method; Adult; *Shock, Septic; Ascorbic Acid/therapeutic use; Saline Solution/therapeutic use; Vasoconstrictor Agents/therapeutic use; Vitamins/therapeutic use

# Resuscitation in Out-of-Hospital Cardiac Arrest Patients With COVID? Never Tell Me the Odds!, Barnicle, Ryan N.

5:883-885. DOI:10.1097/CCM.0000000000005411

# 院外心脏骤停 COVID 患者的复苏？从不告诉我几率！

关键词：Humans; *COVID-19; *Cardiopulmonary Resuscitation; *Emergency Medical Services; *Out-of-Hospital Cardiac Arrest/therapy

# Outcome of Temporary Circulatory Support As a Bridge-to-Left Ventricular Assist Device Strategy in Cardiogenic Shock Patients., Bidaut, Auriane

5:e426-e433. DOI:10.1097/CCM.0000000000005424

Abstract:

OBJECTIVES: Temporary circulatory support (TCS) as a bridge-to-left ventricular assist device (BTL) in cardiogenic shock patients has been increasing, but limited data exists on this BTL strategy. We aimed at analyzing the outcome of BTL patients in a population of cardiogenic shock patients compared with those without TCS at the time of the left ventricular assist device (LVAD) surgery and identify predictors of postoperative mortality in this specific population.

DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016.

SETTING: Nineteen French centers.

PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed.

Patients were divided in three groups: those under TCS at the time of LVAD implantation (n = 173), those with TCS removal before LVAD surgery (n = 24), and those who did not undergo a bridging strategy (n = 152). Primary endpoint was 30-day mortality.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Among the BTL group, 68 (39.3%), 18 (10.4%), and 15 (8.7%) patients were under venoarterial extracorporeal membrane oxygenation, Impella, and IABP support alone, and 72 patients (20.6%) were under multiple TCS support. BTL patients presented similar 30 days survival compared with the TCS removal and non-BTL groups. However, BTL group had a significantly longer ICU duration stay, with two-fold duration of mechanical ventilation time, but the three groups experienced similar postoperative complications.

Multivariate analysis identified three independent predictors of mortality in the BTL group: combined surgery with LVAD, body mass index (BMI), and heart failure (HF) duration. BTL strategy was not an independent predictor of mortality in cardiogenic shock patients who underwent LVAD.

# 临时循环支持作为心源性休克患者桥接至左心室辅助装置策略的结局。

DESIGN: A multicenter retrospective observational study conducted in 19 centers from 2006 to 2016.

SETTING: Nineteen French centers.

PATIENTS: A total of 329 cardiogenic shock patients at the time of LVAD implantation were analyzed.

INTERVENTIONS: None.

CONCLUSIONS: BTL strategy is not associated with a lower survival among cardiogenic shock patients with LVAD implantation. Predictors of mortality are combined surgery with LVAD, higher BMI, and HF duration. 关键词：Humans; Treatment Outcome; Retrospective Studies; *Extracorporeal Membrane Oxygenation/adverse effects; *Heart Failure/complications/surgery; *Heart-Assist Devices/adverse effects; Shock, Cardiogenic/etiology/surgery

# Patient Heterogeneity and the J-Curve Relationship Between Time-to-Antibiotics and the Outcomes of Patients Admitted With Bacterial Infection.

5:799-809. DOI:10.1097/CCM.0000000000005429

Abstract:

OBJECTIVES: Sepsis remains a leading and preventable cause of hospital utilization and mortality in the United States. Despite updated guidelines, the optimal definition of sepsis as well as optimal timing of bundled treatment remain uncertain. Identifying patients with infection who benefit from early treatment is a necessary step for tailored interventions. In this study, we aimed to illustrate clinical predictors of time-to-antibiotics among patients with severe bacterial infection and model the effect of delay on risk-adjusted outcomes across different sepsis definitions.

DESIGN: A multicenter retrospective observational study.

SETTING: A seven-hospital network including academic tertiary care center.

PATIENTS: Eighteen thousand three hundred fifteen patients admitted with severe bacterial illness with or without sepsis by either acute organ dysfunction (AOD) or systemic inflammatory response syndrome positivity.

MEASUREMENTS AND MAIN RESULTS: The primary exposure was time to antibiotics. We identified patient predictors of time-to-antibiotics including demographics, chronic diagnoses, vitals, and laboratory results and determined the impact of delay on a composite of inhospital death or length of stay over 10 days. Distribution of time-to-antibiotics was similar across patients with and without sepsis. For all patients, a J-curve relationship between time-to-antibiotics and outcomes was observed, primarily driven by length of stay among patients without AOD. Patient characteristics provided good to excellent prediction of time-to-antibiotics irrespective of the presence of sepsis. Reduced time-to-antibiotics was associated with improved outcomes for all time points beyond 2.5 hours from presentation across sepsis definitions.

CONCLUSIONS: Antibiotic timing is a function of patient factors regardless of sepsis criteria. Similarly, we show that early administration of antibiotics is associated with improved outcomes in all patients with severe bacterial illness. Our findings suggest identifying infection is a rate-limiting and actionable step that can improve outcomes in septic and nonseptic patients.

# 抗生素使用时间与因细菌感染入院患者结局之间的患者异质性和 J 曲线关系。

目的：在美国，败血症仍是医院使用和死亡的主要和可预防原因。尽管更新了指南，但是败血症的最佳定义以及最佳的捆绑式治疗时机仍不确定。识别从早期治疗中获益的感染患者是定制干预措施的必要步骤。在本研究中，我们的目的是阐明严重细菌感染患者中至抗生素治疗时间的临床预测因素，并在不同的败血症定义中建模延迟对风险调整结局的影响。

设计：多中心回顾性观察性研究。

单位：包括学术性三级医疗中心在内的七医院网络。

患者：183015 例急性器官功能障碍 (AOD) 或全身炎症反应综合征阳性的严重细菌性疾病伴或不伴败血症的患者。

测量和主要结果：主要暴露时间是抗生素。我们确定了抗生素使用时间的患者预测因素，包括人口统计学、慢性诊断、生命体征和实验室结果，并确定了延迟对住院死亡或住院时间超过 10 天的复合终点的影响。有和无败血症患者的至抗生素时间分布相似。对于所有患者，观察到抗生素使用时间与结局之间的 J 曲线关系，主要由无 AOD 患者的住院时间驱动。无论是否存在败血症，患者特征均提供了良好至极佳的抗生素使用时间预测。在不同的败血症定义中，抗生素使用时间缩短与超过 2.5 小时的所有时间点的结局改善相关。

结论：不考虑败血症标准，抗生素治疗时机是患者因素的函数。同样，我们的研究显示，在所有严重细菌性疾病患者中，早期给予抗生素与改善结局相关。我们的研究结果表明，识别感染是一个限速且可采取行动的步骤，可以改善败血症和非败血症患者的结局。关键词：Humans; Retrospective Studies; Hospital Mortality; United States; Anti-Bacterial Agents/therapeutic use; Hospitalization; *Sepsis; *Shock, Septic; *Bacterial Infections/drug therapy

# Impact of the Coronavirus Disease 2019 Pandemic on Moral Distress Among Nurses and Physicians in Spanish ICUs., Rodriguez-Ruiz, Emilio

5:e487-e497. DOI:10.1097/CCM.0000000000005434

Abstract:

OBJECTIVES: To assess the impact of COVID-19 pandemic on moral distress (MD) among healthcare professionals (HCPs) (physicians and nurses) in Spanish ICUs.

DESIGN: Cross-sectional, prospective study.

SETTING: ICUs in Spain.

PARTICIPANTS: HCPs currently working in Spanish ICUs.

INTERVENTIONS: Data were collected via electronic survey with the use of a 50-item questionnaire in two different periods: prepandemic (October-December 2019) and during the second wave of COVID-19 (September-November 2020).

MEASUREMENTS AND MAIN RESULTS: During the prepandemic and pandemic periods, 1,065 (57.1% nurses) and 1,115 (58.5% nurses) HCPs completed the questionnaire, respectively. Higher MD levels were reported during COVID-19 pandemic, particularly among ICU nurses, when compared with the prepandemic period. Before COVID-19, physicians reported significantly higher levels of MD than ICU nurses (80.0 [interquartile range {IQR}, 40.0-135.0] vs 61.0 [IQR, 35.0-133.0]; p = 0.026). These differences disappeared during the pandemic period (81.0 [IQR, 39.0-138.5] vs 74.0 [IQR, 41.0-143.0]; p = 0.837). During the pandemic, younger and less experienced HCPs working in hospital areas that were converted in ICU or in ICUs with multiple occupancy rooms reported higher MD levels. In addition, HCPs who were off work for psychologic burden reported higher MD levels (108.0 [IQR, 66.0-139.0] vs 76.0 [IQR, 40.0-141.0]; p < 0.05). In the prepandemic period, patient-level root causes were the most morally distressing for nurses, whereas physicians reported higher MD on system-level root causes. During the pandemic, both groups reported higher MD on system-level root causes. During COVID-19, significantly more HCPs considered leaving their job due to MD.

CONCLUSIONS: MD has increased among ICU HCPs in Spain during COVID-19 pandemic. Physicians reported higher MD levels than nurses in the prepandemic period, whereas both HCPs groups reported similar MD levels in the pandemic period. Strategies are needed and should be implemented to mitigate MD among HCPs.

# 2019 年冠状病毒病流行对西班牙 ICU 护士和医生的精神压力的影响。

目的：评估 COVID-19 大流行对西班牙 ICU 中医疗保健专业人员 (HCP)（医生和护士）的道德困扰 (MD) 的影响。

设计：横断面、前瞻性研究。

设置：西班牙的 ICU。

参与者：目前在西班牙 ICU 工作的 HCP。

干预：在流行前（2019 年 10 月 - 12 月）和 COVID-19 第二波期间（2020 年 9 月 - 11 月），使用 50 项问卷通过电子调查收集数据。

测量和主要结果：在大流行前和大流行期间，分别有 1,065 名（57.1% 护士）和 1,115 名（58.5% 护士）HCP 完成了问卷。与大流行前期相比，COVID-19 大流行期间报告了更高的 MD 水平，尤其是 ICU 护士。在 COVID-19 之前，医生报告 MD 水平显著高于 ICU 护士（80.0 [四分位距 {IQR}，40.0-135.0] vs 61.0 [IQR，35.0-133.0]；p = 0.026）。这些差异在流行期消失 (81.0 [IQR，39.0-138.5] vs 74.0 [IQR，41.0-143.0]；p = 0.837)。在大流行期间，在医院区域工作的较年轻和经验较少的 HCP（在 ICU 或多占用室的 ICU 中转换）报告 MD 水平较高。此外，由于心理负担而停止工作的 HCP 报告 MD 水平较高 (108.0 [IQR，66.0-139.0] vs 76.0 [IQR，40.0-141.0]；p < 0.05)。在大流行前期，患者级别的根本原因是护士最令人痛苦的道德原因，而医生报告的系统级别根本原因 MD 更高。在大流行期间，两组均报告了较高的系统级根本原因 MD。在 COVID-19 期间，显著更多的 HCP 考虑因 MD 而离开工作。

结论：在西班牙 COVID-19 大流行期间，ICU HCP 中 MD 增加。在大流行前期，医生报告的 MD 水平高于护士，而两个 HCP 组在大流行期报告的 MD 水平相似。需要并应实施策略以减轻 HCP 之间的 MD。关键词：Humans; Prospective Studies; Intensive Care Units; Pandemics; Cross-Sectional Studies; *COVID-19; *Physicians/psychology; Morals

# Simulation Versus Interactive Mobile Learning for Teaching Extracorporeal Membrane Oxygenation to Clinicians: A Randomized Trial., Gannon, Whitney D.

5:e415-e425. DOI:10.1097/CCM.0000000000005376

Abstract:

OBJECTIVES: Extracorporeal membrane oxygenation has become integral to critical care. Data informing optimal extracorporeal membrane oxygenation education modalities are lacking. We aimed to compare the effect of high-fidelity simulation versus interactive mobile learning on extracorporeal membrane oxygenation knowledge acquisition and retention among clinicians.

DESIGN: Observer-blinded, randomized controlled trial.

SETTING: A single academic medical center.

SUBJECTS: Forty-four critical care clinicians with limited extracorporeal membrane oxygenation experience.

INTERVENTIONS: Participants were randomized to receive: 1) simulation: three high-fidelity training scenarios, 2) QuizTime: 15 total multiple-choice questions delivered over 3 weeks via mobile device, or 3) experiential: no formal training. Participants completed a survey, written knowledge examination, and simulation assessment prior to randomization, immediately following the intervention, and 4 month postintervention.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was knowledge about extracorporeal membrane oxygenation assessed by score on the immediate postintervention written examination. Secondary outcomes included performance in extracorporeal membrane oxygenation simulation postintervention and 4 months later assessed by a rater blinded to group assignment. Clinicians randomized to simulation (n = 15), QuizTime (n = 14), and experiential (n = 15) had similar baseline characteristics. Adjusting for baseline knowledge, postintervention examination scores were higher in the simulation group (90.0%; interquartile range, 85.0-90.0%) than the QuizTime group (70.0%; interquartile range, 65.0-80.0%; p = 0.0003) and the experiential group (75.0%; interquartile range, 65.0-80.0%; p = 0.001). Scores did not differ between the groups at 4 months (p > 0.05 in all analyses). In postintervention extracorporeal membrane oxygenation simulations, the simulation group demonstrated shorter time to critical action compared with QuizTime (80.0 s [interquartile range, 54.0-111.0 s] vs 300.0 s [interquartile range 85.0-300.0 s]; p = 0.02) and compared with both QuizTime (45.0 s [interquartile range, 34.0-92.5 s] vs 255.5 s [interquartile range, 102.0-300.0 s]; p = 0.008) and experiential (300.0 s [interquartile range, 58.0-300.0 s]; p = 0.009) at 4 months.

CONCLUSIONS: Simulation was superior to QuizTime and experiential learning with regard to extracorporeal membrane oxygenation knowledge acquisition. Further studies are needed to ascertain the effect of these interventions on knowledge retention, clinical performance, and patient outcomes.

# 对临床医生进行体外膜肺氧合教学的模拟与交互式移动学习：一项随机试验。

目的：体外膜肺氧合已成为重症监护的重要组成部分。缺乏告知最佳体外膜肺氧合教育方式的数据。我们旨在比较高保真模拟与交互式移动学习对临床医生体外膜肺氧合知识获取和保留的影响。

设计：观察者盲法随机对照试验。

单位：单一的学术医学中心。

受试者：44 名体外膜肺氧合经验有限的重症临床医生。

干预：参与者随机接受：1）模拟：三种高保真培训场景，2）QuizTime：3 周内通过移动设备总共提供 15 个多选问题，或 3）经验性：未进行正式培训。受试者在随机分组前、干预后即刻和干预后 4 个月完成调查、书面知识检查和模拟评估。

测量和主要结果：主要结局是对体外膜肺氧合的了解，通过干预后即刻书面检查评分进行评估。次要结局包括介入术后和 4 个月后由对分组设盲的评定者进行体外膜氧合模拟的性能评估。随机分配到模拟组 (n = 15)、QuizTime (n = 14) 和经验性组 (n = 15) 的临床医生具有相似的基线特征。调整基线知识后，模拟组（90.0%；四分位距，85.0-90.0%）的干预后检查评分高于 QuizTime 组（70.0%；四分位距，65.0-80.0%；p = 0.0003）和经验组（75.0%；四分位距，65.0-80.0%；p = 0.001）。第 4 个月时两组间的评分无差异（所有分析中 p > 0.05）。在干预后体外膜氧合模拟中，模拟组显示出比 QuizTime（80.0 s [四分位距，54.0-111.0 s] vs 300.0 s [四分位距 85.0-300.0 s]；p = 0.02）和两种 QuizTime（45.0 s [四分位距，34.0-92.5 s] vs 255.5 s [四分位距，102.0-300.0 s]；p = 0.008）和 4 个月时的体验（300.0 s [四分位距，58.0-300.0 s]；p = 0.009）。

结论：在体外膜肺氧合知识获取方面，模拟优于 QuizTime 和体验式学习。还需要进一步的研究来确定这些干预措施对知识保留、临床表现和患者结局的影响。关键词：Humans; Critical Care; Retrospective Studies; Academic Medical Centers; Computer Simulation; *Extracorporeal Membrane Oxygenation/education; *Simulation Training

# Beyond the Alveolar Epithelium: Plasma Soluble Receptor for Advanced Glycation End Products Is Associated With Oxygenation Impairment, Mortality, and Extrapulmonary Organ Failure in Children With Acute Respiratory Distress Syndrome.

5:837-847. DOI:10.1097/CCM.0000000000005373

Abstract:

OBJECTIVES: Soluble receptor for advanced glycation end products is a known plasma marker of alveolar epithelial injury. However, RAGE is also expressed on cell types beyond the lung, and its activation leads to up-regulation of pro-inflammatory mediators. We sought to examine the relationship between plasma soluble receptor for advanced glycation end products and primary pulmonary dysfunction, extrapulmonary organ dysfunction, and mortality in pediatric acute respiratory distress syndrome patients at two early time points following acute respiratory distress syndrome diagnosis and compare these results to plasma surfactant protein-D, a marker of pure alveolar epithelial injury.

DESIGN: Prospective observational study.

SETTING: Five academic PICUs.

PATIENTS: Two hundred fifty-eight pediatric patients 30 days to 18 years old meeting Berlin Criteria for acute respiratory distress syndrome.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Plasma was collected for soluble receptor for advanced glycation end products and surfactant protein-D measurements within 24 hours (day 1) and 48 to 72 hours (day 3) after acute respiratory distress syndrome diagnosis. Similar to surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with a higher oxygenation index (p < 0.01) and worse lung injury score (p < 0.001) at the time of acute respiratory distress syndrome diagnosis. However, unlike surfactant protein-D, plasma soluble receptor for advanced glycation end products was associated with worse extrapulmonary Pediatric Logistic Organ Dysfunction score during ICU stay (day 3; p < 0.01) and positively correlated with plasma levels of interleukin-6 (p < 0.01), tumor necrosis factor-?± (p < 0.01), and angiopoietin-2 (p < 0.01). Among children with indirect lung injury, plasma soluble receptor for advanced glycation end products was associated with mortality independent of age, sex, race, cancer/bone marrow transplant, and Pediatric Risk of Mortality score (day 3; odds ratio, 3.14; 95% CI, 1.46-6.75; p < 0.01).

CONCLUSIONS: Unlike surfactant protein-D, which is primarily localized to the alveolar epithelium plasma soluble receptor for advanced glycation end products is systemically expressed and correlates with markers of inflammation, extrapulmonary multiple organ dysfunction, and death in pediatric acute respiratory distress syndrome with indirect lung injury. This suggests that unlike surfactant protein-D, soluble receptor for advanced glycation end products is a multifaceted marker of alveolar injury and increased inflammation and that receptor for advanced glycation end products activation may contribute to the pathogenesis of multiple organ failure among children with indirect acute respiratory distress syndrome.

# 除了肺泡上皮：晚期糖基化终末产物的血浆可溶性受体与急性呼吸窘迫综合征儿童中的氧合损害、死亡和肺外器官衰竭相关。

目的：晚期糖基化终末产物的可溶性受体是肺泡上皮损伤的已知血浆标志物。然而，RAGE 也在肺以外的细胞类型上表达，其激活导致促炎介质上调。我们试图检测晚期糖基化终末产物的血浆可溶性受体与原发性肺功能障碍、肺外器官功能障碍、急性呼吸窘迫综合征患儿在急性呼吸窘迫综合征诊断后两个早期时间点的死亡率，并将这些结果与血浆表面活性蛋白 - D（纯肺泡上皮损伤的标志物）进行比较。

设计：前瞻性观察性研究。

单位：5 家学术型 PICU。

患者：258 例符合急性呼吸窘迫综合征柏林标准的 30 天至 18 岁的儿科患者。

干预：无。

测定和主要结果：在急性呼吸窘迫综合征确诊后 24 小时（第 1 天）和 48-72 小时（第 3 天）内采集血浆，用于可溶性晚期糖基化终末产物受体和表面活性蛋白 - D 测量。与表面活性蛋白 D 相似，晚期糖基化终末产物的血浆可溶性受体与急性呼吸窘迫综合征诊断时较高的氧合指数 (p < 0.01) 和较差的肺损伤评分 (p < 0.001) 相关。然而，与表面活性蛋白 - D 不同，晚期糖基化终末产物的血浆可溶性受体与较差的肺外儿科在 ICU 住院期间（第 3 天；p < 0.01）的逻辑器官功能障碍评分相关，并与白介素 - 6 (p < 0.01)、肿瘤坏死因子 - gi±(p < 0.01) 的血浆水平呈正相关。和血管生成素 - 2 (p < 0.01)。在间接肺损伤的儿童中，晚期糖基化终末产物的血浆可溶性受体与死亡率相关，与年龄、性别、人种、癌症 / 骨髓移植和儿童死亡风险评分无关（第 3 天；比值比，3.14；95% CI，1.46-6.75；p < 0.01）。

结论：与主要定位于肺泡上皮的表面活性蛋白 - D 不同，晚期糖基化终末产物的血浆可溶性受体全身表达，并与炎症、肺外多器官功能障碍和间接肺损伤的小儿急性呼吸窘迫综合征死亡标志物相关。这表明，与表面活性蛋白 - D 不同，晚期糖基化终末产物的可溶性受体是肺泡损伤和炎症增加的多方面标志物，晚期糖基化终末产物受体活化可能导致间接急性呼吸窘迫综合征患儿发生多器官衰竭。关键词：Humans; Adolescent; Child; Infant; Infant, Newborn; Child, Preschool; Biomarkers; Lung; Inflammation; *Respiratory Distress Syndrome; *Lung Injury; Epithelium; Glycation End Products, Advanced; Pulmonary Surfactant-Associated Protein D; Receptor for Advanced Glycation End Products; Surface-Active Agents

# Neighborhood Socioeconomic Disadvantage and Disability After Critical Illness.

5:733-741. DOI:10.1097/CCM.0000000000005364

Abstract:

OBJECTIVES: Factors common to socioeconomically disadvantaged neighborhoods, such as low availability of transportation, may limit access to restorative care services for critical illness survivors. Our primary objective was to evaluate whether neighborhood socioeconomic disadvantage was associated with an increased disability burden after critical illness. Our secondary objective was to determine if the effect differed for those discharged to the community compared with those discharged to a facility.

DESIGN: Longitudinal cohort study with linked Medicare claims data.

SETTING: United States.

PATIENTS: One hundred ninety-nine older adults, contributing to 239 ICU admissions, who underwent monthly assessments of disability for 12 months following hospital discharge in 13 different functional tasks from 1998 to 2017.

MEASUREMENTS AND MAIN RESULTS: Neighborhood disadvantage was assessed using the area deprivation index, a 1-100 ranking evaluating poverty, housing, and employment metrics. Those living in disadvantaged neighborhoods (top quartile of scores) were less likely to self-identify as non-Hispanic White compared with those in more advantaged neighborhoods. In adjusted models, older adults living in disadvantaged neighborhoods had a 9% higher disability burden over the 12 months following ICU discharge compared with those in more advantaged areas (rate ratio, 1.09; 95% Bayesian credible interval, 1.02-1.16). In the secondary analysis adjusting for discharge destination, neighborhood disadvantage was associated with a 14% increase in disability burden over 12 months of follow-up (rate ratio, 1.14; 95% credible interval, 1.07-1.21). Disability burden was 10% higher for those living in disadvantaged neighborhoods and discharged home as compared with those discharged to a facility, but this difference was not statistically significant (interaction rate ratio, 1.10; 95% credible interval, 0.98-1.25).

CONCLUSIONS: Neighborhood socioeconomic disadvantage is associated with a higher disability burden in the 12 months after a critical illness. Future studies should evaluate barriers to functional recovery for ICU survivors living in disadvantaged neighborhoods.

# 危重病后的社区社会经济不利因素和残疾。

目的：社会经济地位不利的社区的常见因素，如交通状况较差，可能限制危重疾病幸存者获得恢复性护理服务。我们的主要目的是评估邻里社会经济劣势是否与危重疾病后残疾负担增加相关。我们的次要目的是确定出院进入社区的患者与出院进入机构的患者的影响是否不同。

设计：含医疗保险索赔数据的纵向队列研究。

设置：美国。

患者：1998-2017 年，在出院后 12 个月内，在 13 项不同的功能任务中，对 239 例 ICU 入院的 199 例老年人进行了每月一次的残疾评估。

测量和主要结果：使用面积剥夺指数评估了社区劣势，该指数为 1-100，用于评估贫困、住房和就业指标。与处于更有利环境的人相比，生活在不利环境中的人（得分最高四分位数）不太可能自我认定为非西班牙裔白人。在调整后的模型中，生活在贫困社区的老年人在离开 ICU 后 12 个月内的残疾负担比生活在较贫困地区的老年人高 9%（率比，1.09；95% 贝叶斯置信区间，1.02-1.16）。在校正了出院目的地的次要分析中，邻居劣势与 12 个月随访期间残疾负担增加 14% 相关（率比，1.14；95% 置信区间，1.07-1.21）。居住在贫困社区和出院回家的人与出院回家的人相比，残疾负担高 10%，但这种差异没有统计学意义（相互作用率比，1.10；95% 置信区间，0.98-1.25）。

结论：在危重病后的 12 个月内，周围社会经济劣势与较高的残疾负担相关。未来的研究应评估生活在贫困环境中的 ICU 幸存者的功能恢复障碍。关键词：Humans; Aged; Longitudinal Studies; Socioeconomic Factors; United States/epidemiology; *Critical Illness; Bayes Theorem; *Medicare; Residence Characteristics

# Preexisting Clinical Frailty Is Associated With Worse Clinical Outcomes in Patients With Sepsis., Lee, Hong Yeul

5:780-790. DOI:10.1097/CCM.0000000000005360

Abstract:

OBJECTIVES: Frailty is a multidimensional syndrome or state of increased vulnerability to poor resolution of homoeostasis following a stressor event. Frailty is common in patients with sepsis. Sepsis and frailty are both associated with older age and chronic medical conditions. However, there is limited evidence about the direct association between frailty and sepsis. The aim of this study is to determine the association between preexisting clinical frailty and clinical outcomes in patients with sepsis.

DESIGN: A nationwide propensity score-matched cohort study analyzing data prospectively collected between September 2019 and February 2020.

SETTING: Nineteen tertiary or university-affiliated hospitals in South Korea.

PATIENTS: Adult patients who were diagnosed with sepsis.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Frailty status was assessed using the Clinical Frailty Scale. All patients were classified as "frail" (Clinical Frailty Scale score, 5-9) or "nonfrail" (Clinical Frailty Scale score, 1-4). Propensity score matching identified comparable nonfrail patients. The primary outcome was inhospital mortality. Multivariable logistic regression analysis was used to evaluate the association between frailty and inhospital mortality. The propensity score-matched cohort comprised 468 nonfrail patients and 468 frail patients; all covariate imbalances were alleviated. In the matched cohort (mean age, 69 ?± 14 yr), 27.2% had septic shock at presentation. Inhospital mortality was 34.2% in the frail group and 26.9% in the nonfrail group (p = 0.019). The adjusted odds ratio for inhospital mortality in the frail group compared with the nonfrail group was 2.00 (95% CI, 1.39-2.89; p < 0.001). Among the patients who survived to discharge, the frail group was less likely to be discharged home compared with the nonfrail group, 64.0% versus 81.3%, respectively (p < 0.001).

CONCLUSIONS: In patients with sepsis, preexisting clinical frailty is associated with worse clinical outcomes than that in nonfrail patients, including inhospital mortality and discharge to home.

# 既存临床虚弱与败血症患者临床结局较差相关。

目的：虚弱是一种多维度综合征或应激源事件后对内环境稳态不良缓解的易感性增加的状态。虚弱在败血症患者中常见。败血症和虚弱均与高龄和慢性疾病相关。但是，关于虚弱和败血症之间直接相关性的证据有限。本研究的目的是确定败血症患者中既存的临床虚弱与临床结局之间的相关性。

设计：一项全国倾向评分匹配队列研究，分析 2019 年 9 月至 2020 年 2 月期间前瞻性收集的数据。

单位：韩国 19 家三级或大学附属医院。

患者：确诊为败血症的成人患者。

干预：无。

测量和主要结果：使用临床虚弱量表评估虚弱状态。所有患者均被分类为 “虚弱”（临床虚弱量表评分，5-9）或 “非虚弱”（临床虚弱量表评分，1-4）。倾向评分匹配确定了相当的非虚弱患者。主要结局为住院死亡率。使用多变量 logistic 回归分析评价虚弱与住院死亡率之间的相关性。倾向评分匹配队列包括 468 例非虚弱患者和 468 例虚弱患者；所有协变量不平衡均得到缓解。在匹配的队列中（平均年龄，69±14 岁），27.2% 的患者在就诊时存在脓毒性休克。虚弱组住院死亡率为 34.2%，非虚弱组为 26.9%(p = 0.019)。与非虚弱组相比，虚弱组住院死亡率的调整比值比为 2.00 (95% CI，1.39-2.89；p < 0.001)。在存活出院的患者中，与非虚弱组相比，虚弱组不太可能出院回家，分别为 64.0% 与 81.3%(p < 0.001)。

结论：在败血症患者中，与非虚弱患者相比，预先存在的临床虚弱患者的临床结局更差，包括住院死亡率和出院回家。关键词：Humans; Middle Aged; Aged; Cohort Studies; Aged, 80 and over; Risk Factors; Frail Elderly; *Frailty/complications/epidemiology; *Sepsis/complications/epidemiology

# Hastening Death in Canadian ICUs: End-of-Life Care in the Era of Medical Assistance in Dying., Andersen, Sarah K.

5:742-749. DOI:10.1097/CCM.0000000000005359

Abstract:

OBJECTIVES: Since 2016, Canada has allowed for euthanasia based on strict criteria under federal medical assistance in dying legislation. The purpose of this study was to determine how Canadian intensivists perceive medical assistance in dying and whether they believe their approach to withdrawal of life-sustaining therapies has changed following introduction of medical assistance in dying.

DESIGN: Electronic survey.

SETTING: Participants were recruited from 11 PICU programs and 14 adult ICU programs across Canada. All program leaders for whom contact information was available were approached for participation.

PARTICIPANTS: We invited intensivists and critical care trainees employed between December 2019 and May 2020 to participate using a snowball sampling technique in which department leaders distributed study information. All responses were anonymous. Quantitative data were analyzed using descriptive statistics. Categorical variables were analyzed using Pearson chi-square test.

INTERVENTIONS: Not applicable.

MEASUREMENTS AND MAIN RESULTS: We obtained 150 complete questionnaires (33% response rate), of which 50% were adult practitioners and 50% pediatric. Most were from academic centers (81%, n = 121). Of respondents, 86% (n = 130) were familiar with medical assistance in dying legislation, 71% in favor, 14% conflicted, and 11% opposed. Only 5% (n = 8) thought it had influenced their approach to withdrawal of life-sustaining therapies. Half of participants had no standardized protocol for withdrawal of life-sustaining therapies in their unit, and 41% (n = 62) had observed medications given in disproportionately high doses during withdrawal of life-sustaining therapies, with 13% having personally administered such doses. Most (80%, n = 120) had experienced explicit requests from families to hasten death, and almost half (47%, n = 70) believed it was ethically permissible to intentionally hasten death following withdrawal of life-sustaining therapies.

CONCLUSIONS: Most Canadian intensivists surveyed do not think that medical assistance in dying has changed their approach to end of life in the ICU. A significant minority are ethically conflicted about the current approach to assisted dying/euthanasia in Canada. Almost half believe it is ethical to intentionally hasten death during withdrawal of life-sustaining therapies if death is expected.

# 加拿大 ICU 中的加速死亡：濒死医疗救助时代的临终关怀。

目的：自 2016 年以来，加拿大根据联邦死亡医疗救助法规中的严格标准允许实施安乐死。本研究的目的是确定加拿大重症监护医生如何看待死亡时的医疗援助，以及他们是否认为在引入死亡时的医疗援助后，他们撤除维持生命治疗的方法发生了变化。

设计：电子调查。

设置：参与者从加拿大的 11 个 PICU 项目和 14 个成人 ICU 项目中招募。联系联系所有项目负责人并提供其联系信息。

参加者：我们邀请 2019 年 12 月至 2020 年 5 月期间雇佣的重症监护医生和重症监护学员使用雪球采样技术参加研究，部门负责人在该技术中分发研究信息。所有回复均为匿名。使用描述性统计分析定量数据。分类变量采用 Pearson 卡方检验。

干预：不适用。

测量和主要结果：我们获得了 150 份完整的问卷（33% 应答率），其中 50% 为成人从业者，50% 为儿童。大多数来自学术中心 (81%，n = 121)。在答复者中，86%(n = 130) 熟悉濒死立法方面的医疗援助，71% 赞成，14% 冲突，11% 反对。仅 5%(n = 8) 认为这影响了他们停止维持生命治疗的方法。一半的受试者在其单位中没有停止维持生命治疗的标准化方案，41%(n = 62) 的受试者在停止维持生命治疗期间观察到不成比例的高剂量给药，13% 的受试者亲自给予了此类剂量。大多数 (80%，n = 120) 经历了家庭加速死亡的明确要求，几乎一半 (47%，n = 70) 认为，在停止维持生命的治疗后，在伦理上允许故意加速死亡。

结论：大多数接受调查的加拿大重症监护医生认为，对死亡患者的医疗救助改变了他们在 ICU 中的临终方法。对于加拿大目前的辅助死亡 / 安乐死方法，相当多的少数人在伦理上产生矛盾。几乎一半的人认为，在预期死亡的情况下，在停止维持生命的治疗时故意加速死亡是合乎伦理的。关键词：Humans; Intensive Care Units; Adult; Child; Canada; *Terminal Care; *Euthanasia; Medical Assistance

# Hyperdynamic Left Ventricular Ejection Fraction in ICU Patients With Sepsis., Chotalia, Minesh

5:770-779. DOI:10.1097/CCM.0000000000005315

Abstract:

OBJECTIVES: To evaluate the cause and prognosis of hyperdynamic left ventricular ejection fraction in critically ill patients with sepsis.

DESIGN: Retrospective, single-center cohort study.

SETTING: University Hospital ICU, Birmingham, United Kingdom.

PATIENTS: ICU patients who received a transthoracic echocardiogram within 7 days of sepsis between April 2016 and December 2019.

INTERVENTION: None.

MEASUREMENTS AND MAIN RESULTS: The 90-day mortality rates of normal (55-70%), depressed (< 55%), and hyperdynamic left ventricular ejection fraction (> 70%) were compared. Multivariate logistic regression analysis was performed to determine the association of left ventricular ejection fraction phenotypes with mortality and the association of clinical variables with left ventricular ejection fraction phenotypes. One thousand fourteen patients met inclusion criteria and were 62 years old (interquartile range, 47-72), with mostly respiratory infections (n = 557; 54.9%). Ninety-day mortality was 32.1% (n = 325). Patients with hyperdynamic left ventricular ejection fraction had a higher mortality than depressed and normal left ventricular ejection fraction cohorts (58.9% [n = 103] vs 34.0% [n = 55] vs 24.7% [n = 167]; p < 0.0001, respectively). After multivariate logistic regression, hyperdynamic left ventricular ejection fraction was independently associated with mortality (odds ratio, 3.90 [2.09-7.40]), whereas depressed left ventricular ejection fraction did not (odds ratio, 0.62 [0.28-1.37]). Systemic vascular resistance was inversely associated with hyperdynamic left ventricular ejection fraction (odds ratio, 0.79 [0.58-0.95]), and age, frailty, and ischemic heart disease were associated with depressed left ventricular ejection fraction.

CONCLUSIONS: Hyperdynamic left ventricular ejection fraction was associated with mortality in septic ICU patients and may reflect unmitigated vasoplegia from sepsis. Depressed left ventricular ejection fraction was not associated with mortality but was associated with cardiovascular disease.

# ICU 脓毒症患者的高动力性左心室射血分数。

目的：评估脓毒症重症患者的高动力性左心室射血分数的原因和预后。

设计：回顾性、单中心队列研究。

单位：University Hospital ICU,Birmingham,United Kingdom。

患者：2016 年 4 月至 2019 年 12 月脓毒症 7 天内接受经胸超声心动图检查的 ICU 患者。

干预：无。

测量和主要结果：比较了正常 (55-70%)、抑制 (<55%) 和高动力左心室射血分数 (>70%) 的 90 天死亡率。进行了多变量 logistic 回归分析，以确定左心室射血分数表型与死亡率的相关性以及临床变量与左心室射血分数表型的相关性。1414 名患者符合入选标准，年龄为 62 岁（四分位距：47-72），主要为呼吸道感染 (n = 557；54.9%)。90 天死亡率为 32.1%(n = 325)。左心室射血分数高动力患者的死亡率高于左心室射血分数降低和正常队列（分别为 58.9%[n = 103] vs 34.0%[n = 55] vs 24.7%[n = 167]；p < 0.0001）。多变量 logistic 回归后，高动力性左心室射血分数与死亡率独立相关（比值比，3.90 [2.09-7.40]），而左心室射血分数降低不相关（比值比，0.62 [0.28-1.37]）。全身血管阻力与高动力性左心室射血分数呈负相关（比值比，0.79 [0.58-0.95]），年龄、虚弱和缺血性心脏病与左心室射血分数降低相关。

结论：高动力性左心室射血分数与败血症 ICU 患者的死亡率相关，可能反映了未减轻的败血症所致的血管麻痹。左心室射血分数降低与死亡率无关，但与心血管疾病相关。关键词：Humans; Intensive Care Units; Cohort Studies; Retrospective Studies; Stroke Volume; *Sepsis; *Ventricular Dysfunction, Left/etiology; Ventricular Function, Left

# Coronavirus Disease 2019 and Out-of-Hospital Cardiac Arrest: No Survivors.

5:791-798. DOI:10.1097/CCM.0000000000005374

Abstract:

OBJECTIVES: To describe and compare survival among patients with out-of-hospital cardiac arrest as a function of their status for coronavirus disease 2019.

DESIGN: We performed an observational study of out-of-hospital cardiac arrest patients between March 2020 and December 2020. Coronavirus disease 2019 status (confirmed, suspected, or negative) was defined according to the World Health Organization's criteria.

SETTING: Information on the patients and their care was extracted from the French national out-of-hospital cardiac arrest registry.

The French prehospital emergency medical system has two tiers: the fire department intervenes rapidly to provide basic life support, and mobile ICUs provide advanced life support. The study data (including each patient's coronavirus disease 2019 status) were collected by 95 mobile ICUs throughout France.

PATIENTS: We included 6,624 out-of-hospital cardiac arrest patients: 127 cases with confirmed coronavirus disease 2019, 473 with suspected coronavirus disease 2019, and 6,024 negative for coronavirus disease 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The "confirmed" and "suspected" groups of coronavirus disease 2019 patients had similar characteristics and were more likely to have suffered an out-of-hospital cardiac arrest with a respiratory cause (confirmed: 53.7%, suspected coronavirus disease 2019: 56.5%; p = 0.472) than noncoronavirus disease 2019 patients (14.0%; p < 0.001 vs confirmed coronavirus disease 2019 patients). Advanced life support was initiated for 57.5% of the confirmed coronavirus disease 2019 patients, compared with 64.5% of the suspected coronavirus disease 2019 patients (p = 0.149) and 70.6% of the noncoronavirus disease 2019 ones (p = 0.002). The survival rate at 30-day postout-of-hospital cardiac arrest was 0% in the confirmed coronavirus disease 2019 group, 0.9% in the suspected coronavirus disease 2019 group (p = 0.583 vs confirmed), and 3.5% (p = 0.023) in the noncoronavirus disease 2019 group.

CONCLUSIONS: Our results highlighted a zero survival rate in out-of-hospital cardiac arrest patients with confirmed coronavirus disease 2019. This finding raises important questions with regard to the futility of resuscitation for coronavirus disease 2019 patients and the management of the associated risks.

# 2019 年冠状病毒病和院外心脏骤停：无存活者。

目的：描述和比较 2019 年医院外心脏骤停患者的生存率，作为其冠状病毒疾病状态的函数。

设计：我们对 2020 年 3 月至 2020 年 12 月期间的院外心脏骤停患者进行了观察性研究。根据世界卫生组织的标准定义了 2019 年冠状病毒病状态（确认、疑似或阴性）。

背景：从法国国家院外心脏骤停登记研究中提取患者及其护理的信息。

法国院前急救医疗系统分两层：消防部门快速介入，提供基础生命支持；移动 ICU 提供高级生命支持。研究数据（包括每例患者的冠状病毒病 2019 状态）通过法国 95 个移动 ICU 收集。

患者：我们纳入了 6624 例院外心脏骤停患者：127 例确诊冠状病毒病 2019 例，473 例疑似冠状病毒病 2019 例，6024 例冠状病毒病阴性 2019 例。

干预：无。

测量和主要结果：2019 例 “确诊” 和 “疑似” 冠状病毒病组患者具有相似的特征，与 2019 例非冠状病毒病组患者（14.0%；p < 0.001 vs 证实的冠状病毒病 2019 例患者）。2019 例确诊的冠状病毒疾病患者中 57.5% 启动了高级生命支持，2019 例疑似冠状病毒疾病患者中 64.5% 启动了高级生命支持 (p = 0.149)，2019 例非冠状病毒疾病患者中 70.6% 启动了高级生命支持 (p = 0.002)。确诊的 2019 年冠状病毒病组的 30 天院外心脏骤停生存率为 0%，2019 年疑似冠状病毒病组的 30 天院外心脏骤停生存率为 0.9%（p = 0.583 vs 确诊），2019 年疑似冠状病毒病组的 30 天院外心脏骤停生存率为 3.5%(p = 0.023)。非冠状病毒病 2019 组。

结论：我们的结果强调，确诊为冠状病毒病的院外心脏骤停患者的生存率为零 2019。这一发现引发了关于 2019 例冠状病毒疾病患者复苏无效以及相关风险管理的重要问题。关键词：Humans; Registries; *COVID-19; *Cardiopulmonary Resuscitation/methods; *Emergency Medical Services/methods; *Out-of-Hospital Cardiac Arrest/epidemiology/therapy

# Consensus-Based Guidelines for the Recognition, Diagnosis, and Management of Hemophagocytic Lymphohistiocytosis in Critically Ill Children and Adults., Hines, Melissa R.

5:860-872. DOI:10.1097/CCM.0000000000005361

Abstract:

OBJECTIVE: Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome that often requires critical care support and remains difficult to diagnose. These guidelines are meant to aid in the early recognition, diagnosis, supportive care, and treatment of patients with hemophagocytic lymphohistiocytosis in ICUs.

DATA SOURCES: The literature searches were performed with PubMed (MEDLINE).

STUDY SELECTION: Keywords and medical subject headings terms for literature search included "macrophage activation syndrome," hemophagocytic lymphohistiocytosis," and "hemophagocytic syndrome." DATA EXTRACTION: The Histiocyte Society developed these consensus recommendations on the basis of published reports and expert opinions with level of evidence provided for each recommendation. They were endorsed by the Society of Critical Care Medicine.

DATA SYNTHESIS: Testing for hemophagocytic lymphohistiocytosis should be initiated promptly in all patients admitted to ICUs with an unexplained or disproportionate inflammatory response, especially those with rapid clinical deterioration. Meeting five or more of eight hemophagocytic lymphohistiocytosis 2004 diagnostic criteria serves as a valuable diagnostic tool for hemophagocytic lymphohistiocytosis. Early aggressive critical care interventions are often required to manage the multisystem organ failure associated with hemophagocytic lymphohistiocytosis. Thorough investigation of the underlying triggers of hemophagocytic lymphohistiocytosis, including infections, malignancies, and autoimmune/autoinflammatory diseases, is essential. Early steroid treatment is indicated for patients with familial hemophagocytic lymphohistiocytosis and is often valuable in patients with acquired hemophagocytic lymphohistiocytosis (i.e., secondary hemophagocytic lymphohistiocytosis) without previous therapy, including macrophage activation syndrome (hemophagocytic lymphohistiocytosis secondary to autoimmune/autoinflammatory disease) without persistent or relapsing disease. Steroid treatment should not be delayed, particularly if organ dysfunction is present. In patients with macrophage activation syndrome, whose disease does not sufficiently respond, interleukin-1 inhibition and/or cyclosporine A is recommended. In familial hemophagocytic lymphohistiocytosis and severe, persistent, or relapsing secondary macrophage activation syndrome, the addition of prompt individualized, age-adjusted etoposide treatment is recommended.

CONCLUSIONS: Further studies are needed to determine optimal treatment for patients with hemophagocytic lymphohistiocytosis in ICUs, including the use of novel and adjunct therapies.

# 危重病儿童和成人中噬血细胞性淋巴组织细胞增生症的识别、诊断和管理的基于共识的指南。

目的：噬血细胞性淋巴组织细胞增生症是一种高炎性综合征，通常需要重症监护支持，仍然难以诊断。这些指南旨在帮助 ICU 中噬血细胞性淋巴组织细胞增生症患者的早期识别、诊断、支持治疗和治疗。

资料来源：应用 PubMed (MEDLINE) 进行文献检索。

研究选择：用于文献检索的关键词和医学主题词包括 “巨噬细胞活化综合征”、“嗜血细胞性淋巴组织细胞增生症” 和 “嗜血细胞综合征”。

数据提取：组织细胞学会根据已发表的报告和专家意见制定这些共识建议，并提供每项建议的证据水平。他们得到了重症医学协会的支持。

资料综合：所有入住 ICU 的炎症反应无法解释或不成比例的患者，尤其是临床症状迅速恶化的患者，应及时开始噬血细胞性淋巴组织细胞增生症的检测。满足 2004 年 8 项噬血细胞性淋巴组织细胞增生症中的 5 项或 5 项以上诊断标准，可作为噬血细胞性淋巴组织细胞增生症的一种有价值的诊断工具。通常需要早期积极的重症监护干预来管理与噬血细胞性淋巴组织细胞增生症相关的多系统器官衰竭。必须彻底调查噬血细胞性淋巴组织细胞增生症的潜在触发因素，包括感染、恶性肿瘤和自身免疫性 / 自身炎症性疾病。早期类固醇治疗适用于家族性噬血细胞性淋巴组织细胞增生症患者，在获得性噬血细胞性淋巴组织细胞增生症（即，继发性噬血细胞性淋巴组织细胞增生症），既往未接受过治疗，包括巨噬细胞活化综合征（继发于自身免疫 / 自身炎症性疾病的噬血细胞性淋巴组织细胞增生症），无持续性或复发性疾病。类固醇治疗不应延迟，尤其是存在器官功能障碍时。在疾病疗效不充分的巨噬细胞活化综合征患者中，推荐使用白细胞介素 - 1 抑制剂和 / 或环孢素 A。在家族性噬血细胞性淋巴组织细胞增生症和重度、持续性或复发性继发性巨噬细胞活化综合征中，建议增加及时的个体化、年龄调整的依托泊苷治疗。

结论：需要进一步的研究来确定 ICU 中噬血细胞性淋巴组织细胞增生症患者的最佳治疗，包括使用新型和辅助疗法。关键词：Humans; Adult; Child; Consensus; Critical Illness/therapy; Steroids; *Lymphohistiocytosis, Hemophagocytic/diagnosis/therapy; *Macrophage Activation Syndrome/diagnosis/etiology/therapy; Neoplasm Recurrence, Local/complications

# Extended Lung Ultrasound to Differentiate Between Pneumonia and Atelectasis in Critically Ill Patients: A Diagnostic Accuracy Study.

5:750-759. DOI:10.1097/CCM.0000000000005303

Abstract:

OBJECTIVES: To determine the diagnostic accuracy of extended lung ultrasonographic assessment, including evaluation of dynamic air bronchograms and color Doppler imaging to differentiate pneumonia and atelectasis in patients with consolidation on chest radiograph. Compare this approach to the Simplified Clinical Pulmonary Infection Score, Lung Ultrasound Clinical Pulmonary Infection Score, and the Bedside Lung Ultrasound in Emergency protocol.

DESIGN: Prospective diagnostic accuracy study.

SETTING: Adult ICU applying selective digestive decontamination.

PATIENTS: Adult patients that underwent a chest radiograph for any indication at any time during admission. Patients with acute respiratory distress syndrome, coronavirus disease 2019, severe thoracic trauma, and infectious isolation measures were excluded.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Lung ultrasound was performed within 24 hours of chest radiograph. Consolidated tissue was assessed for presence of dynamic air bronchograms and with color Doppler imaging for presence of flow. Clinical data were recorded after ultrasonographic assessment. The primary outcome was diagnostic accuracy of dynamic air bronchogram and color Doppler imaging alone and within a decision tree to differentiate pneumonia from atelectasis. Of 120 patients included, 51 (42.5%) were diagnosed with pneumonia. The dynamic air bronchogram had a 45% (95% CI, 31-60%) sensitivity and 99% (95% CI, 92-100%) specificity. Color Doppler imaging had a 90% (95% CI, 79-97%) sensitivity and 68% (95% CI, 56-79%) specificity. The combined decision tree had an 86% (95% CI, 74-94%) sensitivity and an 86% (95% CI, 75-93%) specificity. The Bedside Lung Ultrasound in Emergency protocol had a 100% (95% CI, 93-100%) sensitivity and 0% (95% CI, 0-5%) specificity, while the Simplified Clinical Pulmonary Infection Score and Lung Ultrasound Clinical Pulmonary Infection Score had a 41% (95% CI, 28-56%) sensitivity, 84% (95% CI, 73-92%) specificity and 68% (95% CI, 54-81%) sensitivity, 81% (95% CI, 70-90%) specificity, respectively.

CONCLUSIONS: In critically ill patients with pulmonary consolidation on chest radiograph, an extended lung ultrasound protocol is an accurate and directly bedside available tool to differentiate pneumonia from atelectasis. It outperforms standard lung ultrasound and clinical scores.

# 扩展肺部超声鉴别危重患者肺炎和肺不张：一项诊断准确性研究。

目的：确定扩展的肺部超声评估的诊断准确性，包括评价动态空气支气管造影和彩色多普勒成像，以鉴别胸片上实变患者的肺炎和肺不张。将此方法与紧急情况下的简化临床肺部感染评分、肺部超声临床肺部感染评分和床旁肺部超声进行比较。

设计：前瞻性诊断准确性研究。

背景：成人 ICU 应用选择性消化道净化。

患者：在入院期间任何时间因任何指征接受胸部 x 线检查的成人患者。排除急性呼吸窘迫综合征、2019 冠状病毒病、严重胸外伤、感染性隔离措施患者。

干预：无。

测量值和主要结果：在胸片检查后 24 小时内进行肺部超声检查。对合并组织进行动态空气支气管造影评估，并使用彩色多普勒成像评估是否存在血流。超声评估后记录临床数据。主要结局是动态空气支气管造影和彩色多普勒成像单独和在决策树内鉴别肺炎和肺不张的诊断准确性。在纳入的 120 例患者中，51 例 (42.5%) 被诊断为肺炎。动态空气支气管造影的灵敏度为 45%(95% CI，31-60%)，特异性为 99%(95% CI，92-100%)。彩色多普勒成像的敏感性为 90%(95% CI，79-97%)，特异性为 68%(95% CI，56-79%)。联合决策树的灵敏度为 86%(95% CI，74-94%)，特异性为 86%(95% CI，75-93%)。急诊方案中的床旁肺部超声的灵敏度为 100%(95% CI，93-100%)，特异性为 0%(95% CI，0-5%)，而简化临床肺部感染评分和肺部超声临床肺部感染评分的灵敏度为 41%(95% CI，28-56%)，特异性为 84%(95% CI，73-92%)，特异性为 68%（95% CI，54-81%）的灵敏度，81%(95% CI，70-90%) 的特异性。

结论：在胸部 x 线片显示肺实变的重症患者中，扩展的肺部超声方案是鉴别肺炎与肺不张的一种准确、直接床旁可用的工具。其优于标准肺部超声和临床评分。关键词：Humans; Prospective Studies; Critical Illness; Adult; Sensitivity and Specificity; *COVID-19; Lung/diagnostic imaging; *Pneumonia/diagnostic imaging; *Pulmonary Atelectasis/diagnostic imaging; Ultrasonography/methods

# Clinical Benefit of Extubation in Patients on Venoarterial Extracorporeal Membrane Oxygenation., Massart, Nicolas

5:760-769. DOI:10.1097/CCM.0000000000005304

Abstract:

OBJECTIVES: Although patients on venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock are usually supported with mechanical ventilation, it is not clear whether sedation cessation and extubation might improve outcomes.

DESIGN: Retrospective cohort study with propensity score overlap weighting analysis.

SETTING: Three ICUs in a 1,500-bed tertiary university hospital.

PATIENTS: From an overall cohort of 641 patients with venoarterial-extracorporeal membrane oxygenation support, the primary analysis was performed in 344 patients who had been successfully decannulated in order to reduce immortal time bias.

MEASUREMENTS AND MAIN RESULTS: Seventy-five patients (22%) were extubated during extracorporeal membrane oxygenation support and were subsequently decannulated alive. Forty-nine percent received noninvasive ventilation, and 25% had emergency reintubation for respiratory, neurologic, or hemodynamic reasons. Higher Simplified Acute Physiology Score II at admission (odds ratio, 0.97; 95% CI [0.95-0.99]; p = 0.008) was associated with a lower probability of extubation, whereas cannulation in cardiac surgery ICU (odds ratio, 3.14; 95% CI [1.21-8.14]; p = 0.018) was associated with an increased probability. Baseline characteristics were well balanced after propensity score overlap weighting. The number of ICU-free days within 30 days of extracorporeal membrane oxygenation decannulation was significantly higher among extubated patients compared with nonextubated patients (22 d [11-26 d] vs 18 d [7-25 d], respectively; p = 0.036). There were no differences in other outcomes including ventilator-associated pneumonia (odds ratio, 0.96; 95% CI [0.51-1.82]; p = 0.90) and all-cause mortality within 30 days of extracorporeal membrane oxygenation decannulation (5% vs 17%; hazard ratio, 0.54; 95% CI [0.19-1.59]; p = 0.27).As a secondary analysis, outcomes were compared in the overall cohort of 641 venoarterial extracorporeal membrane oxygenation-supported patients. Results were consistent with the primary analysis as extubated patients had a higher number of ICU-free days (18 d [0-24 d] vs 0 d [0-18 d], respectively; < 0.001) and a lower risk of death within 30 days of extracorporeal membrane oxygenation cannulation (hazard ratio, 0.45; 95% CI [0.29-0.71]; p = 0.001).

CONCLUSIONS: Extubation during venoarterial-extracorporeal membrane oxygenation support is safe, feasible, and associated with greater ICU-free days.

# 静脉动脉体外膜肺氧合患者拔管的临床获益。

目的：虽然接受静脉动脉体外膜肺氧合治疗难治性心源性休克的患者通常接受机械通气支持，但尚不清楚停止镇静和拔管是否可改善结局。

设计：采用倾向评分重叠加权分析的回顾性队列研究。

单位：1500 张床位的一所三级大学医院的 3 间 ICU。

患者：在 641 例接受静脉 - 动脉 - 体外膜肺氧合支持的患者组成的整体队列中，对 344 例成功拔管的患者进行了主要分析，以减少永久时间偏倚。

测量结果和主要结果：75 例患者 (22%) 在体外膜肺氧合支持期间拔管，随后存活拔管。49% 接受无创通气，25% 因呼吸、神经或血流动力学原因紧急重新插管。入院时较高的简化急性生理学评分 II（比值比，0.97；95% CI [0.95-0.99]；p = 0.008）与拔管概率较低相关，而在心脏手术 ICU 插管（比值比，3.14；95% CI [1.21-8.14]；p = 0.018）与概率增加相关。倾向评分重叠加权后基线特征平衡良好。与非拔管患者相比，拔管患者体外膜氧合拔管 30 天内无 ICU 的天数显著更高（分别为 22 天 [11-26 天] 与 18 天 [7-25 天]；p = 0.036）。其他结局无差异，包括呼吸机相关性肺炎（比值比，0.96；95% CI [0.51-1.82]；p = 0.90）和体外膜氧合拔管后 30 天内的全因死亡率（5% vs 17%；风险比，0.54；95% CI [0.19-1.59]；p = 0.27）。As 次要分析，比较了 641 例静脉 - 动脉体外膜氧合支持患者的总体队列的结局。结果与主要分析一致，因为拔管患者的无 ICU 天数较多（分别为 18 天 [0-24 天] 与 0 天 [0-18 天]；< 0.001），体外膜氧合插管 30 天内的死亡风险较低（风险比，0.45；95% CI [0.29-0.71]；p = 0.001）。

结论：静脉动脉 - 体外膜肺氧合支持期间拔管安全、可行，并与更长的无 ICU 天数相关。关键词：Humans; Retrospective Studies; *Cardiac Surgical Procedures/adverse effects; *Extracorporeal Membrane Oxygenation/methods; Airway Extubation/adverse effects; Shock, Cardiogenic/etiology/therapy

# The Impact of a Machine Learning Early Warning Score on Hospital Mortality: A Multicenter Clinical Intervention Trial.

4:e413-e414. DOI:10.1097/CCM.0000000000005492

Abstract:

OBJECTIVES: To determine the impact of a machine learning early warning risk score, electronic Cardiac Arrest Risk Triage (eCART), on mortality for elevated-risk adult inpatients.

DESIGN: A pragmatic pre- and post-intervention study conducted over the same 10-month period in 2 consecutive years.

SETTING: Four-hospital community-academic health system.

PATIENTS: All adult patients admitted to a medical-surgical ward.

INTERVENTIONS: During the baseline period, clinicians were blinded to eCART scores. During the intervention period, scores were presented to providers. Scores greater than or equal to 95th percentile were designated high risk prompting a physician assessment for ICU admission. Scores between the 89th and 95th percentiles were designated intermediate risk, triggering a nurse-directed workflow that included measuring vital signs every 2 hours and contacting a physician to review the treatment plan.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was all-cause inhospital mortality. Secondary measures included vital sign assessment within 2 hours, ICU transfer rate, and time to ICU transfer. A total of 60,261 patients were admitted during the study period, of which 6,681 (11.1%) met inclusion criteria (baseline period n = 3,191, intervention period n = 3,490). The intervention period was associated with a significant decrease in hospital mortality for the main cohort (8.8% vs 13.9%; p < 0.0001; adjusted odds ratio [OR], 0.60 [95% CI, 0.52-0.71]). A significant decrease in mortality was also seen for the average-risk cohort not subject to the intervention (0.49% vs 0.26%; p < 0.05; adjusted OR, 0.53 [95% CI, 0.41-0.74]). In subgroup analysis, the benefit was seen in both high- (17.9% vs 23.9%; p = 0.001) and intermediate-risk (2.0% vs 4.0 %; p = 0.005) patients. The intervention period was also associated with a significant increase in ICU transfers, decrease in time to ICU transfer, and increase in vital sign reassessment within 2 hours.

CONCLUSIONS: Implementation of a machine learning early warning score-driven protocol was associated with reduced inhospital mortality, likely driven by earlier and more frequent ICU transfer.

# 机器学习早期警告评分对医院死亡率的影响：一项多中心临床干预试验。

目的：确定机器学习早期预警风险评分，电子心脏骤停风险分级 (eCART) 对高危成人住院患者死亡率的影响。

设计：在连续 2 年的相同 10 个月期间进行的实用干预前和干预后研究。

单位：四医院社区 - 医疗卫生系统。

患者：所有入住内外科病房的成年患者。

干预：基线期间，临床医生对 eCART 评分不知情。在干预期间，将评分提供给提供者。评分大于或等于第 95 百分位数被指定为高风险，提示医生进行 ICU 入院评估。第 89 百分位数和第 95 百分位数之间的评分被指定为中等风险，触发了护士指导的工作流程，包括每 2 小时测量一次生命体征，并联系医生审查治疗计划。

测量和主要结果：主要结局为全因住院死亡率。次要指标包括 2 小时内生命体征评估、转 ICU 率和转 ICU 时间。研究期间共有 60,261 例患者入院，其中 6,681 例 (11.1%) 符合入选标准（基线期 n = 3,191，干预期 n = 3,490）。对于主要队列，介入期与住院死亡率的显著降低相关（8.8% vs 13.9%；p < 0.0001；校正比值比 [OR]，0.60 [95% CI，0.52-0.71]）。在未接受干预的平均风险队列中也观察到死亡率显著降低（0.49% vs 0.26%；p < 0.05；校正 OR，0.53 [95% CI，0.41-0.74]）。在亚组分析中，高危 (17.9% vs 23.9%；p = 0.001) 和中危 (2.0% vs 4.0%；p = 0.005) 患者均可见获益。干预期间也与 ICU 转诊显著增加、至 ICU 转诊时间减少和 2 小时内生命体征再评估增加相关。

结论：实施机器学习早期预警评分驱动方案与住院死亡率降低相关，这可能是由于早期和更频繁的 ICU 转移所致。

# Executive Summary: Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock 2021: Erratum.

4:e409-e410. DOI:10.1097/CCM.0000000000005457

DOI: 10.1097/CCM.0000000000005513

# The authors reply., Spinella, Philip C.

# Executive Summary: Surviving Sepsis Campaign: International Guidelines for the Management of Sepsis and Septic Shock 2021: Erratum.

# The authors reply.

4:e413-e414. DOI:10.1097/CCM.0000000000005513

# The authors reply.

4:e407-e408. DOI:10.1097/CCM.0000000000005421

# Bringing Hidden Biases Into Light: Comments on an Observational Study on the Use of Antifibrinolytics for Pediatric Patients With Life-Threatening Hemorrhage.

# 揭示隐藏的偏倚：关于对危及生命的出血儿科患者使用抗纤溶药物的观察性研究的评论。

关键词：Humans; Child; *Antifibrinolytic Agents/therapeutic use; Bias; Hemorrhage/chemically induced; Platelet Transfusion

# The authors reply., Domecq, Juan Pablo

4:e406-e407. DOI:10.1097/CCM.0000000000005456

# 作者回复。

# Optimal Evidence Grading of Simultaneous Use of Hypertonic Saline and Furosemide for Fluid Overload.

4:e405-e406. DOI:10.1097/CCM.0000000000005419

关键词：Humans; *Heart Failure; *Water-Electrolyte Imbalance; Diuretics/therapeutic use; Furosemide/therapeutic use; Saline Solution, Hypertonic/therapeutic use

# The authors reply.

4:e403-e404. DOI:10.1097/CCM.0000000000005455

# 作者回复。

# Early Vasopressor Initiation Increases Mortality in Patients With Septic Shock: Less Intensive Intervention or More Critically Ill Patients?

4:e402-e403. DOI:10.1097/CCM.0000000000005418

# 早期血管加压药治疗增加感染性休克患者的死亡率：强化干预较少或危重患者更多？

关键词：Humans; Intensive Care Units; Critical Illness/therapy; Vasoconstrictor Agents/therapeutic use; *Shock, Septic/drug therapy/mortality

# The authors reply., Lee, Hong Yeul

4:e400-e402. DOI:10.1097/CCM.0000000000005454

# 作者回复。

# How Should We Use Frailty Evaluation for Patients With Sepsis in the Clinical Practice?

4:e399-e400. DOI:10.1097/CCM.0000000000005417

# 在临床实践中，我们应该如何对败血症患者进行虚弱评估？

关键词：Humans; Hospital Mortality; *Frailty/diagnosis; *Sepsis/diagnosis/therapy

# Stand Alone Renal Doppler to Assess the Risk of Acute Kidney Injury Is Dead: Maybe It Is Time to Consider a Triumvirate?

4:719-721. DOI:10.1097/CCM.0000000000005438

# 独立的肾脏多普勒超声评估急性肾损伤的风险是死亡：也许是时候考虑三联疗法了？

关键词：Humans; Female; Male; Ultrasonography, Doppler; *Acute Kidney Injury/diagnostic imaging/etiology; Kidney/diagnostic imaging

# Vasopressor Therapy Early, or Vasopressors Later? Still an Important Question in Septic Shock., Chalfin, Donald B.

4:717-718. DOI:10.1097/CCM.0000000000005449

# 早期血管加压素治疗或后期血管加压素治疗？仍是感染性休克的重要问题。

关键词：Humans; Norepinephrine; *Shock, Septic/drug therapy; Vasoconstrictor Agents/therapeutic use

# New Movement in Sepsis Immunotherapeutics-A Role for Prokineticin 2?

4:714-716. DOI:10.1097/CCM.0000000000005375

# 败血症免疫治疗的新趋势 - 促动力药 2 的作用？

关键词：Humans; Signal Transduction; *Sepsis/therapy; *Neuropeptides

# Vasopressin: The Impact of Predatory Patents on a Captive ICU Marketplace., Peterson, Lars-Kristofer N.

4:711-714. DOI:10.1097/CCM.0000000000005348

# 血管加压素：捕食性专利对 ICU 捕捉市场的影响。

关键词：*Intensive Care Units; *Vasopressins/therapeutic use

# Early Multimodal Vasopressors-Are We Ready for It?, Wieruszewski, Patrick M.

4:705-708. DOI:10.1097/CCM.0000000000005344

# 早期多模式血管加压药 - 我们准备好了吗？

关键词：*Vasoconstrictor Agents/therapeutic use

# Is the Pao2/Fio2 Ratio in Acute Respiratory Distress Syndrome Another Source of Heterogeneity?, Rachoin, Jean-Sebastien

4:703-705. DOI:10.1097/CCM.0000000000005378

# Pao2/Fio2 比值在急性呼吸窘迫综合征中是否是异质性的另一个来源？

关键词：Humans; Oximetry; *Respiratory Distress Syndrome/therapy

# A Ventilator Mode Cannot Set Itself, Nor Can It Be Solely Responsible for Outcomes.

4:695-699. DOI:10.1097/CCM.0000000000005403

# 呼吸机模式无法自行设置，也无法完全应对结果负责。

关键词：Tidal Volume; *Ventilators, Mechanical

# To Withdraw or to Continue ICU Care: When Is it a Premature Question?

4:693-695. DOI:10.1097/CCM.0000000000005349

# 撤回或继续 ICU 治疗：何时为早产问题？

关键词：Humans; *Intensive Care Units; *Life Support Care

# Inflamed., Nyquist, Paul

4:691-693. DOI:10.1097/CCM.0000000000005293

# 炎症。

# Sepsis: The Gift That Keeps Giving.

4:689-691. DOI:10.1097/CCM.0000000000005381

# 败血症：给予患者的礼物。

关键词：Humans; Cognition; *Sepsis/therapy

# The Many Faces of Prediction Modeling in Critical Care.

4:687-689. DOI:10.1097/CCM.0000000000005409

# 重症监护中的多种预测模型。

关键词：Humans; *Critical Care

# Shining a Light on Diversity in Team Science.

4:685-687. DOI:10.1097/CCM.0000000000005292

# 为团队科学的多样性亮起一盏明灯。

关键词：*Interdisciplinary Research

# The authors reply.

4:e398-e399. DOI:10.1097/CCM.0000000000005453

# 作者回复。

# The authors reply., Chotalia, Minesh

4:e395-e396. DOI:10.1097/CCM.0000000000005452

# 作者回复。

# The authors reply.

4:e411-e412. DOI:10.1097/CCM.0000000000005458

# 作者回复。

# Use of Extracorporeal Membrane Oxygenation in Acutely Poisoned Pediatric Patients in United States: A Retrospective Analysis of the Extracorporeal Life Support Registry From 2003 to 2019.

4:655-664. DOI:10.1097/CCM.0000000000005436

Abstract:

OBJECTIVES: To describe the use of extracorporeal membrane oxygenation (ECMO) in the management of pediatric poisoning in the United States and to identify predictors of mortality.

DESIGN: Retrospective cohort study.

SETTING: Data reported to the Extracorporeal Life Support Organization by 76 U.S. ECMO centers from 2003 to 2019.

PATIENTS: Pediatric patients (0-18 yr) receiving ECMO for poisoning.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: During our study period, 86 cases of acute poisoning were identified and included in the analysis. The median age was 12.0 year and 52.9% were female. The most commonly reported substance exposures were hydrocarbon (n = 17; 19.8%), followed by chemical asphyxiants (n = 14; 16.3%), neuroactive agents (n = 14; 16.3%), opioid/analgesics (n = 13; 15.1%), and cardiovascular agents (n = 12; 14.0%). Single substance exposures were reported in 83.7% of the cases. The intention of the exposure was unknown in 65.1%, self-harm in 20.9% and 10.5% was unintentional exposure. Fifty-six patients (65.1%) survived. Venoarterial ECMO was used more frequently than venovenous ECMO, and its use increased significantly during the study period (p < 0.01).

A bimodal distribution of ECMO support was observed among two age groups: less than or equal to 3 years (n = 34) and 13-17 years (n = 41). Hemodynamic and metabolic parameters improved for all patients with ECMO. Persistent systolic hypotension, acidemia/metabolic acidosis, and elevated Pao2) after 24 hours of ECMO support were associated with mortality. Time from PICU admission to ECMO cannulation was not significantly different between survivors (24.0 hr; interquartile range [IQR], 11.0-58.0 hr) and nonsurvivors (30.5 hr; IQR, 10.0-60.2 hr; p = 0.58). ECMO duration and PICU length of stay were significantly longer in survivors than in nonsurvivors (139.5 vs 70.5 hr; p = 0.007 and 25.0 vs 4.0 d; p = 0.002, respectively).

CONCLUSIONS: ECMO may improve the hemodynamic and metabolic status of poisoned pediatric patients. Persistent hypotension, acidemia/acidosis, and elevated Pao2 after 24 hours of ECMO were associated with mortality.

# 体外膜肺氧合在美国急性中毒儿科患者中的应用：体外生命支持的回顾性分析登记研究（2003 年至 2019 年）。

目的：描述体外膜肺氧合 (ECMO) 在美国儿科中毒管理中的应用，并确定死亡率预测因素。

设计：回顾性队列研究。

设置：数据由 76 家美国 ECMO 中心报告给体外生命支持组织 2003 年至 2019 年。

患者：接受 ECMO 治疗的儿科患者（0-18 岁）中毒。

干预：无。

测量和主要结果：在我们的研究期间期间，确定了 86 例急性中毒病例并纳入分析中。中位年龄为 12.0 岁，52.9% 为女性。最常报告物质暴露是碳氢化合物 (n = 17；19.8%)，其次是化学品窒息药 (n = 14；16.3%)，神经活性药物 (n = 14；16.3%)，阿片类 / 镇痛药 (n = 13；15.1%) 和心血管药物 (n = 12；14.0%)。83.7% 的病例报告了单一物质暴露。目的 65.1% 的暴露未知，20.9% 的自我伤害和 10.5% 的意外伤害暴露量。56 例患者 (65.1%) 存活。更多使用静脉动脉 ECMO 经常高于静脉 - 静脉 ECMO，并且在研究阶段 (p < 0.01)。观察到 ECMO 支持的双峰分布两个年龄组中：小于或等于 3 岁 (n = 34) 和 13-17 岁（n = 41). 所有 ECMO 患者的血液动力学和代谢参数均有所改善。持续性收缩性低血压、酸血症 / 代谢性酸中毒和 Pao2）升高 ECMO 支持 24 小时后与死亡率相关。距离 PICU 的时间存活者之间的 ECMO 插管住院时间无显著差异（24.0 h；四分位距 [IQR]，11.0-58.0 h）和非存活者（30.5 h； IQR，10.0-60.2 h；p = 0.58）。ECMO 持续时间和 PICU 住院时间为存活者显著长于非存活者（139.5 vs 70.5 h；p = 0.007 和 25.0 vs 4.0 d；p = 0.002）。

结论：ECMO 可能改善中毒儿童患者的血液动力学和代谢状态。持续 ECMO 24 小时后出现低血压、酸血症 / 酸中毒和 Pao2 升高与死亡率相关。关键词：Humans; Female; Male; Oxygen; Retrospective Studies; Child; Registries; United States/epidemiology; *Extracorporeal Membrane Oxygenation/adverse effects; *Hypotension/epidemiology/etiology/therapy; *Poisons

# Concise Definitive Review for Reinitiation of Antidepressants, Antipsychotics, and Gabapentinoids in ICU Patients., Cucci, Michaelia D.

4:665-673. DOI:10.1097/CCM.0000000000005415

Abstract:

OBJECTIVE: Concise definitive review of the reinitiation of prior-to-admission neuropsychiatric medications (NPMs) in ICU patients.

DATA SOURCES: Available literature on PubMed and MEDLINE databases.

STUDY SELECTION: Available clinical trials and observational studies addressing the reinitiation of select NPMs (antidepressants, antipsychotics, and gabapentinoids) on various outcomes were included.

DATA EXTRACTION: Eligible studies were identified by authors, and recommendations were summarized.

DATA SYNTHESIS: Agitation and delirium are recognized as common complications of patients in the ICU. While there is literature that suggests patients can acutely withdraw from opioids, less data are known about withdrawal from NPM such as antidepressants, antipsychotics, and gabapentinoids. However, there is some literature that suggests reinitiating some NPMs may lead to reductions in agitation, delirium, and hospital and ICU length of stay.

CONCLUSIONS: Additional larger studies are needed to evaluate the safety and efficacy of reinitiation of select prior-to-admission NPM to prevent agitation and delirium in ICU patients. Multiple factors for NPM reinitiation should be considered, such as reason for admission, organ dysfunction, available route of administration to provide prior-to-admission NPM, concomitant additional medications for agitation and delirium, and safety of these medications for patients in the ICU.

# 对 ICU 患者重新开始抗抑郁药、抗精神病药和加巴喷丁治疗的简要确定性审查。

目的：对 ICU 患者重新开始使用入院前神经精神病药物 (NPM) 进行明确的简要审查。

数据来源：可用 PubMed 和 MEDLINE 数据库相关文献。

研究选择：可用的临床针对重新开始选定 NPM 的试验和观察性研究（抗抑郁药、抗精神病药和加巴喷丁类）对各种结局的影响为包括。

数据提取：由作者确定合格的研究，和总结了建议。

资料综合：躁动和谵妄是被公认为 ICU 患者的常见并发症。而有提示患者可紧急停用阿片类药物的文献，较少数据已知从 NPM 撤药，如抗抑郁药、抗精神病药和加巴喷丁类药物。然而，一些文献建议重新开始一些 NPM 可减少激越、谵妄以及住院和 ICU 时长的停留。

结论：需要更多的大型研究来评价安全性和重新开始特定的入院前 NPM 的有效性，以预防 ICU 患者的激越和谵妄。NPM 重新开始的多种因素应考虑，如入院原因、器官功能障碍、可用提供入院前 NPM 的给药途径，其他伴随治疗治疗激越和谵妄的药物，以及这些药物的安全性 ICU 患者。关键词：Humans; Intensive Care Units; Hospitalization; *Antipsychotic Agents/adverse effects; *Delirium/prevention & control; Antidepressive Agents/adverse effects

4:e396-e397. DOI:10.1097/CCM.0000000000005420

# COVID-19 相关急性呼吸窘迫综合征中右心室受累的病因特异性和预后影响。

关键词：Humans; Prognosis; *COVID-19/complications; *Respiratory Distress Syndrome/etiology; Heart Ventricles

# Proning Responder or Not? This Is the Question., Cinnella, Gilda

4:708-711. DOI:10.1097/CCM.0000000000005400

# 是否剪毛应答者？此为问题。

关键词：Prone Position; *Respiration, Artificial

# Phenotypic Characterization of Right Ventricular Dysfunction and Prognostication in COVID-19-Induced Acute Respiratory Distress Syndrome., Jha, Ajay Kumar

4:e393-e394. DOI:10.1097/CCM.0000000000005416

# COVID-19 诱导的急性呼吸窘迫综合征中右心室功能障碍和预后的表型特征。

关键词：Humans; *COVID-19/complications; *Respiratory Distress Syndrome/etiology; *Ventricular Dysfunction, Right/diagnostic imaging/etiology/physiopathology; Ventricular Function, Right

# Airway Pressure Release Ventilation in Acute Respiratory Failure Due to COVID-19: When One Door Closes., Ghosh, Auyon J.

4:e410-e411. DOI:10.1097/CCM.0000000000005422

# COVID-19 急性呼吸衰竭的气道压力释放通气：当单门关闭。

关键词：Humans; *COVID-19/complications; *Respiratory Insufficiency/etiology/therapy; *Respiratory Distress Syndrome/etiology/therapy; Continuous Positive Airway Pressure

# Performance of Doppler-Based Resistive Index and Semiquantitative Renal Perfusion in Predicting Persistent Acute Kidney Injury According to Operator Experience: Post Hoc Analysis of a Prospective Multicenter Study.

4:e361-e369. DOI:10.1097/CCM.0000000000005372

Abstract:

OBJECTIVES: The Doppler-based resistive index and semiquantitative evaluation of renal perfusion using color Doppler failed to discriminate renal recovery patterns in a recent study. The influence of operator experience on resistive index and semiquantitative evaluation of renal perfusion performances is however unknown. This study aimed at evaluating the performance of resistive index and semiquantitative evaluation of renal perfusion according to the operator experience to predict short-term renal prognosis in critically ill patients.

DESIGN: Preplanned ancillary analysis of a prospective multicenter cohort study.

SETTING: Seven ICUs.

PATIENTS: Unselected ICU patients.

INTERVENTION: Renal Doppler was performed at admission to the ICU. The diagnostic performance of resistive index and semiquantitative evaluation of renal perfusion to predict persistent acute kidney injury at day 3 was evaluated.

MAIN RESULTS: Overall, 371 patients were included, of whom 351 could be assessed for short-term renal recovery. Two thirds of the included patients had acute kidney injury (n = 233; 66.3%), of whom 136 had persistent acute kidney injury (58.4%). Overall performance in discriminating persistent acute kidney injury was however null with an area under the receiver operating characteristic curve less than 0.6 for both resistive index and semiquantitative evaluation of renal perfusion, and no difference across operator experience. A multivariate analysis using logistic regression with the center as a random effect adjusted on the operator experience showed no association between resistive index (odds ratio, 0.02 per international units (95% CI, 0.00-18.60 international units]) or semiquantitative evaluation of renal perfusion (odds ratio, 0.96 per international units [95% CI, 0.43-2.11 international units]) and persistent acute kidney injury. Similar results were obtained within subgroups of expert and nonexpert operators.

CONCLUSIONS: Doppler-based measurements performed by an expert or a nonexpert operator did not discriminate renal recovery patterns and neither modified the risk stratification of acute kidney injury persistence.

# 根据术者经验，多普勒阻力指数和半定量肾灌注在预测持续性急性肾损伤中的性能：前瞻性多中心研究的事后分析。

目的：在最近的一项研究中，使用彩色多普勒对肾脏灌注进行的多普勒阻力指数和半定量评价未能区分肾脏恢复模式。然而，操作人员经验对阻力指数和肾脏灌注性能半定量评估的影响未知。本研究旨在根据操作者经验评价阻力指数和肾脏灌注半定量评价预测重症患者短期肾脏预后的性能。

设计：前瞻性多中心队列研究的预先计划的辅助分析。

设置：7 个 ICU。

患者：未选择的 ICU 患者。

干预：入住 ICU 时进行肾脏多普勒超声。评价了阻力指数和肾脏灌注半定量评价预测第 3 天持续性急性肾损伤的诊断性能。

主要结果：总体而言，共纳入 371 例患者，其中 351 例可评估短期肾功能恢复。三分之二的纳入患者患有急性肾损伤 (n = 233；66.3%)，其中 136 例患有持续性急性肾损伤 (58.4%)。然而，鉴别持续性急性肾损伤的总体性能是无效的，对于阻力指数和肾脏灌注的半定量评估，受试者工作特征曲线下面积均小于 0.6，并且操作人员经验之间没有差异。使用 logistic 回归进行多变量分析，中心作为对操作人员经验进行调整的随机效应，结果显示阻力指数（比值比，0.02 / 国际单位（95% CI，0.00-18.60 国际单位））或肾脏灌注半定量评价（比值比，0.96 / 国际单位 [95% CI，0.43-2.11 国际单位]）和持续性急性肾损伤。在专家和非专家操作员亚组中获得了相似的结果。

结论：由专家或非专家操作人员进行的基于多普勒的测量没有区分肾脏恢复模式，也没有改变急性肾损伤持续性的风险分层。关键词：Humans; Perfusion; Female; Male; Prospective Studies; Cohort Studies; Vascular Resistance; Kidney/diagnostic imaging; *Acute Kidney Injury/diagnostic imaging

# Use of Antifibrinolytics in Pediatric Life-Threatening Hemorrhage: A Prospective Observational Multicenter Study.

4:e382-e392. DOI:10.1097/CCM.0000000000005383

Abstract:

OBJECTIVES: To assess the impact of antifibrinolytics in children with life-threatening hemorrhage.

DESIGN: Secondary analysis of the MAssive Transfusion epidemiology and outcomes In Children study dataset, a prospective observational study of children with life-threatening bleeding events.

SETTING: Twenty-four children's hospitals in the United States, Canada, and Italy.

PATIENTS: Children 0-17 years old who received greater than 40 mL/kg of total blood products over 6 hours or were transfused under activation of massive transfusion protocol. INTERVENTION/EXPOSURE: Children were compared according to receipt of antifibrinolytic medication (tranexamic acid or aminocaproic acid) during the bleeding event.

MEASUREMENTS AND MAIN RESULTS: Patient characteristics, medications administered, and clinical outcomes were analyzed using Cox proportional hazard and Kaplan-Meier survival analysis. The primary outcome was 24-hour mortality. Of 449 patients analyzed, median age was 7 years (2-15 yr), and 55% were male. The etiology of bleeding was 46% traumatic, 34% operative, and 20% medical. Twelve percent received antifibrinolytic medication during the bleeding event (n = 54 unique subjects; n = 18 epsilon aminocaproic acid, n = 35 tranexamic acid, and n = 1 both). The antifibrinolytic group was comparable with the nonantifibrinolytic group on baseline demographic and physiologic parameters; the antifibrinolytic group had longer massive transfusion protocol duration, received greater volume blood products, and received factor VII more frequently. In the antifibrinolytic group, there was significantly less 6-hour mortality overall (6% vs 17%; p = 0.04) and less 6-hour mortality due to hemorrhage (4% vs 14%; p = 0.04). After adjusting for age, bleeding etiology, Pediatric Risk of Mortality score, and plasma deficit, the antifibrinolytic group had decreased mortality at 6- and 24-hour postbleed (adjusted odds ratio, 0.29 [95% CI, 0.09-0.93]; p = 0.04 and adjusted odds ratio, 0.45 [95% CI, 0.21-0.98]; p = 0.04, respectively).

CONCLUSIONS: Administration of antifibrinolytic medications during the life-threatening event was independently associated with improved 6- and 24-hour survivals in bleeding children. Consideration should be given to use of antifibrinolytics in pediatric patients with life-threatening hemorrhage.

# 抗纤溶药物在危及生命的儿科出血中的应用：一项前瞻性、观察性、多中心研究。

目的：评估抗纤溶剂治疗危及生命的出血儿童的影响。

设计：MAssive 输血流行病学和结局的次要分析在儿童研究数据集中，对发生危及生命的出血事件的儿童进行的一项前瞻性观察性研究。

地点：美国、加拿大和意大利的 24 家儿童医院。

患者：接受大于 40 mL/kg 的总血制品超过 6 小时或在大量输血方案激活下进行输血的 0-17 岁儿童。干预 / 暴露：根据出血事件期间抗纤维蛋白溶解药物（氨甲环酸或氨基己酸）的使用情况，对儿童进行比较。

测量和主要结果：使用 Cox 比例风险和 Kaplan-Meier 生存分析对患者特征、给药和临床结局进行分析。主要结局为 24 小时死亡率。在分析的 449 例患者中，中位年龄为 7 岁（2-15 岁），55% 为男性。出血的病因包括 46% 创伤性出血、34% 手术性出血和 20% 药物性出血。12% 的患者在出血事件期间接受了抗纤维蛋白溶解药物（n = 54 例独特受试者；n = 18 例 ε- 氨基己酸，n = 35 例氨甲环酸，n = 1 例两者）。抗纤溶组的基线人口统计学和生理参数与非抗纤溶组相当；抗纤溶组的大量输血方案持续时间更长，接受的血液制品量更大，接受凝血因子 VII 的频率更高。在抗纤溶组，总体 6 小时死亡率显著降低 (6% vs 17%；p = 0.04)，出血导致的 6 小时死亡率降低 (4% vs 14%；p = 0.04)。校正年龄、出血病因、儿科死亡风险评分和血浆缺陷后，抗纤溶组出血后 6 和 24 小时的死亡率下降（校正比值比，0.29 [95% CI，0.09-0.93]；p = 0.04）。和调整后的比值比，0.45 [95% CI，0.21-0.98]；p = 0.04）。

结论：在危及生命的事件中给予抗纤溶药物与出血儿童 6 小时和 24 小时生存率的改善独立相关。在有危及生命出血的儿科患者中，应考虑使用抗纤溶剂。关键词：Humans; Female; Male; Prospective Studies; Adolescent; Child; Infant; Infant, Newborn; Child, Preschool; *Antifibrinolytic Agents/therapeutic use; *Tranexamic Acid/therapeutic use; Aminocaproic Acid/therapeutic use; Hemorrhage/drug therapy/epidemiology/etiology

# Prognostic Factors Associated With Development of Venous Thromboembolism in Critically Ill Patients-A Systematic Review and Meta-Analysis., Tran, Alexandre

4:e370-e381. DOI:10.1097/CCM.0000000000005382

Abstract:

OBJECTIVE: To identify prognostic factors for the development of venous thromboembolism in the ICU.

DATA SOURCES: We searched MEDLINE, EMBASE, and Cochrane CENTRAL from inception to March 1, 2021.

STUDY SELECTION: We included English-language studies describing prognostic factors associated with the development of venous thromboembolism among critically ill patients.

DATA EXTRACTION: Two authors performed data extraction and risk-of-bias assessment. We pooled adjusted odds ratios and adjusted hazard ratios for prognostic factors using random-effects model. We assessed risk of bias using the Quality in Prognosis Studies tool and certainty of evidence using the Grading of Recommendations, Assessment, Development and Evaluations approach.

DATA SYNTHESIS: We included 39 observational cohort studies involving 729,477 patients. Patient factors with high or moderate certainty of association with increased odds of venous thromboembolism include older age (adjusted odds ratio, 1.15; 95% CI, 1.02-1.29 per 10 yr), obesity (adjusted odds ratio, 1.25; 95% CI, 1.18-1.32), active malignancy (adjusted odds ratio, 1.70; 95% CI, 1.18-2.44), history of venous thromboembolism (adjusted odds ratio, 4.77; 95% CI, 3.42-6.65), and history of recent surgery (adjusted odds ratio, 1.77; 95% CI, 1.26-2.47). ICU-specific factors with high or moderate certainty of association with increased risk of venous thromboembolism include sepsis (adjusted odds ratio, 1.41; 95% CI, 1.12-1.78), lack of pharmacologic venous thromboembolism prophylaxis (adjusted odds ratio, 1.80; 95% CI, 1.14-2.84), central venous catheter (adjusted odds ratio, 2.93; 95% CI, 1.98-4.34), invasive mechanical ventilation (adjusted odds ratio, 1.74; 95% CI, 1.36-2.24), and use of vasoactive medication (adjusted odds ratio, 1.86; 95% CI, 1.23-2.81).

CONCLUSIONS: This meta-analysis provides quantitative summaries of the association between patient-specific and ICU-related prognostic factors and the risk of venous thromboembolism in the ICU. These findings provide the foundation for the development of a venous thromboembolism risk stratification tool for critically ill patients.

# 危重患者静脉血栓栓塞预后相关因素的系统评价和荟萃分析。

目的：确定 ICU 中发生静脉血栓栓塞的预后因素。

数据来源：我们检索了 MEDLINE、EMBASE 和 Cochrane CENTRAL，检索日期从开始至 2021 年 3 月 1 日。

研究选择：我们纳入了描述与重症患者发生静脉血栓栓塞相关的预后因素的英文研究。

数据提取：两位作者进行了数据提取和偏倚风险评估。我们使用随机效应模型汇总了预后因素的校正比值比和校正风险比。我们使用预后质量研究工具评估偏倚风险，使用推荐、评估、开发和评价方法分级评估证据的确定性。

资料综合：我们纳入了 39 项观察性队列研究，涉及 729,477 例患者。静脉血栓栓塞比值比升高相关的高度或中度确定的患者因素包括年龄较大（校正比值比，1.15；95% CI，1.02-1.29/10 岁）、肥胖（校正比值比，1.25；95% CI，1.18-1.32）、活动性恶性肿瘤（校正比值比，1.70；95% CI，1.18-2.44），静脉血栓栓塞病史（校正比值比，4.77；95% CI，3.42-6.65）和近期手术史（校正比值比，1.77；95% CI，1.26-2.47）。与静脉血栓栓塞风险增加有高度或中度相关性的 ICU 特异性因素包括脓毒症（调整后比值比，1.41；95% CI，1.12-1.78）、缺乏药物预防静脉血栓栓塞（调整后比值比，1.80；95% CI，1.14-2.84）、中心静脉导管（调整后比值比，2.93；95% CI，1.98-4.34），有创机械通气（校正比值比，1.74；95% CI，1.36-2.24）和血管活性药物的使用（校正比值比，1.86；95% CI，1.23-2.81）。

结论：本荟萃分析定量总结了患者特异性和 ICU 相关预后因素与 ICU 静脉血栓栓塞风险的相关性。这些结果为重症患者静脉血栓栓塞风险分层工具的开发提供了基础。关键词：Humans; Prognosis; Critical Illness; Anticoagulants/therapeutic use; *Central Venous Catheters/adverse effects; *Venous Thromboembolism/drug therapy/epidemiology/etiology

# The Influence of Hypercapnia and Atmospheric Pressure on the Pao2/Fio2 Ratio-Pathophysiologic Considerations, a Case Series, and Introduction of a Clinical Tool.

4:607-613. DOI:10.1097/CCM.0000000000005316

Abstract:

OBJECTIVES: The ratio between Pao2 and Fio2 is used as a marker for impaired oxygenation and acute respiratory distress syndrome classification. However, any discrepancy between Fio2 and o2 fraction in the alveolus affects the Pao2/Fio2 ratio. Correcting the Pao2/Fio2 ratios using the alveolar gas equation may result in an improved reflection of the pulmonary situation. This study investigates the difference between standard and corrected Pao2/Fio2 in magnitude, its correlation with the mortality of acute respiratory distress syndrome classification, and trends over time.

DESIGN: A register and a retrospective study combined with the development of a mathematical model to determine the difference between standard and corrected Pao2/Fio2 ratio for various levels of Paco2 and atmospheric pressure.

SETTING: ICU in a secondary hospital in The Netherlands.

PATIENTS: Patients admitted to the ICU for pneumonia or acute respiratory distress syndrome.

Retrospective cohort: March 1, 2020, till June 1, 2020 (n = 34).

MEASUREMENTS AND MAIN RESULTS: The register was used to determine the 7-day ICU mortality per acute respiratory distress syndrome classification based on the standard and corrected Pao2/Fio2 ratio. The retrospective dataset correlated the Paco2 with Pao2/Fio2 ratio over time in patients with assumed stable oxygenation. The model demonstrated an increased difference between the standard and corrected Pao2/Fio2 ratios by a lower Fio2 and atmospheric pressure and higher Pao2 and Paco2. Reclassification of severe acute respiratory distress syndrome resulted in an increase in mortality from 28.1% for standard Pao2/Fio2 to 30.6% for corrected Pao2/Fio2 ratios. Acute Physiology and Chronic Health Evaluation scores correlated better with 7-day ICU-mortality when corrected Pao2/Fio2 ratio was used for classification. For patients with Fio2 less than 50% (n = 55), change in Paco2 correlated with change in Pao2/Fio2 ratio (r = -0.388; p = 0.003).

INTERVENTIONS: A corrected Pao2/Fio2 ratio was calculated.

CONCLUSIONS: Correcting the Pao2/Fio2 ratio for the alveolar gas equation predominantly affects patients with high ratios between Pao2 and Fio2 and Paco2 and at low atmospheric pressure. Using the corrected Pao2/Fio2 ratio for acute respiratory distress syndrome classification results in improved correlation with the 7-day ICU mortality and increases generalization among acute respiratory distress syndrome studies. The authors provide a free, web-based tool.

# 高碳酸血症和大气压对 Pao2/Fio2 比值的影响 - 病理生理学考量，病例系列，并引入临床工具。

目的：Pao2 和 Fio2 的比值用作氧合受损和急性呼吸窘迫综合征分类的标志物。但是，肺泡中 Fio2 和 o2 分数的任何差异都会影响 Pao2/Fio2 比值。使用肺泡气体方程校正 Pao2/Fio2 比值可能会改善肺部情况的反映。本研究调查了标准和校正 Pao2/Fio2 的幅度差异、其与急性呼吸窘迫综合征分类的死亡率的相关性以及随时间的趋势。

设计：注册研究和回顾性研究结合数学模型的开发，确定不同 Paco2 和大气压水平的标准和校正 Pao2/Fio2 比值之间的差异。

背景：荷兰一家二级医院的 ICU。

患者：因肺炎或急性呼吸窘迫综合征入住 ICU 的患者。

注册队列：2010 年 1 月 1 日至 2020 年 3 月 1 日 (n = 1008)。

回顾性队列：2020 年 3 月 1 日至 2020 年 6 月 1 日 (n = 34)。

测量和主要结果：根据标准和校正的 Pao2/Fio2 比值，通过登记确定每个急性呼吸窘迫综合征分类的 7 天 ICU 死亡率。回顾性数据集在假定氧合稳定的患者中关联了 Paco2 与 Pao2/Fio2 比值随时间的变化。该模型显示，通过较低的 Fio2 和大气压以及较高的 Pao2 和 Paco2，标准和校正的 Pao2/Fio2 比率之间的差异增加。对严重急性呼吸窘迫综合征重新分类导致死亡率从标准 Pao2/Fio2 的 28.1% 增加至校正 Pao2/Fio2 比值的 30.6%。当使用校正的 Pao2/Fio2 比值进行分类时，急性生理学和慢性健康状况评分与 7 天 ICU 死亡率的相关性更好。对于 Fio2 小于 50% 的患者 (n = 55)，Paco2 变化与 Pao2/Fio2 比值变化相关 (r =-0.388；p = 0.003)。

干预：计算校正的 Pao2/Fio2 比值。

结论：针对肺泡气体方程校正 Pao2/Fio2 比值主要影响 Pao2 与 Fio2 和 Paco2 比值较高以及低气压的患者。在急性呼吸窘迫综合征研究中，使用校正的 Pao2/Fio2 比值进行急性呼吸窘迫综合征分类，结果改善了与 7 天 ICU 死亡率的相关性，并增加了普遍性。作者提供了一个免费的、基于网络的工具。关键词：Humans; Oxygen; Retrospective Studies; *Respiratory Distress Syndrome/therapy; *Hypercapnia; Atmospheric Pressure

# Differences and Similarities Among COVID-19 Patients Treated in Seven ICUs in Three Countries Within One Region: An Observational Cohort Study., Mesotten, Dieter

4:595-606. DOI:10.1097/CCM.0000000000005314

Abstract:

OBJECTIVES: To investigate healthcare system-driven variation in general characteristics, interventions, and outcomes in coronavirus disease 2019 (COVID-19) patients admitted to the ICU within one Western European region across three countries.

DESIGN: Multicenter observational cohort study.

SETTING: Seven ICUs in the Euregio Meuse-Rhine, one region across Belgium, The Netherlands, and Germany.

PATIENTS: Consecutive COVID-19 patients supported in the ICU during the first pandemic wave.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Baseline demographic and clinical characteristics, laboratory values, and outcome data were retrieved after ethical approval and data-sharing agreements. Descriptive statistics were performed to investigate country-related practice variation. From March 2, 2020, to August 12, 2020, 551 patients were admitted. Mean age was 65.4 ?± 11.2 years, and 29% were female. At admission, Acute Physiology and Chronic Health Evaluation II scores were 15.0 ?± 5.5, 16.8 ?± 5.5, and 15.8 ?± 5.3 (p = 0.002), and Sequential Organ Failure Assessment scores were 4.4 ?± 2.7, 7.4 ?± 2.2, and 7.7 ?± 3.2 (p < 0.001) in the Belgian, Dutch, and German parts of Euregio, respectively. The ICU mortality rate was 22%, 42%, and 44%, respectively (p < 0.001). Large differences were observed in the frequency of organ support, antimicrobial/inflammatory therapy application, and ICU capacity. Mixed-multivariable logistic regression analyses showed that differences in ICU mortality were independent of age, sex, disease severity, comorbidities, support strategies, therapies, and complications.

CONCLUSIONS: COVID-19 patients admitted to ICUs within one region, the Euregio Meuse-Rhine, differed significantly in general characteristics, applied interventions, and outcomes despite presumed genetic and socioeconomic background, admission diagnosis, access to international literature, and data collection are similar. Variances in healthcare systems' organization, particularly ICU capacity and admission criteria, combined with a rapidly spreading pandemic might be important drivers for the observed differences. Heterogeneity between patient groups but also healthcare systems should be presumed to interfere with outcomes in coronavirus disease 2019.

# 一个地区内三个国家中 7 个 ICU 治疗的 COVID-19 患者的差异和相似性：一项观察性队列研究。

目的：研究西欧地区三个国家 2019 年 (COVID-19) 期间入住 ICU 的冠状病毒病患者的卫生保健系统驱动的一般特征、干预措施和结局的变化。

设计：多中心观察性队列研究。

设置：Euregio Meuse-Rhine 的 7 间 ICU，比利时、荷兰和德国的一个地区。

患者：在第一次大流行期间，ICU 连续支持 19 例患者。

干预：无。

测量和主要结果：在伦理批准和数据共享协议后，检索基线人口统计学和临床特征、实验室检查值和结局数据。进行描述性统计以研究国家相关实践变化。2020 年 3 月 2 日至 2020 年 8 月 12 日，共收治 551 例患者。平均年龄为 65.4±11.2 岁，29% 为女性。入院时，比利时、荷兰和德国部分 Euregio 的急性生理学和慢性健康状况评分 II 评分分别为 15.0?±5.5、16.8?±5.5 和 15.8?±5.3 (p = 0.002)，序贯器官衰竭评估评分分别为 4.4?±2.7、7.4?±2.2 和 7.7?±3.2 (p < 0.001)。ICU 死亡率分别为 22%、42% 和 44%(p < 0.001)。观察到器官支持频率、抗微生物 / 炎症治疗应用和 ICU 容量有较大差异。混合多变量 logistic 回归分析显示，ICU 死亡率的差异与年龄、性别、疾病严重程度、合并症、支持策略、治疗和并发症无关。

结论：尽管假定遗传和社会经济背景、入院诊断、查阅国际文献和数据收集相似，但在一个地区 (Euregio Meuse-Rhine) 内入住 ICU 的 COVID-19 患者在一般特征、应用的干预措施和结局方面存在显著差异。卫生保健系统组织的差异，特别是 ICU 能力和入院标准，以及迅速蔓延的大流行可能是观察到差异的重要驱动因素。应假定患者组之间以及医疗保健系统之间的异质性干扰 2019 年冠状病毒疾病的结局。关键词：Humans; Treatment Outcome; Female; Male; Middle Aged; Aged; APACHE; Cohort Studies; Critical Care/*methods; Logistic Models; *Intensive Care Units/organization & administration/statistics & numerical data; COVID-19/mortality/*therapy; Europe/epidemiology; Patient Acuity; Patient Transfer

# Vasopressor Initiation Within 1 Hour of Fluid Loading Is Associated With Increased Mortality in Septic Shock Patients: Analysis of National Registry Data.

4:e351-e360. DOI:10.1097/CCM.0000000000005363

Abstract:

OBJECTIVES: To investigate whether administration of a vasopressor within 1 hour of first fluid loading affected mortality and organ dysfunction in septic shock patients.

DESIGN: Prospective, multicenter, observational study.

SETTING: Sixteen tertiary or university hospitals in the Republic of Korea.

PATIENTS: Patients with septic shock (n = 415) were classified into early and late groups according to whether the vasopressor was initiated within 1 hour of the first resuscitative fluid load. Early (n = 149) patients were 1:1 propensity matched to late (n = 149) patients.

INTERVENTIONS: None.

MEASUREMENT AND MAIN RESULTS: The median time from the initial fluid bolus to vasopressor was shorter in the early group (0.3 vs 2.3 hr). There was no significant difference in the fluid bolus volume within 6 hours (33.2 vs 35.9 mL/kg) between the groups. The Sequential Organ Failure Assessment score and lactate level on day 3 in the ICU were significantly higher in the early group than that in the late group (Sequential Organ Failure Assessment, 9.2 vs 7.7; lactate level, 2.8 vs 1.7 mmol/L). In multivariate Cox regression analyses, early vasopressor use was associated with a significant increase in the risk of 28-day mortality (hazard ratio, 1.83; 95% CI, 1.26-2.65).

CONCLUSIONS: Vasopressor initiation within 1 hour of fluid loading was associated with higher 28-day mortality in patients with septic shock.

# 在脓毒性休克患者中，液体负荷 1 小时内开始血管加压药治疗与死亡率增加相关：国家登记数据的分析。

目的：研究在首次液体负荷 1 小时内给予血管加压药是否影响感染性休克患者的死亡率和器官功能障碍。

设计：前瞻性、多中心、观察性研究。

单位：韩国的 16 家三级或大学医院。

患者：根据首次复苏液体负荷 1 小时内是否启动血管加压药，将感染性休克患者 (n = 415) 分为早期组和晚期组。早期 (n = 149) 患者与晚期 (n = 149) 患者的 1:1 倾向匹配。

干预：无。

测量和主要结果：早期组从初始液体推注至血管加压药的中位时间较短 (0.3 vs 2.3 h)。各组之间 6 小时内的液体推注量无显著差异 (33.2 vs 35.9 mL/kg)。ICU 第 3 天序贯器官衰竭评估评分和乳酸盐水平，早期组显著高于晚期组（序贯器官衰竭评估，9.2 vs 7.7；乳酸盐水平，2.8 vs 1.7 mmol/L）。在多变量 Cox 回归分析中，早期使用血管加压素与 28 天死亡风险显著增加相关（风险比，1.83；95% CI，1.26-2.65）。

结论：在脓毒性休克患者中，液体负荷 1 小时内启动血管加压药与 28 天死亡率较高相关。关键词：Humans; Prospective Studies; Registries; *Shock, Septic; Vasoconstrictor Agents/therapeutic use; Lactic Acid

# Association Between Vasopressin Rebranding and Utilization in Patients With Septic Shock., Sacha, Gretchen L.

4:644-654. DOI:10.1097/CCM.0000000000005305

Abstract:

OBJECTIVES: Vasopressin is suggested as an adjunct to norepinephrine in patients with septic shock. However, after vasopressin was rebranded in November 2014, its cost exponentially increased. Utilization patterns of vasopressin after its rebranding are unclear. The objective of this study was to determine if there is an association between the rebranding of vasopressin in November 2014 and its utilization in vasopressor-dependent patients with severe sepsis or septic shock.

DESIGN: Retrospective, multicenter, database study between January 2010 and March 2017.

SETTING: Premier Healthcare Database hospitals.

PATIENTS: Adult patients admitted to an ICU with severe sepsis or septic shock, who received at least one vasoactive agent for two or more calendar days were included.

INTERVENTIONS: The proportion of patients who received vasopressin and vasopressin cost was assessed before and after rebranding, and evaluated with segmented regression.

MEASUREMENTS AND MAIN RESULTS: Among 294,733 patients (mean age, 66 ?± 15 yr), 27.8% received vasopressin, and ICU mortality was 26.5%. The proportion of patients receiving vasopressin was higher after rebranding (31.2% postrebranding vs 25.8% prerebranding). Before vasopressin rebranding, the quarterly proportion of patients who received vasopressin had an increasing slope (prerebranding slope 0.41% [95% CI, 0.35-0.46%]), with no difference in slope detected after vasopressin rebranding (postrebranding slope, 0.47% [95% CI, 0.29-0.64%]). After vasopressin rebranding, mean vasopressin cost per patient was higher ($527 ?± 1,130 vs $77 ?± 160), and the quarterly slope of vasopressin cost was higher (change in slope $77.18 [95% CI, $75.73-78.61]). Total vasopressin billed cost postrebranding continually increased by ~$294,276 per quarter from less than $500,000 in Q4 2014 to over $3,000,000 in Q1 2017.

CONCLUSIONS: After vasopressin rebranding, utilization continued to increase quarterly despite a significant increase in vasopressin cost. Vasopressin appeared to have price inelastic demand in septic shock.

# 在感染性休克患者中血管加压素重塑和使用的相关性。

目的：血管加压素被建议用作脓毒性休克患者去甲肾上腺素的辅助治疗。然而，在 2014 年 11 月血管加压素被更名后，其成本呈指数增长。加压素品牌重塑后的使用模式尚不清楚。本研究的目的是确定 2014 年 11 月血管加压素重塑与其在伴有重度败血症或感染性休克的血管加压素依赖性患者中的使用是否相关。

设计：回顾性、多中心、数据库研究，2010 年 1 月至 2017 年 3 月。

设置：Premier Healthcare 数据库医院。

患者：因重度败血症或感染性休克入住 ICU 的成人患者，至少接受一种血管活性药物 2 天或以上。

干预：评估重塑品牌前后使用血管加压素和血管加压素费用的患者比例，并用分段回归进行评价。

测量值和主要结果：294,733 例患者（平均年龄，66 μm±15 岁）中，27.8% 接受血管加压素治疗，ICU 死亡率为 26.5%。重塑品牌后，接受血管加压素的患者比例较高（重塑品牌后 31.2% vs 重塑品牌前 25.8%）。在血管加压素重塑前，每季度接受血管加压素的患者比例斜率增加（重塑前斜率 0.41%[95% CI，0.35-0.46%]），血管加压素重塑后检测到斜率无差异（重塑后斜率 0.47%[95% CI，0.29-0.64%]）。血管加压素重塑后，每例患者的平均血管加压素成本较高（分别为 527 美元 ±1,130 和 77 美元 ±160），且血管加压素成本的季度斜率较高（斜率变化为 77.18 美元 [95% CI，75.73-78.61 美元]）。贴标后的血管加压素总成本每季度增加约 294,276 美元，从 2014 年第 4 季度的不足 500,000 美元增加至 2017 年第 1 季度的超过 3,000,000 美元。

结论：加压素重塑品牌后，尽管加压素成本显著增加，但每季度使用率仍持续增加。在脓毒性休克中，血管加压素似乎具有价格无弹性需求。关键词：Humans; Middle Aged; Aged; Aged, 80 and over; Retrospective Studies; *Shock, Septic; Vasoconstrictor Agents/therapeutic use; Norepinephrine/therapeutic use; Vasopressins/therapeutic use

# Influence of Geopolitics on Severity and Outcome in COVID-19.

4:700-702. DOI:10.1097/CCM.0000000000005325

# COVID-19 中地缘政治对严重程度和结局的影响。

关键词：Humans; *COVID-19

# Use of Airway Pressure Release Ventilation in Patients With Acute Respiratory Failure Due to COVID-19: Results of a Single-Center Randomized Controlled Trial., Ibarra-Estrada, Miguel ??

4:586-594. DOI:10.1097/CCM.0000000000005312

Abstract:

OBJECTIVES: Airway pressure release ventilation is a ventilatory mode characterized by a mandatory inverse inspiratory:expiratory ratio with a very short expiratory phase, aimed to avoid derecruitment and allow spontaneous breathing. Recent basic and clinical evidence suggests that this mode could be associated with improved outcomes in patients with acute respiratory distress syndrome. The aim of this study was to compare the outcomes between airway pressure release ventilation and traditional ventilation targeting low tidal volume, in patients with severe coronavirus disease 2019.

DESIGN: Single-center randomized controlled trial.

SETTING: ICU of a Mexican referral center dedicated to care of patients with confirmed diagnosis of coronavirus disease 2019.

PATIENTS: Ninety adult intubated patients with acute respiratory distress syndrome associated with severe coronavirus disease 2019.

INTERVENTIONS: Within 48 hours after intubation, patients were randomized to either receive ventilatory management with airway pressure release ventilation or continue low tidal volume ventilation.

MEASUREMENTS AND MAIN RESULTS: Forty-five patients in airway pressure release ventilation group and 45 in the low tidal volume group were included. Ventilator-free days were 3.7 (0-15) and 5.2 (0-19) in the airway pressure release ventilation and low tidal volume groups, respectively (p = 0.28). During the first 7 days, patients in airway pressure release ventilation had a higher Pao2/Fio2 (mean difference, 26 [95%CI, 13-38]; p < 0.001) and static compliance (mean difference, 3.7 mL/cm H2O [95% CI, 0.2-7.2]; p = 0.03), higher mean airway pressure (mean difference, 3.1 cm H2O [95% CI, 2.1-4.1]; p < 0.001), and higher tidal volume (mean difference, 0.76 mL/kg/predicted body weight [95% CI, 0.5-1.0]; p < 0.001). More patients in airway pressure release ventilation had transient severe hypercapnia, defined as an elevation of Pco2 at greater than or equal to 55 along with a pH less than 7.15 (42% vs 15%; p = 0.009); other outcomes were similar. Overall mortality was 69%, with no difference between the groups (78% in airway pressure release ventilation vs 60% in low tidal volume; p = 0.07).

CONCLUSIONS: In conclusion, when compared with low tidal volume, airway pressure release ventilation was not associated with more ventilator-free days or improvement in other relevant outcomes in patients with severe coronavirus disease 2019.

# COVID-19 急性呼吸衰竭患者中气道压力释放通气的使用：一项单中心随机对照试验的结果。

目的：气道压力释放通气是一种通气模式，其特征为强制的反向吸气：呼气比，呼气相极短，旨在避免去整流和允许自主呼吸。近期的基础和临床证据表明，这种模式可能与急性呼吸窘迫综合征患者的结局改善相关。本研究旨在比较 2019 年重症冠状病毒病患者中气道压力释放通气与传统低潮气量靶向通气的结局。

设计：单中心随机对照试验。

背景：2019 年墨西哥转诊中心 ICU，专门护理确诊为冠状病毒病的患者。

患者：2019 年 90 例严重冠状病毒疾病相关急性呼吸窘迫综合征成人插管患者。

干预：插管后 48 小时内，患者随机接受气道压力释放通气的通气管理或继续低潮气量通气。

测量和主要结果：气道压力释放通气组 45 例，低潮气量组 45 例。气道压力释放通气组和低潮气量组的无通气天数分别为 3.7 (0-15) 和 5.2 (0-19) 天 (p = 0.28)。在前 7 天，气道压力释放通气患者的 Pao2/Fio2（平均差异，26 [95% CI，13-38]；p < 0.001）和静态顺应性（平均差异，3.7 mL/cm H2O [95% CI，0.2-7.2]；p = 0.03）更高，平均气道压力（平均差异，3.1 cm H2O [95% CI，2.1-4.1]；p < 0.001）更高，潮气量较高（平均差异，0.76 mL/kg/ 预测体重 [95% CI，0.5-1.0]；p < 0.001）。气道压力释放通气组中有更多患者发生了一过性重度高碳酸血症，定义为 Pco2 升高≥55，且 pH 值 < 7.15 (42% vs 15%；p = 0.009)；其他结局相似。总体死亡率为 69%，组间无差异（气道压力释放通气为 78%，低潮气量为 60%；p = 0.07）。

结论：总之，与低潮气量相比，在 2019 年重度冠状病毒病患者中，气道压力释放通气与无呼吸机天数增加或其他相关结局改善无关。关键词：Humans; Female; Male; Middle Aged; Aged; Adult; Tidal Volume; Mexico; *Continuous Positive Airway Pressure; COVID-19/*complications/mortality; Respiration, Artificial/*methods; Respiratory Distress Syndrome/etiology/mortality/*therapy

# The Return on Investment of a Province-Wide Quality Improvement Initiative for Reducing In-Hospital Sepsis Rates and Mortality in British Columbia, Canada., Khowaja, Asif Raza

4:e340-e350. DOI:10.1097/CCM.0000000000005353

Abstract:

OBJECTIVES: Sepsis is a life-threatening medical emergency. There is a paucity of information on whether quality improvement approaches reduce the in-hospital sepsis caseload or save lives and decrease the healthcare system and society's cost at the provincial/national levels. This study aimed to assess the outcomes and economic impact of a province-wide quality improvement initiative in Canada.

DESIGN: Retrospective population-based study with interrupted time series and return on investment analyses.

SETTING: The sepsis cases and deaths averted over time for British Columbia were calculated and compared with the rest of Canada (excluding Quebec and three territories).

PATIENTS: Aggregate data were obtained from the Canadian Institute for Health Information on risk-adjusted in-hospital sepsis rates and sepsis mortality in acute care sites across Canada.

INTERVENTIONS: In 2012, the British Columbia Sepsis Network was formed to reduce sepsis occurrence and mortality through education, knowledge translation, and quality improvement.

MEASUREMENTS AND MAIN RESULTS: A return on investment analysis compared the financial investment for the British Columbia Sepsis Network with the savings from averted sepsis occurrence and mortality. An estimated 981 sepsis cases and 172 deaths were averted in the post-British Columbia Sepsis Network period (2014-2018). The total cost, including the development and implementation of British Columbia Sepsis Network, was $449,962. Net savings due to cases averted after program costs were considered were $50.6 million in 2018. This translates into a return of $112.5 for every dollar invested.

CONCLUSIONS: British Columbia Sepsis Network appears to have averted a greater number of sepsis cases and deaths in British Columbia than the national average and yielded a positive return on investment. Our findings strengthen the policy argument for targeted quality improvement initiatives for sepsis care and provide a model of care for other provinces in Canada and elsewhere globally.

# 加拿大不列颠哥伦比亚省降低院内败血症率和死亡率的省级质量改进倡议的投资回报。

目的：败血症是一种危及生命的医学急症。关于质量改进方法是否可减少院内败血症病例负荷或挽救生命，以及降低省级 / 国家级医疗保健系统和社会成本的信息很少。本研究旨在评估加拿大省级质量改进倡议的结果和经济影响。

设计：回顾性人群研究，中断时间序列和投资回报分析。

设置：计算了不列颠哥伦比亚随时间推移避免的败血症病例和死亡，并与加拿大其他地区（不包括魁北克和三个地区）进行比较。

患者：从加拿大卫生信息研究所获得了加拿大急性护理中心经风险调整的院内败血症发生率和败血症死亡率的汇总数据。

干预：2012 年成立不列颠哥伦比亚败血症网络，通过教育、知识翻译和质量改进，减少败血症发生和死亡。

测量值和主要结果：投资回报分析比较了不列颠哥伦比亚败血症网络的财政投入与避免败血症发生和死亡产生的节约。在不列颠哥伦比亚败血症网络后期（2014-2018 年），估计避免了 981 例败血症病例和 172 例死亡。包括开发和实施不列颠哥伦比亚败血症网络在内的总费用为 449,962 美元。在 2018 年，考虑到项目费用后避免的病例净节省额为 5060 万美元。这意味着每投资一美元，回报就达到 112.5 美元。

结论：不列颠哥伦比亚省败血症网络在不列颠哥伦比亚省似乎避免了比全国平均水平更多的败血症病例和死亡，并产生了积极的投资回报率。我们的发现加强了败血症护理目标质量改进措施的政策论据，并为加拿大其他省份和全球其他地方提供了护理模式。关键词：Humans; Retrospective Studies; *Sepsis/therapy; *Quality Improvement; Hospitals; British Columbia/epidemiology

# Prone Position in COVID-19 and -COVID-19 Acute Respiratory Distress Syndrome: An International Multicenter Observational Comparative Study., Camporota, Luigi

4:633-643. DOI:10.1097/CCM.0000000000005354

Abstract:

OBJECTIVES: Prone position is used in acute respiratory distress syndrome and in coronavirus disease 2019 acute respiratory distress syndrome. However, it is unclear how responders may be identified and whether an oxygenation response improves outcome. The objective of this study was to quantify the response to prone position, describe the differences between coronavirus disease 2019 acute respiratory distress syndrome and acute respiratory distress syndrome, and explore variables associated with survival.

DESIGN: Retrospective, observational, multicenter, international cohort study.

SETTING: Seven ICUs in Italy, United Kingdom, and France.

PATIENTS: Three hundred seventy-six adults (220 coronavirus disease 2019 acute respiratory distress syndrome and 156 acute respiratory distress syndrome).

INTERVENTION: None.

MEASUREMENTS AND MAIN RESULTS: Preproning, a greater proportion of coronavirus disease 2019 acute respiratory distress syndrome patients had severe disease (53% vs 40%), worse Pao2/Fio2 (13.0 kPa [interquartile range, 10.5-15.5 kPa] vs 14.1 kPa [interquartile range, 10.5-18.6 kPa]; p = 0.017) but greater compliance (38 mL/cm H2O [interquartile range, 27-53 mL/cm H2O] vs 31 mL/cm H2O [interquartile range, 21-37 mL/cm H2O]; p < 0.001). Patients with coronavirus disease 2019 acute respiratory distress syndrome had a longer median time from intubation to prone position (2.0 d [interquartile range, 0.7-5.0 d] vs 1.0 d [interquartile range, 0.5-2.9 d]; p = 0.03). The proportion of responders, defined by an increase in Pao2/Fio2 greater than or equal to 2.67 kPa (20 mm Hg), upon proning, was similar between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome (79% vs 76%; p = 0.5). Responders had earlier prone position (1.4 d [interquartile range, 0.7-4.2 d] vs 2.5 d [interquartile range, 0.8-6.2 d]; p = 0.06)]. Prone position less than 24 hours from intubation achieved greater improvement in oxygenation (11 kPa [interquartile range, 4-21 kPa] vs 7 kPa [interquartile range, 2-13 kPa]; p = 0.002). The variables independently associated with the "responder" category were Pao2/Fio2 preproning (odds ratio, 0.89 kPa-1 [95% CI, 0.85-0.93 kPa-1]; p < 0.001) and interval between intubation and proning (odds ratio, 0.94 d-1 [95% CI, 0.89-0.99 d-1]; p = 0.019). The overall mortality was 45%, with no significant difference observed between acute respiratory distress syndrome and coronavirus disease 2019 acute respiratory distress syndrome. Variables independently associated with mortality included age (odds ratio, 1.03 yr-1 [95% CI, 1.01-1.05 yr-1]; p < 0.001); interval between hospital admission and proning (odds ratio, 1.04 d-1 [95% CI, 1.002-1.084 d-1]; p = 0.047); and change in Pao2/Fio2 on proning (odds ratio, 0.97 kPa-1 [95% CI, 0.95-0.99 kPa-1]; p = 0.002).

CONCLUSIONS: Prone position, particularly when delivered early, achieved a significant oxygenation response in ~80% of coronavirus disease 2019 acute respiratory distress syndrome, similar to acute respiratory distress syndrome. This response was independently associated with improved survival.

# COVID-19 和 - COVID-19 急性呼吸窘迫综合征的俯卧位：一项国际多中心观察性比较研究。

目的：仰卧位用于急性呼吸窘迫综合征和冠状病毒病 2019 年急性呼吸窘迫综合征。但是，尚不清楚如何识别应答者以及氧合反应是否改善结局。本研究的目的是量化俯卧位时的反应，描述 2019 年冠状病毒病急性呼吸窘迫综合征和急性呼吸窘迫综合征之间的差异，并探索与生存期相关的变量。

设计：回顾性、观察性、多中心、国际队列研究。

设置：意大利、英国和法国的 7 个 ICU。

患者：376 例成人（220 例冠状病毒病 2019 例急性呼吸窘迫综合征和 156 例急性呼吸窘迫综合征）。

干预：无。

测量值和主要结果：预测，更大比例的冠状病毒病 2019 急性呼吸窘迫综合征患者患有重度疾病 (53% vs 40%)，Pao2/Fio2 较差（13.0 kPa [四分位距，10.5-15.5 kPa] vs 14.1 kPa [四分位距，10.5-18.6 kPa]；p = 0.017），但依从性较高（38 mL/cm H2O [四分位距，27-53 mL/cm H2O] 对比 31 mL/cm H2O [四分位距，21-37 mL/cm H2O]；p < 0.001）。2019 年，冠状病毒疾病急性呼吸窘迫综合征患者从插管至俯卧位的中位时间较长（2.0 天 [四分位距，0.7-5.0 天] vs 1.0 天 [四分位距，0.5-2.9 天]；p = 0.03）。急性呼吸窘迫综合征和冠状病毒病 2019 年急性呼吸窘迫综合征之间应答者的比例相似 (79% vs 76%；p = 0.5)，应答者定义为减少时 Pao2/Fio2 升高≥2.67 kPa (20 mmHg)。应答者的俯卧位时间更早（1.4 天 [四分位距，0.7-4.2 天] vs 2.5 天 [四分位距，0.8-6.2 天]；p = 0.06）]。插管后不到 24 小时的俯卧位实现了更大的氧合改善（11 kPa [四分位距，4-21 kPa] vs 7kPa [四分位距，2-13 kPa]；p = 0.002）。与 “应答者” 类别独立相关的变量为 Pao2/Fio2 预扩增（比值比，0.89 kPa-1 [95% CI，0.85-0.93 kPa-1]；p < 0.001）和插管与预扩增之间的间隔（比值比，0.94 d-1 [95% CI，0.89-0.99 d-1]；p = 0.019）。总体死亡率为 45%，急性呼吸窘迫综合征与冠状病毒病 2019 急性呼吸窘迫综合征无显著差异。与死亡率独立相关的变量包括年龄（比值比，1.03-1 岁 [95% CI，1.01-1.05-1 岁]；p < 0.001）；入院与去毛时间间隔（比值比，1.04-1 岁 - 1 [95% CI，1.002-1.084-1 岁]；p = 0.047）；去毛时间 Pao2/Fio2 的变化（比值比，0.97 kPa-1 [95% CI，0.95-0.99 kPa-1]；p = 0.002）。

结论：仰卧位，尤其是早期分娩时，在 2019 年急性呼吸窘迫综合征（类似于急性呼吸窘迫综合征）中约 80% 的冠状病毒疾病患者获得了显著的氧合反应。该缓解与生存期改善独立相关。关键词：Humans; Female; Male; Middle Aged; Aged; Intensive Care Units; Retrospective Studies; Europe; Odds Ratio; Lung/physiopathology; Patient Positioning; Respiration, Artificial/*methods; *Prone Position; COVID-19/complications/physiopathology/*therapy; Respiratory Distress Syndrome/etiology/physiopathology/*therapy; Respiratory Function Tests

# Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock.

4:614-623. DOI:10.1097/CCM.0000000000005317

Abstract:

OBJECTIVES: To determine the association of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.

DESIGN: Retrospective, observational study using segmented and multivariable logistic regression to evaluate the associations of catecholamine dose, lactate concentration, and timing from shock onset at vasopressin initiation with in-hospital mortality.

SETTING: Multiple hospitals within the Cleveland Clinic Health System.

PATIENTS: Adult patients who met criteria for septic shock based on the U.S. Centers for Disease Control and Prevention Adult Sepsis Event definition.

INTERVENTIONS: All patients received continuous infusion vasopressin as an adjunct to catecholamine vasopressors.

MEASUREMENTS AND MAIN RESULTS: In total, 1,610 patients were included with a mean Acute Physiology and Chronic Health Evaluation III 109.0 ?± 35.1 and Sequential Organ Failure Assessment 14.0 ?± 3.5; 41% of patients survived the hospital admission. At the time of vasopressin initiation, patients had median (interquartile range) lactate concentration 3.9 mmol/L (2.3-7.2 mmol/L), norepinephrine-equivalent dose 25 ??g/min (18-40 ??g/min), and 5.3 hours (2.1-12.2 hr) elapsed since shock onset. The odds of in-hospital mortality increased 20.7% for every 10 ??g/min increase in norepinephrine-equivalent dose up to 60 ??g/min at the time of vasopressin initiation (adjusted odds ratio, 1.21 [95% CI, 1.09-1.34]), but no association was detected when the norepinephrine-equivalent dose exceeded 60 ??g/min (adjusted odds ratio, 0.96 [95% CI, 0.84-1.10]). There was a significant interaction between timing of vasopressin initiation and lactate concentration (p = 0.02) for the association with in-hospital mortality. A linear association between increasing in-hospital mortality was detected for increasing lactate concentration at the time of vasopressin initiation, but no association was detected for time elapsed from shock onset.

CONCLUSIONS: Higher norepinephrine-equivalent dose at vasopressin initiation and higher lactate concentration at vasopressin initiation were each associated higher in-hospital mortality in patients with septic shock who received vasopressin.

# 在感染性休克患者中，血管加压素开始治疗时儿茶酚胺剂量、乳酸盐和休克持续时间与死亡率的相关性。Association of Catecholamine Dose, Lactate, and Shock Duration at Vasopressin Initiation With Mortality in Patients With Septic Shock.

目的：确定儿茶酚胺剂量、乳酸盐浓度和血管加压素启动时休克发作时间与住院死亡率的相关性。

设计：采用分段和多变量逻辑回归的回顾性、观察性研究，以评价儿茶酚胺剂量、乳酸盐浓度和血管加压素启动时自休克开始的时间与住院死亡率的相关性。

单位：克利夫兰诊所卫生系统内的多家医院。

患者：根据美国疾病控制和预防中心成人败血症事件定义，符合感染性休克标准的成人患者。

干预：所有患者均接受血管加压素持续输注，作为儿茶酚胺类血管加压素的辅助治疗。

测量值和主要结果：共纳入 1610 例患者，平均急性生理学和慢性健康状况评分 III 为 109.0 μm±35.1，序贯器官衰竭评估为 14.0 μm±3.5；41% 的患者住院期间存活。在开始血管加压素治疗时，患者的中位（四分位距）乳酸盐浓度为 3.9 mmol/L (2.3-7.2 mmol/L)，去甲肾上腺素当量剂量为 25 μg/min (18-40 μg/min)，自休克发生后持续 5.3h (2.1-12.2 h)。血管加压素开始治疗时，去甲肾上腺素当量剂量每增加 10 μg/min，至 60 μg/min，住院死亡率增加 20.7%（调整后比值比，1.21 [95% CI，1.09-1.34]），但当去甲肾上腺素当量剂量超过 60 μg/min 时，未检测到相关性（调整后比值比，0.96 [95% CI，1.09-1.34]）。0.84-1.10]). 血管加压素启动时间和乳酸盐浓度之间有显著相互作用 (p = 0.02)，与住院死亡率相关。在血管加压素治疗开始时，发现乳酸盐浓度升高与住院死亡率增加之间存在线性关系，但未发现与休克发作时间相关。

结论：在血管加压素开始治疗时，较高的去甲肾上腺素等效剂量和血管加压素开始治疗时较高的乳酸盐浓度均与接受血管加压素治疗的感染性休克患者中较高的住院死亡率相关。关键词：Humans; Adult; Retrospective Studies; *Shock, Septic/drug therapy; Vasoconstrictor Agents/therapeutic use; Lactic Acid; Norepinephrine/therapeutic use; Vasopressins/therapeutic use; Catecholamines/therapeutic use

# Benchmarking Inpatient Mortality Using Electronic Medical Record Data: A Retrospective, Multicenter Analytical Observational Study.

4:543-553. DOI:10.1097/CCM.0000000000005301

Abstract:

OBJECTIVES: To develop a model to benchmark mortality in hospitalized patients using accessible electronic medical record data.

DESIGN: Univariate analysis and multivariable logistic regression were used to identify variables collected during the first 24 hours following admission to test for risk factors associated with the end point of hospital mortality. Models were built using specific diagnosis (International Classification of Diseases, 9th Edition or International Classification of Diseases, 10th Edition) captured at discharge, rather than admission diagnosis, which may be discordant. Variables were selected based, in part, on prior the Acute Physiology and Chronic Health Evaluation methodology and included primary diagnosis information plus three aggregated indices (physiology, comorbidity, and support). A Physiology Index was created using parsimonious nonlinear modeling of heart rate, mean arterial pressure, temperature, respiratory rate, hematocrit, platelet counts, and serum sodium. A Comorbidity Index incorporates new or ongoing diagnoses captured by the electronic medical record during the preceding year. A Support Index considered 10 interventions such as mechanical ventilation, selected IV drugs, and hemodialysis. Accuracy was determined using area under the receiver operating curve for discrimination, calibration curves, and modified Brier score for calibration.

SETTING AND PATIENTS: We used deidentified electronic medical record data from 74,434 adult inpatients (ICU and ward) at 15 hospitals from 2010 to 2013 to develop the mortality model and validated using data for additional 49,752 patients from the same 15 hospitals. A second revalidation was accomplished using data on 83,684 patients receiving care at six hospitals between 2014 and 2016. The model was also validated on a subset of patients with an ICU stay on day 1.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: This model uses physiology, comorbidity, and support indices, primary diagnosis, age, lowest Glasgow Coma Score, and elapsed time since hospital admission to predict hospital mortality. In the initial validation cohort, observed mortality was 4.04% versus predicted mortality 4.12% (Student t test, p = 0.37). In the revalidation using a different set of hospitals, predicted and observed mortality were 2.66% and 2.99%, respectively. Area under the receiver operating curve were 0.902 (0.895-0.909) and 0.884 (0.877-0.891), respectively, and calibration curves show a close relationship of observed and predicted mortalities. In the evaluation of the subset of ICU patients on day1, the area under the receiver operating curve was 0.87, with an observed mortality of 8.78% versus predicted mortality of 8.93% (Student t test, p = 0.52) and a standardized mortality ratio of 0.98 (0.932-1.034).

CONCLUSIONS: Variables considered by traditional ICU prognostic models accurately benchmark patient mortality for patients receiving care in multiple hospital locations, not only the ICU. Unlike Acute Physiology and Chronic Health Evaluation, this model relies on electronic medical record data alone and does not require personnel to collect the independent predictor variables. Assessing the model's utility for benchmarking hospital performance will require prospective testing in a larger representative sample of hospitals.

# 使用电子病历数据建立住院患者死亡率基准：一项回顾性、多中心、分析性观察性研究。

目的：使用可访问的电子病历数据开发一个以住院患者死亡率为基准的模型。

设计：使用单变量分析和多变量 logistic 回归来确定入院后最初 24 小时收集的变量，以检验与医院死亡率终点相关的风险因素。使用出院时采集的具体诊断（国际疾病分类第 9 版或国际疾病分类第 10 版）而不是入院诊断（可能不一致）建立模型。选择的变量部分基于之前的急性生理学和慢性健康状况评价方法，包括主要诊断信息加三个综合指数（生理学、合并症和支持）。使用心率、平均动脉压、体温、呼吸率、红细胞压积、血小板计数和血清钠的简约非线性模型创建生理学指数。合并症指数包括前一年通过电子病历采集的新的或正在进行的诊断。支持指数考虑了 10 种干预措施，如机械通气、选定 IV 药物和血液透析。使用受试者工作曲线下面积（用于鉴别）、校准曲线和改良 Brier 评分（用于校准）确定准确度。

设置和患者：我们使用了 2010-2013 年 15 家医院 74,434 例成人住院患者（ICU 和病房）的去身份识别电子病历数据，以开发死亡率模型，并使用来自相同 15 家医院的额外 49,752 例患者的数据进行验证。使用 2014 年至 2016 年在 6 家医院接受治疗的 83,684 例患者的数据完成了第二次再验证。该模型也在第 1 天留住 ICU 的患者子集中进行了验证。

干预：无。

测量和主要结果：该模型使用生理学、合并症和支持指数、初步诊断、年龄、最低 Glasgow 昏迷评分和自入院后经过的时间预测住院死亡率。在初始验证队列中，观察到的死亡率为 4.04%，预测死亡率为 4.12%（Student t 检验，p = 0.37）。在使用不同医院的再验证中，预测和观察死亡率分别为 2.66% 和 2.99%。受试者工作曲线下面积分别为 0.902 (0.895-0.909) 和 0.884 (0.877-0.891)，校准曲线显示观察到的和预测的死亡率之间存在密切的关系。在评估 ICU 患者亚组的第 1 天，受试者工作曲线下面积为 0.87，观察到的死亡率为 8.78%，而预测的死亡率为 8.93%（Student t 检验，p = 0.52），标准化死亡率比为 0.98 (0.932-1.034)。

结论：通过传统 ICU 预后模型考虑的变量准确地标定了在多个医院位置接受护理的患者的死亡率，而不仅仅是 ICU。与急性生理学和慢性健康评估不同，该模型仅依赖于电子病历数据，不需要人员收集独立预测变量。评估该模型对医院绩效的效用将需要在更大的代表性医院样本中进行前瞻性检验。关键词：Humans; Prospective Studies; Intensive Care Units; Adult; Retrospective Studies; Hospital Mortality; Inpatients; *Benchmarking; *Electronic Health Records

# Vascular Thrombosis in Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Multicenter Study.

4:624-632. DOI:10.1097/CCM.0000000000005322

Abstract:

OBJECTIVES: Coronavirus disease 2019 has been reported to be a prothrombotic condition; however, multicenter data comparing this with other viral pneumonias in those requiring extracorporeal membrane oxygenation are lacking. We conducted a multicenter study using whole-body CT to examine the prevalence, severity, and nature of vascular complications in coronavirus disease 2019 in comparison with patients with other viral pneumonias.

DESIGN: We analyzed whole-body CT scans for the presence of vascular thrombosis (defined as pulmonary artery thrombus, venous thrombus, systemic arterial thrombus, or end-organ infarct). The severity, distribution, and morphology of pulmonary artery thrombus were characterized. Competing risk cumulative incidence analysis was used to compare survival with discharge.

SETTING: Three centers of the English national extracorporeal membrane oxygenation service.

PATIENTS: Consecutive patients admitted with either coronavirus disease 2019 or noncoronavirus disease 2019 viral pneumonia admitted from January 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: One-hundred thirty-six patients (45.2 ± 10.6 yr old, 39/146 [27%] female) requiring extracorporeal membrane oxygenation support underwent whole-body CT scans at admission. Of these, 86 had coronavirus disease 2019 pneumonia, and 50 had noncoronavirus disease 2019 viral pneumonia. Vascular thrombosis was seen more often in patients with coronavirus disease 2019 (odds ratio, 12.9 [95% CI 4.5-36.8]). In those with coronavirus disease 2019, 57 (73%) demonstrated pulmonary artery thrombus or pulmonary perfusion defects. Eighty-two percent of thrombus exhibited emboli-like morphology. The location of pulmonary artery thrombus and parenchymal perfusion defects was only concordant in 30% of cases. The risk of mortality was higher in those with coronavirus disease 2019 compared with noncoronavirus disease 2019 pneumonia (χ2 = 3.94; p = 0.047). Mortality was no different in coronavirus disease 2019 patients with or without vascular thrombosis (χ2 = 0.44; p = 0.51).

CONCLUSIONS: In patients who received extracorporeal membrane oxygenation, coronavirus disease 2019 is associated with a higher prevalence of vascular thrombosis compared with noncoronavirus disease viral pneumonias. The pattern of pulmonary vascular changes suggests concurrent embolic disease and small vessel disease. Despite this, vascular thrombosis was not linked to poorer short-term prognosis in those with coronavirus disease 2019.

# 需要体外膜肺氧合的重度 COVID-19 中的血管血栓形成：一项多中心研究。Vascular Thrombosis in Severe COVID-19 Requiring Extracorporeal Membrane Oxygenation: A Multicenter Study.

目的：据报告，2019 年的冠状病毒病是一种血栓前疾病；然而，缺乏在需要体外膜肺氧合的患者中比较该疾病与其他病毒性肺炎的多中心数据。我们进行了一项多中心研究，使用全身 CT 检查 2019 年冠状病毒病中血管并发症的患病率、严重程度和性质，并与其他病毒性肺炎患者进行比较。

设计：我们分析了全身 CT 扫描是否存在血管血栓（定义为肺动脉血栓、静脉血栓、体循环动脉血栓或终末器官梗死）。描述肺动脉血栓的严重程度、分布和形态。使用竞争风险累积发生率分析比较出院时的生存率。

单位：英国国家体外膜肺氧合服务中心 3 家。

患者：2019 年 1 月至 2019 年 1 月期间，连续收治的冠状病毒病或非冠状病毒病 2019 病毒性肺炎患者。

干预：无。

测量值和主要结果：136 例（45.2 μm±10.6 岁，39/146 [27%] 例女性）需要体外膜肺氧合支持的患者在入院时接受了全身 CT 扫描。其中，2019 年有 86 例冠状病毒病肺炎，2019 年有 50 例非冠状病毒病病毒性肺炎。2019 年，在冠状病毒疾病患者中更常观察到血管血栓形成（比值比，12.9 [95% CI 4.5-36.8]）。2019 年，在冠状病毒疾病患者中，57 例 (73%) 表现出肺动脉血栓或肺灌注缺陷。82% 的血栓呈现栓子样形态。30% 的病例肺动脉血栓和实质灌注缺损的位置一致。2019 年，冠状病毒疾病患者的死亡风险高于 2019 年非冠状病毒疾病患者的肺炎风险 (χ2=3.94；p=0.047)。死亡率为 2019 例有或无血管疾病的冠状病毒病患者无差异血栓形成 (χ2=0.44；p=0.51)。

结论：在接受体外膜肺氧合，冠状病毒病 2019 相关与非冠状病毒病相比，血管血栓形成的患病率更高病毒性肺炎。肺血管改变的模式提示同时发生栓塞性疾病和小血管疾病。尽管如此，血管血栓形成仍 2019 年，与冠状病毒病患者较差的短期预后无关。关键词：Humans; Female; Male; Middle Aged; Prognosis; Adult; Tomography, X-Ray Computed; *Extracorporeal Membrane Oxygenation; COVID-19/*complications/therapy; Pneumonia, Viral/*complications/therapy; Thrombosis/diagnostic imaging/*etiology

# Identifying Prokineticin2 as a Novel Immunomodulatory Factor in Diagnosis and Treatment of Sepsis., Yu, Xiaoyan

4:674-684. DOI:10.1097/CCM.0000000000005335

Abstract:

OBJECTIVES: Sepsis remains a highly lethal disease, whereas the precise reasons for death remain poorly understood. Prokineticin2 is a secreted protein that regulates diverse biological processes. Whether prokineticin2 is beneficial or deleterious to sepsis and the underlying mechanisms remain unknown.

DESIGN: Prospective randomized animal investigation and in vitro studies.

SETTING: Research laboratory at a medical university hospital.

SUBJECTS: Prokineticin2 deficiency and wild-type C57BL/6 mice were used for in vivo studies; sepsis patients by Sepsis-3 definitions, patient controls, and healthy controls were used to obtain blood for in vitro studies.

INTERVENTIONS: Prokineticin2 concentrations were measured and analyzed in human septic patients, patient controls, and healthy individuals. The effects of prokineticin2 on sepsis-related survival, bacterial burden, organ injury, and inflammation were assessed in an animal model of cecal ligation and puncture-induced polymicrobial sepsis. In vitro cell models were also used to study the role of prokineticin2 on antibacterial response of macrophages.

MEASUREMENTS AND MAIN RESULTS: Prokineticin2 concentration is dramatically decreased in the patients with sepsis and septic shock compared with those of patient controls and healthy controls. Furthermore, the prokineticin2 concentration in these patients died of sepsis or septic shock is significantly lower than those survival patients with sepsis or septic shock, indicating the potential value of prokineticin2 in the diagnosis of sepsis and septic shock, as well as the potential value in predicting mortality in adult patients with sepsis and septic shock. In animal model, recombinant prokineticin2 administration protected against sepsis-related deaths in both heterozygous prokineticin2 deficient mice and wild-type mice and alleviated sepsis-induced multiple organ damage. In in vitro cell models, prokineticin2 enhanced the phagocytic and bactericidal functions of macrophage through signal transducers and activators of transcription 3 pathway which could be abolished by signal transducers and activators of transcription 3 inhibitors S3I-201. Depletion of macrophages reversed prokineticin2-mediated protection against polymicrobial sepsis.

CONCLUSIONS: This study elucidated a previously unrecognized role of prokineticin2 in clinical diagnosis and treatment of sepsis. The proof-of-concept study determined a central role of prokineticin2 in alleviating sepsis-induced death by regulation of macrophage function, which presents a new strategy for sepsis immunotherapy.

# 在脓毒症的诊断和治疗中确定 Prokineticin2 是一种新型的免疫调节因子。

目的：败血症仍是一种高度致死性疾病，而对死亡的确切原因仍知之甚少。Prokineticin2 是一种分泌蛋白，调节多种生物过程。prokineticin2 是否有益或对败血症有害，其潜在机制仍不清楚。

设计：前瞻性随机动物研究和体外研究。

设置：在医科大学医院的研究实验室。

受试者：趋化因子 2 体内研究使用缺陷型和野生型 C57BL/6 小鼠；败血症按照脓毒血症 - 3 定义的患者、患者对照和健康对照为用于获取血液以进行体外研究。

干预：促凝血酶原激酶 2 测定并分析了人类败血症患者中的浓度，患者对照组和健康个体。胃泌素 2 在脓毒症相关疾病中的作用在一项盲肠结扎和穿刺诱导多微生物败血症动物模型。In 体外细胞模型也被用于研究促凝血酶原激酶 2 对巨噬细胞的抗菌反应。

测量和主要结果：脓毒血症患者的胃泌素 2 浓度显著降低感染性休克与患者对照和健康对照相比。此外，这些患者的胃泌素 2 浓度死于败血症或感染性休克显著低于脓毒症生存患者或感染性休克，表明促胃动素 2 在以下疾病诊断中的潜在价值败血症和感染性休克，以及预测死亡率的潜在价值脓毒症和脓毒性休克成人患者。在动物模型中，重组在两项研究中，给予促凝血酶原激酶 2 均可预防败血症相关死亡杂合子 prokineticin2 缺陷小鼠和野生型小鼠，并减轻脓毒症引起的多器官损害。体外细胞模型，促动力药 2 通过信号增强巨噬细胞的吞噬和杀菌功能转录 3 通路的转导因子和激活子，可被信号转导因子和转录激活子 3 抑制剂 S3I-201。巨噬细胞的耗竭逆转了促凝血酶原激酶 2 介导的保护作用多微生物败血症。

结论：本研究阐明了之前在败血症的临床诊断和治疗中未认识到促胃动素 2 的作用。概念验证研究确定了 prokineticin2 在通过调节巨噬细胞功能减轻败血症诱导的死亡，提出了脓毒症免疫治疗的新策略。关键词：Humans; Prospective Studies; Animals; Disease Models, Animal; Mice, Inbred C57BL; Mice; *Sepsis; *Shock, Septic; Macrophages

# Immune Profiling Demonstrates a Common Immune Signature of Delayed Acquired Immunodeficiency in Patients With Various Etiologies of Severe Injury.

4:565-575. DOI:10.1097/CCM.0000000000005270

Abstract:

OBJECTIVES: The host response plays a central role in the pathophysiology of sepsis and severe injuries. So far, no study has comprehensively described the overtime changes of the injury-induced immune profile in a large cohort of critically ill patients with different etiologies.

DESIGN: Prospective observational cohort study.

SETTING: Adult ICU in a University Hospital in Lyon, France.

PATIENTS: Three hundred fifty-three septic, trauma, and surgical patients and 175 healthy volunteers were included in the REAnimation Low Immune Status Marker study.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Extensive immune profiling was performed by assessing cellular phenotypes and functions, protein, and messenger RNA levels at days 1-2, 3-4, and 5-7 after inclusion using a panel of 30 standardized immune markers. Using this immunomonitoring panel, no specificity in the immune profile was observed among septic, trauma, and surgical patients. This common injury-induced immune response was characterized by an initial adaptive (i.e., physiologic) response engaging all constituents of the immune system (pro- and anti-inflammatory cytokine releases, and innate and adaptive immune responses) but not associated with increased risk of secondary infections. In contrary, the persistence in a subgroup of patients of profound immune alterations at the end of the first week after admission was associated with increased risk of secondary infections independently of exposure to invasive devices. The combined monitoring of markers of pro-/anti-inflammatory, innate, and adaptive immune responses allowed a better enrichment of patients with risk of secondary infections in the selected population.

CONCLUSIONS: Using REAnimation Low Immune Status Marker immunomonitoring panel, we detected delayed injury-acquired immunodeficiency in a subgroup of severely injured patients independently of primary disease. Critically ill patients' immune status could be captured through the combined monitoring of a common panel of complementary markers of pro-/anti-inflammatory, innate, and adaptive immune responses. Such immune monitoring needs to be incorporated in larger study cohorts with more extensive immune surveillance to develop specific hypothesis allowing for identification of biological systems affecting altered immune function related to late infection in the setting of acute systemic injury.

# 免疫分析显示，在各种严重损伤病因的患者中，迟发性获得性免疫缺陷的常见免疫特征。

目的：宿主反应在败血症和重度损伤的病理生理学中发挥重要作用。到目前为止，尚无研究对一项大型队列研究中损伤诱导的免疫特征随时间的变化不同病因的重症患者。

设计：前瞻性观察性队列研究。

地点：里昂大学医院的成人 ICU，法国。

患者：353 例败血症、创伤和手术患者和 175 名健康志愿者被纳入 REAnimation Low Immune Status 标记物研究。

干预：无。

测量和主要结果：广泛通过评估细胞表型和功能进行免疫分析，入组后第 1-2、3-4 和 5-7 天的蛋白和信使 RNA 水平一组 30 种标准化免疫标志物。使用该免疫监测组合，否观察到败血症、创伤和外科手术之间免疫特征的特异性患者。这种常见损伤诱导的免疫反应的特征为初始适应性（即，生理学）反应包含所有的免疫系统（促炎和抗炎细胞因子释放，以及先天和适应性免疫应答），但与继发性风险增加无关感染。相反，在显著患者亚组中的持续性入院后第一周结束时的免疫改变与独立于侵袭性暴露的继发性感染风险增加器械。先天性免疫 / 抗炎标志物的联合监测，和适应性免疫应答使得有风险的患者得到更好的富集的选择人群中继发感染。

结论：使用 REAnimation Low Immune Status Marker 免疫监测 panel，我们检测到延迟重度损伤患者亚组中的损伤获得性免疫缺陷与原发疾病无关。重症患者的免疫状态可能为通过共同补充小组的联合监测采集促炎 / 抗炎、固有和适应性免疫应答的标志物。此类免疫监测需要纳入更大的研究队列和更多的广泛的免疫监视以产生允许以下情况的特定假设识别影响以下相关免疫功能改变的生物系统急性全身损伤背景下的晚期感染。关键词：Humans; Prospective Studies; Critical Illness; Biomarkers; *Coinfection/complications; *Sepsis/complications

# Diversity of Authors of Publications From the Canadian Critical Care Trials Group.

4:535-542. DOI:10.1097/CCM.0000000000005284

Abstract:

OBJECTIVES: Diverse perspectives improve the quality of scholarly initiatives. The demographic and professional diversity of scientists who contribute to critical care research and publications has not been described for the Canadian Critical Care Trials Group. Our objective was to describe the diversity of authors of publications from the Canadian Critical Care Trials Group.

DESIGN: We conducted a quantitative content analysis of peer-reviewed articles published on behalf of the Canadian Critical Care Trials Group.

SETTING: All peer-reviewed articles that were published on behalf of the Canadian Critical Care Trials Group between 1994 and October 2020.

SUBJECTS: For each publication, we recorded the study design, the number of authors, and national or international collaboration. For the lead author, the senior author, and each coauthor, we recorded the following facets of diversity: gender, professional role, medical discipline, geographic location, academic stage, and visible minority status.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We identified 354 eligible publications; 74% (263/354) reported observational cohort studies, randomized trials, and surveys. Of 4,246 authors, 1,205 were unique individuals. The mean (sd) number of authors per publication was 12 (7.1). Of all 4,246 authors, 37% were women, and 13.7% were members of a visible minority group. Of all lead or senior authors, 40% and 34% respectively were women; 15% of lead and 10% of senior authors were members of a visible minority group. Three-quarters (73%) of publications listed authors from more than one profession, and more than half (54%) listed authors from more than one medical discipline. Nearly half of publications (45%) listed authors who were early career faculty, 33% listed authors who were trainees, and 67% listed authors who were from visible minority groups. Authors from different provinces and from different countries were listed in 67% and 40% of publications, respectively.

CONCLUSIONS: Authors of Canadian Critical Care Trials Group publications are diverse with regard to demographic and professional characteristics.

# 来自加拿大重症监护试验组的出版物作者的多样性。

目的：多角度可提高学术倡议的质量。贡献于以下领域的科学家的人口统计学和专业多样性尚未描述加拿大的重症监护研究和出版物重症监护试验组。我们的目的是描述来自加拿大关键治疗试验组的出版物作者。

设计：我们对发表于代表加拿大重症医学试验组。

设置：所有同行评审代表加拿大重症医学试验组发表的文章 1994 年至 2020 年 10 月。

受试者：对于每份出版物，我们记录了研究设计、作者数量以及国家或国际合作。对于主要作者、资深作者和每名共同作者，我们记录了多样性的以下方面：性别、专业角色、医学学科，地理位置、学术阶段和明显的少数民族地位。

干预：无。

测量和主要结果：我们确定了 354 篇合格出版物；74% (263/354) 报告了观察性队列研究、随机试验和调查。在 4,246 位作者中，1,205 位是独特的个体。平均 (sd) 作者人数每个出版物为 12 (7.1)。在 4,246 名作者中，37% 为女性，13.7% 为是可见的少数群体的成员。在所有主要或资深作者中，40% 和 34% 为女性；15% 的主要作者和 10% 的资深作者为成员的可见少数群体。四分之三 (73%) 的出版物列出了作者来自一个以上职业，超过一半 (54%) 的上市作者来自更多职业超过医学学科。近半数的出版物 (45%) 列出了作者早期教员职业，33% 列出作者为培训者，67% 列出作者来自明显少数群体的作者。67% 和 40% 的出版物分别列出了来自不同省份和不同国家的作者。

结论：加拿大重症护理试验组出版物的作者在人口统计学和专业特征方面存在差异。关键词：Humans; Female; Male; Canada; Research Design; *Critical Care; *Authorship; Professional Role; Publications

# Risk of Dementia and Structural Brain Changes Following Nonneurological Infections During 9-Year Follow-Up.

4:554-564. DOI:10.1097/CCM.0000000000005313

Abstract:

OBJECTIVES: Given the strong association between systemic inflammation and cognitive decline, we aimed to determine whether nonneurologic infections are associated with accelerated cognitive decline and structural changes in the brain using pre- and post-infection neuropsychologic assessments and repeated brain MR images.

DESIGN: Additional analysis of the prospective observational Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort study.

SETTING: Single-center study at the Radboud university medical center, Nijmegen, The Netherlands, between January 2006 and September 2015.

PATIENTS: Five-hundred three participants (50-85 yr old) with cerebral small vessel disease were included and followed for 9 years.

MEASUREMENTS AND MAIN RESULTS: Participants underwent repeated cognitive measurements and brain MRI. Infectious events were collected. Sepsis episodes were analyzed, and additionally, patients were stratified in three groups: having had a severe infectious episode (e.g., sepsis or hospitalization for infection), a mild, or no infectious episode. Development of dementia, trajectories of cognition, and structural brain changes on MRI in the subsequent follow-up periods were compared between the groups. Complete infectious data were available from 331 patients (mean age 64 ?± 8 yr, 57% males). Twenty-nine participants (9%) suffered from a sepsis episode, 69 (21%) from a severe, 201 (61%) from a mild, and 61 (18%) had no infectious episode during follow-up. After correction for age, baseline cognition, and brain volume, each sepsis episode remained associated with an 82% increased risk to develop dementia within the follow-up period (hazard ratio, 1.82; 95% CI, 1.07-3.10; p = 0.027). Infections had no effect on the trajectory of structural changes to the brain after correction for baseline differences.

CONCLUSIONS: In this 9-year observational follow-up study, sepsis episodes were associated with subsequent development of dementia. Nonneurologic infections had no effect on the trajectory of structural cerebral changes.

# 9 年随访期间非神经系统感染后痴呆和脑结构性变化的风险。

目的：考虑到系统性炎症与认知衰退之间的强相关性，我们旨在使用感染前和感染后神经心理学评估和重复脑部 MR 成像来确定非神经系统感染是否与认知衰退加速和大脑结构变化相关。

设计：对前瞻性观察性 Radboud University Nijmegen 扩散张量和磁共振队列研究进行附加分析。

设置：2006 年 1 月至 2015 年 9 月在荷兰奈梅亨 Radboud 大学医学中心进行的单中心研究。

患者：纳入 503 例脑小血管疾病参与者（50-85 岁），并随访 9 年。

测量和主要结果：受试者接受重复认知测量和脑 MRI。收集感染事件。分析了败血症发作，此外，将患者分为 3 组：发生重度感染发作（例如，败血症或因感染住院）、轻度或无感染发作。比较了两组在后续随访期间痴呆的发生、认知轨迹和 MRI 显示的结构性大脑变化。获得了 331 例患者（平均年龄 64 岁 ±8 岁，57% 为男性）的完整感染数据。随访期间，29 例受试者 (9%) 发生脓毒症，69 例 (21%) 发生重度脓毒症，201 例 (61%) 发生轻度脓毒症，61 例 (18%) 未发生感染。校正年龄、基线认知和脑容量后，在随访期间，每一次脓毒症发作均与发生痴呆的风险增加 82% 相关（风险比，1.82；95% CI，1.07-3.10；p = 0.027）。校正基线差异后，感染对大脑结构变化轨迹无影响。

结论：在这项为期 9 年的观察随访研究中，败血症发作与随后发生的痴呆相关。非神经系统感染对大脑结构变化的轨迹没有影响。关键词：Humans; Female; Male; Middle Aged; Aged; Cohort Studies; Follow-Up Studies; *Sepsis/complications; *Cognitive Dysfunction/complications/etiology; *Dementia/epidemiology/etiology; Brain/diagnostic imaging/pathology; Magnetic Resonance Imaging/adverse effects

# The Association Between the Decision to Withdraw Life-Sustaining Therapy and Patient Mortality in U.K. ICUs.

4:576-585. DOI:10.1097/CCM.0000000000005306

Abstract:

OBJECTIVES: Differences in decisions to limit life-sustaining therapy are often supported by perceptions that patients receive unnecessary and expensive treatment which provide negligible survival benefit. However, the assumption behind those beliefs-that is, that life-sustaining therapy provides no significant marginal survival benefit-remains unproven. Our objective was to quantify the effects of variations in decisions to withdraw or withhold life-sustaining treatment on 180-day mortality in critically ill patients.

DESIGN: Retrospective observational cohort study of a national clinical database.

SETTING: Adult ICUs participating in the Intensive Care National Audit and Research Center Case Mix Program in the United Kingdom.

PATIENTS: Adult patients admitted to general ICUs between April 1, 2009, and March 31, 2016.

MEASUREMENTS AND MAIN RESULTS: During the study period, 795,721 patients were admitted to 247 ICUs across the United Kingdom. A decision to withdraw or withhold life-sustaining treatment was made for 92,327 patients (11.6%). A multilevel model approach was used to estimate ICU-level practice variation. The ICU-level practice variation was then used as an instrument to measure the effects of decision to withdraw or withhold life-sustaining treatment on 180-day mortality. The marginal population was estimated to be 5.9% of the total cohort. A decision to withdraw or withhold life-sustaining treatment was associated with a marginal increase in 180-day mortality of 25.6% (95% CI, 23.2-27.9%).

CONCLUSIONS: Decision to withdraw or withhold life-sustaining treatment in critically ill adults in the United Kingdom was associated with increased 180-day mortality in the marginal patients. The increased mortality from a decision to withdraw or withhold life-sustaining treatment in the marginal patient may be informative when establishing patients' preferences and evaluating the cost-effectiveness of intensive treatments.

# 英国 ICU 中停止维持生命治疗的决定与患者死亡率之间的相关性。

目的：限制维持生命治疗决策的差异通常得到以下观念的支持：患者接受不必要和昂贵的治疗，而这些治疗提供的生存获益可忽略不计。然而，这些信念背后的假设 - 即维持生命的治疗不能提供显著的边际生存获益 - 仍未证实。我们的目的是量化不同决定撤回或暂停维持生命治疗对重症患者 180 天死亡率的影响。

设计：国家临床数据库回顾性观察性队列研究。

设置：英国国家审计和研究中心重症监护病例混合项目的成人 ICU。

患者：2009 年 4 月 1 日至 2016 年 3 月 31 日期间入住普通 ICU 的成人患者。

测量和主要结果：在研究期间，英国共有 795,721 例患者入住 247 间 ICU。92,327 例患者 (11.6%) 决定停止或暂停维持生命治疗。使用多水平模型方法估计 ICU 水平实践变化。然后，将 ICU - 水平实践变化用作测量决定停止或暂停维持生命治疗对 180 天死亡率影响的工具。估计边缘人群占总队列的 5.9%。决定停止或暂停维持生命治疗与 180 天死亡率小幅增加 25.6%(95% CI，23.2-27.9%) 相关。

结论：在英国的危重成人中，决定停止或暂停维持生命的治疗与边缘患者中增加的 180 天死亡率相关。在确定患者的偏好和评估强化治疗的成本效益时，边缘患者决定停止或暂停维持生命治疗可能会增加死亡率。关键词：Humans; Adult; Retrospective Studies; *Intensive Care Units; *Critical Illness/therapy; Decision Making; Life Support Care; Withholding Treatment

# Hysteresis and Lung Recruitment in Acute Respiratory Distress Syndrome Patients: A CT Scan Study: Erratum.

3:e339. DOI:10.1097/CCM.0000000000005448

# The authors reply., Marshall, John C.

3:e337-e338. DOI:10.1097/CCM.0000000000005413

# Hysteresis and Lung Recruitment in Acute Respiratory Distress Syndrome Patients: A CT Scan Study: Erratum.

# The authors reply.

3:e339. DOI:10.1097/CCM.0000000000005448

# The authors reply.

3:e336-e337. DOI:10.1097/CCM.0000000000005370

# Altered Metabolic Resource Allocation May Play Important Role in Multiple Organ Dysfunction Syndrome., Qu, Hong Ping

# 代谢资源分配改变可能在多器官功能障碍综合征中发挥重要作用。

关键词：Humans; *Multiple Organ Failure/physiopathology; *Resource Allocation

# The authors reply.

3:e335-e336. DOI:10.1097/CCM.0000000000005406

# 作者回复。

# Look Back, Look Forward, but Use a Fresh Look.

3:e334. DOI:10.1097/CCM.0000000000005369

# 回顾、向前看，但是请使用新鲜的回顾。

# The author replies., Oh, Tak Kyu

3:e333. DOI:10.1097/CCM.0000000000005387

# 作者回复。

# How to Preserve Quality of Life Following Extracorporeal Membrane Oxygenation Explantation.

3:e332-e333. DOI:10.1097/CCM.0000000000005368

# 如何维持体外膜肺氧合移植后的生活质量。

关键词：Quality of Life; *Extracorporeal Membrane Oxygenation

# The authors reply., Rass, Verena

3:e331-e332. DOI:10.1097/CCM.0000000000005402

# 作者回复。

# The RAISE Score: A Possible Tool to Better Identify Subarachnoid Hemorrhage Patients Who Might Benefit From Early Tracheostomy?

3:e329-e330. DOI:10.1097/CCM.0000000000005367

# RAISE 评分：一种可能的工具，可更好地识别从早期气管造口术中获益的蛛网膜下腔出血患者？

关键词：Humans; Critical Care; Respiration, Artificial; *Tracheostomy; *Subarachnoid Hemorrhage/surgery

# The authors reply.

3:e328-e329. DOI:10.1097/CCM.0000000000005407

# 作者回复。

# Mischaracterizing the Data Regarding Hypertonic Saline., Lapham, David A.

3:e327-e328. DOI:10.1097/CCM.0000000000005366

# 对高渗盐水相关数据的错误描述。

关键词：*Saline Solution; Hypertonic/therapeutic use

# The authors reply.

3:e325-e326. DOI:10.1097/CCM.0000000000005410

# 作者回复。

# Assessing Risk Factors and Associated Adverse Outcomes of Acute Kidney Injury After Neonatal Cardiac Surgery.

3:e324-e325. DOI:10.1097/CCM.0000000000005365

# 评估新生儿心脏手术后急性肾损伤的风险因素和相关不良结局。

关键词：Humans; Risk Factors; Infant, Newborn; *Cardiac Surgical Procedures/adverse effects; *Acute Kidney Injury/epidemiology/etiology

# The authors reply., Duprey, Matthew S.

3:e323-e324. DOI:10.1097/CCM.0000000000005405

# 作者回复。

# Concerns With Association Between Incident Delirium Treatment With Haloperidol and Mortality in Critically Ill Adults.

3:e322-e323. DOI:10.1097/CCM.0000000000005358

# 危重病成人中氟哌啶醇治疗谵妄事件与死亡率之间相关性的担忧。

关键词：Humans; Intensive Care Units; Adult; *Delirium/drug therapy/mortality; *Haloperidol/therapeutic use; Critical Illness/mortality/therapy

# The authors reply.

3:e321-e322. DOI:10.1097/CCM.0000000000005412

# 作者回复。

# Why Clinicians Should Adopt Routine Neuroimaging After Extracorporeal Membrane Oxygenation.

3:528-531. DOI:10.1097/CCM.0000000000005401

# 为什么临床医生应在体外膜肺氧合术后采用常规神经影像学检查。

关键词：Neuroimaging; *Extracorporeal Membrane Oxygenation/methods

# The IMPACT of Transitional Care Management in Sepsis., Chatterjee, Arjun B.

3:525-527. DOI:10.1097/CCM.0000000000005336

# 败血症过渡期护理管理的影响。

关键词：Humans; *Sepsis/therapy; *Transitional Care; Health Services

# Taking a New SLANT on Postcardiac Arrest Prognostication?

3:519-522. DOI:10.1097/CCM.0000000000005341

# 是否在心脏骤停后预后中使用新的 SLANT？

关键词：Humans; *Cardiopulmonary Resuscitation; *Out-of-Hospital Cardiac Arrest/therapy

# Improving Sepsis Care: Is It Research? Promoting Clarity in a Zone of Confusion.

3:516-519. DOI:10.1097/CCM.0000000000005279

# 改善败血症治疗：是否为研究？促进意识模糊区域的清晰度。

关键词：Humans; *Sepsis/diagnosis/therapy; *Confusion

# Panacea or Perplexing?

3:513-516. DOI:10.1097/CCM.0000000000005278

# 万能药还是困扰？

# Tocilizumab: A Role for Biomarker-Directed Therapy?, Strich, Jeffrey R.

3:510-513. DOI:10.1097/CCM.0000000000005281

# 托珠单抗：生物标记物导向治疗的作用？

关键词：Biomarkers; *Antibodies, Monoclonal, Humanized/therapeutic use

# Time Out: More Observation Time to Allow for Stronger Science, Sharper Prognostic Tools, and Better Outcomes in Cardiac Arrest Survivors., Duarte, Siena

3:507-510. DOI:10.1097/CCM.0000000000005330

# 结束时间：留出更多的观察时间，以便更有力的科学、更清晰的预后工具和更好的心搏骤停幸存者结局。

关键词：Humans; Prognosis; Survivors; *Out-of-Hospital Cardiac Arrest/therapy

# Physical Rehabilitation in the ICU: Is It Worth the Effort?, Laghi, Franco

3:504-507. DOI:10.1097/CCM.0000000000005289

# ICU 中的身体康复：是否值得努力？

关键词：*Intensive Care Units; *Quality of Life

# Pediatric Acute Respiratory Distress Syndrome-Will We Be Able to Predict It and Eventually Prevent It?, Ciomartan, Tatiana C.

3:501-504. DOI:10.1097/CCM.0000000000005324

# 小儿急性呼吸窘迫综合征？？我们是否能够对其进行预测并最终预防？

关键词：Humans; Child; Infant, Newborn; *Respiratory Distress Syndrome, Newborn; *Respiratory Distress Syndrome/prevention & control

# Is Ventilator-Associated Pneumonia More Frequent in Patients With Coronavirus Disease 2019?

3:522-524. DOI:10.1097/CCM.0000000000005389

# 2019 年冠状病毒病患者的呼吸机相关性肺炎是否更常见？

关键词：Humans; Intensive Care Units; *COVID-19; SARS-CoV-2; Respiration, Artificial/adverse effects; *Pneumonia, Ventilator-Associated/epidemiology

# Tranexamic Acid in Gastrointestinal Bleeding: A Systematic Review and Meta-Analysis.

3:e313-e319. DOI:10.1097/CCM.0000000000005362

Abstract:

OBJECTIVES: Tranexamic acid is proposed as a treatment for gastrointestinal bleeding. The Haemorrhage Alleviation with Tranexamic Acid-Intestinal System trial evaluated extended-use (24 hr) high-dose tranexamic acid, prompting a reappraisal for tranexamic acid in gastrointestinal bleeding.

DATA SOURCES: We conducted a systematic review and meta-analysis of randomized controlled trials comparing tranexamic acid with usual care or placebo in adults with gastrointestinal bleeding. We searched MEDLINE, EMBASE, and CENTRAL (inception to September 2019).

DATA SELECTION: Two reviewers independently screened citations, extracted data, and assessed the risk of bias using the Cochrane risk of bias tool in duplicate. The main outcomes were mortality, bleeding, and adverse events.

DATA EXTRACTION: Studies were analyzed as high-dose IV tranexamic acid versus all other dosing strategies for tranexamic acid using fixed-effects models. We assessed certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach.

DATA SYNTHESIS: Five randomized controlled trials evaluated extended-use high-dose IV tranexamic acid, seven evaluating low-dose IV or enteral tranexamic acid. Extended-use high-dose IV tranexamic acid did not reduce mortality (relative risk, 0.98%; 95% CI, 0.88-1.09; I2 = 63%; high certainty) or bleeding (relative risk, 0.92; 95% CI, 0.82-1.04; p = 0.17 and absolute risk differences, -0.7%; 95% CI, -1.5 to 0.3; high certainty) but resulted in a small increase in deep venous thrombosis (relative risk, 2.01; 95% CI, 1.08-3.72; I2 = 0%), pulmonary embolism (relative risk, 1.78; 95% CI, 1.06-3.0; I2 = 0%), and seizure (relative risk, 1.73; 95% CI, 1.03-2.93) with high certainty. Low-dose IV/enteral tranexamic acid did not reduce mortality (relative risk, 0.62; 95% CI, 0.36-1.09; I2 = 0%) but did reduce risk of rebleeding (relative risk, 0.5; 95% CI, 0.33-0.75; I2 = 9%) and need for surgery (relative risk, 0.58; 95% CI, 0.38-0.88; I2 = 11%), with moderate certainty.

CONCLUSIONS: Extended-use high-dose IV tranexamic acid does not improve mortality or bleeding outcomes and increases adverse events. Low-dose/enteral tranexamic acid may be effective in reducing hemorrhage; more evidence is required to demonstrate its safety.

# 氨甲环酸在胃肠道出血中的应用：一项系统回顾和荟萃分析。

目的：氨甲环酸拟用于治疗胃肠道出血。使用氨甲环酸 - 肠系统缓解出血的试验评价了延长使用 (24 h) 高剂量氨甲环酸，促使对胃肠道出血中氨甲环酸进行重新评价。

资料来源：我们对比较氨甲环酸与常规护理或安慰剂治疗成人胃肠道出血的随机对照试验进行了系统回顾和荟萃分析。检索 MEDLINE、EMBASE 和 CENTRAL（开始至 2019 年 9 月）。

数据选择：两名审查员独立筛选引文、提取数据，并使用 Cochrane 偏倚风险工具重复评估偏倚风险。主要结局为死亡率、出血和不良事件。

数据提取：使用固定效应模型分析高剂量 IV 氨甲环酸与氨甲环酸所有其他给药策略的研究。我们使用推荐评估、开发和评价方法分级评估证据的确定性。

资料综合：5 项随机对照试验评价了扩大使用的高剂量 IV 氨甲环酸，7 项评价了低剂量 IV 或肠内氨甲环酸。延长使用大剂量 IV 氨甲环酸没有降低死亡率（相对风险，0.98%；95% CI，0.88-1.09；I2 = 63%；高度确定性）或出血率（相对风险，0.92；95% CI，0.82-1.04；p = 0.17 和绝对风险差异，-0.7%；95% CI，-1.5 至 0.3；高确定性），但导致深静脉血栓形成（相对风险，2.01；95% CI，1.08-3.72；I2 = 0%）、肺栓塞（相对风险，1.78；95% CI，1.06-3.0；I2 = 0%）和癫痫发作（相对风险，1.73；95% CI，1.03-2.93）小幅增加，具有高确定性。低剂量 IV / 肠内氨甲环酸没有降低死亡率（相对风险，0.62；95% CI，0.36-1.09；I2 = 0%），但是降低了再出血风险（相对风险，0.5；95% CI，0.33-0.75；I2 = 9%）和需要手术的风险（相对风险，0.58；95% CI，0.38-0.88；I2 = 11%），具有中度确定性。

结论：延长使用大剂量 IV 氨甲环酸不能改善死亡率或出血结局，并增加不良事件。低剂量 / 肠内氨甲环酸可能有效减少出血；需要更多证据证明其安全性。关键词：Humans; Antifibrinolytic Agents/*therapeutic use; Gastrointestinal Hemorrhage/*drug therapy/mortality; Length of Stay/statistics & numerical data; Secondary Prevention/statistics & numerical data; Tranexamic Acid/*therapeutic use

# The Coronavirus Disease 2019 Pandemic Impacts Burnout Syndrome Differently Among Multiprofessional Critical Care Clinicians-A Longitudinal Survey Study., Moll, Vanessa

3:440-448. DOI:10.1097/CCM.0000000000005265

Abstract:

OBJECTIVES: To determine the impact of coronavirus disease 2019 on burnout syndrome in the multiprofessional ICU team and to identify factors associated with burnout syndrome.

DESIGN: Longitudinal, cross-sectional survey.

SETTING: All adult ICUs within an academic health system.

SUBJECTS: Critical care nurses, advanced practice providers, physicians, respiratory therapists, pharmacists, social workers, and spiritual health workers were surveyed on burnout in 2017 and during the coronavirus disease 2019 pandemic in 2020.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Burnout syndrome and contributing factors were measured using the Maslach Burnout Inventory of Health and Human Service and Areas of Worklife Survey. Response rates were 46.5% (572 respondents) in 2017 and 49.9% (710 respondents) in 2020. The prevalence of burnout increased from 59% to 69% (p < 0.001). Nurses were disproportionately impacted, with the highest increase during the pandemic (58-72%; p < 0.0001) with increases in emotional exhaustion and depersonalization, and personal achievement decreases. In contrast, although burnout was high before and during coronavirus disease 2019 in all specialties, most professions had similar or lower burnout in 2020 as they had in 2017. Physicians had the lowest rates of burnout, measured at 51% and 58%, respectively. There was no difference in burnout between clinicians working in ICUs who treated coronavirus disease 2019 than those who did not (71% vs 67%; p = 0.26). Burnout significantly increased in females (71% vs 60%; p = 0.001) and was higher than in males during the pandemic (71% vs 60%; p = 0.01).

CONCLUSIONS: Burnout syndrome was common in all multiprofessional ICU team members prior to and increased substantially during the pandemic, independent of whether one treated coronavirus disease 2019 patients. Nurses had the highest prevalence of burnout during coronavirus disease 2019 and had the highest increase in burnout from the prepandemic baseline. Female clinicians were significantly more impacted by burnout than males. Different susceptibility to burnout syndrome may require profession-specific interventions as well as work system improvements.

# 2019 年冠状病毒病对多专业重症临床医生中倦怠综合征不同影响的纵向调查研究。

目的：确定 2019 年冠状病毒病对多专业 ICU 团队中倦怠综合征的影响，并确定与倦怠综合征相关的因素。

设计：纵向横断面调查。

设置：学术卫生系统内的所有成人 ICU。

受试者：2017 年和 2020 年冠状病毒病 2019 年大流行期间，调查了重症护士、高级执业医师、医生、呼吸治疗师、药剂师、社会工作者和精神卫生工作者的倦怠情况。

干预：无。

测量和主要结果：使用 Maslach 健康与人类服务部倦怠量表和工作生活调查领域对倦怠综合征和影响因素进行测量。2017 年应答率为 46.5%（572 名应答者），2020 年为 49.9%（710 名应答者）。倦怠的患病率从 59% 增加至 69%(p < 0.001)。护士受到不成比例的影响，在大流行期间增幅最高 (58-72%；p < 0.0001)，情绪衰竭和人格解体增加，个人成就降低。相比之下，虽然 2019 年之前和期间冠状病毒病在所有专业中倦怠程度均很高，但 2020 年大部分职业的倦怠程度与 2017 年相似或更低。医生的倦怠率最低，分别为 51% 和 58%。2019 年治疗冠状病毒病的 ICU 临床医生的倦怠与未治疗的临床医生无差异 (71% vs 67%；p = 0.26)。女性倦怠显著增加 (71% vs 60%；p = 0.001)，在大流行期间高于男性 (71% vs 60%；p = 0.01)。

结论：在流行之前，Burnout 综合征在所有多专业 ICU 团队成员中很常见，并在流行期间大幅增加，与是否治疗 2019 例冠状病毒病无关。2019 年，护士在冠状病毒疾病期间的倦怠患病率最高，且倦怠相对于大流行前基线的增幅最高。女性临床医生受倦怠的影响显著高于男性。对倦怠综合征的不同易感性可能需要职业特异性干预以及工作系统改进。关键词：Humans; Female; Male; Middle Aged; Adult; Longitudinal Studies; Prevalence; Pandemics; Cross-Sectional Studies; SARS-CoV-2; COVID-19/*epidemiology; Burnout, Professional/*epidemiology; Critical Care Nursing/statistics & numerical data; Critical Care/*statistics & numerical data; Intensive Care Units/*statistics & numerical data; Patient Care Team/statistics & numerical data; Personnel, Hospital/*psychology

# Association Between Urine Output and Mortality in Critically Ill Patients: A Machine Learning Approach., Heffernan, Aaron J.

3:e263-e271. DOI:10.1097/CCM.0000000000005310

Abstract:

OBJECTIVES: Current definitions of acute kidney injury use a urine output threshold of less than 0.5 mL/kg/hr, which have not been validated in the modern era. We aimed to determine the prognostic importance of urine output within the first 24 hours of admission to the ICU and to evaluate for variance between different admission diagnoses.

DESIGN: Retrospective cohort study.

SETTING: One-hundred eighty-three ICUs throughout Australia and New Zealand from 2006 to 2016.

PATIENTS: Patients greater than or equal to 16 years old who were admitted with curative intent who did not regularly receive dialysis. ICU readmissions during the same hospital admission and patients transferred from an external ICU were excluded.

MEASUREMENTS AND MAIN RESULTS: One hundred and sixty-one thousand nine hundred forty patients were included with a mean urine output of 1.05 mL/kg/hr and an overall in-hospital mortality of 7.8%. A urine output less than 0.47 mL/kg/hr was associated with increased unadjusted in-hospital mortality, which varied with admission diagnosis. A machine learning model (extreme gradient boosting) was trained to predict in-hospital mortality and examine interactions between urine output and survival. Low urine output was most strongly associated with mortality in postoperative cardiovascular patients, nonoperative gastrointestinal admissions, nonoperative renal/genitourinary admissions, and patients with sepsis.

CONCLUSIONS: Consistent with current definitions of acute kidney injury, a urine output threshold of less than 0.5 mL/kg/hr is modestly predictive of mortality in patients admitted to the ICU. The relative importance of urine output for predicting survival varies with admission diagnosis.

# 危重患者中尿量与死亡率之间的相关性：机器学习方法。

目的：急性肾损伤的当前定义采用小于 0.5 mL/kg/hr 的尿量阈值，这在现代尚未得到验证。我们旨在确定入 ICU 后最初 24 小时内尿量的预后重要性，并评估不同入院诊断之间的差异。

设计：回顾性队列研究。

设置：2006 年至 2016 年，澳大利亚和新西兰的 183 间 ICU。

患者：大于等于 16 岁，以治愈为目的入院，未定期接受透析的患者。排除在同一医院住院期间再次入住 ICU 和从外部 ICU 转出的患者。

测量值和主要结果：1611940 例患者的平均尿量为 1.05 mL/kg/hr，总体住院死亡率为 7.8%。尿量低于 0.47 mL/kg/hr 与未经调整的住院死亡率增加相关，住院诊断不同。培训了机器学习模型（极端梯度增强），以预测住院死亡率，并检查尿量和生存率之间的相互作用。在术后心血管疾病患者、非手术胃肠道疾病患者、非手术肾脏 / 泌尿生殖系统疾病患者和脓毒症患者中，尿量减少与死亡率的相关性最强。

结论：与当前急性肾损伤的定义一致，小于 0.5 mL/kg/hr 的尿排出量阈值可中度预测 ICU 住院患者的死亡率。尿量预测生存率的相对重要性因入院诊断而异。关键词：Humans; Female; Male; Middle Aged; Prognosis; Aged; Adult; Young Adult; Retrospective Studies; Australia; New Zealand; Hospital Mortality; *Intensive Care Units; Acute Kidney Injury/diagnosis/*mortality/*urine; Critical Illness/*mortality; Machine Learning

# Increased Incidence of Ventilator-Acquired Pneumonia in Coronavirus Disease 2019 Patients: A Multicentric Cohort Study.

3:449-459. DOI:10.1097/CCM.0000000000005297

Abstract:

OBJECTIVES: Little is known about the epidemiology of ventilator-acquired pneumonia among coronavirus disease 2019 patients such as incidence or etiological agents. Some studies suggest a higher risk of ventilator-associated pneumonia in this specific population.

DESIGN: Cohort exposed/nonexposed study among the REA-REZO surveillance network.

SETTING: Multicentric; ICUs in France.

PATIENTS: The coronavirus disease 2019 patients at admission were matched on the age, sex, center of inclusion, presence of antimicrobial therapy at admission, patient provenance, time from ICU admission to mechanical ventilation, and Simplified Acute Physiology Score II at admission to the patients included between 2016 and 2019 within the same surveillance network (1:1).

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The overall incidence of ventilator-associated pneumonia, the cumulative incidence, and hazard rate of the first and the second ventilator-associated pneumonia were estimated. In addition, the ventilator-associated pneumonia microbiological ecology and specific resistant pattern in coronavirus disease 2019 exposed and nonexposed patients were compared. Medication data were not collected. A total of 1,879 patients were included in each group. The overall incidence of ventilator-associated pneumonia was higher among coronavirus disease 2019 exposed patients (25.5; 95% CI [23.7-27.45] vs 15.4; 95% CI [13.7-17.3] ventilator-associated pneumonia per 1,000 ventilation days). The cumulative incidence was higher for the first and the second ventilator-associated pneumonia among the coronavirus disease 2019 exposed patients (respective Gray test p < 0.0001 and 0.0167). The microbiological ecology and resistance were comparable between groups with a predominance of Enterobacterales and nonfermenting Gram-negative bacteria. The documented resistance pattern was similar between groups, except for a lower rate of methicillin-resistant Staphylococcus aureus in the coronavirus disease 2019 exposed patient (6% vs 23%; p = 0.013).

CONCLUSIONS: There was a higher incidence of ventilator-associated pneumonia occurring among coronavirus disease 2019 patient compared with the general ICU population, with a similar microbiological ecology and resistance pattern.

# 2019 年冠状病毒疾病患者中呼吸机获得性肺炎的发病率增加：一项多中心队列研究。

目的：关于 2019 例冠状病毒疾病患者中呼吸机获得性肺炎的流行病学情况，如发病率或病原体，我们知之甚少。一些研究表明，在这一特定人群中，呼吸机相关性肺炎的风险较高。

设计：REA-REZO 监测网络中队列暴露 / 非暴露研究。

设置：多中心；法国的 ICU。

患者：2019 例患者入院时的冠状病毒病在年龄、性别、入选中心、入院时是否进行抗微生物治疗、患者来源、从 ICU 入院至机械通气的时间、和 2016 年至 2019 年期间同一监测网络内纳入的患者入院时的简化急性生理学评分 II (1:1)。

干预：无。

测量和主要结果：对呼吸机相关性肺炎的总发病率、第一和第二呼吸机相关性肺炎的累积发病率和危害率进行了估计。此外，比较了 2019 年暴露和未暴露患者中冠状病毒病的呼吸机相关性肺炎微生物学生态和特定耐药模式。未收集用药数据。每组共纳入 1879 例患者。2019 年暴露于冠状病毒病的患者中，呼吸机相关性肺炎的总发生率较高（25.5；95% CI [23.7-27.45] vs 15.4；95% CI [13.7-17.3]，呼吸机相关性肺炎 / 1000 个通气日）。2019 年暴露于冠状病毒病的患者中，首次和第二次呼吸机相关性肺炎的累积发生率较高（相应 Gray 检验 p < 0.0001 和 0.0167）。以肠杆菌科细菌和非发酵革兰氏阴性菌为主的治疗组之间的微生物学生态和耐药性相当。除了 2019 年暴露于冠状病毒疾病的患者中耐甲氧西林金黄色葡萄球菌的发生率较低 (6% vs 23%；p = 0.013) 外，记录的组间耐药模式相似。

结论：2019 例冠状病毒病患者发生呼吸机相关性肺炎的发生率高于普通 ICU 人群，具有相似的微生物学生态和耐药模式。关键词：Humans; Female; Male; Middle Aged; Prospective Studies; Aged; SARS-CoV-2; Drug Resistance, Bacterial; COVID-19/*epidemiology; Intensive Care Units/*statistics & numerical data; France/epidemiology; Pneumonia, Ventilator-Associated/*epidemiology/microbiology; Respiration, Artificial/*adverse effects; Simplified Acute Physiology Score

# Barotrauma in Coronavirus Disease 2019 Patients Undergoing Invasive Mechanical Ventilation: A Systematic Literature Review., Belletti, Alessandro

3:491-500. DOI:10.1097/CCM.0000000000005283

Abstract:

OBJECTIVE: There are concerns of a high barotrauma rate in coronavirus disease 2019 patients with acute respiratory distress syndrome receiving invasive mechanical ventilation. However, a few studies were published, and reported rates were highly variable. We performed a systematic literature review to identify rates of barotrauma, pneumothorax, and pneumomediastinum in coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation.

DATA SOURCE: PubMed and Scopus were searched for studies reporting barotrauma event rate in adult coronavirus disease 2019 patients receiving invasive mechanical ventilation.

STUDY SELECTION: We included all studies investigating adult patients with coronavirus disease 2019 acute respiratory distress syndrome requiring mechanical ventilation. Case reports, studies performed outside ICU setting, and pediatric studies were excluded. Two investigators independently screened and selected studies for inclusion.

DATA EXTRACTION: Two investigators abstracted data on study characteristics, rate of pneumothorax, pneumomediastinum and overall barotrauma events, and mortality. When available, data from noncoronavirus disease 2019 acute respiratory distress syndrome patients were also collected. Pooled estimates for barotrauma, pneumothorax, and pneumomediastinum were calculated.

DATA SYNTHESIS: A total of 13 studies with 1,814 invasively ventilated coronavirus disease 2019 patients and 493 noncoronavirus disease 2019 patients were included. A total of 266/1,814 patients (14.7%) had at least one barotrauma event (pooled estimates, 16.1% [95% CI, 11.8-20.4%]). Pneumothorax occurred in 132/1,435 patients (pooled estimates, 10.7%; 95% CI, 6.7-14.7%), whereas pneumomediastinum occurred in 162/1,432 patients (pooled estimates, 11.2%; 95% CI, 8.0-14.3%). Mortality in coronavirus disease 2019 patients who developed barotrauma was 111/198 patients (pooled estimates, 61.6%; 95% CI, 50.2-73.0%). In noncoronavirus disease 2019 acute respiratory distress syndrome patients, barotrauma occurred in 31/493 patients (6.3%; pooled estimates, 5.7%; 95% CI, -2.1% to 13.5%).

CONCLUSIONS: Barotrauma occurs in one out of six coronavirus disease 2019 acute respiratory distress syndrome patients receiving invasive mechanical ventilation and is associated with a mortality rate of about 60%. Barotrauma rate may be higher than noncoronavirus disease 2019 controls.

# 2019 例接受侵入性机械通气的冠状病毒疾病患者中的气压伤：一项系统性文献综述。

目的：在 2019 例接受有创机械通气的急性呼吸窘迫综合征患者中，存在冠状病毒疾病患者气压伤率较高的问题。但是，发表了几项研究，报告的发生率具有高度变异性。我们进行了系统性文献综述，以确定 2019 年接受有创机械通气的急性呼吸窘迫综合征患者中冠状病毒病的气压伤、气胸和纵隔气肿的发生率。

资料来源：检索 PubMed 和 Scopus 中 2019 例接受有创机械通气的成人冠状病毒病患者报告气压伤事件发生率的研究。

研究选择：我们纳入了所有研究冠状病毒病 2019 年急性呼吸窘迫综合征需要机械通气的成人患者的研究。排除了病例报告、在 ICU 外进行的研究和儿科研究。两名研究者独立筛选和选择研究纳入。

数据提取：两名研究者提取了关于研究特征、气胸、纵隔气肿和总体气压伤事件发生率以及死亡率的数据。当可用时，还收集了非冠状病毒病 2019 例急性呼吸窘迫综合征患者的数据。计算了气压伤、气胸和纵隔气肿的合并估计值。

资料综合：共纳入 13 项研究，1814 例侵入性通气的冠状病毒病 2019 例患者，493 例非冠状病毒病 2019 例患者。总计 266/1,814 例患者 (14.7%) 至少发生 1 起气压伤事件（汇总估计值，16.1%[95% CI，11.8-20.4%]）。132/1,435 例患者发生气胸（汇总估计值，10.7%；95% CI，6.7-14.7%），而 162/1,432 例患者发生纵隔气肿（汇总估计值，11.2%；95% CI，8.0-14.3%）。2019 年发生气压伤的冠状病毒疾病患者的死亡率为 111/198 例（合并估计值，61.6%；95% CI，50.2%）-73.0%). 在非冠状病毒病 2019 例急性呼吸窘迫综合征患者中，31/493 例患者发生气压伤（6.3%；汇总估计值，5.7%；95% CI，-2.1% 至 13.5%）。

结论：在 2019 例接受有创机械通气的急性呼吸窘迫综合征患者中，6 例冠状病毒病中 1 例发生气压伤，死亡率约为 60%。气压伤发生率可能高于非冠状病毒病 2019 对照组。关键词：Humans; SARS-CoV-2; COVID-19/mortality/*therapy; Respiration, Artificial/*adverse effects; Barotrauma/*etiology/mortality; Mediastinal Emphysema/*etiology/mortality; Pneumothorax/*etiology/mortality

# IV Vitamin C in Critically Ill Patients: A Systematic Review and Meta-Analysis.

3:e304-e312. DOI:10.1097/CCM.0000000000005320

Abstract:

OBJECTIVES: To conduct a systematic review and meta-analysis to evaluate the impact of IV vitamin C on outcomes in critically ill patients.

DATA SOURCES: Systematic search of MEDLINE, EMBASE, CINAHL, and the Cochrane Register of Controlled Trials.

STUDY SELECTION: Randomized controlled trials testing IV vitamin C in critically ill patients.

DATA ABSTRACTION: Two independent reviewers abstracted patient characteristics, treatment details, and clinical outcomes.

DATA SYNTHESIS: Fifteen studies involving 2,490 patients were identified. Compared with placebo, IV vitamin C administration is associated with a trend toward reduced overall mortality (relative risk, 0.87; 95% CI, 0.75-1.00; p = 0.06; test for heterogeneity I2 = 6%). High-dose IV vitamin C was associated with a significant reduction in overall mortality (relative risk, 0.70; 95% CI, 0.52-0.96; p = 0.03), whereas low-dose IV vitamin C had no effect (relative risk, 0.94; 95% CI, 0.79-1.07; p = 0.46; test for subgroup differences, p = 0.14). IV vitamin C monotherapy was associated with a significant reduction in overall mortality (relative risk, 0.64; 95% CI, 0.49-0.83; p = 0.006), whereas there was no effect with IV vitamin C combined therapy. No trial reported an increase in adverse events related to IV vitamin C.

CONCLUSIONS: IV vitamin C administration appears safe and may be associated with a trend toward reduction in overall mortality. High-dose IV vitamin C monotherapy may be associated with improved overall mortality, and further randomized controlled trials are warranted.

# 危重病患者静脉注射维生素 C：一项系统回顾和荟萃分析。

目的：实施一项系统性审查和荟萃分析，以评价 IV 维生素 C 对重症患者结局的影响。

数据来源：系统检索 MEDLINE、EMBASE、CINAHL 和 Cochrane 临床对照试验注册数据库。

研究选择：在重症患者中检验 IV 维生素 C 的随机对照试验。

数据摘要：两名独立的审查员摘录了患者特征、治疗细节和临床结局。

数据综合：确定了涉及 2490 例患者的 15 项研究。与安慰剂相比，IV 维生素 C 给药与总死亡率降低的趋势相关（相对风险，0.87；95% CI，0.75-1.00；p = 0.06；异质性检验 I2 = 6%）。高剂量 IV 维生素 C 与总死亡率显著降低相关（相对风险，0.70；95% CI，0.52-0.96；p = 0.03），而低剂量 IV 维生素 C 无影响（相对风险，0.94；95% CI，0.79-1.07；p = 0.46；亚组差异检验，p = 0.14）。IV 维生素 C 单药治疗与总死亡率显著降低相关（相对风险，0.64；95% CI，0.49-0.83；p = 0.006），而 IV 维生素 C 联合治疗无影响。没有试验报告与 IV 维生素 C 相关的不良事件增加。

结论：IV 维生素 C 给药似乎是安全的，并且可能与总死亡率降低的趋势有关。高剂量 IV 维生素 C 单药治疗可能与总死亡率改善相关，还需要进一步的随机对照试验。关键词：Humans; Treatment Outcome; Dose-Response Relationship, Drug; Critical Illness/*therapy; Antioxidants/*therapeutic use; Ascorbic Acid/*therapeutic use; Sepsis/*drug therapy/mortality

# The Effectiveness of High-Flow Nasal Cannula in Coronavirus Disease 2019 Pneumonia: A Retrospective Cohort Study.

3:e253-e262. DOI:10.1097/CCM.0000000000005309

Abstract:

OBJECTIVES: High-flow nasal cannula is widely used in acute hypoxemic respiratory failure due to coronavirus disease 2019, yet data regarding its effectiveness is lacking. More evidence is needed to guide patient selection, timing of high-flow nasal cannula initiation, and resource allocation. We aimed to assess time to discharge and time to death in severe coronavirus disease 2019 in patients treated with high-flow nasal cannula compared with matched controls. We also evaluated the ability of the respiratory rate-oxygenation ratio to predict progression to invasive mechanical ventilation.

DESIGN: Time-dependent propensity score matching was used to create pairs of individuals who were then analyzed in a Cox proportional-hazards regression model to estimate high-flow nasal cannula's effect on time to discharge and time to death. A secondary analysis excluded high-flow nasal cannula patients intubated within 6 hours of admission. A Cox proportional-hazards regression model was used to assess risk of invasive mechanical ventilation among high-flow nasal cannula patients stratified by respiratory rate-oxygenation.

SETTING: The five hospitals of the Johns Hopkins Health System.

PATIENTS: All patients who were admitted with a laboratory-confirmed diagnosis of coronavirus disease 2019 were eligible for inclusion.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: High-flow nasal cannula was associated with longer median time to discharge: 10.6 days (interquartile range, 7.1-15.8 d) versus 7.8 days (interquartile range, 4.9-12.1 d). Respiratory rate-oxygenation index performed poorly in predicting ventilation or death. In the primary analysis, there was no significant association between high-flow nasal cannula and hazard of death (adjusted hazard ratio, 0.79; 95% CI, 0.57-1.09). Excluding patients intubated within 6 hours of admission, high-flow nasal cannula was associated with reduced hazard of death (adjusted hazard ratio, 0.67; 95% CI, 0.45-0.99).

CONCLUSIONS: Among unselected patients with severe coronavirus disease 2019 pneumonia, high-flow nasal cannula was not associated with a statistically significant reduction in hazard of death. However, in patients not mechanically ventilated within 6 hours of admission, high-flow nasal cannula was associated with a significantly reduced hazard of death.

# 高流量鼻导管在 2019 年冠状病毒病肺炎治疗中的有效性：一项回顾性队列研究。

目的：高流量鼻导管广泛用于 2019 年冠状病毒病引起的急性低氧性呼吸衰竭，但缺乏其有效性相关数据。需要更多的证据来指导患者选择、高流量鼻插管开始的时机和资源分配。我们旨在评估与匹配的对照组相比，接受高流量鼻插管治疗的患者在 2019 年重度冠状病毒疾病的出院时间和至死亡时间。我们还评估了呼吸频率 - 氧合比预测有创机械通气进展的能力。

设计：使用时间依赖性倾向评分匹配创建成对个体，然后在 Cox 比例风险回归模型中进行分析，以估计高流量鼻插管对出院时间和至死亡时间的影响。次要分析排除了入院 6 小时内接受插管的高流量鼻插管患者。使用 Cox 比例风险回归模型评估高流量鼻插管患者中有创机械通气的风险，患者按呼吸频率 - 氧合进行分层。

单位：约翰霍普金斯卫生系统的 5 家医院。

患者：所有 2019 年经实验室确诊为冠状病毒病的患者均有资格入选。

干预：无。

测量值和主要结果：高流量鼻插管与较长的中位出院时间相关：10.6 天（四分位距，7.1-15.8 天）对比 7.8 天（四分位距，4.9-12.1 天）。呼吸频率 - 氧合指数在预测通气或死亡方面表现不佳。在主要分析中，高流量鼻插管与死亡风险之间无显著相关性（校正的风险比，0.79；95% CI，0.57-1.09）。排除入院 6 小时内接受插管的患者，高流量鼻插管与死亡风险降低相关（调整后风险比，0.67；95% CI，0.45-0）。99). 结论：在未选择的 2019 年重症冠状病毒病肺炎患者中，高流量鼻插管与死亡风险统计学显著降低无关。但是，在入院 6 小时内未接受机械通气的患者中，高流量鼻插管与死亡风险显著降低相关。关键词：Humans; Female; Male; Middle Aged; Time Factors; Aged; Length of Stay; Retrospective Studies; Equipment Design; SARS-CoV-2; Patient Selection; Proportional Hazards Models; Respiratory Rate; COVID-19/mortality/*therapy; Cannula/*classification

# Routine Neuroimaging: Understanding Brain Injury in Pediatric Extracorporeal Membrane Oxygenation.

3:480-490. DOI:10.1097/CCM.0000000000005308

Abstract:

OBJECTIVES: This project aims to describe brain injuries on routine neuroimaging in a large single-center neonatal and pediatric cohort supported by extracorporeal membrane oxygenation. The study also aims to examine the association of these injuries with neurocognitive outcomes in survivors and identify laboratory findings associated with neurologic injury.

DESIGN: Retrospective observational single-center cohort study.

SETTING: Tertiary care PICU.

PATIENTS: Pediatric patients with noncardiac indications for extracorporeal membrane oxygenation supported by venoarterial or venovenous extracorporeal membrane oxygenation, with on-extracorporeal membrane oxygenation brain CT or postextracorporeal membrane oxygenation brain CT/MRI.

INTERVENTIONS: Extracorporeal membrane oxygenation support.

MEASUREMENTS AND MAIN RESULTS: Occurrence of brain injury on CT and MRI was reviewed; injuries were scored. Clinical and laboratory results associated with injury were identified. Survivor neurocognitive outcomes were obtained using the Pediatric Overall Performance Category scale and Pediatric Cerebral Performance Category scale. Of 132 imaged patients, 98 (74%) had radiological evidence of brain injury. Mean injury score was 6.5 (?± 3.8). Head ultrasounds and clinician suspicion performed poorly in suspecting the presence of injury. Of 104 respondents to neurodevelopmental assessments, 61 (59%) had normal scores; 12.5%, 17%, and 11.5% had mild, moderate, or severe disability. A neuroimaging score greater than 10 was associated with an unfavorable outcome on the Pediatric Cerebral Performance Category (odds ratio, 3.4; p < 0.01) and Pediatric Overall Performance Category (odds ratio, 1.7; p < 0.05). Ischemic injury correlated with worse neurodevelopmental outcome. Preextracorporeal membrane oxygenation lactate, Vasoactive-Inotropic Scores, transaminitis, elevated bilirubin and creatinine levels, and thrombocytopenia were associated with injury occurrence.

CONCLUSIONS: Brain injury is frequent in extracorporeal membrane oxygenation patients, although the majority of survivors have favorable neurocognitive outcomes. More research is needed in order to understand the etiology of such injuries. Head ultrasound and clinician suspicion are not sensitive in detecting extracorporeal membrane oxygenation-related brain injuries. Protocolizing postextracorporeal membrane oxygenation imaging with brain MRI allows the identification of injuries and provision of timely neurocognitive intervention.

# 常规神经影像学：了解儿童体外膜肺氧合中的脑损伤。

目的：本项目旨在描述由体外膜肺氧合支持的大型单中心新生儿和儿科队列中常规神经影像学的脑损伤。本研究的目的还包括检查这些损伤与幸存者神经认知结果的相关性，并确定与神经损伤相关的实验室结果。

设计：回顾性观察性单中心队列研究。

单位：三级监护 PICU。

患者：采用静脉 - 动脉或静脉 - 静脉体外膜氧合支持进行体外膜氧合的非心脏适应症儿科患者，进行体外膜氧合脑部 CT 或体外膜氧合后脑部 CT/MRI。

干预：体外膜肺氧合支持。

测量和主要结果：审查 CT 和 MRI 的脑损伤发生率；对损伤进行评分。确定了与损伤相关的临床和实验室结果。使用儿科整体性能分类量表和儿科大脑性能分类量表获得存活者神经认知结局。在 132 例成像患者中，98 例 (74%) 有脑损伤的放射学证据。平均损伤评分为 6.5 (?±3.8)。头部超声和临床医生怀疑其表现不佳，怀疑存在损伤。在 104 名神经发育评估的应答者中，61 名 (59%) 评分正常；12.5%、17% 和 11.5% 有轻度、中度或重度残疾。神经影像学评分大于 10 与儿童大脑功能分类（比值比，3.4；p < 0.01）和儿童整体功能分类（比值比，1.7；p < 0.05）的不良结局相关。缺血性损伤与较差的神经发育结局相关。体外膜氧合乳酸、血管活性药物评分、转氨酶、胆红素和肌酐水平升高以及血小板减少与损伤发生相关。

结论：虽然大多数存活者有良好的神经认知结局，但脑损伤在体外膜肺氧合患者中较为常见。需要更多的研究来了解这种损伤的病因。头部超声和临床医生怀疑对检测体外膜氧合相关脑损伤不敏感。脑 MRI 的程序化体外膜氧合后成像允许识别损伤并提供及时的神经认知干预。关键词：Humans; Female; Male; Prognosis; Cohort Studies; Adolescent; Retrospective Studies; Child; Infant, Newborn; *Intensive Care Units, Pediatric; *Severity of Illness Index; Brain Injuries/*diagnosis/*etiology; Extracorporeal Membrane Oxygenation/*adverse effects; Intracranial Hemorrhages/diagnosis/etiology

# Coronavirus Disease 2019 Tracheostomy Candidacy, Ceteris Paribus Assumptions, and Tracking Survivorship Data.

3:e320-e321. DOI:10.1097/CCM.0000000000005338

# Coronavirus Disease 2019 气管造口术候选资格、Ceteris Paribus 假设和追踪生存率数据。

关键词：Humans; *COVID-19; SARS-CoV-2; *Tracheostomy; Survivorship

# Prognostic and Predictive Biomarkers in Patients With Coronavirus Disease 2019 Treated With Tocilizumab in a Randomized Controlled Trial., Tom, Jennifer

3:398-409. DOI:10.1097/CCM.0000000000005229

Abstract:

OBJECTIVES: To explore candidate prognostic and predictive biomarkers identified in retrospective observational studies (interleukin-6, C-reactive protein, lactate dehydrogenase, ferritin, lymphocytes, monocytes, neutrophils, d-dimer, and platelets) in patients with coronavirus disease 2019 pneumonia after treatment with tocilizumab, an anti-interleukin-6 receptor antibody, using data from the COVACTA trial in patients hospitalized with severe coronavirus disease 2019 pneumonia.

DESIGN: Exploratory analysis from a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial.

SETTING: Hospitals in North America and Europe.

PATIENTS: Adults hospitalized with severe coronavirus disease 2019 pneumonia receiving standard care.

INTERVENTION: Randomly assigned 2:1 to IV tocilizumab 8 mg/kg or placebo.

MEASUREMENTS AND MAIN RESULTS: Candidate biomarkers were measured in 295 patients in the tocilizumab arm and 142 patients in the placebo arm. Efficacy outcomes assessed were clinical status on a seven-category ordinal scale (1, discharge; 7, death), mortality, time to hospital discharge, and mechanical ventilation (if not receiving it at randomization) through day 28. Prognostic and predictive biomarkers were evaluated continuously with proportional odds, binomial or Fine-Gray models, and additional sensitivity analyses. Modeling in the placebo arm showed all candidate biomarkers except lactate dehydrogenase and d-dimer were strongly prognostic for day 28 clinical outcomes of mortality, mechanical ventilation, clinical status, and time to hospital discharge. Modeling in the tocilizumab arm showed a predictive value of ferritin for day 28 clinical outcomes of mortality (predictive interaction, p = 0.03), mechanical ventilation (predictive interaction, p = 0.01), and clinical status (predictive interaction, p = 0.02) compared with placebo.

CONCLUSIONS: Multiple biomarkers prognostic for clinical outcomes were confirmed in COVACTA. Ferritin was identified as a predictive biomarker for the effects of tocilizumab in the COVACTA patient population; high ferritin levels were associated with better clinical outcomes for tocilizumab compared with placebo at day 28.

# 2019 年在一项随机对照试验中接受托珠单抗治疗的冠状病毒疾病患者的预后和预测生物标志物。

目的：探索在回顾性观察性研究（白细胞介素 - 6、C - 反应蛋白、乳酸脱氢酶、铁蛋白、淋巴细胞、单核细胞、中性粒细胞、d - 二聚体和血小板）中鉴别的冠状病毒病 2019 年肺炎患者在接受抗白细胞介素 - 6 受体抗体托珠单抗治疗后的候选预后和预测性生物标志物，使用在 2019 年因重症冠状病毒病肺炎住院的患者中进行的 COVACTA 试验的数据。

设计：一项多中心、随机化、双盲、安慰剂对照、iii 期试验的探索性分析。

设置：北美和欧洲的医院。

患者：2019 年住院治疗重症冠状病毒病的肺炎成人患者，接受标准治疗。

干预：以 2:1 的比例随机分配至托珠单抗 8 mg/kg IV 组或安慰剂组。

测量和主要结果：在 tocilizumab 组 295 例患者和安慰剂组 142 例患者中测量了候选生物标志物。评估的有效性结局为 7 类序数量表（1，出院；7，死亡）上的临床状态、死亡率、出院时间和机械通气（如果随机化时未接受）至第 28 天。使用比例优势、二项式或 Fine-Gray 模型以及额外的敏感性分析，对预后和预测性生物标志物进行连续评估。安慰剂组建模显示，除乳酸脱氢酶和 d - 二聚体外，所有候选生物标志物对第 28 天死亡率、机械通气、临床状态和出院时间等临床结局具有强预后性。与安慰剂相比，托珠单抗组的建模显示铁蛋白对第 28 天死亡率（预测性相互作用，p = 0.03）、机械通气（预测性相互作用，p = 0.01）和临床状态（预测性相互作用，p = 0.02）的临床结局具有预测价值。

结论：COVACTA 研究证实了多个临床结局预后生物标志物。铁蛋白被确定为 COVACTA 患者人群中托珠单抗作用的预测性生物标志物；在第 28 天，与安慰剂相比，铁蛋白水平较高与托珠单抗更好的临床结局相关。关键词：Humans; Female; Male; Prognosis; Double-Blind Method; Length of Stay; Respiration, Artificial; Biomarkers; SARS-CoV-2; Inflammation Mediators/metabolism; Patient Discharge; Antibodies, Monoclonal, Humanized/administration & dosage/adverse effects/*therapeutic use; COVID-19/*drug therapy/*epidemiology/mortality

# Single Nucleotide Variant in FAS Associates With Organ Failure and Soluble Fas Cell Surface Death Receptor in Critical Illness.

3:e284-e293. DOI:10.1097/CCM.0000000000005333

Abstract:

OBJECTIVES: Multiple organ failure in critically ill patients is associated with poor prognosis, but biomarkers contributory to pathogenesis are unknown. Previous studies support a role for Fas cell surface death receptor (Fas)-mediated apoptosis in organ dysfunction. Our objectives were to test for associations between soluble Fas and multiple organ failure, identify protein quantitative trait loci, and determine associations between genetic variants and multiple organ failure.

DESIGN: Retrospective observational cohort study.

SETTING: Four academic ICUs at U.S. hospitals.

PATIENTS: Genetic analyses were completed in a discovery (n = 1,589) and validation set (n = 863). Fas gene expression and flow cytometry studies were completed in outpatient research participants (n = 250).

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: In discovery and validation sets of critically ill patients, we tested for associations between enrollment plasma soluble Fas concentrations and Sequential Organ Failure Assessment score on day 3. We conducted a genome-wide association study of plasma soluble Fas (discovery n = 1,042) and carried forward a single nucleotide variant in the FAS gene, rs982764, for validation (n = 863). We further tested whether the single nucleotide variant in FAS (rs982764) was associated with Sequential Organ Failure Assessment score, FAS transcriptional isoforms, and Fas cell surface expression. Higher plasma soluble Fas was associated with higher day 3 Sequential Organ Failure Assessment scores in both the discovery (?? = 4.07; p < 0.001) and validation (?? = 6.96; p < 0.001) sets. A single nucleotide variant in FAS (rs982764G) was associated with lower plasma soluble Fas concentrations and lower day 3 Sequential Organ Failure Assessment score in meta-analysis (-0.21; p = 0.02). Single nucleotide variant rs982764G was also associated with a lower relative expression of the transcript for soluble as opposed to transmembrane Fas and higher cell surface expression of Fas on CD4+ T cells.

CONCLUSIONS: We found that single nucleotide variant rs982764G was associated with lower plasma soluble Fas concentrations in a discovery and validation population, and single nucleotide variant rs982764G was also associated with lower organ dysfunction on day 3. These findings support further study of the Fas pathway as a potential mediator of organ dysfunction in critically ill patients.

# 危重症患者中与器官衰竭和可溶性 FAS 细胞表面死亡受体相关的 FAS 中的单核苷酸变异。

目的：重症患者的多器官功能衰竭与预后不良相关，但发病机制的生物标志物未知。既往研究支持 Fas 细胞表面死亡受体 (Fas) 介导的细胞凋亡在器官功能障碍中的作用。我们的目的是检测可溶性 Fas 与多器官衰竭之间的相关性，确定蛋白质数量性状位点，并确定遗传变异体与多器官衰竭之间的相关性。

设计：回顾性观察性队列研究。

单位：美国医院 4 间学术 ICU。

患者：在一个发现 (n = 1,589) 和验证集 (n = 863) 中完成了遗传分析。在门诊研究参与者 (n = 250) 中完成了 Fas 基因表达和流式细胞术研究。

干预：无。

测量和主要结果：在危重患者的发现和验证组中，我们在第 3 天检测了入组血浆可溶性 Fas 浓度和序贯器官衰竭评估评分之间的相关性。我们进行了血浆可溶性 Fas 的全基因组关联研究（发现 n = 1，042），并在 FAS 基因中结转一个单核苷酸变异体 rs982764 进行验证 (n = 863)。我们进一步检测了 FAS (rs982764) 中的单核苷酸变异是否与序贯器官衰竭评估评分、FAS 转录亚型和 FAS 细胞表面表达相关。血浆可溶性 Fas 水平较高与第 3 天序贯器官衰竭评估评分较高相关，无论是发现组 (?? = 4.07；p < 0.001) 还是验证组 (?? = 6.96；p < 0.001)。在荟萃分析中，FAS 中的单核苷酸变异体 (rs982764G) 与血浆可溶性 FAS 浓度降低和第 3 天序贯器官衰竭评估评分降低相关 (-0.21；p = 0.02)。单核苷酸变异体 rs982764G 也与可溶性转录本相对表达较低（与跨膜 Fas 相反）和 CD4 + T 细胞上 Fas 的细胞表面表达较高相关。

结论：我们发现单核苷酸变异体 rs982764G 与发现和验证人群中较低的血浆可溶性 Fas 浓度相关，并且单核苷酸变异体 rs982764G 也与第 3 天的下器官功能障碍有关。这些发现支持进一步研究 Fas 通路作为危重患者器官功能障碍的潜在介质。关键词：Humans; Female; Male; Middle Aged; Aged; Intensive Care Units; Adult; Biomarkers; Apoptosis; Genotype; Critical Illness/*epidemiology; fas Receptor/blood/*genetics; Genome-Wide Association Study; Multiple Organ Failure/blood/*epidemiology; Organ Dysfunction Scores; Polymorphism, Single Nucleotide

# Neuromuscular Blocker Use in Critically Ill Children: Assessing Mortality Risk by Propensity Score-Weighted Analysis.

3:e294-e303. DOI:10.1097/CCM.0000000000005334

Abstract:

OBJECTIVES: We aim to describe the use of continuous infusion of neuromuscular blocking agents in mechanically ventilated critically ill children and to test its association with in-hospital mortality.

DESIGN: Multicenter, registry-based, observational, two-cohort-comparison retrospective study using prospectively collected data from a web-based national registry.

SETTING: Seventeen PICUs in Italy.

PATIENTS: We included children less than 18 years who received mechanical ventilation and a neuromuscular blocking agent infusion from January 2010 to October 2017. A propensity score-weighted Cox regression analysis was used to assess the relationship between the use of neuromuscular blocking agents and in-hospital mortality.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Of the 23,227 patients admitted to the PICUs during the study period, 3,823 patients were included. Patients who received a continuous infusion of neuromuscular blocking agent were more likely to be younger (p < 0.001), ex-premature (p < 0.001), and presenting with less chronic respiratory insufficiency requiring home mechanical ventilation (p < 0.001). Reasons for mechanical ventilation significantly differed between patients who received a continuous infusion of neuromuscular blocking agent and patients who did not receive a continuous infusion of neuromuscular blocking agent, with a higher frequency of respiratory and cardiac diagnosis among patients who received neuromuscular blocking agents compared with other diagnoses (all p < 0.001). The covariates were well balanced in the propensity-weighted cohort. The mortality rate significantly differed among the two cohorts (patients who received a continuous infusion of neuromuscular blocking agent 21% vs patients who did not receive a continuous infusion of neuromuscular blocking agent 11%; p < 0.001 by weighted logistic regression). Patients who received a continuous infusion of neuromuscular blocking agent experienced longer mechanical ventilation and PICU stay (both p < 0.001 by weighted logistic regression). A weighted Cox regression analysis found the use of neuromuscular blocking agents to be a significant predictor of in-hospital mortality both in the unadjusted analysis (hazard ratio, 1.7; 95% CI, 1.3-2.2) and in the adjusted one (hazard ratio, 1.6; 95% CI, 1.2-2.1).

CONCLUSIONS: Thirteen percent of mechanically ventilated children in PICUs received neuromuscular blocking agents. When adjusting for selection bias with a propensity score approach, the use of neuromuscular blocking agent was found to be a significant predictor of in-hospital mortality.

# 神经肌肉阻滞剂在危重病儿童中的使用：通过倾向评分加权分析评估死亡风险。

目的：我们的目的是描述在机械通气的重症儿童中持续输注神经肌肉阻滞剂的使用，并检测其与住院死亡率的相关性。

设计：采用基于网络的国家登记研究中前瞻性收集的数据进行的多中心、基于登记研究、观察性、两队列比较回顾性研究。

设置：意大利 17 家 PICU。

患者：我们纳入了 2010 年 1 月至 2017 年 10 月接受机械通气和神经肌肉阻滞剂输注的 18 岁以下儿童。倾向评分加权 Cox 回归分析用于评估神经肌肉阻滞剂的使用与住院死亡率之间的关系。

干预：无。

测量和主要结果：在研究期间入住 PICU 的 23,227 例患者中，3,823 例患者入组。接受神经肌肉阻滞剂连续输注的患者更可能更年轻 (p < 0.001)、早早 (p < 0.001)，并且表现出需要家庭机械通气的慢性呼吸功能不全更少 (p < 0.001)。接受神经肌肉阻滞剂连续输注的患者与未接受神经肌肉阻滞剂连续输注的患者之间，机械通气的原因显著不同，与其他诊断相比，接受神经肌肉阻滞剂的患者中呼吸和心脏诊断的频率更高（所有 p < 0.001）。倾向加权队列中的协变量平衡良好。两个队列的死亡率显著不同（持续输注神经肌肉阻滞剂的患者是 21%，没有持续输注神经肌肉阻滞剂的患者是 11%；加权 logistic 回归分析 p < 0.001）。持续输注神经肌肉阻滞剂的患者经历了更长的机械通气和 PICU 停留时间（加权 logistic 回归均为 p < 0.001）。加权 Cox 回归分析发现，在未调整的分析（风险比 1.7；95% CI 1.3-2.2）和调整的分析（风险比 1.6；95% CI 1.2-2.1）中，神经肌肉阻滞剂的使用是住院死亡率的显著预测因素。

结论：PICU 中 13% 的机械通气儿童接受了神经肌肉阻滞剂。当用倾向评分方法调整选择偏倚时，发现使用神经肌肉阻滞剂是住院死亡率的显著预测因素。关键词：Hemodynamics; Humans; Male; Cohort Studies; Propensity Score; Adolescent; Retrospective Studies; Child; Child, Preschool; Critical Illness/*therapy; Italy; Respiration, Artificial/*methods; Neuromuscular Blocking Agents/*therapeutic use; Respiratory Distress Syndrome/*drug therapy/mortality

# Electrical Impedance Tomography Monitoring of Bronchoalveolar Lavage in Patients With Acute Respiratory Distress Syndrome., Franchineau, Guillaume

3:e231-e240. DOI:10.1097/CCM.0000000000005302

Abstract:

OBJECTIVES: The impact of bronchoalveolar lavage on regional ventilation in mechanically ventilated patients with acute respiratory distress syndrome has rarely been described. Our objectives were use electrical impedance tomography to describe lung impedance variation post bronchoalveolar lavage and identify morphologic patterns according to respiratory failure severity.

DESIGN: Monocenter physiologic study on mechanically ventilated patients.

SETTING: University medical ICU.

INTERVENTIONS: After a recruitment maneuver, tidal impedance variation distributions (a surrogate for impact of bronchoalveolar lavage on tidal volume distribution), end-expiratory lung impedance (correlated with end-expiratory lung volume and used to quantify postbronchoalveolar lavage derecruitment), respiratory mechanics, and blood gases were recorded before and over 6 hours post bronchoalveolar lavage with Pao2 to the Fio2 ratio. Patients were grouped according to their prebronchoalveolar lavage, that is, Pao2 to the Fio2 ratio less than 200 or greater than or equal to 200.

RESULTS: Twenty-one patients (median [interquartile range] age 55 yr [50-58 yr]; 13 males), 13 with Pao2 to the Fio2 ratio less than 200, were included. Unlike that latter group, bronchoalveolar lavage significantly impacted tidal impedance variation distribution in patients with Pao2 to the Fio2 ratio greater than or equal to 200, with a ventilation shift to the contralateral lung (from 54% to 42% in the bronchoalveolar lavage side), which persisted up to 6 hours post bronchoalveolar lavage. Similarly, end-expiratory lung impedance was less distributed in the bronchoalveolar lavage side post procedure of patients with Pao2 to the Fio2 ratio greater than or equal to 200, but the difference did not reach statistical significance (p = 0.09). As reported for tidal impedance variation, end-expiratory lung impedance distribution in patients with severe or moderate acute respiratory distress syndrome did not change significantly during the 6 hours post bronchoalveolar lavage. Although bronchoalveolar lavage effects on gas exchanges were minor in all patients, static compliance in patients with Pao2 to the Fio2 ratio greater than or equal to 200 was significantly lower post bronchoalveolar lavage (p = 0.04).

CONCLUSIONS: The negative impact of bronchoalveolar lavage on regional ventilation, which persisted at least 6 hours, appeared to be more profound in patients with normal lung function or mild acute respiratory distress syndrome. In contrast, regional ventilation, lung recruitment, respiratory mechanics, and gas exchanges were modestly impacted by the bronchoalveolar lavage in patients with severe or moderate acute respiratory distress syndrome. That finding is reassuring and supports not summarily proscribing bronchoalveolar lavage for the most severely ill with acute respiratory distress syndrome.

# 电阻抗断层成像监测急性呼吸窘迫综合征患者的支气管肺泡灌洗。

目的：在急性呼吸窘迫综合征的机械通气患者中，很少描述支气管肺泡灌洗对局部通气的影响。我们的目的是使用电阻抗断层扫描来描述支气管肺泡灌洗后的肺阻抗变化，并根据呼吸衰竭的严重程度确定形态学模式。

设计：机械通气患者的单中心生理学研究。

单位：大学医学中心。

干预：复张操作后，潮气阻抗变化分布（支气管肺泡灌洗对潮气量分布影响的替代指标），呼气末肺阻抗（与呼气末肺容量相关，并用于定量支气管肺泡灌洗后呼吸力学），在使用 Pao2/Fio2 比率进行支气管肺泡灌洗之前和之后 6 小时，记录血气。根据患者的支气管肺泡灌洗术前情况进行分组，即 Pao2 与 Fio2 的比值小于 200 或大于等于 200。

结果：纳入 21 例患者（中位 [四分位距] 年龄 55 岁 [50-58 岁]；13 例男性），13 例 Pao2 与 Fio2 比值小于 200。与后一组不同，支气管肺泡灌洗显著影响 Pao2 与 Fio2 比值大于或等于 200 的患者的潮气阻抗变化分布，通气转移至对侧肺（支气管肺泡灌洗侧从 54% 至 42%），其持续至支气管肺泡灌洗后 6 小时。同样，在 Pao2 与 Fio2 比率大于或等于 200 的患者中，呼气末肺阻抗在术后支气管肺泡灌洗侧的分布较少，但差异未达到统计学显著性 (p = 0.09)。根据潮气阻抗变化的报告，重度或中度急性呼吸窘迫综合征患者的呼气末肺阻抗分布在支气管肺泡灌洗后 6 小时期间无显著变化。尽管在所有患者中，支气管肺泡灌洗对气体交换的影响较小，但在支气管肺泡灌洗后，Pao2 与 Fio2 比率大于或等于 200 的患者的静态依从性显著较低 (p = 0.04)。

结论：在肺功能正常或轻度急性呼吸窘迫综合征患者中，至少持续 6 小时的支气管肺泡灌洗对局部通气的负面影响似乎更明显。相比之下，在重度或中度急性呼吸窘迫综合征患者中，支气管肺泡灌洗中度影响了局部通气、肺复张、呼吸力学和气体交换。该结果是可靠的，并支持对急性呼吸窘迫综合征最严重的患者不立即禁止支气管肺泡灌洗。关键词：Humans; Male; Middle Aged; Monitoring, Physiologic/methods; Respiratory Function Tests; *Electric Impedance; Bronchoalveolar Lavage/*methods; Respiratory Distress Syndrome/*diagnostic imaging/*therapy; Respiratory Mechanics

# Epidemiology and Outcomes of Critically Ill Children at Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.

3:363-374. DOI:10.1097/CCM.0000000000005287

Abstract:

OBJECTIVES: Interventional trials aimed at pediatric acute respiratory distress syndrome prevention require accurate identification of high-risk patients. In this study, we aimed to characterize the frequency and outcomes of children meeting "at risk for pediatric acute respiratory distress syndrome" criteria as defined by the Pediatric Acute Lung Injury Consensus Conference.

DESIGN: Planned substudy of the prospective multicenter, international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study conducted during 10 nonconsecutive weeks (May 2016-June 2017).

SETTING: Thirty-seven international PICUs.

PATIENTS: Three-hundred ten critically ill children meeting Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We evaluated the frequency of children at risk for pediatric acute respiratory distress syndrome and rate of subsequent pediatric acute respiratory distress syndrome diagnosis and used multivariable logistic regression to identify factors associated with subsequent pediatric acute respiratory distress syndrome. Frequency of at risk for pediatric acute respiratory distress syndrome was 3.8% (95% CI, 3.4-5.2%) among the 8,122 critically ill children who were screened and 5.8% (95% CI, 5.2-6.4%) among the 5,334 screened children on positive pressure ventilation or high-flow oxygen. Among the 310 at-risk children, median age was 2.1 years (interquartile range, 0.5-7.3 yr). Sixty-six children (21.3%) were subsequently diagnosed with pediatric acute respiratory distress syndrome, a median of 22.6 hours (interquartile range, 9.8-41.0 hr) later. Subsequent pediatric acute respiratory distress syndrome was associated with increased mortality (21.2% vs 3.3%; p < 0.001) and longer durations of invasive ventilation and PICU care. Subsequent pediatric acute respiratory distress syndrome rate did not differ by respiratory support modality at the time of meeting at risk criteria but was independently associated with lower initial saturation:Fio2 ratio, progressive tachycardia, and early diuretic administration.

CONCLUSIONS: The Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria identify critically ill children at high risk of pediatric acute respiratory distress syndrome and poor outcomes. Interventional trials aimed at pediatric acute respiratory distress syndrome prevention should target patients early in their illness course and include patients on high-flow oxygen and positive pressure ventilation.

# 具有儿科急性呼吸窘迫综合征风险的危重患儿的流行病学和结局：一项儿科急性呼吸窘迫综合征发病率和流行病学研究。

目的：旨在预防儿科急性呼吸窘迫综合征的干预性试验需要准确识别高危患者。在本研究中，我们旨在描述符合儿科急性肺损伤共识会议定义的 “儿科急性呼吸窘迫综合征风险” 标准的儿童的频率和结局。

设计：前瞻性、多中心、国际儿科急性呼吸窘迫综合征发病率和流行病学研究的计划子研究，在非连续 10 周内进行（2016 年 5 月 2017 年 6 月）。

设置：37 个国际 PICU。

患者：符合儿科急性肺损伤共识会议 “儿科急性呼吸窘迫综合征高危” 标准的 310 例重症儿童。

干预：无。

测量和主要结果：我们评估了有急性呼吸窘迫综合征风险的儿童的频率和随后的儿科急性呼吸窘迫综合征的确诊率，并使用多变量 logistic 回归来确定与随后的儿科急性呼吸窘迫综合征相关的因素。在接受筛选的 8,122 例重症儿童中，发生急性呼吸窘迫综合征风险的频率为 3.8%(95% CI,3.4-5.2%)，在接受正压通气或高流量氧治疗的 5,334 例接受筛选的儿童中，发生急性呼吸窘迫综合征风险的频率为 5.8%(95% CI,5.2-6.4%)。310 例高危儿童的中位年龄为 2.1 岁（四分位距：0.5-7.3 岁）。66 名儿童 (21.3%) 随后被诊断为急性呼吸窘迫综合征，中位时间 22.6h（四分位距 9.8-41.0 h）。后续的儿科急性呼吸窘迫综合征与死亡率增加（21.2% 与 3.3%；p < 0.001）以及有创通气和 PICU 护理的持续时间更长相关。随后的儿科急性呼吸窘迫综合征发生率在符合风险标准时通过呼吸支持方式无差异，但与较低的初始饱和度独立相关：Fio2 比率、进展性心动过速和早期利尿剂给药。

结论：儿科急性肺损伤共识会议 “儿科急性呼吸窘迫综合征高危” 标准确定了儿科急性呼吸窘迫综合征高风险和不良结局的危重儿童。旨在预防儿科急性呼吸窘迫综合征的干预性试验应针对病程早期的患者，并纳入接受高流量氧气和正压通气的患者。关键词：Humans; Female; Male; Prospective Studies; Time Factors; Adolescent; Child; Outcome Assessment, Health Care; Child, Preschool; *Intensive Care Units, Pediatric; Acute Lung Injury/epidemiology/therapy; Critical Illness/mortality/*therapy; Respiration, Artificial/statistics & numerical data; Respiratory Distress Syndrome/*epidemiology/*therapy

# Effect of a Multicomponent Sepsis Transition and Recovery Program on Mortality and Readmissions After Sepsis: The Improving Morbidity During Post-Acute Care Transitions for Sepsis Randomized Clinical Trial., Taylor, Stephanie Parks

3:469-479. DOI:10.1097/CCM.0000000000005300

Abstract:

OBJECTIVES: To evaluate whether a nurse navigator-led, multicomponent Sepsis Transition And Recovery program improves 30-day mortality and readmission outcomes after sepsis hospitalization.

DESIG: n: Multisite pragmatic randomized clinical trial.

SETTING: Three hospitals in North Carolina from January 2019 to March 2020.

PATIENTS: Eligible patients hospitalized for suspected sepsis and deemed high-risk for mortality or readmission by validated internal risk models.

INTERVENTIONS: Patients were randomized to receive usual care alone (i.e., routine transition support, outpatient care; n = 342) or additional Sepsis Transition And Recovery support (n = 349). The 30-day intervention involved a multicomponent transition service led by a nurse navigator through telephone and electronic health record communication to facilitate best practice postsepsis care strategies during and after hospitalization including: postdischarge medication review, evaluation for new impairments or symptoms, monitoring comorbidities, and palliative care approach when appropriate. Clinical oversight was provided by a Hospital Medicine Transition Services team.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of mortality or hospital readmission at 30 days. Logistic regression models were constructed to evaluate marginal and conditional odds ratios (adjusted for prognostic covariates: age, comorbidity, and organ dysfunction at enrollment). Among 691 randomized patients (mean age = 63.7 ?± 15.1 yr; 52% female), a lower percentage of patients in the Sepsis Transition And Recovery group experienced the primary outcome compared with the usual care group (28.7% vs 33.3%; risk difference, 4.7%; odds ratio, 0.80; 95% CI, 0.58-1.11; adjusted odds ratio, 0.80; 95% CI, 0.64-0.98). There were 74 deaths (Sepsis Transition And Recovery: 33 [9.5%] vs usual care: 41 [12.0%]) and 155 rehospitalizations (Sepsis Transition And Recovery: 71 [20.3%] vs usual care: 84 [24.6%]).

CONCLUSIONS: In a multisite randomized clinical trial of patients hospitalized with sepsis, patients provided with a 30-day program using a nurse navigator to provide best practices for postsepsis care experienced a lower proportion of either mortality or rehospitalization within 30 days after discharge. Further research is needed to understand the contextual factors associated with successful implementation.

# 多组分败血症转换和恢复项目对败血症后死亡率和再入院的影响：败血症急性治疗后转换期间发病率的改善：随机临床试验。

目的：评估护士导航员主导的多组分脓毒症转换和恢复项目是否改善脓毒症住院后 30 天死亡率和再入院结局。

设计：n：多中心实用随机临床试验。

地点：2019 年 1 月至 2020 年 3 月，北卡罗莱纳州的三家医院。

患者：因疑似败血症住院的合格患者，通过验证的内部风险模型确定为死亡或再入院的高风险。

干预：患者随机接受单独常规护理（即，常规过渡支持，门诊护理；n = 342）或额外的败血症过渡和恢复支持 (n = 349)。30 天干预涉及由护士领航员通过电话和电子健康记录通信进行的多组分转换服务，以促进住院期间和住院后最佳实践败血症后护理策略，包括：出院后药物审查，新损伤或症状评价，监测合并症，以及适当的姑息治疗方法。由医院医学过渡服务团队进行临床监督。

测量和主要结果：主要结局是 30 天时死亡率或再入院率的复合终点。构建 Logistic 回归模型，评价边际和条件比值比（根据预后协变量调整：入组时年龄、合并症和器官功能障碍）。691 例随机化患者（平均年龄为 63.7±15.1 岁；52% 为女性）中，与常规治疗组相比，败血症转化和恢复组出现主要结局的患者百分比较低（28.7% vs 33.3%；风险差异，4.7%；比值比，0.80；95% CI，0.58-1.11；调整后比值比，0.80；95% CI，0.64-0.98）。有 74 例死亡（败血症转化和恢复：33 例 [9.5%] 与常规护理：41 例 [12.0%]）和 155 例再次住院（败血症转化和恢复：71 例 [20.3%] 与常规护理：84 例 [24.6%]）. 结论：在一项对因败血症住院患者进行的多中心随机临床试验中，为败血症后护理提供最佳实践的患者提供 30 天程序，患者出院后 30 天内死亡或再次住院的比例较低。需要进一步研究以了解与成功实施相关的背景因素。关键词：Humans; Female; Male; Middle Aged; Aged; Emergency Service, Hospital; Risk Factors; Outcome Assessment, Health Care; Aftercare/*statistics & numerical data; Patient Discharge/*statistics & numerical data; Patient Readmission/*statistics & numerical data; Sepsis/*nursing/*rehabilitation; Transitional Care/*statistics & numerical data

# Descriptive Epidemiology and Outcomes of Nonventilated Hospital-Acquired, Ventilated Hospital-Acquired, and Ventilator-Associated Bacterial Pneumonia in the United States, 2012-2019.

3:460-468. DOI:10.1097/CCM.0000000000005298

Abstract:

OBJECTIVES: Multiple randomized controlled trials exploring the outcomes of patients with ventilator-associated bacterial pneumonia and hospital-acquired bacterial pneumonia have noted that hospital-acquired bacterial pneumonia patients who require subsequent ventilated hospital-acquired bacterial pneumonia suffered higher mortality than either those who did not (nonventilated hospital-acquired bacterial pneumonia) or had ventilator-associated bacterial pneumonia. We examined the epidemiology and outcomes of all three conditions in a large U.S. database.

DESIGN: Retrospective cohort.

SETTING: Two hundred fifty-three acute-care hospitals, United States, contributing data (including microbiology) to Premier database, 2012-2019.

PATIENTS: Patients with hospital-acquired bacterial pneumonia or ventilator-associated bacterial pneumonia identified based on a slightly modified previously published International Classification of Diseases, 9th Edition/International Classification of Diseases, 10th Edition-Clinical Modification algorithm.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Among 17,819 patients who met enrollment criteria, 26.5% had nonventilated hospital-acquired bacterial pneumonia, 25.6% vHAPB, and 47.9% ventilator-associated bacterial pneumonia. Ventilator-associated bacterial pneumonia predominated in the Northeastern United States and in large urban teaching hospitals. Patients with nonventilated hospital-acquired bacterial pneumonia were oldest (mean 66.7 ?± 15.1 yr) and most likely White (76.9%), whereas those with ventilator-associated bacterial pneumonia were youngest (59.7 ?± 16.6 yr) and least likely White (70.3%). Ventilated hospital-acquired bacterial pneumonia was associated with the highest comorbidity burden (mean Charlson score 4.1 ?± 2.8) and ventilator-associated bacterial pneumonia with the lowest (3.2 ?± 2.5). Similarly, hospital mortality was highest among patients with ventilated hospital-acquired bacterial pneumonia (29.2%) and lowest in nonventilated hospital-acquired bacterial pneumonia (11.7%), with ventilator-associated bacterial pneumonia in-between (21.3%). Among survivors, 24.5% of nonventilated hospital-acquired bacterial pneumonia required a rehospitalization within 30 days of discharge, compared with 22.5% among ventilated hospital-acquired bacterial pneumonia and 18.8% ventilator-associated bacterial pneumonia. Unadjusted hospital length of stay after infection onset was longest among ventilator-associated bacterial pneumonia and shortest among nonventilated hospital-acquired bacterial pneumonia patients.

Median total hospital costs mirrored length of stay: ventilator-associated bacterial pneumonia $77,657, ventilated hospital-acquired bacterial pneumonia $62,464, and nonventilated hospital-acquired bacterial pneumonia $39,911.

CONCLUSIONS: Both hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia remain associated with significant mortality and cost in the United States. Our analyses confirm that of all three conditions, ventilated hospital-acquired bacterial pneumonia carries the highest risk of death. In contrast, ventilator-associated bacterial pneumonia remains most costly. Nonventilated hospital-acquired bacterial pneumonia survivors were most likely to require a readmission within 30 days of discharge.

# 美国非通气性医院获得性、通气性医院获得性和呼吸机相关细菌性肺炎的描述性流行病学和结局，2012-2019。

目的：探索呼吸机相关细菌性肺炎和医院获得性细菌性肺炎患者结局的多项随机对照试验表明，需要后续通气的医院获得性细菌性肺炎患者的死亡率高于未接受后续通气的患者（非通气）。住院获得性细菌性肺炎）或患有呼吸机相关细菌性肺炎。我们在一个大型美国数据库中检查了所有三种疾病的流行病学和结局。

设计：回顾性队列研究。

设置：253 家美国急症医院，为 Premier 数据库提供数据（包括微生物学），2012-2019。

患者：根据先前发表的国际疾病分类第 9 版 / 国际疾病分类第 10 版 - 临床修订算法略微修订的标准确定的医院获得性细菌性肺炎或呼吸机相关细菌性肺炎患者。

干预：无。

测量值和主要结果：在符合入组标准的 17819 例患者中，26.5% 患有非通气型医院获得性细菌性肺炎，25.6% 患有 vHAPB，47.9% 患有呼吸机相关细菌性肺炎。在美国东北部和大型城市教学医院，呼吸机相关细菌性肺炎占主导地位。非通气型医院获得性细菌性肺炎患者年龄最大（平均 66.7?15.1 岁），最可能为白人 (76.9%)，而呼吸机相关细菌性肺炎患者年龄最小（59.7?16.6 岁），不太可能为白人 (70.3%)。通气性医院获得性细菌性肺炎与最高的合并症负担相关（平均 Charlson 评分 4.1±2.8），与呼吸机相关细菌性肺炎相关的合并症负担最低 (3.2?±2.5)。同样，呼吸机治疗的医院获得性细菌性肺炎患者的住院死亡率最高 (29.2%)，非呼吸机治疗的医院获得性细菌性肺炎患者的住院死亡率最低 (11.7%)，呼吸机相关细菌性肺炎患者的住院死亡率为 (21.3%)。在存活者中，24.5% 的非通气医院获得性细菌性肺炎患者在出院后 30 天内需要再次住院治疗，而通气医院获得性细菌性肺炎患者中为 22.5%，呼吸机相关细菌性肺炎患者中为 18.8%。在呼吸机相关细菌性肺炎中，感染发生后未经调整的住院时间最长，在非通气的医院获得性细菌性肺炎患者中最短。

中位总住院费用反映了住院时间：呼吸机相关细菌性肺炎 $77,657，通气医院获得性细菌性肺炎 $62,464，非通气医院获得性细菌性肺炎 $39,911。

结论：在美国，医院获得性细菌性肺炎和呼吸机相关细菌性肺炎均与显著的死亡率和费用相关。我们的分析证实，在所有三种情况中，通气型医院获得性细菌性肺炎的死亡风险最高。相比之下，呼吸机相关细菌性肺炎的治疗费用仍然最高。非通气的医院获得性细菌性肺炎生存者在出院后 30 天内最可能需要再次入院。关键词：Humans; Female; Male; Middle Aged; Time Factors; Adult; Young Adult; Retrospective Studies; Outcome Assessment, Health Care; Hospital Mortality; United States; *Severity of Illness Index; Cost of Illness; Cross Infection/economics/*epidemiology; Healthcare-Associated Pneumonia/economics/*epidemiology; Pneumonia, Bacterial/economics/*epidemiology; Pneumonia, Ventilator-Associated/economics/*epidemiology

# A Simple Risk Score for Predicting Neurologic Outcome in Out-of-Hospital Cardiac Arrest Patients After Targeted Temperature Management.

3:428-439. DOI:10.1097/CCM.0000000000005266

Abstract:

OBJECTIVES: Although several risk factors for outcomes of out-of-hospital cardiac arrest patients have been identified, the cumulative risk of their combinations is not thoroughly clear, especially after targeted temperature management. Therefore, we aimed to develop a risk score to evaluate individual out-of-hospital cardiac arrest patient risk at early admission after targeted temperature management regarding poor neurologic status at discharge.

DESIGN: Retrospective observational cohort study.

SETTING: Two large academic medical networks in the United States.

PATIENTS: Out-of-hospital cardiac arrest survivors treated with targeted temperature management with age of 18 years old or older.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Based on the odds ratios, five identified variables (initial nonShockable rhythm, Leucocyte count < 4 or > 12 K/??L after targeted temperature management, total Adrenalin [epinephrine] ?‰? 5 mg, lack of oNlooker cardiopulmonary resuscitation, and Time duration of resuscitation ?‰? 20 min) were assigned weighted points. The sum of the points was the total risk score known as the SLANT score (range 0-21 points) for each patient. Based on our risk prediction scores, patients were divided into three risk categories as moderate-risk group (0-7), high-risk group (8-14), and very high-risk group (15-21). Both the ability of our risk score to predict the rates of poor neurologic outcomes at discharge and in-hospital mortality were significant under the Cochran-Armitage trend test (p < 0.001 and p < 0.001, respectively).

CONCLUSIONS: The risk of poor neurologic outcomes and in-hospital mortality of out-of-hospital cardiac arrest survivors after targeted temperature management is easily assessed using a risk score model derived using the readily available information. Its clinical utility needed further investigation.

# 一种预测靶向温度管理后院外心脏骤停患者神经结局的简单风险评分。

目的：虽然已经确定了院外心脏骤停患者结局的几个风险因素，但其联合治疗的累积风险尚不完全清楚，特别是在进行针对性温度管理后。因此，我们旨在开发一个风险评分来评价个体院外心脏骤停患者在出院时神经功能状态较差的针对性温度管理后早期入院时的风险。

设计：回顾性观察性队列研究。

单位：美国两个大型学术医疗网络。

患者：院外心脏骤停幸存者接受针对性温度管理，年龄在 18 岁或以上。

干预：无。

测量值和主要结果：基于比值比，5 个确定的变量（初始不可休克节律、目标温度管理后白细胞计数 <4 或> 12 K/?L、总肾上腺素 [肾上腺素] ≥ 5 mg、无 oNlooker 心肺复苏、和复苏持续时间 ≥ 20 min）指定加权点。评分之和是被称为每例患者的 SLANT 评分（范围 0-21 分）的总风险评分。根据我们的风险预测评分，将患者分为 3 个风险类别，中度风险组 (0-7)、高风险组 (8-14) 和极高风险组 (15-21)。在 Cochran-Armitage 趋势检验中，我们的风险评分预测出院时较差神经学结局发生率和住院死亡率的能力均显著（分别为 p < 0.001 和 p < 0.001）。

结论：采用现有信息得出的风险评分模型，易于评估靶向温度管理后院外心脏骤停存活者的不良神经系统结局和院内死亡率风险。其临床实用性需要进一步研究。关键词：Humans; Treatment Outcome; Female; Male; Middle Aged; Prognosis; Time Factors; Aged; Adult; Cohort Studies; Risk Factors; Retrospective Studies; *Cardiopulmonary Resuscitation; Hypothermia, Induced/*mortality; Out-of-Hospital Cardiac Arrest/mortality/*therapy; Survivors/*statistics & numerical data

# Association Between Pandemic Coronavirus Disease 2019 Public Health Measures and Reduction in Critical Care Utilization Across ICUs in Alberta, Canada.

3:353-362. DOI:10.1097/CCM.0000000000005275

Abstract:

OBJECTIVES: The coronavirus disease 2019 pandemic has disrupted critical care services across the world. In anticipation of surges in the need for critical care services, governments implemented "lockdown" measures to preserve and create added critical care capacity. Herein, we describe the impact of lockdown measures on the utilization of critical care services and patient outcomes compared with nonlockdown epochs in a large integrated health region.

DESIGN: This was a population-based retrospective cohort study.

SETTING: Seventeen adult ICUs across 14 acute care hospitals in Alberta, Canada.

PATIENTS: All adult (age ?‰? 15 yr) patients admitted to any study ICU.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The main exposure was ICU admission during "lockdown" occurring between March 16, 2020, and June 30, 2020.

This period was compared with two nonpandemic control periods: "year prior" (March 16, 2019, to June 30, 2019) and "pre lockdown" immediately prior (November 30, 2019, to March 15, 2020). The primary outcome was the number of ICU admissions.

Secondary outcomes included the following: daily measures of ICU utilization, ICU duration of stay, avoidable delay in ICU discharge, and occupancy; and patient outcomes. Mixed multilevel negative binomial regression and interrupted time series regression were used to compare rates of ICU admissions between periods. Multivariable regressions were used to compare patient outcomes between periods. During the lockdown, there were 3,649 ICU admissions (34.1 [8.0] ICU admissions/d), compared with 4,125 (38.6 [9.3]) during the prelockdown period and 3,919 (36.6 [8.7]) during the year prior. Mean bed occupancy declined significantly during the lockdown compared with the nonpandemic periods (78.7%, 95.9%, and 96.4%; p < 0.001). Avoidable ICU discharge delay also decreased significantly (42.0%, 53.2%, and 58.3%; p < 0.001). During the lockdown, patients were younger, had fewer comorbid diseases, had higher acuity, and were more likely to be medical admissions compared with the nonpandemic periods. Adjusted ICU and hospital mortality and ICU and hospital lengths of stay were significantly lower during the lockdown compared with nonpandemic periods.

CONCLUSIONS: The coronavirus disease 2019 lockdown resulted in substantial changes to ICU utilization, including a reduction in admissions, occupancy, patient lengths of stay, and mortality.

# 2019 年加拿大艾伯塔省 ICU 中流行冠状病毒病公共卫生措施与减少重症监护利用之间的相关性。

目的：2019 年的冠状病毒病大流行扰乱了全球的重症监护服务。预期危重症护理服务需求激增，各国政府实施了 “封锁” 措施，以保持和创造额外的危重症护理能力。在此，我们描述了在一个大型综合健康地区，与非封锁时期相比，封锁措施对重症监护服务利用和患者结局的影响。

设计：这是一项基于人群的回顾性队列研究。

设置：加拿大艾伯塔省 14 家急症护理医院的 17 个成人 ICU。

患者：所有入住任何研究 ICU 的成人（年龄 ≥ 15 岁）患者。

干预：无。

测量和主要结果：主要暴露是 2020 年 3 月 16 日至 2020 年 6 月 30 日期间发生的 “封锁” 期间入住 ICU。

将这一时期与两个非大流行控制时期进行比较：“前一年”（2019 年 3 月 16 日至 2019 年 6 月 30 日）和紧邻的 “预锁定”（2019 年 11 月 30 日至 2020 年 3 月 15 日）。主要结局是 ICU 住院次数。

次要结局包括以下指标：ICU 每日利用率、ICU 住院时间、ICU 出院可避免的延迟和占用时间；以及患者结局。使用混合多级负二项回归和中断时间序列回归来比较不同时期的 ICU 入院率。使用多变量回归比较不同时期的患者结局。在封锁期间，共有 3,649 次 ICU 入院（34.1 [8.0] 次 ICU 入院 / 天），相比之下，封锁前期有 4,125 次（38.6 [9.3] 次），前一年有 3,919 次（36.6 [8.7] 次）。与无大流行期相比，封锁期间平均床位使用率显著下降（78.7%、95.9% 和 96.4%；p < 0.001）。可避免的 ICU 出院延迟也显著减少（42.0%、53.2% 和 58.3%；p < 0.001）。在封锁期间，与非大流行期相比，患者更年轻，合并症更少，急性程度更高，更可能是内科入院。在封锁期间，调整后的 ICU 和住院死亡率以及 ICU 和住院时间显著低于非大流行期间。

结论：2019 年冠状病毒病的封锁导致了 ICU 利用率的实质性改变，包括入院率、占用率、患者住院时间和死亡率的降低。关键词：Humans; Female; Male; Middle Aged; Aged; APACHE; Adult; Critical Care; Retrospective Studies; Pandemics; Hospital Mortality; Age Factors; Sex Factors; Comorbidity; SARS-CoV-2; COVID-19/*epidemiology; Patient Discharge; Alberta/epidemiology; Intensive Care Units/*statistics & numerical data; Bed Occupancy; Communicable Disease Control/*statistics & numerical data; Hospitalization/statistics & numerical data; Public Health

# Improving Timeliness of Antibiotic Administration Using a Provider and Pharmacist Facing Sepsis Early Warning System in the Emergency Department Setting: A Randomized Controlled Quality Improvement Initiative., Tarabichi, Yasir

3:418-427. DOI:10.1097/CCM.0000000000005267

Abstract:

OBJECTIVES: Results of pre-post intervention studies of sepsis early warning systems have been mixed, and randomized clinical trials showing efficacy in the emergency department setting are lacking. Additionally, early warning systems can be resource-intensive and may cause unintended consequences such as antibiotic or IV fluid overuse. We assessed the impact of a pharmacist and provider facing sepsis early warning systems on timeliness of antibiotic administration and sepsis-related clinical outcomes in our setting.

DESIGN: A randomized, controlled quality improvement initiative.

SETTING: The main emergency department of an academic, safety-net healthcare system from August to December 2019.

PATIENTS: Adults presenting to the emergency department.

INTERVENTION: Patients were randomized to standard sepsis care or standard care augmented by the display of a sepsis early warning system-triggered flag in the electronic health record combined with electronic health record-based emergency department pharmacist notification.

MEASUREMENTS AND MAIN RESULTS: The primary process measure was time to antibiotic administration from arrival. A total of 598 patients were included in the study over a 5-month period (285 in the intervention group and 313 in the standard care group). Time to antibiotic administration from emergency department arrival was shorter in the augmented care group than that in the standard care group (median, 2.3 hr [interquartile range, 1.4-4.7 hr] vs 3.0 hr [interquartile range, 1.6-5.5 hr]; p = 0.039). The hierarchical composite clinical outcome measure of days alive and out of hospital at 28 days was greater in the augmented care group than that in the standard care group (median, 24.1 vs 22.5 d; p = 0.011). Rates of fluid resuscitation and antibiotic utilization did not differ.

CONCLUSIONS: In this single-center randomized quality improvement initiative, the display of an electronic health record-based sepsis early warning system-triggered flag combined with electronic health record-based pharmacist notification was associated with shorter time to antibiotic administration without an increase in undesirable or potentially harmful clinical interventions.

# 在急诊室使用提供者和药剂师应对败血症预警系统来提高抗生素给药的时效性：一项随机对照质量改进倡议。

目的：败血症预警系统的干预前 - 干预后研究结果好坏参半，缺乏显示在急诊科环境中疗效的随机临床试验。此外，早期预警系统可能是资源密集的，可能导致意外后果，如抗生素或静脉输液过量。我们评估了药剂师和面对败血症预警系统的提供者对抗生素给药时效性和我们环境中败血症相关临床结局的影响。

设计：一项随机化、对照质量改进倡议。

背景：2019 年 8 月至 12 月，学术级安全网医疗保健系统的主要急诊科。

患者：前往急诊科就诊的成人。

干预：将患者随机分配至标准败血症治疗组或标准治疗组，通过在电子健康记录中显示败血症早期预警系统触发的标志并结合基于电子健康记录的急诊科药剂师通知进行强化。

测量和主要结果：主要过程测量是从到达开始抗生素给药的时间。在 5 个月期间，共有 598 例患者被纳入研究（干预组 285 例，标准治疗组 313 例）。增强护理组从到达急诊室至抗生素给药时间比标准护理组短（中位数 2.3 h [四分位距，1.4-4.7 h] vs 3.0 h [四分位距，1.6-5.5 h]；p = 0.039）。增强护理组第 28 天的存活和出院天数的分层复合临床结局指标大于标准护理组（中位数，24.1 vs 22.5 天；p = 0.011）。液体复苏率和抗生素使用率没有差异。

结论：在该单中心随机质量改善计划中，显示基于电子健康记录的败血症预警系统触发的标志结合基于电子健康记录的药剂师通知与抗生素给药时间更短相关，而不良或潜在有害临床干预的增加。关键词：Humans; Algorithms; Anti-Bacterial Agents/*therapeutic use; Sepsis/*drug therapy; *Clinical Protocols; Emergency Service, Hospital/*organization & administration; Process Assessment, Health Care; Quality Improvement/*organization & administration; Time-to-Treatment/*statistics & numerical data

# Peripheral Oxygen Saturation Facilitates Assessment of Respiratory Dysfunction in the Sequential Organ Failure Assessment Score With Implications for the Sepsis-3 Criteria.

3:e272-e283. DOI:10.1097/CCM.0000000000005318

Abstract:

OBJECTIVES: Sequential Organ Failure Assessment score is the basis of the Sepsis-3 criteria and requires arterial blood gas analysis to assess respiratory function. Peripheral oxygen saturation is a noninvasive alternative but is not included in neither Sequential Organ Failure Assessment score nor Sepsis-3. We aimed to assess the association between worst peripheral oxygen saturation during onset of suspected infection and mortality.

DESIGN: Cohort study of hospital admissions from a main cohort and emergency department visits from four external validation cohorts between year 2011 and 2018. Data were collected from electronic health records and prospectively by study investigators.

SETTING: Eight academic and community hospitals in Sweden and Canada.

PATIENTS: Adult patients with suspected infection episodes.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The main cohort included 19,396 episodes (median age, 67.0 [53.0-77.0]; 9,007 [46.4%] women; 1,044 [5.4%] died). The validation cohorts included 10,586 episodes (range of median age, 61.0-76.0; women 42.1-50.2%; mortality 2.3-13.3%). Peripheral oxygen saturation levels 96-95% were not significantly associated with increased mortality in the main or pooled validation cohorts. At peripheral oxygen saturation 94%, the adjusted odds ratio of death was 1.56 (95% CI, 1.10-2.23) in the main cohort and 1.36 (95% CI, 1.00-1.85) in the pooled validation cohorts and increased gradually below this level. Respiratory assessment using peripheral oxygen saturation 94-91% and less than 91% to generate 1 and 2 Sequential Organ Failure Assessment points, respectively, improved the discrimination of the Sequential Organ Failure Assessment score from area under the receiver operating characteristics 0.75 (95% CI, 0.74-0.77) to 0.78 (95% CI, 0.77-0.80; p < 0.001). Peripheral oxygen saturation/Fio2 ratio had slightly better predictive performance compared with peripheral oxygen saturation alone, but the clinical impact was minor.

CONCLUSIONS: These findings provide evidence for assessing respiratory function with peripheral oxygen saturation in the Sequential Organ Failure Assessment score and the Sepsis-3 criteria. Our data support using peripheral oxygen saturation thresholds 94% and 90% to get 1 and 2 Sequential Organ Failure Assessment respiratory points, respectively. This has important implications primarily for emergency practice, rapid response teams, surveillance, research, and resource-limited settings.

# 周围血氧饱和度有助于在序贯器官衰竭评估评分中评估呼吸功能障碍，具有脓毒血症 - 3 标准的意义。

目的：序贯器官衰竭评估评分是脓毒血症 - 3 标准的基础，需要动脉血气分析评估呼吸功能。外周血氧饱和度是一种非侵入性的替代指标，但在序贯器官衰竭评估评分和脓毒血症 - 3 评分中均未纳入。我们旨在评估疑似感染发作期间最差外周血氧饱和度与死亡率之间的相关性。

设计：2011 年至 2018 年间，对主要队列的入院情况和 4 个外部验证队列的急诊科就诊情况进行队列研究。数据收集自电子健康记录，由研究者前瞻性收集。

单位：瑞典和加拿大的 8 家学术和社区医院。

患者：具有疑似感染发作的成人患者。

干预：无。

测量和主要结果：主要队列包括 19,396 起事件（中位年龄，67.0 [53.0-77.0]；9,007 [46.4%] 例女性；1,044 [5.4%] 例死亡）。验证队列包括 10586 起发作（中位年龄范围 61.0-76.0 岁；女性 42.1-50.2%；死亡率 2.3-13.3%）。在主要队列或合并验证队列中，外周血氧饱和度水平 96-95% 与死亡率增加无显著相关性。在外周血氧饱和度为 94% 时，主要队列和合并验证队列的死亡校正比值比分别为 1.56 (95% CI，1.10-2.23) 和 1.36 (95% CI，1.00-1.85)，并逐渐低于该水平。使用外周血氧饱和度 94-91% 和小于 91% 分别生成 1 个和 2 个序贯器官衰竭评估点的呼吸评估，提高了序贯器官衰竭评估评分从接收者操作特征下面积 0.75 (95% CI，0.74-0.77) 到 0.78（95% CI，0.77-0.80；p < 0.001). 与单独外周血氧饱和度相比，外周血氧饱和度 / Fio2 比值具有略好的预测性能，但临床影响较小。

结论：这些结果提供了在序贯器官衰竭评估评分和败血症 - 3 标准中使用外周血氧饱和度评估呼吸功能的证据。我们的数据支持使用外周血氧饱和度阈值 94% 和 90% 分别获得 1 个和 2 个序贯器官衰竭评估呼吸点。这对急救实践、快速响应团队、监测、研究和资源有限的环境具有重要影响。关键词：Humans; Female; Male; Middle Aged; Aged; Cohort Studies; Retrospective Studies; Hospital Mortality; Systemic Inflammatory Response Syndrome; Oxygen Consumption/*physiology; Oxygen/blood; *Intensive Care Units; *Organ Dysfunction Scores; Oxygen Saturation/*physiology; Sepsis/*blood/*mortality

# Physical Rehabilitation in the ICU: A Systematic Review and Meta-Analysis.

3:375-388. DOI:10.1097/CCM.0000000000005285

Abstract:

OBJECTIVES: Significant variability exists in physical rehabilitation modalities and dosage used in the ICU. Our objective was to investigate the effect of physical rehabilitation in ICU on patient outcomes, the impact of task-specific training, and the dose-response profile.

DATA SOURCES: A systematic search of Ovid MEDLINE, Cochrane Library, EMBASE, and CINAHL plus databases was undertaken on the May 28, 2020.

STUDY SELECTION: Randomized controlled trials and controlled clinical trials investigating physical rehabilitation commencing in the ICU in adults were included. Outcomes included muscle strength, physical function, duration of mechanical ventilation, ICU and hospital length of stay, mortality, and health-related quality of life. Two independent reviewers assessed titles, abstracts, and full texts against eligibility criteria.

DATA EXTRACTION: Details on intervention for all groups were extracted using the template for intervention description and replication checklist.

DATA SYNTHESIS: Sixty trials were included, with a total of 5,352 participants. Random-effects pooled analysis showed that physical rehabilitation improved physical function at hospital discharge (standardized mean difference, 0.22; 95% CI, 0.00-0.44), reduced ICU length of stay by 0.8 days (mean difference, -0.80 d; 95% CI, -1.37 to -0.23 d), and hospital length of stay by 1.75 days (mean difference, -1.75 d; 95% CI, -3.03 to -0.48 d). Physical rehabilitation had no impact on the other outcomes. The intervention was more effective in trials where the control group received low-dose physical rehabilitation and in trials that investigated functional exercises.

CONCLUSIONS: Physical rehabilitation in the ICU improves physical function and reduces ICU and hospital length of stay. However, it does not appear to impact other outcomes.

# ICU 中的身体康复：一项系统回顾和荟萃分析。

目的：ICU 中的身体康复模式和使用剂量存在显著差异。我们的目的是研究 ICU 中身体康复对患者结局的影响、任务特定训练的影响和剂量 - 反应特征。

资料来源：于 2020 年 5 月 28 日系统检索 Ovid MEDLINE、Cochrane Library、EMBASE 和 CINAHL plus 数据库。

研究选择：纳入从 ICU 开始的成人肢体康复的随机对照试验和对照临床试验。结局包括肌力、身体功能、机械通气持续时间、ICU 和住院时间、死亡率和健康相关生活质量。两名独立的审查员根据合格性标准评估标题、摘要和全文。

数据提取：使用干预描述和复制检查表模板提取所有组的干预详情。

数据综合：共纳入 60 项试验，共计 5352 例参与者。随机效应合并分析显示，身体康复改善了出院时的身体功能（标准化平均差异，0.22；95% CI，0.00-0.44），ICU 住院时间缩短了 0.8 天（平均差异，-0.80 天；95% CI，-1.37 至 - 0.23 天），住院时间缩短了 1.75 天（平均差异，-1.75 天；95% CI，-3.03 至 - 0.48 天）。身体康复对其他结局无影响。在对照组接受低剂量身体康复治疗的试验和研究功能锻炼的试验中，这种干预更有效。

结论：ICU 的身体康复改善了身体功能，减少了 ICU 和住院时间。但是，它似乎不会影响其他结局。关键词：Humans; *Muscle Strength; *Intensive Care Units; Length of Stay/statistics & numerical data; Critical Illness/*rehabilitation; Exercise Therapy/statistics & numerical data; Patient Discharge/statistics & numerical data; Physical Therapy Modalities/*statistics & numerical data; Respiration, Artificial/nursing

# Postmortem Evidence of Brain Inflammatory Markers and Injury in Septic Patients: A Systematic Review., Barichello, Tatiana

3:e241-e252. DOI:10.1097/CCM.0000000000005307

Abstract:

OBJECTIVES: Sepsis is a life-threatening organ dysfunction caused by a host's unregulated immune response to eliminate the infection. After hospitalization, sepsis survivors often suffer from long-term impairments in memory, attention, verbal fluency, and executive functioning. To understand the effects of sepsis and the exacerbated peripheral inflammatory response in the brain, we asked the question: What are the findings and inflammatory markers in the brains of deceased sepsis patients? To answer this question, we conducted this systematic review by the recommendations of Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

DATA SOURCES: Relevant studies were identified by searching the PubMed/National Library of Medicine, PsycINFO, EMBASE, Bibliographical Index in Spanish in Health Sciences, Latin American and Caribbean Health Sciences Literature, and Web of Science databases for peer-reviewed journal articles published on April 05, 2021.

STUDY SELECTION: A total of 3,745 articles were included in the primary screening; after omitting duplicate articles, animal models, and reviews, 2,896 articles were selected for the study. These studies were selected based on the title and abstract, and 2,772 articles were still omitted based on the exclusion criteria.

DATA EXTRACTION: The complete texts of the remaining 124 articles were obtained and thoroughly evaluated for the final screening, and 104 articles were included.

DATA SYNTHESIS: The postmortem brain had edema, abscess, hemorrhagic and ischemic injuries, infarction, hypoxia, atrophy, hypoplasia, neuronal loss, axonal injuries, demyelination, and necrosis.

CONCLUSIONS: The mechanisms by which sepsis induces brain dysfunction are likely to include vascular and neuronal lesions, followed by the activation of glial cells and the presence of peripheral immune cells in the brain.

# 脓毒血症患者脑部炎症标志物和损伤的尸检证据：一项系统回顾。

目的：败血症是一种危及生命的器官功能障碍，由宿主为消除感染而产生的不受调节的免疫应答所致。住院后，败血症幸存者通常会出现记忆、注意力、语言流畅性和执行功能的长期损害。为了了解败血症和大脑外周炎症反应加剧的影响，我们提出了以下问题：在死亡的败血症患者的大脑中有哪些发现和炎症标志物？为了回答这个问题，我们通过推荐的系统评价和荟萃分析首选报告项目进行了这项系统评价。

资料来源：通过检索 PubMed / 美国国家医学图书馆、PsycINFO、EMBASE、西班牙健康科学参考书目索引、拉丁美洲和加勒比海健康科学文献和 Web of Science 数据库中 2021 年 4 月 5 日发表的同行评议期刊文章，查找相关研究。

研究选择：初筛共纳入 3745 篇文献，省略重复文献、动物模型和综述后，选择 2896 篇文献进行研究。根据标题和摘要选择这些研究，根据排除标准仍遗漏 2772 篇文献。

资料提炼：获取其余 124 篇文献的完整正文，全面评价后进行最终筛选，纳入 104 篇文献。

资料综合：尸检后脑出现水肿、脓肿、出血和缺血性损伤、梗死、缺氧、萎缩、发育不全、神经元缺失、轴突损伤、脱髓鞘和坏死。

结论：脓毒症诱导脑功能障碍的机制很可能包括血管和神经元病变，其次是胶质细胞的活化和脑内外周免疫细胞的存在。关键词：Humans; Magnetic Resonance Imaging; Biomarkers; Atrophy/pathology; Autopsy; Brain/*diagnostic imaging/*metabolism/pathology; Inflammation/*diagnostic imaging/*metabolism/pathology; Sepsis/diagnostic imaging/*metabolism/*pathology

# Bursting at the Seams: Barotrauma in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome Patients., Hossain, Saamia

3:531-534. DOI:10.1097/CCM.0000000000005291

# 伤口破裂：冠状病毒病 2019 年急性呼吸窘迫综合征患者的气压伤。

关键词：Humans; *COVID-19; SARS-CoV-2; *Respiratory Distress Syndrome/therapy; *Barotrauma

# Should We Prolong the Observation Period for Neurological Recovery After Cardiac Arrest?, Tsai, Min-Shan

3:389-397. DOI:10.1097/CCM.0000000000005264

Abstract:

OBJECTIVES: To evaluate whether the recommended observation period of 7 days for cardiac arrest survivors is sufficient for conscious recovery and to identify the variables associated with eventual neurologic recovery among patients with delayed awakening.

DESIGN: A retrospective cohort study.

SETTING: A single tertiary medical center.

PATIENTS: Five-hundred twenty-nine nontraumatic adult cardiac arrest survivors with prearrest favorable neurologic function (Cerebral Performance Category 1-2) who survived to hospital discharge during 2011-2019.

INTERVENTIONS: The enrolled patients were classified into favorable (Cerebral Performance Category 1-2) and poor (Cerebral Performance Category 3-4) neurologic recovery according to their neurologic function at hospital discharge. Among patients with favorable neurologic recovery, those who recovered within 7 days were assigned to the early recovery group or after 7 days as the late recovery group.

MEASUREMENTS AND MAIN RESULTS: There were 395 patients exhibiting favorable neurologic recovery (n = 357 in the early group, n = 38 in late group) and 134 patients exhibiting poor neurologic recovery (poor recovery group). Among patients who remained unconscious on day 7, delayed awakening was associated with male sex (odds ratio [OR], 3.905; 95% CI, 1.153-13.221), prehospital return of spontaneous circulation (OR, 7.628; 95% CI, 2.084-27.922), therapeutic hypothermia (OR, 4.320; 95% CI, 1.624-11.488), and extracorporeal cardiopulmonary resuscitation (OR, 4.508; 95% CI, 1.414-14.371). Being transferred from another hospital, however, was less likely to be associated with delayed awakening (OR, 0.061; 95% CI, 0.009-0.431). The median duration for patients to regain clear consciousness in the late recovery group was 12.12 days. No patient who recovered consciousness had an unfavorable electroencephalography pattern, however, in patients with poor recovery, the 7-day electroencephalography showed 45 patients with generalized suppression (33.6%), two with burst suppression (1.5%), 14 with seizure/epileptic discharge (10.5%), and one with status epilepticus (0.7%).

CONCLUSIONS: Up to 9.6% of cardiac arrest patients with favorable outcomes recover consciousness after the recommended 7 days of observation, indicating the observation time of 7 days seems justified but longer duration may be needed. The results of the culturally and clinically isolated population may limit the application to other population.

# 我们是否应该延长心脏骤停后神经功能恢复的观察期？

目的：评价心脏骤停幸存者推荐的 7 天观察期是否足以使意识恢复，并确定与延迟觉醒患者最终神经功能恢复相关的变量。

设计：回顾性队列研究。

地点：一家三级医疗中心。

患者：在 2011-2019 年期间存活至出院的 529 例非创伤性成人心脏骤停生存者，其停前神经功能良好（脑功能 1-2 类）。

干预：根据出院时的神经功能，将入组患者分类为良好（脑功能 1-2 类）和不良（脑功能 3-4 类）神经功能恢复。在神经功能恢复良好的患者中，7 天内恢复的患者归为早期恢复组，7 天后恢复的患者归为晚期恢复组。

测量和主要结果：395 例患者神经功能恢复良好（早期组 n = 357，晚期组 n = 38），134 例患者神经功能恢复较差（恢复较差组）。在第 7 天保持无意识的患者中，苏醒延迟与男性（比值比 [OR]，3.905；95% CI，1.153-13.221）、院前自主循环恢复 (OR，7.628；95% CI，2.084-27.922)、治疗性低体温 (OR，4.320；95% CI，1.624-11.488) 和体外心肺复苏（OR，4.508；95% CI，1.414-14.371). 但是，从另一家医院转诊的患者不太可能与觉醒延迟相关 (OR，0.061；95% CI，0.009-0.431)。后期恢复组患者恢复意识的中位时间为 12.12 天。意识恢复的患者均无不良脑电图模式，然而，在恢复不良的患者中，7 天脑电图显示 45 例患者出现了全身性抑制 (33.6%)，2 例出现了爆发抑制 (1.5%)，14 例出现了癫痫发作 / 癫痫性放电 (10.5%)，1 例出现了癫痫持续状态 (0.7%)。

结论：高达 9.6% 结局良好的心脏骤停患者在推荐的 7 天观察后恢复意识，表明 7 天的观察时间似乎是合理的，但可能需要更长的持续时间。文化和临床上孤立的人群的结果可能限制了其他人群的应用。关键词：Humans; Treatment Outcome; Female; Male; Middle Aged; Time Factors; Aged; Adult; Retrospective Studies; Patient Discharge/*statistics & numerical data; Survivors/*statistics & numerical data; Cardiopulmonary Resuscitation/*statistics & numerical data; Heart Arrest/*rehabilitation; Neurologic Examination/*statistics & numerical data

# Race Does Not Impact Sepsis Outcomes When Considering Socioeconomic Factors in Multilevel Modeling.

3:410-417. DOI:10.1097/CCM.0000000000005217

Abstract:

OBJECTIVES: To determine whether race is a major determinant of sepsis outcomes when controlling for socioeconomic factors.

DESIGN: Retrospective cohort study.

SETTING: Barnes-Jewish Hospital a 1,350 bed academic medical center.

PATIENTS: Eleven-thousand four-hundred thirty-two patients hospitalized between January 2010 and April 2017 with sepsis and septic shock.

INTERVENTIONS: Multilevel random effects modeling was employed whereby patients were nested within ZIP codes. Individual patient characteristics and socioeconomic variables aggregated at the ZIP code level (education, employment status, income, poverty level, access to healthcare) were included in the model.

MEASUREMENTS AND MAIN RESULTS: In hospital mortality, length of stay, need for vasopressors, and mechanical ventilation were the main endpoints. Black patients had more comorbidities than White patients except for cirrhosis and malignancy. In unadjusted comparisons, White individuals were more likely to require mechanical ventilation and had higher mortality rates and longer hospital stays for both low- and high-income groups. When nesting within ZIP codes and accounting for socioeconomic variables, race did not have a significant effect on mortality. Non-White races had lower odds ratio for mechanical ventilation.

CONCLUSIONS: Our study demonstrates that race is not an independent risk factor for sepsis mortality, as well as sepsis-related length of stay. We should expand our inquiry into determinants of sepsis outcomes by including socioeconomic variables.

# 在多级建模中考虑社会经济因素时，人种不会影响败血症结局。

目的：在控制社会经济因素时，确定人种是否为败血症结局的主要决定因素。

设计：回顾性队列研究。

单位：Barnes-Jewish Hospital a 1,350 bed academic medical center。

患者：2010 年 1 月至 2017 年 4 月间有 11432 名败血症和感染性休克患者住院。

干预：采用多级随机效应模型，将患者嵌套在 ZIP 编码内。该模型纳入了 ZIP 编码水平（教育、就业状况、收入、贫困水平、获得医疗保健）汇总的个体患者特征和社会经济学变量。

测量和主要结果：住院死亡率、住院时间、血管加压素需求和机械通气是主要终点。除肝硬化和恶性肿瘤外，黑人患者的合并症多于白人患者。在未校正的比较中，白人个体更可能需要机械通气，低收入组和高收入组的死亡率更高，住院时间更长。当在 ZIP 编码下嵌套并考虑社会经济学变量时，人种对死亡率无显著影响。非白人种族的机械通气比值比较低。

结论：我们的研究表明，人种不是败血症死亡率以及败血症相关住院时间的独立风险因素。我们应通过纳入社会经济变量来扩大对败血症结局决定因素的调查。关键词：Humans; Retrospective Studies; Outcome Assessment, Health Care; Hospital Mortality; Socioeconomic Factors; *Severity of Illness Index; *Health Status Disparities; Racial Groups/*statistics & numerical data; Sepsis/ethnology/*mortality; Shock, Septic/mortality

# Pathophysiologic Signature of Impending ICU Hypoglycemia in Bedside Monitoring and Electronic Health Record Data: Model Development and External Validation., Horton, William B.

3:e221-e230. DOI:10.1097/CCM.0000000000005171

Abstract:

OBJECTIVES: We tested the hypothesis that routine monitoring data could describe a detailed and distinct pathophysiologic phenotype of impending hypoglycemia in adult ICU patients.

DESIGN: Retrospective analysis leading to model development and validation.

SETTING: All ICU admissions wherein patients received insulin therapy during a 4-year period at the University of Virginia Medical Center. Each ICU was equipped with continuous physiologic monitoring systems whose signals were archived in an electronic data warehouse along with the entire medical record.

PATIENTS: Eleven thousand eight hundred forty-seven ICU patient admissions.

INTERVENTIONS: The primary outcome was hypoglycemia, defined as any episode of blood glucose less than 70 mg/dL where 50% dextrose injection was administered within 1 hour. We used 61 physiologic markers (including vital signs, laboratory values, demographics, and continuous cardiorespiratory monitoring variables) to inform the model.

MEASUREMENTS AND MAIN RESULTS: Our dataset consisted of 11,847 ICU patient admissions, 721 (6.1%) of which had one or more hypoglycemic episodes. Multivariable logistic regression analysis revealed a pathophysiologic signature of 41 independent variables that best characterized ICU hypoglycemia. The final model had a cross-validated area under the receiver operating characteristic curve of 0.83 (95% CI, 0.78-0.87) for prediction of impending ICU hypoglycemia. We externally validated the model in the Medical Information Mart for Intensive Care III critical care dataset, where it also demonstrated good performance with an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.77-0.81).

CONCLUSIONS: We used data from a large number of critically ill inpatients to develop and externally validate a predictive model of impending ICU hypoglycemia. Future steps include incorporating this model into a clinical decision support system and testing its effects in a multicenter randomized controlled clinical trial.

# 床旁监测和电子病历数据中 ICU 即将发生低血糖的病理生理学特征：模型开发和外部验证。

目的：我们检验了以下假设：常规监测数据可以描述 ICU 成人患者即将发生低血糖的详细和独特的病理生理表型。

设计：通过回顾性分析开发和验证模型。

设置：弗吉尼亚大学医学中心所有 4 年内患者接受胰岛素治疗的 ICU 入院。每间 ICU 均配备了连续生理监测系统，其信号与整个病历一起存档在电子数据仓库中。

患者：1847 例 ICU 患者入院。

干预：主要结局为低血糖，定义为血糖低于 70 mg/dL 的任何发作，在 1 小时内注射 50% 葡萄糖。我们使用 61 个生理标志物（包括生命体征、实验室检查值、人口统计学和连续心肺监测变量）来告知模型。

测量值和主要结果：我们的数据集包括 11847 例 ICU 患者，其中 721 例 (6.1%) 发生一次或多次低血糖发作。多变量逻辑回归分析显示病理生理学特征的 41 个独立变量最能描述 ICU 低血糖。最终模型在预测即将发生 ICU 低血糖的受试者工作特征曲线下面积为 0.83 (95% CI，0.78-0.87)。我们在 Medical Information Mart for Intensive Care III 急救护理数据集中对该模型进行了外部验证，其还表现出良好的性能，受试者操作特征曲线下面积为 0.79 (95% CI，0.77-0.81)。

结论：我们使用大量危重住院患者的数据来开发和外部验证即将发生 ICU 低血糖的预测模型。未来的步骤包括将该模型纳入临床决策支持系统，并在多中心随机对照临床试验中检验其效果。关键词：Humans; Monitoring, Physiologic; Male; Middle Aged; Retrospective Studies; ROC Curve; *Intensive Care Units; Critical Illness/epidemiology; Critical Care/*statistics & numerical data; Machine Learning; Electronic Health Records/*statistics & numerical data; Hypoglycemia/*diagnosis; Point-of-Care Testing/*statistics & numerical data

# Tidal Volume-Dependent Activation of the Renin-Angiotensin System in Experimental Ventilator-Induced Lung Injury.

2:e220. DOI:10.1097/CCM.0000000000005495

Abstract:

OBJECTIVES: Ventilator-induced lung injury (VILI) is a major contributor to morbidity and mortality in critically ill patients. Mechanical damage to the lungs is potentially aggravated by the activation of the renin-angiotensin system (RAS). This article describes RAS activation profiles in VILI and discusses the effects of angiotensin (Ang) 1-7 supplementation or angiotensin-converting enzyme (ACE) inhibition with captopril as protective strategies.

DESIGN: Animal study.

SETTING: University research laboratory.

SUBJECTS: C57BL/6 mice.

INTERVENTIONS: Anesthetized mice (n = 12-18 per group) were mechanically ventilated with low tidal volume (LVT, 6 mL/kg), high tidal volume (HVT, 15 mL/kg), or very high tidal volume (VHVT, 30 mL/kg) for 4 hours, or killed after 3 minutes (sham). Additional VHVT groups received infusions of 60 ??g/kg/hr Ang 1-7 or a single dose of 100 mg/kg captopril.

MEASUREMENTS AND MAIN RESULTS: VILI was characterized by increased bronchoalveolar lavage fluid levels of interleukin (IL)-6, keratinocyte-derived cytokine, and macrophage inflammatory protein-2 (MIP2). The Ang metabolites in plasma measured with liquid chromatography tandem mass spectrometry showed a strong activation of the classical (Ang I, Ang II) and alternative RAS (Ang 1-7, Ang 1-5), with highest concentrations found in the HVT group. Although the lung-tissue ACE messenger RNA expression was unchanged, its protein expression showed a dose-dependent increase under mechanical ventilation. The ACE2 messenger RNA expression decreased in all ventilated groups, whereas ACE2 protein levels remained unchanged. Both captopril and Ang 1-7 led to markedly increased Ang 1-7 plasma levels, decreased Ang II levels, and ACE activity (Ang II/Ang I ratio), and effectively prevented VILI.

CONCLUSIONS: VILI is accompanied by a strong activation of the RAS. Based on circulating Ang metabolite levels and tissue expression of RAS enzymes, classical ACE-dependent and alternative RAS cascades were activated in the HVT group, whereas classical RAS activation prevailed with VHVT ventilation. Ang 1-7 or captopril protected from VILI primarily by modifying the systemic RAS profile.

# 实验性呼吸机诱导肺损伤中肾素 - 血管紧张素系统的潮气量依赖性激活。

目的：呼吸机诱导肺损伤 (VILI) 是重症患者发病和死亡的主要原因。肾素 - 血管紧张素系统 (RAS) 的激活可能会加重肺脏的机械损伤。本文描述了 VILI 中的 RAS 激活特征，并讨论了血管紧张素 (Ang) 1-7 补充或卡托普利作为保护策略的血管紧张素转换酶 (ACE) 抑制的影响。

设计：动物研究。

单位：大学研究室。

受试者：C57BL/6 小鼠。

干预：麻醉小鼠（n = 12-18 / 组）接受低潮气量 (LVT，6 mL/kg)、高潮气量 (HVT，15 mL/kg) 或极高潮气量 (VHVT，30 mL/kg) 机械通气 4 小时，或 3 min 后处死（假手术）。其他 VHVT 组接受 60?g/kg/hr Ang 1-7 输注或 100 mg/kg 卡托普利单次给药。

测量和主要结果：VILI 的特征为支气管肺泡灌洗液中白细胞介素 (IL)-6、角质形成细胞衍生的细胞因子和巨噬细胞炎性蛋白 - 2 (MIP2) 水平升高。采用液相色谱串联质谱法测定的血浆中的 Ang 代谢物显示经典 (Ang I、Ang II) 和替代 RAS (Ang 1-7、Ang 1-5) 强烈激活，HVT 组浓度最高。尽管肺组织 ACE 信使 RNA 表达没有变化，但其蛋白表达在机械通气下呈剂量依赖性增加。所有通气组的 ACE2 信使 RNA 表达均下降，而 ACE2 蛋白水平保持不变。卡托普利和 Ang 1-7 均导致 Ang 1-7 血浆水平显著升高，降低 Ang II 水平和 ACE 活性（Ang II/Ang I 比值），并有效预防 VILI。

结论：VILI 伴有 RAS 的强烈激活。基于循环中的 Ang 代谢产物水平和 RAS 酶的组织表达，HVT 组中经典的 ACE 依赖性和替代性 RAS 级联被激活，而 VHVT 通气中经典的 RAS 激活占优势。血管紧张素 1-7 或卡托普利主要通过改变系统性 RAS 谱来保护 VILI。

# The ??1-Adrenergic Receptor Contributes to Sepsis-Induced Immunosuppression Through Modulation of Regulatory T-Cell Inhibitory Function.

2:e220. DOI:10.1097/CCM.0000000000005444

Abstract:

OBJECTIVES: Although cardiovascular benefits of??1-adrenergic receptor blockade have been described in sepsis, little is known about its impact on the adaptive immune response, specifically CD4 T cells. Herein, we study the effects of ??1-adrenergic receptor modulation on CD4 T-cell function in a murine model of sepsis.

DESIGN: Experimental study.

SETTING: University laboratory.

SUBJECTS: C57BL/6 mice.

INTERVENTIONS: High-grade sepsis was induced by cecal ligation and puncture in wild-type mice (??1+/+) with or without esmolol (a selective ??1-adrenergic receptor blocker) or in ??1-adrenergic receptor knockout mice (??1-/-). At 18 hours after surgery, echocardiography was performed with blood and spleen collected to analyze lymphocyte function.

MEASUREMENTS AND MAIN RESULTS: At 18 hours, ??1+/+ cecal ligation and puncture mice exhibited characteristics of high-grade sepsis and three surrogate markers of immunosuppression, namely decreased splenic CD4 T cells, reduced CD4 T-cell proliferation, and increased regulatory T lymphocyte cell proportions. Pharmacologic and genetic ??1-adrenergic receptor blockade reversed the impact of sepsis on CD4 T and regulatory T lymphocyte proportions and maintained CD4 T-cell proliferative capacity. ??1-adrenergic receptor blocked cecal ligation and puncture mice also exhibited a global decrease in both pro- and anti-inflammatory mediators and improved in vivo cardiovascular efficiency with maintained cardiac power index despite the expected decrease in heart rate.

CONCLUSIONS: ??1-adrenergic receptor activation enhances regulatory T lymphocyte inhibitory function and thus contributes to sepsis-induced immunosuppression. This can be attenuated by ??1-adrenergic receptor blockade, suggesting a potential immunoregulatory role for this therapy in the management of sepsis.

DOI: 10.1097/CCM.0000000000005503

# ?1 - 肾上腺素能受体通过调节调节性 T 细胞抑制功能参与败血症诱导的免疫抑制。

目的：尽管已有人描述败血症患者接受？？1 - 肾上腺素能受体阻断的心血管获益，但对于其对适应性免疫应答尤其是 CD4 T 细胞的影响知之甚少。在此，我们在败血症的小鼠模型中，研究？1 - 肾上腺素能受体调节对 cd4t 细胞功能的影响。

设计：实验研究。

单位：大学实验室。

受试者：C57BL/6 小鼠。

干预：在有或无艾司洛尔（选择性 Ι?1 - 肾上腺素能受体阻滞剂）的野生型小鼠 (Ι?1 +/+) 或 Ι?1 - 肾上腺素能受体基因敲除小鼠 (Ι?1-/-) 中，通过盲肠结扎和穿刺诱导高级别脓毒症。术后 18 小时，采集血液和脾脏进行超声心动图检查，分析淋巴细胞功能。

测量值和主要结果：18 小时时，??1 +/+ 盲肠结扎和穿刺小鼠表现出高度败血症特征和 3 种免疫抑制替代标志物，即脾脏 CD4 T 细胞减少、CD4 T 细胞增殖减少和调节性 T 淋巴细胞比例增加。药理学和遗传学的？1 - 肾上腺素能受体阻断逆转了败血症对 CD4 T 和调节性 T 淋巴细胞比例的影响，并维持了 CD4 T 细胞的增殖能力。nct014?1 - 肾上腺素能受体阻断盲肠结扎和穿刺的小鼠也表现出促炎和抗炎介质的整体减少，体内心血管效率改善，尽管预期心率下降，但心脏功率指数保持不变。

结论：rec?1 - 肾上腺素能受体活化增强了调节性 T 淋巴细胞的抑制功能，从而有助于败血症诱导的免疫抑制。这一效应可通过钙通道阻滞剂和肾上腺素能受体的阻断而减弱，提示这种治疗在败血症管理中具有潜在的免疫调节作用。

# Standardized Care Is Better Than Individualized Care for the Majority of Critically Ill Patients: Erratum.

DOI: 10.1097/CCM.0000000000005445

# Orange You Wishing There Were Definitive Randomized Controlled Trials Already?: Erratum.

# 21st Century Evidence: Randomized Controlled Trials Versus Systematic Reviews and Meta-Analyses: Erratum.

2:e220. DOI:10.1097/CCM.0000000000005442

# The authors reply.

2:e218-e219. DOI:10.1097/CCM.0000000000005386

# Standardized Care Is Better Than Individualized Care for the Majority of Critically Ill Patients: Erratum.

# Orange You Wishing There Were Definitive Randomized Controlled Trials Already?: Erratum.

2:e220. DOI:10.1097/CCM.0000000000005444

# 21st Century Evidence: Randomized Controlled Trials Versus Systematic Reviews and Meta-Analyses: Erratum.

2:e220. DOI:10.1097/CCM.0000000000005442

# The authors reply.

2:e220. DOI:10.1097/CCM.0000000000005445

# Orange You Wishing There Were Definitive Randomized Controlled Trials Already?: Erratum.

2:e220. DOI:10.1097/CCM.0000000000005444

# 21st Century Evidence: Randomized Controlled Trials Versus Systematic Reviews and Meta-Analyses: Erratum.

2:e220. DOI:10.1097/CCM.0000000000005442

# The authors reply.

2:e217-e218. DOI:10.1097/CCM.0000000000005326

关键词：Humans; *Heart Arrest; Adrenal Cortex Hormones

# Efficacy and Safety of Corticosteroid Therapy in Patients With Cardiac Arrest.

# 心脏骤停患者中皮质类固醇治疗的疗效和安全性。

关键词：Humans; *Cardiopulmonary Resuscitation; *Heart Arrest/chemically induced/drug therapy; Adrenal Cortex Hormones/adverse effects

# The authors reply., Acosta, Juli??n N.

2:e215-e216. DOI:10.1097/CCM.0000000000005388

# 作者回复。

# Hemoglobin Level at Admission Is Less Important., Ye, Tian

2:e214-e215. DOI:10.1097/CCM.0000000000005323

# 入院时血红蛋白水平不太重要。

关键词：Humans; *Hemoglobins/analysis; *Hospitalization

# Online Editorial Board Acknowledgment.

2:e103-e108. DOI:10.1097/CCM.0000000000005446

# Pediatric Delirium: We Have Come a Long Way, and We Have Only Just Begun., Traube, Chani

2:350-352. DOI:10.1097/CCM.0000000000005277

# Online Editorial Board Acknowledgment.

# Pediatric Delirium: We Have Come a Long Way, and We Have Only Just Begun.

2:e103-e108. DOI:10.1097/CCM.0000000000005446

# Pediatric Delirium: We Have Come a Long Way, and We Have Only Just Begun.

2:349-350. DOI:10.1097/CCM.0000000000005257

关键词：Humans; Child; *Delirium; Intensive Care Units, Pediatric

# How Much Fluid Should I Give to My Patient on a Ventilator?

# 使用呼吸机给患者输注多少液体？

关键词：Humans; Ventilators, Mechanical; *Home Care Services; *Pneumonia, Ventilator-Associated

# Further Exploration of MARS.

2:346-348. DOI:10.1097/CCM.0000000000005202

# MARS 的进一步探索。

# Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation.

2:343-345. DOI:10.1097/CCM.0000000000005342

# 静脉 - 静脉体外膜氧合期间的俯卧位。

关键词：Humans; Prone Position; *Respiratory Distress Syndrome/therapy; *Extracorporeal Membrane Oxygenation; Patient Positioning

# Are We Still Withdrawing Too Soon?-Predictors of Late Awakening After Cardiac Arrest.

2:338-340. DOI:10.1097/CCM.0000000000005379

# 我们是否还在很快退出？- 心脏骤停后晚醒的预测因素。

关键词：Humans; *Hypothermia, Induced; *Heart Arrest/therapy

# The Big Consequences of Small Discrepancies: Why Racial Differences in Pulse Oximetry Errors Matter., Holder, Andre L.

2:335-337. DOI:10.1097/CCM.0000000000005447

# 小偏差的重大后果：为什么脉搏血氧测量错误存在人种差异。

关键词：*Oximetry; *Oxygen; Race Factors

# RBC Transfusion in Venovenous Extracorporeal Membrane Oxygenation: A Multicenter Cohort Study., Raasveld, Senta Jorinde

2:224-234. DOI:10.1097/CCM.0000000000005398

Abstract:

OBJECTIVES: In the general critical care patient population, restrictive transfusion regimen of RBCs has been shown to be safe and is yet implemented worldwide. However, in patients on venovenous extracorporeal membrane oxygenation, guidelines suggest liberal thresholds, and a clear overview of RBC transfusion practice is lacking. This study aims to create an overview of RBC transfusion in venovenous extracorporeal membrane oxygenation.

DESIGN: Mixed method approach combining multicenter retrospective study and survey.

SETTING: Sixteen ICUs worldwide.

PATIENTS: Patients receiving venovenous extracorporeal membrane oxygenation between January 2018 and July 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was the proportion receiving RBC, the amount of RBC units given daily and in total. Furthermore, the course of hemoglobin over time during extracorporeal membrane oxygenation was assessed. Demographics, extracorporeal membrane oxygenation characteristics, and patient outcome were collected. Two-hundred eight patients received venovenous extracorporeal membrane oxygenation, 63% male, with an age of 55 years (45-62 yr), mainly for acute respiratory distress syndrome. Extracorporeal membrane oxygenation duration was 9 days (5-14 d). Prior to extracorporeal membrane oxygenation, hemoglobin was 10.8 g/dL (8.9-13.0 g/dL), decreasing to 8.7 g/dL (7.7-9.8 g/dL) during extracorporeal membrane oxygenation. Nadir hemoglobin was lower on days when a transfusion was administered (8.1 g/dL [7.4-9.3 g/dL]). A vast majority of 88% patients received greater than or equal to 1 RBC transfusion, consisting of 1.6 U (1.3-2.3 U) on transfusion days. This high transfusion occurrence rate was also found in nonbleeding patients (81%). Patients with a liberal transfusion threshold (hemoglobin > 9 g/dL) received more RBC in total per transfusion day and extracorporeal membrane oxygenation day. No differences in survival, hemorrhagic and thrombotic complication rates were found between different transfusion thresholds. Also, 28-day mortality was equal in transfused and nontransfused patients.

CONCLUSIONS: Transfusion of RBC has a high occurrence rate in patients on venovenous extracorporeal membrane oxygenation, even in nonbleeding patients. There is a need for future studies to find optimal transfusion thresholds and triggers in patients on extracorporeal membrane oxygenation.

# 静脉 - 静脉体外膜氧合中的 RBC 输血：一项多中心队列研究。

目的：在一般重症监护患者人群中，已证实 RBC 的限制性输血方案是安全的，且尚未实施全球。但是，在接受静脉 - 静脉体外膜的患者中指南建议自由的阈值和对 RBC 的清晰概述缺乏输血实践。本研究旨在创建 RBC 概述静脉 - 静脉体外膜肺氧合中的输血。

设计：混合多中心回顾性研究与调查相结合的方法。

设置：全球 16 间 ICU。

患者：接受静脉 - 静脉体外治疗的患者 2018 年 1 月至 2019 年 7 月期间的膜氧合。

干预：无。

测量和主要结果：主要结局是接受 RBC，每日给予的 RBC 单位数量和总数量。此外，病程评估了体外膜氧合期间血红蛋白随时间的变化。人口统计学、体外膜肺氧合特征和患者收集结局。208 例患者接受了静脉 - 静脉输注体外膜肺氧合，63% 男性，年龄 55 岁（45-62 岁） yr），主要用于急性呼吸窘迫综合征。体外膜氧合持续时间为 9 天（5-14 天）。体外膜之前氧合，血红蛋白为 10.8 g/dL (8.9-13.0 g/dL)，降低至 8.7 g/dL (7.7-9.8 g/dL)。血红蛋白最低值输血天数减少 (8.1 g/dL [7.4-9.3 g/dL])。A 绝大多数 88% 的患者接受了大于或等于 1 个 RBC 输血，输血日 1.6 U (1.3-2.3 U)。如此之高在非出血患者中也发现输血发生率 (81%)。输血阈值较宽（血红蛋白 > 9 g/dL）的患者接受更多的每个输血日和体外膜氧合日的总 RBC。No 发现生存率、出血和血栓并发症发生率存在差异不同输血阈值之间。此外，28 天死亡率与输血和非输血患者。

结论：RBC 输血具有高接受静脉 - 静脉体外膜氧合的患者的发生率，即使在非出血患者中。未来的研究需要找到最优的体外膜患者的输血阈值和触发因素氧合作用。关键词：Humans; Treatment Outcome; Female; Male; Middle Aged; Adult; Cohort Studies; Retrospective Studies; Australia; Netherlands; Intensive Care Units/organization & administration/statistics & numerical data; Italy; Belgium; Croatia; Erythrocyte Transfusion/methods/*standards/statistics & numerical data; Extracorporeal Membrane Oxygenation/methods/*statistics & numerical data; Sweden

# Coronavirus Disease 2019 Temperature Trajectories Correlate With Hyperinflammatory and Hypercoagulable Subphenotypes.

2:212-223. DOI:10.1097/CCM.0000000000005397

Abstract:

OBJECTIVES: Body temperature trajectories of infected patients are associated with specific immune profiles and survival. We determined the association between temperature trajectories and distinct manifestations of coronavirus disease 2019.

DESIGN: Retrospective observational study.

SETTING: Four hospitals within an academic healthcare system from March 2020 to February 2021.

PATIENTS: All adult patients hospitalized with coronavirus disease 2019.

INTERVENTIONS: Using a validated group-based trajectory model, we classified patients into four previously defined temperature trajectory subphenotypes using oral temperature measurements from the first 72 hours of hospitalization. Clinical characteristics, biomarkers, and outcomes were compared between subphenotypes.

MEASUREMENTS AND MAIN RESULTS: The 5,903 hospitalized coronavirus disease 2019 patients were classified into four subphenotypes: hyperthermic slow resolvers (n = 1,452, 25%), hyperthermic fast resolvers (1,469, 25%), normothermics (2,126, 36%), and hypothermics (856, 15%). Hypothermics had abnormal coagulation markers, with the highest d-dimer and fibrin monomers (p < 0.001) and the highest prevalence of cerebrovascular accidents (10%, p = 0.001). The prevalence of venous thromboembolism was significantly different between subphenotypes (p = 0.005), with the highest rate in hypothermics (8.5%) and lowest in hyperthermic slow resolvers (5.1%). Hyperthermic slow resolvers had abnormal inflammatory markers, with the highest C-reactive protein, ferritin, and interleukin-6 (p < 0.001). Hyperthermic slow resolvers had increased odds of mechanical ventilation, vasopressors, and 30-day inpatient mortality (odds ratio, 1.58; 95% CI, 1.13-2.19) compared with hyperthermic fast resolvers. Over the course of the pandemic, we observed a drastic decrease in the prevalence of hyperthermic slow resolvers, from representing 53% of admissions in March 2020 to less than 15% by 2021. We found that dexamethasone use was associated with significant reduction in probability of hyperthermic slow resolvers membership (27% reduction; 95% CI, 23-31%; p < 0.001).

CONCLUSIONS: Hypothermics had abnormal coagulation markers, suggesting a hypercoagulable subphenotype. Hyperthermic slow resolvers had elevated inflammatory markers and the highest odds of mortality, suggesting a hyperinflammatory subphenotype. Future work should investigate whether temperature subphenotypes benefit from targeted antithrombotic and anti-inflammatory strategies.

# 冠状病毒病 2019 温度轨迹与高炎性和高凝性亚表型相关。

目的：感染患者的体温曲线与特定免疫特征和生存期相关。我们确定了 2019 年冠状病毒病的温度轨迹和不同表现。

设计：回顾性观察性研究。

单位：一家内四家医院 2020 年 3 月至 2021 年 2 月期间的学术医疗系统。

患者：所有成人 2019 年冠状病毒病住院患者。

干预：使用经验证的基于小组的轨迹模型，我们将患者分为四组之前定义的使用口腔温度的温度轨迹亚表型住院前 72 小时的测量值。临床比较亚表型之间的特征、生物标志物和结局。

测量和主要结果：2019 年 5,903 例住院冠状病毒病患者分为 4 个亚表型：高温慢消退型（n = 1,452，25%）、高温快速解决者 (1,469，25%)、常温（2,126， 36%）和低体温 (856，15%)。体温过低导致凝血标志物异常， d - 二聚体和纤维蛋白单体最高 (p < 0.001)，纤维蛋白单体最高脑血管意外的患病率 (10%，p = 0.001)。以下疾病的患病率静脉血栓栓塞在亚表型之间有显著差异（p = 0.005），其中低温最高 (8.5%)，高温最低缓慢消退者 (5.1%)。体温过高缓慢消退者有异常炎症具有最高 C 反应蛋白、铁蛋白和白细胞介素 - 6 的标志物（p < 0.001). 体温过高的缓慢恢复者增加了机械通气的几率，血管加压药和 30 天住院死亡率（比值比，1.58；95% CI， 1.13-2.19）与高温快速解毒器相比。整个过程大流行期间，我们观察到高温缓慢型流感的患病率急剧下降缓解者，从 2020 年 3 月占入院的 53% 降至 2020 年 3 月的 15% 以下 2021. 我们发现使用地塞米松与显著减少体温过高缓慢消退者的比例（降低 27%；95% CI， 23-31%; p < 0.001). 结论：低体温患者存在凝血标志物异常，提示高凝亚表型。体温过高缓慢消退者炎症标志物升高和死亡率最高，表明高炎性亚表型。未来的工作应该调查是否温度亚表型获益于靶向抗血栓形成和抗炎策略。关键词：Humans; Female; Male; Middle Aged; Aged; Cohort Studies; Retrospective Studies; Academic Medical Centers; Biomarkers/blood; Inflammation; SARS-CoV-2; Blood Coagulation; *Phenotype; Anti-Inflammatory Agents/therapeutic use; Organ Dysfunction Scores; *Body Temperature; COVID-19/*pathology; Dexamethasone/therapeutic use; Hyperthermia/*pathology; Hypothermia/*pathology

# Disparities in Hypoxemia Detection by Pulse Oximetry Across Self-Identified Racial Groups and Associations With Clinical Outcomes.

2:204-211. DOI:10.1097/CCM.0000000000005394

Abstract:

OBJECTIVES: To assess disparities in hypoxemia detection by pulse oximetry across self-identified racial groups and associations with clinical outcomes.

DESIGN: Observational cohort study from May 5, 2018, to December 31, 2020.

SETTING: Three academic medical centers in the United States.

PATIENTS: Adults greater than or equal to 18 years who self-identified as White, Black, Asian, or American Indian admitted to the ICU or undergoing surgery during inpatient hospitalization with simultaneous measurements of pulse oximetry-estimated oxygen saturation and arterial blood gas-derived oxygen saturation.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Multivariable models were employed to assess the relationships between race, occult hypoxemia (i.e., arterial blood gas-derived oxygen saturation < 88% despite pulse oximetry-estimated oxygen saturation ?‰? 92%), and clinical outcomes of hospital mortality and hospital-free days. One-hundred twenty-eight-thousand two-hundred eighty-five paired pulse oximetry-estimated oxygen saturation-arterial blood gas-derived oxygen saturation measurements were included from 26,603 patients. Pulse oximetry-estimated oxygen saturation on average overestimated arterial blood gas-derived oxygen saturation by 1.57% (1.54-1.61%). Black, Asian, and American Indian patients were more likely to experience occult hypoxemia during hospitalization (estimated probability 6.2% [5.1-7.6%], 6.6% [4.9-8.8%], and 6.6% [4.4-10.0%], respectively) compared with White patients (3.6% [3.4-3.8%]). Black patients had increased odds of occult hypoxemia compared with White patients after adjustment (odds ratio, 1.65; 1.28-2.14; p < 0.001). Differences in occult hypoxemia between Asian and American Indian patients compared with White patients were not significant after adjustment (odds ratio, 1.53; 0.95-2.47; p = 0.077 and odds ratio, 1.31; 0.80-2.16; p = 0.288, respectively). Occult hypoxemia was associated with increased odds of mortality in surgical (odds ratio, 2.96; 1.20-7.28; p = 0.019) and ICU patients (1.36; 1.03-1.80; p = 0.033). Occult hypoxemia was associated with fewer hospital-free days in surgical (-2.5 d [-3.9 to -1.2 d]; p < 0.001) but not ICU patients (0.4 d [-0.7 to 1.4 d]; p = 0.500).

CONCLUSIONS: Occult hypoxemia is more common in Black patients compared with White patients and is associated with increased mortality, suggesting potentially important outcome implications for undetected hypoxemia. It is imperative to validate pulse oximetry with expanded racial inclusion.

# 通过脉搏血氧测定法检测自我识别的人种组中低氧血症的差异以及与临床结局的相关性。

目的：在自我确认的人种组中，通过脉搏血氧定量法评估低氧血症检测的差异，以及与临床结局的相关性。

设计： 2018 年 5 月 5 日至 2020 年 12 月 31 日的观察性队列研究。

设置：3 个美国学术医学中心。

患者：大于或等于自称为白人、黑人、亚洲人或美国印第安人的 18 岁以下儿童入住 ICU 或在住院期间接受手术同时测量脉搏血氧饱和度 - 估计血氧饱和度和动脉血气氧饱和度。

干预：无。测量和主要结果：采用多变量模型评估关系人种之间，隐匿性低氧血症（即，动脉血气衍生的氧气脉搏血氧仪估计的氧饱和度？？？92%，饱和度 <88%），以及住院死亡率和无住院天数的临床结局。100 估计的 2,800,285 对脉搏血氧饱和度氧饱和度 - 动脉血气衍生的氧饱和度测量值为纳入了 26,603 例患者。脉搏血氧饱和度 - 估计血氧饱和度平均高估动脉血气衍生氧饱和度 1.57% (1.54-1.61%). 黑人、亚洲人和美洲印第安人患者更可能住院期间出现隐匿性低氧血症（估计概率 6.2%）分别为 [5.1-7.6%]、6.6%[4.9-8.8%] 和 6.6%[4.4-10.0%]）白人患者 (3.6%[3.4-3.8%])。黑人患者的隐匿性几率增加校正后低氧血症与白人患者相比（比值比，1.65； 1.28-2.14; p < 0.001). 亚裔和美国人之间隐匿性低氧血症的差异之后，印度患者与白人患者相比无显著性校正（比值比，1.53；0.95-2.47；p = 0.077 和比值比，1.31；分别为 0.80-2.16；p = 0.288）。隐匿性低氧血症与手术死亡率增加（比值比，2.96；1.20-7.28；p = 0.019）和 ICU 患者 (1.36；1.03-1.80；p = 0.033)。隐匿性低氧血症相关手术期间无住院天数更少（-2.5 天 [-3.9 至 - 1.2 天]；p < 0.001）但不是 ICU 患者（0.4 天 [-0.7 至 1.4 天]；p = 0.500）。

结论：隐性与白人患者相比，低氧血症在黑人患者中更常见，与死亡率增加相关，提示潜在重要结局对未检测到的低氧血症的影响。必须验证脉冲血氧定量法，包含扩大的人种。关键词：Humans; Female; Male; Middle Aged; Aged; Cohort Studies; Academic Medical Centers/organization & administration/statistics & numerical data; Arizona; Florida; Hypoxia/*diagnosis/ethnology; Minnesota; Outcome Assessment, Health Care/methods/*statistics & numerical data; Oximetry/instrumentation/methods/*standards; Oxygen/analysis/blood; Racial Groups/ethnology/*statistics & numerical data; Self Report/statistics & numerical data; Skin Pigmentation/*physiology

# Lung- and Diaphragm-Protective Ventilation by Titrating Inspiratory Support to Diaphragm Effort: A Randomized Clinical Trial., de Vries, Heder J.

2:192-203. DOI:10.1097/CCM.0000000000005395

Abstract:

OBJECTIVES: Lung- and diaphragm-protective ventilation is a novel concept that aims to limit the detrimental effects of mechanical ventilation on the diaphragm while remaining within limits of lung-protective ventilation. The premise is that low breathing effort under mechanical ventilation causes diaphragm atrophy, whereas excessive breathing effort induces diaphragm and lung injury. In a proof-of-concept study, we aimed to assess whether titration of inspiratory support based on diaphragm effort increases the time that patients have effort in a predefined "diaphragm-protective" range, without compromising lung-protective ventilation.

DESIGN: Randomized clinical trial.

SETTING: Mixed medical-surgical ICU in a tertiary academic hospital in the Netherlands.

PATIENTS: Patients (n = 40) with respiratory failure ventilated in a partially-supported mode.

INTERVENTIONS: In the intervention group, inspiratory support was titrated hourly to obtain transdiaphragmatic pressure swings in the predefined "diaphragm-protective" range (3-12 cm H2O). The control group received standard-of-care.

MEASUREMENTS AND MAIN RESULTS: Transdiaphragmatic pressure, transpulmonary pressure, and tidal volume were monitored continuously for 24 hours in both groups. In the intervention group, more breaths were within "diaphragm-protective" range compared with the control group (median 81%; interquartile range [64-86%] vs 35% [16-60%], respectively; p < 0.001). Dynamic transpulmonary pressures (20.5 ?± 7.1 vs 18.5 ?± 7.0 cm H2O; p = 0.321) and tidal volumes (7.56 ?± 1.47 vs 7.54 ?± 1.22 mL/kg; p = 0.961) were not different in the intervention and control group, respectively.

CONCLUSIONS: Titration of inspiratory support based on patient breathing effort greatly increased the time that patients had diaphragm effort in the predefined "diaphragm-protective" range without compromising tidal volumes and transpulmonary pressures. This study provides a strong rationale for further studies powered on patient-centered outcomes.

# 通过滴定吸气支持对膈肌用力的肺和膈肌保护性通气：一项随机化临床试验。

目的：肺和隔膜保护性通气是一个新概念，旨在限制机械通气对隔膜的有害作用同时保持在肺保护通气的限值内。前提是机械通气时呼吸费力小，导致膈肌萎缩，而过度的呼吸用力会导致膈肌和肺损伤。在 a 中概念验证研究，我们旨在评估吸气滴定是否基于膈肌做功的支持增加了患者做功的时间预定义的 “隔膜保护” 范围，不影响肺保护通风。

设计：随机临床试验。

设置：混合内科 - 外科荷兰一家三级学术医院的 ICU。

患者：患者（n = 40）患有呼吸衰竭，在部分支持模式下通气。

干预：在干预组中，每小时调整一次吸气支持以获得预定义的经膈肌压力波动 “隔膜 - 保护” 范围 (3-12 cm H2O)。对照组接受标准治疗。

测量和主要结果：经膈肌压力，连续监测 24 小时的跨肺压和潮气量两组的小时数。在干预组中，更多的呼吸在 “隔膜保护” 范围与对照组相比（中位数 81%；四分位距 [64-86%] vs 35%[16-60%]；p < 0.001）。动态跨肺压 (20.5?7.1 vs 18.5?±7.0 cm H2O；p = 0.321) 和潮气量注射体积（分别为 7.56±1.47 和 7.54±1.22 mL/kg；p = 0.961）在干预组和对照组。

结论：滴定基于患者呼吸努力的吸气支持大大增加了时间患者的膈肌用力在预定的 “膈肌保护” 范围内不影响潮气量和跨肺压。本研究为以患者为中心的进一步研究提供了强有力的依据结局。关键词：Humans; Female; Male; Middle Aged; Intensive Care Units/organization & administration/statistics & numerical data; Netherlands/epidemiology; Diaphragm/*metabolism/physiopathology; Lung/*metabolism/physiopathology; Respiration, Artificial/methods/*standards/statistics & numerical data; Respiratory Insufficiency/epidemiology/prevention & control/therapy; Work of Breathing/drug effects/*physiology

# Optimal Cerebral Perfusion Pressure During Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage., Weiss, Miriam

2:183-191. DOI:10.1097/CCM.0000000000005396

Abstract:

OBJECTIVES: The recommendation of induced hypertension for delayed cerebral ischemia treatment after aneurysmal subarachnoid hemorrhage has been challenged recently and ideal pressure targets are missing. A new concept advocates an individual cerebral perfusion pressure where cerebral autoregulation functions best to ensure optimal global perfusion. We characterized optimal cerebral perfusion pressure at time of delayed cerebral ischemia and tested the conformity of induced hypertension with this target value.

DESIGN: Retrospective analysis of prospectively collected data.

SETTING: University hospital neurocritical care unit.

PATIENTS: Thirty-nine aneurysmal subarachnoid hemorrhage patients with invasive neuromonitoring (20 with delayed cerebral ischemia, 19 without delayed cerebral ischemia).

INTERVENTIONS: Induced hypertension greater than 180 mm Hg systolic blood pressure.

MEASUREMENTS AND MAIN RESULTS: Changepoint analysis was used to calculate significant changes in cerebral perfusion pressure, optimal cerebral perfusion pressure, and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure 48 hours before delayed cerebral ischemia diagnosis. Optimal cerebral perfusion pressure increased 30 hours before the onset of delayed cerebral ischemia from 82.8 ?± 12.5 to 86.3 ?± 11.4 mm Hg (p < 0.05). Three hours before delayed cerebral ischemia, a changepoint was also found in the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure (decrease from -0.2 ?± 11.2 to -7.7 ?± 7.6 mm Hg; p < 0.05) with a corresponding increase in pressure reactivity index (0.09 ?± 0.33 to 0.19 ?± 0.37; p < 0.05). Cerebral perfusion pressure at time of delayed cerebral ischemia was lower than in patients without delayed cerebral ischemia in a comparable time frame (cerebral perfusion pressure delayed cerebral ischemia 81.4 ?± 8.3 mm Hg, no delayed cerebral ischemia 90.4 ?± 10.5 mm Hg; p < 0.05). Inducing hypertension resulted in a cerebral perfusion pressure above optimal cerebral perfusion pressure (+12.4 ?± 8.3 mm Hg; p < 0.0001). Treatment response (improvement of delayed cerebral ischemia: induced hypertension+ [n = 15] or progression of delayed cerebral ischemia: induced hypertension- [n = 5]) did not correlate to either absolute values of cerebral perfusion pressure or optimal cerebral perfusion pressure, nor the resulting difference (cerebral perfusion pressure [p = 0.69]; optimal cerebral perfusion pressure [p = 0.97]; and the difference of cerebral perfusion pressure and optimal cerebral perfusion pressure [p = 0.51]).

CONCLUSIONS: At the time of delayed cerebral ischemia occurrence, there is a significant discrepancy between cerebral perfusion pressure and optimal cerebral perfusion pressure with worsening of autoregulation, implying inadequate but identifiable individual perfusion. Standardized induction of hypertension resulted in cerebral perfusion pressures that exceeded individual optimal cerebral perfusion pressure in delayed cerebral ischemia patients. The potential benefit of individual blood pressure management guided by autoregulation-based optimal cerebral perfusion pressure should be explored in future intervention studies.

# 动脉瘤性蛛网膜下腔出血后迟发性脑缺血期间的最佳脑灌注压。

目的：对动脉瘤性蛛网膜下腔出血后诱导高血压用于迟发性脑缺血治疗的建议提出质疑近期和理想的压力目标缺失。新概念支持脑自动调节功能的个体脑灌注压确保最佳整体灌注。我们描述了最佳脑功能迟发型脑缺血时灌注压及一致性检验的诱导高血压以该目标值。

设计：回顾性分析前瞻性收集的数据。

单位：大学医院神经重症监护单位。

患者：39 例动脉瘤性蛛网膜下腔出血患者侵入性神经监测（20 例有延迟脑缺血，19 例无延迟脑缺血）。

干预：诱导的高血压大于 180 mmHg 收缩压。

测量和主要结果：变更点分析为用于计算脑灌注压的显著变化，最佳脑灌注压，以及脑灌注压的差值延迟性脑缺血前 48 小时的最佳脑灌注压诊断。最佳脑灌注压在以下前 30 小时升高迟发性脑缺血发作，从 82.8±12.5 到 86.3±11.4 mmHg（p <0.05). 迟发性脑缺血前 3 小时也发现变点在脑灌注压的差异和最佳脑灌注压力（从 - 0.2Ι±11.2 降至 - 7.7Ι±7.6 mmHg；p < 0.05），其中压力反应性指数相应增加（0.09 μm±0.33 至 0.19 μm±0.37；p < 0.05). 延迟性脑缺血时的脑灌注压为在相当时间内低于无迟发性脑缺血的患者脑灌注压延迟脑缺血 81.4 μm±8.3 mmHg，无迟发性脑缺血 90.4 μm±10.5 mmHg；p < 0.05）。诱发高血压导致脑灌注压高于最佳脑灌注压力 (+ 12.4?8.3 mmHg；p < 0.0001)。治疗缓解（改善迟发性脑缺血：诱发高血压 +[n = 15] 或进展迟发性脑缺血：诱导的高血压 -[n = 5]）与以下症状无关脑灌注压绝对值或最佳脑灌注压灌注压，也未得到相应的差异（脑灌注压 [p = 0.69]；最佳脑灌注压 [p = 0.97]；以及脑灌注压和最佳脑灌注压 [p = 0.51]）。

结论：在迟发性脑缺血发生时，存在脑灌注压与最佳脑灌注压之间存在显著差异灌注压伴随自动调节恶化，提示不充分但可识别的个体灌注。高血压规范化诱导导致脑灌注压超过个体最佳灌注压迟发性脑缺血患者的脑灌注压。电位基于自动调节指导的个体血压管理获益在将来的干预中应探索最佳的脑灌注压研究。关键词：Humans; Female; Male; Middle Aged; Adult; Retrospective Studies; Cerebrovascular Circulation/*physiology; *Time Factors; Brain Ischemia/*etiology/physiopathology; Subarachnoid Hemorrhage/*complications/physiopathology; Tertiary Care Centers/organization & administration/statistics & numerical data

# Transfusion-Associated Delirium in Children: No Difference Between Short Storage Versus Standard Issue RBCs.

2:173-182. DOI:10.1097/CCM.0000000000005393

Abstract:

OBJECTIVES: Primary objective is to determine if transfusion of short storage RBCs compared with standard issue RBCs reduced risk of delirium/coma in critically ill children. Secondary objective is to assess if RBC transfusion was independently associated with delirium/coma.

DESIGN: This study was performed in two stages. First, we compared patients receiving either short storage or standard RBCs in a multi-institutional prospective randomized controlled trial. Then, we compared all transfused patients in the randomized controlled trial with a single-center cohort of nontransfused patients matched for confounders of delirium/coma.

SETTING: Twenty academic PICUs who participated in the Age of Transfused Blood in Critically Ill Children trial.

PATIENTS: Children 3 days to 16 years old who were transfused RBCs within the first 7 days of admission.

INTERVENTIONS: Subjects were randomized to either short storage RBC study arm (defined as RBCs stored for up to seven days) or standard issue RBC study arm. In addition, subjects were screened for delirium prior to transfusion and every 12 hours after transfusion for up to 3 days.

MEASUREMENTS AND MAIN RESULTS: Primary outcome measure was development of delirium/coma within 3 days of initial transfusion. Additional outcome measures were dose-response relationship between volume of RBCs transfused and delirium/coma, and comparison of delirium/coma rates between transfused patients and individually matched nontransfused patients. We included 146 subjects in the stage I analysis; 69 were randomized to short storage RBCs and 77 to standard issue. There was no significant difference in delirium/coma development between study arms (79.5% vs 70.1%; p = 0.184). In the stage II analysis, adjusted odds for delirium in the transfused cohort was more than eight-fold higher than in the nontransfused matched cohort, even after controlling for hemoglobin (adjusted odds ratio, 8.9; CI, 2.8-28.4; p < 0.001).

CONCLUSIONS: RBC transfusions (and not anemia) are independently associated with increased odds of subsequent delirium/coma. However, storage age of RBCs does not affect delirium risk.

# 儿童输血相关性谵妄：短期储存与标准发放 RBC 之间无差异。

目的：主要目的是确定与标准输注 RBC 相比，输注短储存 RBC 是否可降低下列患者的谵妄 / 昏迷风险重症儿童。次要目的是评估 RBC 输血是否与谵妄 / 昏迷独立相关。

设计：本研究在两个阶段。首先，我们比较了接受短期储存或多机构前瞻性随机对照试验中的标准 RBC。然后，我们将随机对照试验中的所有输血患者与单个中心队列的非输血患者匹配混杂因素谵妄 / 昏迷。

单位：20 位年龄在危重病儿童输血试验。

患者：儿童 3 天至 16 岁，入院前 7 天内输注 RBC。

干预：受试者随机分配至短期储存 RBC 研究组（定义为 RBC 储存长达 7 天）或标准问题 RBC 研究组。In 此外，受试者在输血前和每 12 小时一次接受谵妄筛查输注后数小时，最长持续 3 天。

测量和主要结果：主要结局指标为初始治疗 3 天内发生谵妄 / 昏迷输血。其他结局指标为剂量 - 效应关系 RBC 输血量和谵妄 / 昏迷，以及谵妄 / 昏迷比较输血患者与个体匹配的非输血患者之间的比率患者。我们在 I 期分析中纳入了 146 例受试者；其中 69 例被随机分配至短期储存 RBC 和 77 至标准问题。无显著性差异研究组之间谵妄 / 昏迷的发生率 (79.5% vs 70.1%；p = 0.184)。In II 期分析，输血队列中谵妄的校正比值比为比非输血匹配队列高 8 倍以上，即使在控制血红蛋白（校正比值比，8.9；CI，2.8-28.4；p < 0.001）。

结论：红细胞输注（而不是贫血）与以下独立相关增加继发谵妄 / 昏迷的几率。但是，RBC 的储存时间不影响谵妄风险。关键词：Humans; Female; Male; Prospective Studies; Animals; Child; Disease Models, Animal; Rats, Sprague-Dawley; Rats; Odds Ratio; Surveys and Questionnaires; *Time Factors; Blood Banks/methods/*statistics & numerical data; Blood Transfusion/methods/*statistics & numerical data; Delirium/*etiology/therapy; Erythrocytes/metabolism/*physiology

# Ake Grenvik, MD, PhD, MCCM., Pinsky, Michael R.

2:171-172. DOI:10.1097/CCM.0000000000005408

# Ake Grenvik，MD，PhD，MCCM。

# The authors reply.

2:e210-e211. DOI:10.1097/CCM.0000000000005391

# 作者回复。

关键词：Humans; Biomarkers; *COVID-19; SARS-CoV-2; *Respiratory Distress Syndrome; *Ventricular Dysfunction, Right

# The authors reply., Chotalia, Minesh

2:e213-e214. DOI:10.1097/CCM.0000000000005390

# 作者回复。

# Rapid Development and Deployment of an Intensivist-Led Venovenous Extracorporeal Membrane Oxygenation Cannulation Program.

2:e154-e161. DOI:10.1097/CCM.0000000000005282

Abstract:

OBJECTIVES: To determine the safety and efficacy of a rapidly deployed intensivist-led venovenous extracorporeal membrane oxygenation cannulation program in a preexisting extracorporeal membrane oxygenation program.

DESIGN: A retrospective observational before-and-after study of 40 patients undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation in an established cannulation program by cardiothoracic surgeons versus a rapidly deployed medical intensivist cannulation program.

SETTING: An adult ICU in a tertiary academic medical center in Camden, NJ.

PATIENTS: Critically ill adult subjects with severe respiratory failure undergoing percutaneous cannulation for venovenous extracorporeal membrane oxygenation.

INTERVENTIONS: Percutaneous cannulation for venovenous extracorporeal membrane oxygenation performed by cardiothoracic surgeons compared with cannulations performed by medical intensivists.

MEASUREMENTS AND MAIN RESULTS: Venovenous extracorporeal membrane oxygenation cannulation site attempts were retrospectively reviewed. Subject demographics, specialty of physician performing cannulation, type of support, cannulation configuration, cannula size, imaging guidance, success rate, and complications were recorded and summarized. Twenty-two cannulations were performed by three cardiothoracic surgeons in 11 subjects between September 2019 and February 2020. The cannulation program rapidly transitioned to an intensivist-led and performed program in March 2020. Fifty-seven cannulations were performed by eight intensivists in 29 subjects between March 2020 and December 2020. Mean body mass index for subjects did not differ between groups (33.86 vs 35.89; p = 0.775). There was no difference in days on mechanical ventilation prior to cannulation, configuration, cannula size, or discharge condition. There was no difference in success rate of cannulation on first attempt per cannulation site (95.5 vs 96.7; p = 0.483) or major complication rate per cannulation site (4.5 vs 3.5; p = 1).

CONCLUSIONS: There is no difference between success and complication rates of percutaneous venovenous extracorporeal membrane oxygenation canulation when performed by cardiothoracic surgeons versus medical intensivist in an already established extracorporeal membrane oxygenation program. A rapidly deployed cannulation program by intensivists for venovenous extracorporeal membrane oxygenation can be performed with high success and low complication rates.

# 强化静脉 - 静脉体外膜氧合插管项目的快速开发和部署。

目的：确定快速展开的重症监护 - 主导的静脉 - 静脉体外膜肺氧合插管的安全性和疗效预存体外膜肺氧合项目中的项目。

设计：A 对 40 名接受经皮插管行静脉 - 静脉体外膜肺氧合由心胸外科医生与快速导管插入术确定的插管方案部署了内科重症监护插管项目。

背景：成人 ICU 新泽西州卡姆登第三学术医学中心。

患者：重症成人接受经皮插管治疗的重度呼吸衰竭受试者静脉 - 静脉体外膜肺氧合。

干预：经皮静脉 - 静脉体外膜肺氧合插管心胸外科医生与内科插管的比较重症监护医生。

测量和主要结果：静脉 - 静脉体外膜对氧合插管部位尝试进行了回顾性审查。受试者人口统计学、行插管术的医生的专业、支持类型，插管结构、插管尺寸、成像引导、成功率，以及记录并总结并发症。22 例插管 2019 年 9 月由 3 名心胸外科医生在 11 名受试者中进行和 2020 年 2 月。插管程序快速转变为重症监护医师主导并于 2020 年 3 月开展的项目。57 例插管在 2020 年 3 月至 2020 年 12 月。治疗组间受试者的平均体重指数无差异 (33.86 vs 35.89；p = 0.775)。机械通气天数无差异插管、配置、插管尺寸或排出前通气条件。首次插管成功率无差异尝试通过插管部位 (95.5 vs 96.7；p = 0.483) 或重大并发症发生率每个插管部位 (4.5 vs 3.5；p = 1)。

结论：无差异介于经皮静脉 - 静脉体外的成功率和并发症发生率之间由心胸外科医生与已确立的体外膜肺氧合的内科重症监护医生程序。重症监护医生开展的静脉 - 静脉快速置入术项目体外膜肺氧合成功率高，成功率低并发症发生率。关键词：Humans; Female; Male; Middle Aged; Aged; Retrospective Studies; Extracorporeal Membrane Oxygenation/methods/*statistics & numerical data; Academic Medical Centers/organization & administration/statistics & numerical data; *Time Factors; Catheterization/methods/*statistics & numerical data; Health Services/statistics & numerical data/supply & distribution/*trends; Intensive Care Units/organization & administration/*statistics & numerical data; Internal Medicine/methods/statistics & numerical data; New Jersey

2:e109-e116. DOI:10.1097/CCM.0000000000005234

Abstract:

OBJECTIVES: Access to personal health records in an ICU by persons involved in the patient's care (referred to broadly as "family members" below) has the potential to increase engagement and reduce the negative psychologic sequelae of such hospitalizations. Currently, little is known about patient preferences for information sharing with a designated family member in the ICU. We sought to understand the information-sharing preferences of former ICU patients and their family members and to identify predictors of information-sharing preferences.

DESIGN: We performed an internet survey that was developed by a broad, multidisciplinary team of stakeholders. Formal pilot testing of the survey was conducted prior to internet survey administration to study subjects.

SETTING: Internet survey.

SUBJECTS: Subjects included English-speaking adults who had an ICU experience or a family member with ICU experience between 2013 and 2016. We used panel sampling to ensure an ethnically representative sample of the U.S. population.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: One thousand five hundred twenty surveys were submitted, and 1,470 were included in analysis. The majority of respondents (93.6%) stated that they would want to share present and past medical history, either all or that related to their ICU stay, with a designated family member of their choosing. The majority (79%) would also want their designated family member to be able to access that information from a home computer. Although most respondents preferred to share all types of information, they indicated varying levels of willingness to share specific types of more sensitive information. Information-sharing preferences did not differ by age, sex, ethnicity, or type of prior experience in the ICU (i.e., patient or family member).

CONCLUSIONS: In the context of an ICU admission, sharing personal health information with a person of the patient's choosing appears desirable for most patients and family members. Policies and implementation of regulations should take this into consideration.

# 数字信息共享中隐私与访问的平衡评估。

目的：参与患者护理的人员（下文统称为 “家庭成员”）在 ICU 中查阅个人健康记录具有可能增加参与并减少下列不良心理后遗症此类住院。目前，关于患者的偏好知之甚少与 ICU 指定的家庭成员共享信息。我们试图了解既往 ICU 患者及其信息分享偏好家庭成员和识别信息共享偏好的预测因素。

设计：我们进行了一项互联网调查，该调查由一个广泛的，利益相关者多学科团队。调查的正式试点试验是在对研究受试者进行网络调查之前进行。

设置：网络调查。

受试者：受试者包括说英语的成年人， 2013 年至 2016 年有 ICU 经验或家庭成员有 ICU 经验。We 使用样本组采样，以确保美国的种族代表性样本。人群。

干预：无。

测量和主要结果：1505 提交了 120 份调查，其中 1470 份被纳入分析。事件大多数回答者 (93.6%) 表示他们希望分享现在和既往病史，包括所有或与其 ICU 住院相关病史，且指定其选择的家庭成员。大多数 (79%) 也希望其指定的家庭成员能够从家中访问该信息计算机。尽管大多数受访者倾向于分享所有类型的信息，他们表示不同程度的愿意分享特定类型的更多敏感信息。不同年龄的信息共享偏好无差异，性别、种族或 ICU 既往经验类型（即患者或家人）成员）。

结论：在入住 ICU 的背景下，共享个人健康大多数人希望获得患者选择的信息患者和家属。法规的政策与执行应考虑到这一点。关键词：Humans; Female; Male; Middle Aged; Adult; Surveys and Questionnaires; Confidentiality/*standards/trends; Health Services Accessibility/*standards/trends; Information Dissemination/*methods; Patient Preference/psychology/statistics & numerical data

# Anisocoria and Poor Pupil Reactivity by Quantitative Pupillometry in Patients With Intracranial Pathology., Prescott, Brenton R.

2:e143-e153. DOI:10.1097/CCM.0000000000005272

Abstract:

OBJECTIVES: To describe the prevalence and associated risk factors of new onset anisocoria (new pupil size difference of at least 1 mm) and its subtypes: new onset anisocoria accompanied by abnormal and normal pupil reactivities in patients with acute neurologic injuries.

DESIGN: We tested the association of patients who experienced new onset anisocoria subtypes with degree of midline shift using linear regression. We further explored differences between quantitative pupil characteristics associated with first-time new onset anisocoria and nonnew onset anisocoria at preceding observations using mixed effects logistic regression, adjusting for possible confounders.

SETTING: All quantitative pupil observations were collected at two neuro-ICUs by nursing staff as standard of care.

PATIENTS: We conducted a retrospective two-center study of adult patients with intracranial pathology in the ICU with at least a 24-hour stay and three or more quantitative pupil measurements between 2016 and 2018.

MEASUREMENTS AND MAIN RESULTS: We studied 221 patients (mean age 58, 41% women). Sixty-three percent experienced new onset anisocoria. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity occurring at any point during hospitalization was significantly associated with maximum midline shift (?? = 2.27 per mm; p = 0.01). The occurrence of new onset anisocoria accompanied by objective evidence of normal pupil reactivity was inversely associated with death (odds ratio, 0.34; 95% CI, 0.16-0.71; p = 0.01) in adjusted analyses. Subclinical continuous pupil size difference distinguished first-time new onset anisocoria from nonnew onset anisocoria in up to four preceding pupil observations (or up to 8 hr prior). Minimum pupil reactivity between eyes also distinguished new onset anisocoria accompanied by objective evidence of abnormal pupil reactivity from new onset anisocoria accompanied by objective evidence of normal pupil reactivity prior to first-time new onset anisocoria occurrence.

CONCLUSIONS: New onset anisocoria occurs in over 60% of patients with neurologic emergencies. Pupil reactivity may be an important distinguishing characteristic of clinically relevant new onset anisocoria phenotypes. New onset anisocoria accompanied by objective evidence of abnormal pupil reactivity was associated with midline shift, and new onset anisocoria accompanied by objective evidence of normal pupil reactivity had an inverse relationship with death. Distinct quantitative pupil characteristics precede new onset anisocoria occurrence and may allow for earlier prediction of neurologic decline. Further work is needed to determine whether quantitative pupillometry sensitively/specifically predicts clinically relevant anisocoria, enabling possible earlier treatments.

# 颅内病变患者瞳孔不等大和瞳孔反应不良（定量瞳孔测量）。

目的：描述新发瞳孔不等大（新瞳孔大小差异至少 1 mm）及其亚型的患病率和相关风险因素：新起始瞳孔不等大伴瞳孔反应异常和正常急性神经损伤患者。

设计：我们检测了出现新发瞳孔不等亚型伴中线程度的患者使用线性回归进行偏移。我们进一步探索了与首次新发相关的定量瞳孔特征使用混合显微镜在先前观察时观察到的瞳孔不等和非新发瞳孔不等 logistic 回归效应，校正可能的混杂因素。

设置：全部由护理人员在两间神经 - ICU 收集定量瞳孔观察结果作为标准治疗。

患者：我们进行了一项回顾性两中心研究 ICU 中至少 24 小时内有颅内病变的成人患者 2016 年至 2018 年期间停留和三次或三次以上定量瞳孔测量。

测量和主要结果：我们研究了 221 例患者（平均年龄 58 岁，41% 为女性）。63% 的患者出现新发瞳孔不等大。新发瞳孔不等大伴有在任何时间发生的瞳孔反应异常的客观证据住院期间，最大中线显著相关偏移 (Δ? = 2.27/mm；p = 0.01)。新发瞳孔不等大的发生伴有正常瞳孔反应性的客观证据为反校正后与死亡相关（比值比，0.34；95% CI，0.16-0.71；p = 0.01）分析。首次区分亚临床连续瞳孔大小差异在之前多达 4 个瞳孔中，非新发瞳孔不等大导致新发瞳孔不等大观察（或 8 h 前）。双眼之间的最低瞳孔反应性也区分新发瞳孔不等伴异常的客观证据新发瞳孔大小不等引起的瞳孔反应性伴客观证据首次新发瞳孔不等大发生前瞳孔反应正常。

结论：超过 60% 的神经科患者出现新发瞳孔不等紧急情况。瞳孔反应可能是一个重要的鉴别特征临床相关的新发瞳孔不等表型。新发瞳孔不等大伴随瞳孔反应性异常的客观证据与伴有中线移位和新发瞳孔不等大，伴有客观证据正常瞳孔反应性与死亡呈负相关。显著定量瞳孔特征先于新发瞳孔不等大发生，且可能允许更早预测神经功能衰退。需要进一步的工作确定定量瞳孔测量是否可灵敏 / 特异地预测临床相关的瞳孔大小不等，能够进行早期治疗。关键词：Humans; Female; Male; Middle Aged; Adult; Cohort Studies; Retrospective Studies; Intensive Care Units/organization & administration/statistics & numerical data; Anisocoria/*complications/epidemiology; Brain/*pathology/physiopathology; Reflex, Pupillary/*physiology

# Targeted Temperature Management in Out-of-Hospital Cardiac Arrest With Shockable Rhythm: A Post Hoc Analysis of the Coronary Angiography After Cardiac Arrest Trial.

2:e129-e142. DOI:10.1097/CCM.0000000000005271

Abstract:

OBJECTIVES: The optimal targeted temperature in patients with shockable rhythm is unclear, and current guidelines recommend targeted temperature management with a correspondingly wide range between 32?°C and 36?°C. Our aim was to study survival and neurologic outcome associated with targeted temperature management strategy in postarrest patients with initial shockable rhythm.

DESIGN: Observational substudy of the Coronary Angiography after Cardiac Arrest without ST-segment Elevation trial.

SETTING: Nineteen hospitals in The Netherlands.

PATIENTS: The Coronary Angiography after Cardiac Arrest trial randomized successfully resuscitated patients with shockable rhythm and absence of ST-segment elevation to a strategy of immediate or delayed coronary angiography. In this substudy, 459 patients treated with mild therapeutic hypothermia (32.0-34.0?°C) or targeted normothermia (36.0-37.0?°C) were included. Allocation to targeted temperature management strategy was at the discretion of the physician.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: After 90 days, 171 patients (63.6%) in the mild therapeutic hypothermia group and 129 (67.9%) in the targeted normothermia group were alive (hazard ratio, 0.86 [95% CI, 0.62-1.18]; log-rank p = 0.35; adjusted odds ratio, 0.89; 95% CI, 0.45-1.72). Patients in the mild therapeutic hypothermia group had longer ICU stay (4 d [3-7 d] vs 3 d [2-5 d]; ratio of geometric means, 1.32; 95% CI, 1.15-1.51), lower blood pressures, higher lactate levels, and increased need for inotropic support. Cerebral Performance Category scores at ICU discharge and 90-day follow-up and patient-reported Mental and Physical Health Scores at 1 year were similar in the two groups.

CONCLUSIONS: In the context of out-of-hospital cardiac arrest with shockable rhythm and no ST-elevation, treatment with mild therapeutic hypothermia was not associated with improved 90-day survival compared with targeted normothermia. Neurologic outcomes at 90 days as well as patient-reported Mental and Physical Health Scores at 1 year did not differ between the groups.

# 院外心脏骤停伴可电击节律的目标温度管理：心脏骤停后冠状动脉造影的事后分析试验。

目的：伴有可电击节律的患者的最佳目标温度尚不清楚，现行指南推荐采用相应地，温度范围在 32 ℃至 36 ℃之间。我们的目的是研究生存期与目标温度管理策略相关的神经系统结局初始可电击节律的停搏后患者。

设计：观察性无 ST 段的心搏骤停后冠状动脉造影亚组研究升高试验。

单位：荷兰的 19 家医院。

患者：心搏骤停试验后冠状动脉造影成功随机化对伴有可电击心律和无 ST 段抬高的患者进行复苏立即或延迟冠状动脉造影策略。在该子研究中，459 接受轻度治疗性低体温 (32.0-34.0 ℃) 或靶向治疗的患者包括正常体温 (36.0 ℃-37.0 ℃)。分配至目标温度管理策略由医生决定。

干预：无。

测量和主要结果：90 天后，171 例 (63.6%) 轻度治疗性低温组 129 例 (67.9%)，靶向常温组 129 例存活（风险比，0.86 [95% CI，0.62-1.18]；对数秩检验 p = 0.35；校正比值比，0.89；95% CI，0.45-1.72）。轻度治疗的患者低温组 ICU 停留时间较长（4 d [3-7 d] vs 3d [2-5 d]; 几何均值，1.32；95% CI，1.15-1.51），较低血压，较高乳酸盐对正性肌力支持的需求增加。大脑功能分类 ICU 出院和 90 天随访时的评分以及患者报告的精神和两组 1 年时的身体健康评分相似。

结论：在院外心脏骤停，伴有可电击节律，无 ST 段抬高，轻度治疗性低体温治疗与与目标体温正常相比，90 天生存率改善。神经系统结局第 90 天时以及第 1 天时患者报告的心理和身体健康评分治疗组之间的年份没有差异。关键词：Humans; Treatment Outcome; Female; Male; Middle Aged; Aged; Netherlands; Coronary Angiography/*methods/statistics & numerical data; Electric Countershock/*statistics & numerical data; Hypothermia, Induced/methods/*standards/statistics & numerical data; Out-of-Hospital Cardiac Arrest/epidemiology/*therapy; Resuscitation/methods/statistics & numerical data

# Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest., Su, Chenglei

2:e189-e198. DOI:10.1097/CCM.0000000000005268

Abstract:

OBJECTIVES: To investigate the therapeutic potential and underlying mechanisms of exogenous nicotinamide adenine dinucleotide+ on postresuscitation myocardial and neurologic dysfunction in a rat model of cardiac arrest.

DESIGN: Thirty-eight rats were randomized into three groups: 1) Sham, 2) Control, and 3) NAD. Except for the sham group, untreated ventricular fibrillation for 6 minutes followed by cardiopulmonary resuscitation was performed in the control and NAD groups. Nicotinamide adenine dinucleotide+ (20 mg/kg) was IV administered at the onset of return of spontaneous circulation.

SETTING: University-affiliated research laboratory.

SUBJECTS: Sprague-Dawley rats.

INTERVENTIONS: Nicotinamide adenine dinucleotide+.

MEASUREMENTS AND MAIN RESULTS: Hemodynamic and myocardial function were measured at baseline and within 4 hours following return of spontaneous circulation. Survival analysis and Neurologic Deficit Score were performed up to 72 hours after return of spontaneous circulation. Adenosine triphosphate (adenosine triphosphate) level was measured in both brain and heart tissue. Mitochondrial respiratory chain function, acetylation level, and expression of Sirtuin3 and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 (NDUFA9) in isolated mitochondrial protein from both brain and heart tissue were evaluated at 4 hours following return of spontaneous circulation. The results demonstrated that nicotinamide adenine dinucleotide+ treatment improved mean arterial pressure (at 1 hr following return of spontaneous circulation, 94.69 ?± 4.25 mm Hg vs 89.57 ?± 7.71 mm Hg; p < 0.05), ejection fraction (at 1 hr following return of spontaneous circulation, 62.67% ?± 6.71% vs 52.96% ?± 9.37%; p < 0.05), Neurologic Deficit Score (at 24 hr following return of spontaneous circulation, 449.50 ?± 82.58 vs 339.50 ?± 90.66; p < 0.05), and survival rate compared with that of the control group. The adenosine triphosphate level and complex I respiratory were significantly restored in the NAD group compared with those of the control group. In addition, nicotinamide adenine dinucleotide+ treatment activated the Sirtuin3 pathway, down-regulating acetylated-NDUFA9 in the isolated mitochondria protein.

CONCLUSIONS: Exogenous nicotinamide adenine dinucleotide+ treatment attenuated postresuscitation myocardial and neurologic dysfunction. The responsible mechanisms may involve the preservation of mitochondrial complex I respiratory capacity and adenosine triphosphate production, which involves the Sirtuin3-NDUFA9 deacetylation.

# 外源性烟酰胺腺嘌呤二核苷酸减轻心脏骤停大鼠模型复苏后心肌和神经功能障碍。

目的：研究外源性烟酰胺腺嘌呤二核苷酸 + 对复苏后心肌和心脏骤停大鼠模型中的神经功能障碍。

设计：38 大鼠随机分为 3 组：1）假手术组，2）对照组和 3）NAD 组。除外对于假手术组，未处理心室颤动 6 min，然后对照组和 NAD 组进行心肺复苏。在以下时间点 IV 给予烟酰胺腺嘌呤二核苷酸 +(20 mg/kg) 自主循环恢复。

单位：大学附属研究实验室。

受试者：Sprague-Dawley 大鼠。

干预：烟酰胺腺嘌呤二核苷酸 +。

测量和主要结果：血流动力学和心肌功能在基线和自发恢复后 4 小时内进行测量循环。进行生存期分析和神经功能缺损评分，直至自主循环恢复后 72 小时。三磷酸腺苷在大脑和心脏组织中测量（三磷酸腺苷）水平。线粒体呼吸链功能、乙酰化水平和 Sirtuin3 和 NADH 脱氢酶（泛醌）1α 亚复合物，9 (NDUFA9) 在在以下时间点评估了脑和心脏组织中分离的线粒体蛋白自主循环恢复后 4 小时。结果证明烟酰胺腺嘌呤二核苷酸 + 治疗改善平均动脉压（自主循环恢复后 1 h，94.69 μm±4.25 mmHg vs 89.57 μm） ?±7.71 mmHg；p < 0.05），射血分数（恢复至基线后 1 h）自发循环，62.67%?6.71% vs 52.96%?9.37%；p < 0.05），神经系统缺陷评分（自主循环恢复后 24 h，449.50 μm± 82.58 vs 339.50?±90.66；p < 0.05），生存率与对照组。三磷酸腺苷水平和复合物 I 呼吸与对照组相比，NAD 组显著恢复。此外，烟酰胺腺嘌呤二核苷酸 + 治疗激活 Sirtuin3 通路，下调分离线粒体蛋白中的乙酰化 - NDUFA9。

结论：外源性烟酰胺腺嘌呤二核苷酸 + 治疗减弱复苏后心肌和神经功能障碍。负责人机制可能涉及线粒体复合物 I 呼吸功能的保存能力和三磷酸腺苷的生成，其中涉及 Sirtuin3-NDUFA9 去乙酰化。关键词：Animals; Disease Models, Animal; Rats; Heart Arrest/*complications/drug therapy; Heart Failure/*drug therapy/prevention & control; NAD/*pharmacology/therapeutic use; Nervous System Diseases/*drug therapy/prevention & control; Rats, Sprague-Dawley/injuries/metabolism; Resuscitation/methods/*standards/statistics & numerical data

# Continuous Versus Routine Standardized Electroencephalogram for Outcome Prediction in Critically Ill Adults: Analysis From a Randomized Trial., Beuchat, Isabelle

2:329-334. DOI:10.1097/CCM.0000000000005311

Abstract:

OBJECTIVES: To investigate electroencephalogram (EEG) features' relation with mortality or functional outcome after disorder of consciousness, stratifying patients between continuous EEG and routine EEG.

DESIGN: Retrospective analysis of data from a randomized controlled trial.

SETTING: Multiple adult ICUs.

PATIENTS: Data from 364 adults with acute disorder of consciousness, randomized to continuous EEG (30-48 hr; n = 182) or repeated 20-minute routine electroencephalogram (n = 182).

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Correlations between electrographic features and mortality and modified Rankin scale at 6 months (good 0-2) were assessed. Background continuity, higher frequency, and reactivity correlated with survival and good modified Rankin scale.

Rhythmic and periodic patterns carried dual prognostic information: lateralized periodic discharges were associated with mortality and bad modified Rankin scale. Generalized rhythmic delta activity correlated with survival, good modified Rankin scale, and lower occurrence of status epilepticus. Presence of sleep-spindles and continuous EEG background was associated with good outcome in the continuous EEG subgroup. In the routine EEG group, a model combining background frequency, continuity, reactivity, sleep-spindles, and lateralized periodic discharges was associated with mortality at 70.91% (95% CI, 59.62-80.10%) positive predictive value and 63.93% (95% CI, 58.67-68.89%) negative predictive value. In the continuous EEG group, a model combining background continuity, reactivity, generalized rhythmic delta activity, and lateralized periodic discharges was associated with mortality at 84.62% (95%CI, 75.02-90.97) positive predictive value and 74.77% (95% CI, 68.50-80.16) negative predictive value.

CONCLUSIONS: Standardized EEG interpretation provides reliable prognostic information. Continuous EEG provides more information than routine EEG.

# 在危重成人中比较连续与常规标准化脑电图用于结局预测：一项随机试验的分析。

目的：研究意识障碍后脑电图 (EEG) 特征与死亡率或功能结局的关系，分层连续 EEG 和常规 EEG 之间的患者。

设计：回顾性分析的数据来自一项随机对照试验。

设置：多个成人 ICU。

患者：数据来自 364 例急性意识障碍成人患者，随机分配至连续 EEG (30-48 h；n = 182) 或重复 20 min 常规脑电图 (n = 182)。

干预：无。测量和主要结果：电波图特征与死亡率之间的相关性和改良评估了 6 个月时的 Rankin 量表（良好 0-2 分）。背景连续性，较高与生存期和良好改良 Rankin 评分相关的频率和反应性刻度。

节律和周期模式具有双重预后信息：偏侧周期性放电与死亡率和不良改良相关 Rankin 量表。全身节律性 δ 活动与生存率相关，良好改良 Rankin 量表，癫痫持续状态发生率较低。存在睡眠 - 纺锤波和连续 EEG 背景与良好的结局相关连续 EEG 亚组。在常规 EEG 组，模型结合背景频率、连续性、反应性、睡眠 - 纺锤波和单侧化周期性放电与死亡率相关，为 70.91%（95% CI， 59.62-80.10%）的阳性预测值和 63.93%(95% CI，58.67-68.89%) 阴性预测值。在连续脑电图组，模型结合背景连续性、反应性、全身节律性 δ 活动，以及单侧周期性放电与死亡率相关，为 84.62%（95% CI， 75.02-90.97）阳性预测值和 74.77%(95% CI，68.50-80.16) 阴性预测值。

结论：标准化脑电图解读提供了可靠的预后信息。连续 EEG 提供的信息比常规更多脑电图。关键词：Humans; Female; Male; Middle Aged; Prognosis; Adult; Retrospective Studies; ROC Curve; Critical Illness/therapy; Intensive Care Units/organization & administration/statistics & numerical data; Outcome Assessment, Health Care/methods/*statistics & numerical data; *Time Factors; Area Under Curve; Electroencephalography/*methods/standards/statistics & numerical data; Seizures/*diagnosis/epidemiology/physiopathology

# Beneficial Effect of Prone Positioning During Venovenous Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019., Zaaqoq, Akram M.

2:275-285. DOI:10.1097/CCM.0000000000005296

Abstract:

OBJECTIVES: The study investigated the impact of prone positioning during venovenous extracorporeal membrane oxygenation support for coronavirus disease 2019 acute respiratory failure on the patient outcome.

DESIGN: An observational study of venovenous extracorporeal membrane oxygenation patients. We used a multistate survival model to compare the outcomes of patients treated with or without prone positioning during extracorporeal membrane oxygenation, which incorporates the dynamic nature of prone positioning and adjusts for potential confounders.

SETTING: Seventy-two international institutions participating in the Coronavirus Disease 2019 Critical Care Consortium international registry.

PATIENTS: Coronavirus disease 2019 patients who were supported by venovenous extracorporeal membrane oxygenation during the study period.

INTERVENTION: None.

MEASUREMENTS AND MAIN RESULTS: There were 232 coronavirus disease 2019 patients at 72 participating institutions who were supported with venovenous extracorporeal membrane oxygenation during the study period from February 16, 2020, to October 31, 2020. Proning was used in 176 patients (76%) before initiation of extracorporeal membrane oxygenation and in 67 patients (29%) during extracorporeal membrane oxygenation. Survival to hospital discharge was 33% in the extracorporeal membrane oxygenation prone group versus 22% in the extracorporeal membrane oxygenation supine group. Prone positioning during extracorporeal membrane oxygenation support was associated with reduced mortality (hazard ratio, 0.31; 95% CI, 0.14-0.68).

CONCLUSIONS: Our study highlights that prone positioning during venovenous extracorporeal membrane oxygenation support for refractory coronavirus disease 2019-related acute respiratory distress syndrome is associated with reduced mortality. Given the observational nature of the study, a randomized controlled trial of prone positioning on venovenous extracorporeal membrane oxygenation is needed to confirm these findings.

# 2019 年冠状病毒病静脉 - 静脉体外膜氧合期间俯卧位的有益作用。

目的：本研究调查了在冠状病毒病的静脉 - 静脉体外膜肺氧合支持过程中俯卧位的影响 2019 年急性呼吸衰竭对患者结局的影响。

设计：观察性研究对静脉 - 静脉体外膜肺氧合患者的研究。我们使用了多状态生存模型，比较接受或体外膜肺氧合过程中无俯卧位，结合了俯卧位的动态特性，并调整了潜在体位混杂因素。

背景：72 家国际机构参与 2019 年冠状病毒病重症监护联盟国际登记。

患者：冠状病毒病 2019 例静脉 - 静脉支持患者研究期间的体外膜肺氧合。

干预：无。

测量值和主要结果：有 232 例冠状病毒病 2019 例患者在 72 家静脉 - 静脉支持的参与机构 2 月 16 日研究期间的体外膜肺氧合， 2020 年，至 2020 年 10 月 31 日。之前 176 例患者 (76%) 使用过剪毛术 67 例患者 (29%) 开始体外膜肺氧合治疗体外膜肺氧合。患者的出院生存率为 33% 体外膜肺氧合倾向组 vs. 22% 体外膜肺氧合仰卧位组。术中俯卧位体外膜肺氧合支持与死亡率降低相关（风险比，0.31；95% CI，0.14-0.68）。

结论：我们的研究强调静脉 - 静脉体外膜肺氧合支持期间的俯卧位难治性冠状病毒病 2019 相关急性呼吸窘迫综合征与死亡率降低相关。鉴于以下观察性质静脉 - 静脉俯卧位的随机对照研究需要体外膜肺氧合来证实这些结果。关键词：Humans; Female; Male; Middle Aged; Adult; Hospital Mortality; *SARS-CoV-2; Patient Discharge; *Extracorporeal Membrane Oxygenation; *Prone Position; COVID-19/complications/*therapy; Patient Positioning/*methods; Probability; Respiratory Distress Syndrome/etiology/*therapy

# Late Awakening Is Common in Settings Without Withdrawal of Life-Sustaining Therapy in Out-of-Hospital Cardiac Arrest Survivors Who Undergo Targeted Temperature Management.

2:235-244. DOI:10.1097/CCM.0000000000005274

Abstract:

OBJECTIVES: We investigated awakening time and characteristics of awakening compared nonawakening and factors contributing to poor neurologic outcomes in out-of-hospital cardiac arrest survivors in no withdrawal of life-sustaining therapy settings.

DESIGN: Retrospective analysis of the Korean Hypothermia Network Pro registry.

SETTING: Multicenter ICU.

PATIENTS: Adult (?‰? 18 yr) comatose out-of-hospital cardiac arrest survivors who underwent targeted temperature management at 33-36?°C between October 2015 and December 2018.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We measured the time from the end of rewarming to awakening, defined as a total Glasgow Coma Scale score greater than or equal to 9 or Glasgow Coma Scale motor score equals to 6. The primary outcome was awakening time. The secondary outcome was 6-month neurologic outcomes (poor outcome: Cerebral Performance Category 3-5). Among 1,145 out-of-hospital cardiac arrest survivors, 477 patients (41.7%) regained consciousness 30 hours (6-71 hr) later, and 116 patients (24.3%) awakened late (72 hr after the end of rewarming). Young age, witnessed arrest, shockable rhythm, cardiac etiology, shorter time to return of spontaneous circulation, lower serum lactate level, absence of seizures, and multisedative requirement were associated with awakening. Of the 477 who woke up, 74 (15.5%) had poor neurologic outcomes. Older age, liver cirrhosis, nonshockable rhythm, noncardiac etiology, a higher Sequential Organ Failure Assessment score, and higher serum lactate levels were associated with poor neurologic outcomes. Late awakeners were more common in the poor than in the good neurologic outcome group (38/74 [51.4%] vs 78/403 [19.4%]; p < 0.001). The awakening time (odds ratio, 1.005; 95% CIs, 1.003-1.008) and late awakening (odds ratio, 3.194; 95% CIs, 1.776-5.746) were independently associated with poor neurologic outcomes.

CONCLUSIONS: Late awakening after out-of-hospital cardiac arrest was common in no withdrawal of life-sustaining therapy settings and the probability of awakening decreased over time.

# 在接受靶向治疗的院外心脏骤停幸存者中，在未停止生命维持治疗的情况下，延迟觉醒很常见温度管理。

目的：我们研究了觉醒时间和觉醒特征，比较了觉醒前和导致较差神经系统结局的因素未撤除生命维持治疗的院外心脏骤停幸存者治疗设置。

设计：韩国低体温回顾性分析 Network Pro 注册表。

设置：多中心 ICU。

患者：成人（ ≥ 18 岁）接受靶向疗法的院外心脏骤停幸存者 2015 年 10 月至 2018 年 12 月期间，在 33-36 ℃下进行温度管理。

干预：无。

测量和主要结果：我们测量了从复温结束至觉醒，定义为总 Glasgow 昏迷量表评分大于等于 9 分或格拉斯哥昏迷量表运动评分等于 6 分。主要结局是觉醒时间。次要结局是 6 个月时的神经系统结局结局（不良结局：脑功能 3-5 级）。1,145 例患者中院外心脏骤停幸存者，477 例患者 (41.7%) 重新获得 30h (6-71 h) 后意识清醒，116 例患者 (24.3%) 苏醒较晚（复温结束后 72 h）。年幼，有目击者，令人震惊心律，心脏病因，自主循环恢复时间较短，血清乳酸水平降低、无癫痫发作和需要多种镇静剂与觉醒相关。在 477 名醒来的患者中，74 名 (15.5%) 较差神经系统结局。高龄、肝硬化、无电击节律、非心源性病因学，序贯器官衰竭评估评分较高，血清乳酸盐水平与较差的神经系统结局相关。晚醒者为较差组比良好神经学结局组更常见 (38/74)[51.4%] 对比 78/403 [19.4%]；p < 0.001）。觉醒时间（比值比，1.005；95% CI， 1.003-1.008）和晚期苏醒（比值比，3.194；95% CI，1.776-5.746）与较差的神经系统结局独立相关。

结论：晚期院外心脏骤停后觉醒常见于无撤药维持生命的治疗环境和苏醒的概率降低时间。关键词：Humans; Female; Male; Middle Aged; Aged; Cohort Studies; Retrospective Studies; Statistics, Nonparametric; Intensive Care Units/organization & administration/statistics & numerical data; *Time Factors; Hypothermia, Induced/methods/*standards/statistics & numerical data; Out-of-Hospital Cardiac Arrest/*complications/epidemiology/mortality; Republic of Korea/epidemiology; Survivors/statistics & numerical data; Withholding Treatment/*statistics & numerical data

# Extracorporeal Life Support for Respiratory Failure in Patients With Electronic Cigarette or Vaping Product Use-Associated Lung Injury.

2:e173-e182. DOI:10.1097/CCM.0000000000005299

Abstract:

OBJECTIVES: Electronic cigarette or vaping product use-associated lung injury is a clinical entity that can lead to respiratory failure and death. Despite the severity of electronic cigarette or vaping product use-associated lung injury, the role of extracorporeal life support in its management remains unclear. Our objective was to describe the clinical characteristics and outcomes of patients with electronic cigarette or vaping product use-associated lung injury who received extracorporeal life support.

DESIGN: We performed a retrospective review of records of electronic cigarette or vaping product use-associated lung injury patients who received extracorporeal life support. Standardized data were collected via direct contact with extracorporeal life support centers. Data regarding presentation, ventilatory management, extracorporeal life support details, and outcome were analyzed.

SETTING: This was a multi-institutional, international case series with patients from 10 different institutions in three different countries.

PATIENTS: Patients who met criteria for confirmed electronic cigarette or vaping product use-associated lung injury (based on previously reported diagnostic criteria) and were placed on extracorporeal life support were included. Patients were identified via literature review and by direct contact with extracorporeal life support centers.

MEASUREMENTS AND MAIN RESULTS: Data were collected for 14 patients ranging from 16 to 45 years old. All had confirmed vape use within 3 months of presentation. Nicotine was the most commonly used vaping product. All patients had respiratory symptoms and radiographic evidence of bilateral pulmonary opacities. IV antibiotics and corticosteroids were universally initiated. Patients were intubated for 1.9 days (range, 0-6) prior to extracorporeal life support initiation. Poor oxygenation and ventilation were the most common indications for extracorporeal life support. Five patients showed evidence of ventricular dysfunction on echocardiography. Thirteen patients (93%) were placed on venovenous extracorporeal life support, and one patient required multiple rounds of extracorporeal life support. Total extracorporeal life support duration ranged from 2 to 37 days. Thirteen patients survived to hospital discharge; one patient died of septic shock.

CONCLUSIONS: Electronic cigarette or vaping product use-associated lung injury can cause refractory respiratory failure and hypoxemia. These data suggest that venovenous extracorporeal life support can be an effective treatment option for profound, refractory respiratory failure secondary to electronic cigarette or vaping product use-associated lung injury.

# 电子香烟或挥发产品使用相关肺损伤患者呼吸衰竭的体外生命支持。

目的：电子香烟或挥发产品使用相关的肺损伤是一种可导致呼吸衰竭和死亡的临床疾病。尽管电子香烟或挥发产品使用相关的肺损伤的严重程度，尚不清楚体外生命支持在其管理中的作用。我们的目的是描述患者的临床特征和结局电子香烟或蒸汽产品使用相关的肺损伤，接受体外生命支持。

设计：我们进行了一项回顾性审查电子香烟或挥发产品使用相关肺损伤记录接受体外生命支持的患者。标准化数据为通过直接联系体外生命支持中心收集。数据关于表现、通气管理、体外生命支持对详细信息和结局进行了分析。

背景：这是一家多机构， 10 家不同机构的患者组成的 3 个国际病例系列不同国家。

患者：符合确认的电子吸烟或挥发产品使用相关的肺损伤（基于既往信息）报告诊断标准），并接受体外生命支持包括。通过文献综述和直接联系识别患者体外生命支持中心。

测量和主要结果：数据收集了年龄范围为 16 至 45 岁的 14 例患者。均已确认就诊后 3 个月内使用 vape。尼古丁是最常用的挥发产物。所有患者均有呼吸系统症状和放射学证据双侧肺部阴影。IV 抗生素和皮质类固醇普遍启动。术前患者插管 1.9 天（范围 0-6）开始体外生命支持。氧合和通气不良是最常见的体外生命支持适应症。5 例患者显示超声心动图显示心室功能不全的证据。13 例患者 (93%) 接受静脉 - 静脉体外生命支持，1 例患者需要多轮体外生命支持。完全体外生命支持持续时间范围为 2-37 天。13 例患者存活至医院出院；1 例患者死于感染性休克。

结论：电子香烟或挥发性产品使用相关肺损伤可导致难治性呼吸系统疾病衰竭和低氧血症。这些数据表明，静脉 - 静脉体外支持可作为严重、难治性呼吸系统疾病的有效治疗选择电子香烟或蒸汽产品使用相关肺继发失效损伤。关键词：Humans; Female; Male; Middle Aged; Adult; Adolescent; Retrospective Studies; Extracorporeal Membrane Oxygenation/methods/*statistics & numerical data; Electronic Nicotine Delivery Systems/*statistics & numerical data; Lung Injury/complications/epidemiology/*etiology; Lung/abnormalities/physiopathology; Respiratory Insufficiency/epidemiology/*etiology; Vaping/*adverse effects/epidemiology

# Right Ventricular Dysfunction and Its Association With Mortality in Coronavirus Disease 2019 Acute Respiratory Distress Syndrome: Do Not Focus on Not Reliable Markers!, Petit, Matthieu

2:e209-e210. DOI:10.1097/CCM.0000000000005328

# 冠状病毒病 2019 年急性呼吸窘迫综合征中右心室功能障碍及其与死亡率的相关性：不关注不可靠标记！

关键词：Humans; *COVID-19; SARS-CoV-2; *Respiratory Distress Syndrome; Ventricular Function, Right; *Ventricular Dysfunction, Right

# Association of Socioeconomic Status With Postdischarge Pediatric Resource Use and Quality of Life., Kachmar, Alicia G.

2:e117-e128. DOI:10.1097/CCM.0000000000005261

Abstract:

OBJECTIVES: Socioeconomic factors may impact healthcare resource use and health-related quality of life, but their association with postcritical illness outcomes is unknown. This study examines the associations between socioeconomic status, resource use, and health-related quality of life in a cohort of children recovering from acute respiratory failure.

DESIGN: Secondary analysis of data from the Randomized Evaluation of Sedation Titration for Respiratory Failure clinical trial.

SETTING: Thirty-one PICUs.

PATIENTS: Children with acute respiratory failure enrolled whose parent/guardians consented for follow-up.

MEASUREMENTS AND MAIN RESULTS: Resource use included in-home care, number of healthcare providers, prescribed medications, home medical equipment, emergency department visits, and hospital readmission. Socioeconomic status was estimated by matching residential address to census tract-based median income. Health-related quality of life was measured using age-based parent-report instruments. Resource use interviews with matched census tract data (n = 958) and health-related quality of life questionnaires (n = 750/958) were assessed. Compared with high-income children, low-income children received care from fewer types of healthcare providers (?? = -0.4; p = 0.004), used less newly prescribed medical equipment (odds ratio = 0.4; p < 0.001), and had more emergency department visits (43% vs 33%; p = 0.04). In the youngest cohort (< 2 yr old), low-income children had lower quality of life scores from physical ability (-8.6 points; p = 0.01) and bodily pain/discomfort (+8.2 points; p < 0.05). In addition, health-related quality of life was lower in those who had more healthcare providers and prescribed medications. In older children, health-related quality of life was lower if they had prescribed medications, emergency department visits, or hospital readmission.

CONCLUSIONS: Children recovering from acute respiratory failure have ongoing healthcare resource use. Yet, lower income children use less in-home and outpatient services and use more hospital resources. Continued follow-up care, especially in lower income children, may help identify those in need of ongoing healthcare resources and those at-risk for decreased health-related quality of life.

# 社会经济状况与出院后儿科资源利用和生活质量的相关性。

目的：社会经济因素可能影响医疗保健资源的使用和健康相关生活质量，但其与危重病后的相关性结局未知。本研究考察了社会经济与儿童队列中的状态、资源利用和健康相关生活质量急性呼吸衰竭好转。

设计：数据的次要分析来自针对呼吸衰竭的镇静滴定随机评估临床试验。

设置：31 个 PICU。

患者：急性儿童呼吸衰竭入组，其父母 / 监护人同意进行随访。

测量和主要结果：资源使用包括家庭护理，医疗保健提供者、处方药、家庭医疗设备、急救科室访视和再次入院。估计社会经济状况将居住地址与基于人口普查示踪的收入中位数相匹配。使用基于年龄的父母报告测量健康相关生活质量仪器。资源利用访谈匹配的人口普查道数据 (n = 958) 和评估了健康相关生活质量问卷 (n = 750/958)。与高收入儿童相比，低收入儿童获得的护理更少类型的医疗保健提供者 (? =-0.4；p = 0.004)，使用较少的新处方医疗设备（比值比 = 0.4；p < 0.001），急诊次数更多科室访视 (43% vs 33%；p = 0.04)。最年轻队列（< 2 岁），低收入儿童的体能生活质量评分较低 (-8.6) 评分；p = 0.01）和身体疼痛 / 不适（+ 8.2 分；p < 0.05）。In 此外，健康相关生活质量较低的患者医疗保健提供者和处方药物。在大龄儿童中，如果他们接受过处方药物治疗，则健康相关生活质量较低，急诊科就诊或再次入院。

结论：儿童正在从急性呼吸衰竭中恢复，持续使用医疗保健资源。然而，收入较低的儿童使用较少的家庭和门诊服务，使用较多医院资源。继续进行随访护理，尤其是在低收入人群中儿童，可能有助于确定需要持续医疗资源的人群和存在健康相关生活质量下降风险的患者。关键词：Humans; Female; Male; Child; Infant; Child, Preschool; Patient Discharge/statistics & numerical data; *Social Class; Health Resources/standards/statistics & numerical data/*supply & distribution; Intensive Care Units, Pediatric/organization & administration/statistics & numerical data; Patient Acceptance of Health Care/*statistics & numerical data; Quality of Life/*psychology

# Fluid Balance and Ventilator-Associated Events Among Patients Admitted to ICUs in China: A Nested Case-Control Study.

2:307-316. DOI:10.1097/CCM.0000000000005227

Abstract:

OBJECTIVES: Fluid therapy is an important component of intensive care management, however, optimal fluid management is unknown. The relationship between fluid balance and ventilator-associated events has not been well established. This study investigated the dose-response relationship between fluid balance and ventilator-associated events.

DESIGN: Nested case-control study.

SETTING: The study was based on a well-established, research-oriented registry of healthcare-associated infections at ICUs of West China Hospital system (Chengdu, China).

PATIENTS: A total of 1,528 ventilator-associated event cases with 3,038 matched controls, who consistently underwent mechanical ventilation for at least 4 days from April 1, 2015, to December 31, 2018, were included.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We calculated cumulative fluid balance within 4 days prior to ventilator-associated event occurrence. A weighted Cox proportional hazards model with restricted cubic splines was used to evaluate the dose-response relationship. A nonlinear relationship between fluid balance and all three tiers of ventilator-associated events, patients with fluid balance between -1 and 0 L had the lowest risk (p < 0.05 for nonlinear test). The risk of ventilator-associated event was significantly higher in patients with positive fluid balance (4 d cumulative fluid balance: 1 L: 1.19; 3 L: 1.92; 5 L: 2.58; 7 L: 3.24), but not in those with negative fluid balance (-5 L: 1.34; -3 L: 1.14; -1 L: 0.98).

CONCLUSIONS: There was nonlinear relationship between fluid balance and all three tiers of ventilator-associated event, with an fluid balance between -1 and 0 L corresponding to the lowest risk. Positive but not negative fluid balance increased the risk of ventilator-associated events, with higher positive fluid balance more likely to lead to ventilator-associated events.

# 中国 ICU 患者的液体平衡和呼吸机相关事件：一项巢式病例对照研究。

目的：液体治疗是重症监护管理的重要组成部分，但是，尚不清楚最佳的液体管理。液体之间的关系尚未充分确定平衡和呼吸机相关事件。此研究调查了液体平衡和以下之间的剂量 - 反应关系呼吸机相关事件。

设计：巢式病例对照研究。

设置：研究基于一项完善的以研究为导向的登记研究华西医院（成都，中国）。

患者：共计 1,528 例呼吸机相关事件病例，3,038 例匹配的对照，持续接受机械通气至少 2015 年 4 月 1 日至 2018 年 12 月 31 日，共 4 天。

干预：无。

测量和主要结果：我们计算了累积液体平衡呼吸机相关事件发生前 4 天内。加权 Cox 使用限制三次样条的比例风险模型评估剂量 - 反应关系。液体平衡与所有三级呼吸机相关事件、体液平衡患者 between -1 和 0 L 之间的风险最低（非线性检验 p <0.05）。下列风险呼吸机相关事件在阳性液体平衡（4 天累积液体平衡：1 L：1.19；3 L：1.92；5 L：2.58；7 L：3.24），但液体负平衡者（-5l：1.34；-3l：1.14； -1 L: 0.98). 结论：液体平衡之间存在非线性关系和所有三层呼吸机相关事件，液体平衡介于 -1 和 0 L 对应于最低风险。阳性但非阴性液体平衡增加了呼吸机相关事件的风险，正性更高体液平衡更可能导致呼吸机相关事件。关键词：Humans; Female; Male; Middle Aged; Aged; Case-Control Studies; China/epidemiology; Intensive Care Units/organization & administration/statistics & numerical data; Fluid Therapy/adverse effects/methods/statistics & numerical data; Respiration, Artificial/*adverse effects/instrumentation; Ventilators, Mechanical/*adverse effects/statistics & numerical data; Water-Electrolyte Balance/drug effects/*physiology

# Long-Term Acute Care Hospital Outcomes of Mechanically Ventilated Patients With Coronavirus Disease 2019., Saad, Marina

2:256-263. DOI:10.1097/CCM.0000000000005193

Abstract:

OBJECTIVES: To describe the clinical characteristics and outcomes of adult patients with coronavirus disease 2019 requiring weaning from prolonged mechanical ventilation.

DESIGN: Observational cohort study of patients admitted to two long-term acute care hospitals from April 1, 2020, to March 31, 2021.

SETTING: Two long-term acute care hospitals specialized in weaning from prolonged mechanical ventilation in the Chicagoland area, Illinois, United States.

PATIENTS: Adult (?‰? 18 yr old) ICU survivors of respiratory failure caused by severe acute respiratory syndrome coronavirus 2 pneumonia receiving prolonged mechanical ventilation.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: During the study period, 158 consecutive patients were transferred to the long-term acute care hospitals for weaning from prolonged ventilation. Demographic, clinical, and laboratory data were collected and analyzed. Final date of follow-up was June 1, 2021. Prior to long-term acute care hospital transfer, median length of stay at the acute care hospital was 41.0 days and median number of ventilator days was 35. Median age was 60.0 years, 34.8% of patients were women, 91.8% had a least one comorbidity, most commonly hypertension (65.8%) and diabetes (53.2%). The percentage of weaning success was 70.9%. The median duration of successful weaning was 8 days. Mortality was 9.6%. As of June 1, 2021, 19.0% of patients had been discharged home, 70.3% had been discharged to other facilities, and 1.3% were still in the long-term acute care hospitals.

CONCLUSIONS: Most patients with coronavirus disease 2019 transferred to two Chicago-area long-term acute care hospitals successfully weaned from prolonged mechanical ventilation.

# 2019 年机械通气的冠状病毒病患者长期急性护理医院结局。

目的：描述 2019 年需要长期停药的冠状病毒病成人患者的临床特征和结局机械通气。

设计：入院患者的观察性队列研究至 2020 年 4 月 1 日至 2021 年 3 月 31 日的两家长期急症护理医院。

背景：两家长期专门从事戒断治疗的长期急症治疗医院美国伊利诺斯州奇拉戈兰地区的机械通风。

患者：因下列原因导致呼吸衰竭的 ICU 成人（ ≥ 18 岁）生存者严重急性呼吸综合征冠状病毒 2 型肺炎接受长期治疗机械通气。

干预：无。

测量和主要结果：在研究期间，158 例连续患者转入长期急性护理医院，用于从长期通气断开。收集并分析人口统计学、临床和实验室数据。最终随访日期为 2021 年 6 月 1 日。在长期急症医院之前转入急诊医院时，中位住院时间为 41.0 天呼吸机使用天数中位数为 35 天。中位年龄为 60.0 岁，患者为女性，91.8% 至少有一种合并症，最常见高血压 (65.8%) 和糖尿病 (53.2%)。断奶成功的百分比为 70.9%. 成功断奶的中位持续时间为 8 天。死亡率为 9.6%。截至 2021 年 6 月 1 日，19.0% 的患者已出院回家，70.3% 的患者已出院后转至其他机构，1.3% 的患者仍在接受长期紧急治疗医院。

结论：2019 年大部分冠状病毒病患者转成功脱离芝加哥地区的两家长期急症护理医院长时间机械通气。关键词：Humans; Treatment Outcome; Female; Male; Middle Aged; Aged; Length of Stay; Cohort Studies; *SARS-CoV-2; Patient Discharge; *Ventilator Weaning; *Respiration, Artificial; Patient Transfer; COVID-19/complications/*therapy; *Hospitals, Special; Chicago/epidemiology; Respiratory Insufficiency/etiology/*therapy

# Comparison of Machine Learning Methods for Predicting Outcomes After In-Hospital Cardiac Arrest.

2:e162-e172. DOI:10.1097/CCM.0000000000005286

Abstract:

OBJECTIVES: Prognostication of neurologic status among survivors of in-hospital cardiac arrests remains a challenging task for physicians. Although models such as the Cardiac Arrest Survival Post-Resuscitation In-hospital score are useful for predicting neurologic outcomes, they were developed using traditional statistical techniques. In this study, we derive and compare the performance of several machine learning models with each other and with the Cardiac Arrest Survival Post-Resuscitation In-hospital score for predicting the likelihood of favorable neurologic outcomes among survivors of resuscitation.

DESIGN: Analysis of the Get With The Guidelines-Resuscitation registry.

SETTING: Seven-hundred fifty-five hospitals participating in Get With The Guidelines-Resuscitation from January 1, 2001, to January 28, 2017.

PATIENTS: Adult in-hospital cardiac arrest survivors.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Of 117,674 patients in our cohort, 28,409 (24%) had a favorable neurologic outcome, as defined as survival with a Cerebral Performance Category score of less than or equal to 2 at discharge. Using patient characteristics, pre-existing conditions, prearrest interventions, and periarrest variables, we constructed logistic regression, support vector machines, random forests, gradient boosted machines, and neural network machine learning models to predict favorable neurologic outcome. Events prior to October 20, 2009, were used for model derivation, and all subsequent events were used for validation. The gradient boosted machine predicted favorable neurologic status at discharge significantly better than the Cardiac Arrest Survival Post-Resuscitation In-hospital score (C-statistic: 0.81 vs 0.73; p < 0.001) and outperformed all other machine learning models in terms of discrimination, calibration, and accuracy measures. Variables that were consistently most important for prediction across all models were duration of arrest, initial cardiac arrest rhythm, admission Cerebral Performance Category score, and age.

CONCLUSIONS: The gradient boosted machine algorithm was the most accurate for predicting favorable neurologic outcomes in in-hospital cardiac arrest survivors. Our results highlight the utility of machine learning for predicting neurologic outcomes in resuscitated patients.

# 预测院内心脏骤停后结局的学习机方法比较。

目的：对于医生而言，院内心脏骤停幸存者的神经系统状态预后仍然是一项具有挑战性的任务。尽管模型如下因为心脏骤停存活率院内复苏后评分有用为了预测神经系统结局，使用传统方法统计技术。在本研究中，我们推导并比较了几个相互关联的机器学习模型和心搏骤停模型复苏后生存院内评分用于预测以下可能性复苏幸存者的良好神经系统结局。

设计：分析指南的获取 - 复苏注册。

设置：700 参与指南获取的 55 家医院 - 复苏来自 2001 年 1 月 1 日至 2017 年 1 月 28 日。

患者：院内心脏骤停成人存活者。

干预：无。

测量和主要结果：117,674 在我们的队列中，28,409 例 (24%) 患者具有良好的神经系统结局，因为定义为脑功能分级评分小于或等于 1 分的生存期出院时等于 2。使用患者特征、既存疾病，停搏前干预和停搏期间变量，我们构建了逻辑回归，支持向量机，随机图像，梯度增强机器，和用于预测有利神经系统的神经学模型结局。将 2009 年 10 月 20 日之前的事件用于模型推导，并且所有后续事件均用于验证。梯度增强机器出院时预测的良好神经系统状态显著优于院内复苏后心脏骤停存活率评分（C 统计量：0.81） vs 0.73；p < 0.001），在性能方面优于所有其他机器学习模型的鉴别、校准和准确度测量。变量在所有模型中对预测始终最重要的是停搏，初期心脏骤停节律，入院脑功能分类评分和年龄。

结论：梯度增强的机器算法是最准确预测院内心脏手术良好的神经系统结局逮捕幸存者。我们的结果强调了机器学习对于预测复苏患者的神经系统结局。关键词：Humans; Female; Male; Middle Aged; Prognosis; Aged; Cohort Studies; ROC Curve; Outcome Assessment, Health Care/methods/*statistics & numerical data; Area Under Curve; Survivors/statistics & numerical data; Forecasting/*methods; Heart Arrest/*complications/epidemiology/mortality; Machine Learning/*standards/statistics & numerical data

# A Systematic Review and Pooled Prevalence of Delirium in Critically Ill Children.

2:317-328. DOI:10.1097/CCM.0000000000005260

Abstract:

OBJECTIVES: Pediatric delirium is a neuropsychiatric disorder with disrupted cerebral functioning due to underlying disease and/or critical care treatment. Pediatric delirium can be classified as hypoactive, hyperactive, and mixed. This systematic review was conducted to estimate the pooled prevalence of pediatric delirium using validated assessment tools in children (Cornell Assessment of Pediatric Delirium, Pediatric Confusion Assessment Method for the ICU, PreSchool Confusion Assessment Method for the ICU, Pediatric Confusion Assessment Method for the ICU Severity Scale, and Sophia Observation Withdrawal Symptoms Pediatric Delirium scale), identify modifiable and nonmodifiable risk factors, and explore the association of pediatric delirium with clinical outcomes.

DATA SOURCES: A systematic search of PubMed, EMBASE, and CINAHL databases was undertaken for full articles pertaining to pediatric delirium prevalence.

STUDY SELECTION: No language or date barriers were set.

Studies were included where the following eligibility criteria were met: study design aimed to estimate pediatric delirium prevalence arising from treatment in the intensive care setting, using a validated tool. Only randomized controlled trials, cross-sectional studies, or cohort studies allowing an estimate of the prevalence of pediatric delirium were included.

DATA EXTRACTION: Data were extracted by the primary researcher (D.S.) and accuracy checked by coauthors.

DATA SYNTHESIS: A narrative synthesis and pooled prevalence meta-analysis were undertaken.

CONCLUSIONS: Pediatric delirium, as determined by the Cornell Assessment of Pediatric Delirium score, is estimated to occur in 34% of critical care admissions. Eight of 11 studies reporting on subtype identified hypoactive delirium as most prevalent (46-81%) with each of the three remaining reporting either hyperactive (44%), mixed (57%), or equal percentages of hypoactive and mixed delirium (43%) as most prevalent. The development of pediatric delirium is associated with cumulative doses of benzodiazepines, opioids, the number of sedative classes used, deep sedation, and cardiothoracic surgery. Increased time mechanically ventilated, length of stay, mortality, healthcare costs, and associations with decreased quality of life after discharge were also found. Multi-institutional and longitudinal studies are required to better determine the natural history, true prevalence, long-term outcomes, management strategies, and financial implications of pediatric delirium.

# 危重病儿童中谵妄的系统审查和汇总患病率。

目的：儿科谵妄是一种神经精神疾病，由于基础疾病和 / 或重症监护治疗而导致脑功能破坏。儿童谵妄可分为活动减退型、活动过度型和混合型。此进行了系统性审查，以估计儿科患者的汇总患病率使用经验证的儿童谵妄评估工具（Cornell 评估儿科谵妄，ICU 儿科意识模糊评估方法，学前 ICU 意识模糊评估方法，儿童意识模糊评估方法 ICU 严重程度量表和 Sophia 观察儿童戒断症状谵妄量表），确定可改变和不可改变的风险因素，并探索儿科谵妄与临床结局的相关性。

数据来源：A 全面检索 PubMed、EMBASE 和 CINAHL 数据库与儿童谵妄患病率相关的文章。

研究选择：否设置语言或日期障碍。纳入了以下研究符合合格性标准：旨在估计儿童谵妄的研究设计在重症监护条件下使用经验证的工具。仅随机对照试验、横断面研究或允许估计儿童谵妄患病率的队列研究包括：包括。

数据提取：由主要研究者 (D.S.) 提取数据。并由共同作者检查准确度。

数据综合：叙述综合和进行汇总患病率荟萃分析。

结论：儿童谵妄，根据儿科谵妄评分的 Cornell 评估，估计在 34% 的重症监护住院患者中发生。11 项研究中的 8 项报告了亚型确定活动减退性谵妄为最常见 (46-81%)，其余 3 例报告活动过度 (44%)、混合 (57%) 或相等活动减退和混合性谵妄 (43%) 的百分比最常见。事件儿童谵妄的发生与以下药物的累积剂量相关：苯二氮卓类、阿片类、使用的镇静类别数量、深度镇静和胸心外科。机械通气时间、住院时间延长，死亡率、医疗费用以及与生活质量下降的相关性还发现出院后。多机构和纵向研究为需要更好地确定自然史、真实患病率、长期儿科结局、管理策略和财务影响谵妄。关键词：Humans; Risk Factors; *Prevalence; Critical Illness/*classification/epidemiology; Delirium/*diagnosis/epidemiology/etiology

# Unassisted Return of Spontaneous Circulation Following Withdrawal of Life-Sustaining Therapy During Donation After Circulatory Determination of Death in a Child., Zier, Judith L.

2:e183-e188. DOI:10.1097/CCM.0000000000005273

Abstract:

OBJECTIVES: To describe the unassisted return of spontaneous circulation following withdrawal of life-sustaining treatment in a child.

DESIGN: Case report based on clinical observation and medical record review.

SETTING: Community Children's Hospital.

PATIENT: Two-year old child.

INTERVENTIONS: Following hypoxic-ischemic brain injury, the child was taken to the operating room for withdrawal of life-sustaining treatment during controlled donation after circulatory determination of death.

MEASUREMENTS AND MAIN RESULTS: In addition to direct observation by experienced pediatric critical care providers, the child was monitored with electrocardiography, pulse oximetry, and invasive blood pressure via femoral arterial catheter in addition to direct observation by experienced pediatric critical care providers. Unassisted return of spontaneous circulation occurred greater than 2 minutes following circulatory arrest and was accompanied by return of respiration.

CONCLUSIONS: We provide the first report of unassisted return of spontaneous circulation following withdrawal of life-sustaining treatment in a child. In our case, return of spontaneous circulation occurred in the setting of controlled donation after circulatory determination of death and was accompanied by return of respiration. Return of spontaneous circulation greater than 2 minutes following circulatory arrest in our patient indicates that 2 minutes of observation is insufficient to ensure that cessation of circulation is permanent after withdrawal of life-sustaining treatment in a child.

# 确定循环死亡后捐献期间停止维持生命治疗后自发循环的无辅助恢复儿童。

目的：描述儿童生命维持治疗停止后自主循环的无辅助恢复。

设计：病例报告基于临床观察和病历审查。

设置：社区儿童医院。

患者：2 岁儿童。

干预：如下缺氧缺血性脑损伤，患儿被送入手术室控制献血后，停止维持生命的治疗循环确定死亡。

测量和主要结果：除由有经验的儿科重症监护医生直接观察，通过心电图、脉搏血氧饱和度和侵入性血液监测除直接观察外，通过股动脉导管测量血压经验丰富的儿科重症监护医生。无协助自主返回循环在停循环后超过 2 min 发生，伴随呼吸恢复。

结论：我们提供了第一份报告撤药后自主循环的无辅助恢复儿童维持生命的治疗。在我们的病例中，自发恢复在循环后控制献血的情况下进行循环确定死亡，伴随呼吸恢复。返还循环骤停后超过 2 min 的自主循环我们的患者表示观察 2 min 不足以确保在停止维持生命的治疗后，循环永久性停止儿童治疗。关键词：Humans; Male; Child, Preschool; *Withholding Treatment; Brain Death/physiopathology; Life Support Care/*methods; Pediatrics/methods/standards; Return of Spontaneous Circulation/*physiology; Shock/complications/*therapy

# The Intriguing, Still Undercovered, Clinical Role of Echocardiography in Critically Ill Coronavirus Disease Patients., Lazzeri, Chiara

2:e212-e213. DOI:10.1097/CCM.0000000000005290

# 超声心动图在危重症冠状病毒病患者中的重要临床作用，目前仍未阐明。

关键词：Humans; Echocardiography; *COVID-19; *Critical Illness

# The Role of the Long-Term Acute Care Hospital Following Critical Illness-Has the Coronavirus Disease 2019 Pandemic Demonstrated Their Usefulness or Emphasized Their Downside?

2:341-343. DOI:10.1097/CCM.0000000000005206

# 危重病后长期急性护理医院的作用 - 冠状病毒病 2019 年流行病证实了其有用性或重要性它们的缺点？

关键词：Humans; *COVID-19; SARS-CoV-2; Hospitals; *Pandemics; Critical Illness/epidemiology

# Trends in ICU Mortality From Coronavirus Disease 2019: A Tale of Three Surges., Auld, Sara C.

2:245-255. DOI:10.1097/CCM.0000000000005185

Abstract:

OBJECTIVES: To determine the association between time period of hospitalization and hospital mortality among critically ill adults with coronavirus disease 2019.

DESIGN: Observational cohort study from March 6, 2020, to January 31, 2021.

SETTING: ICUs at four hospitals within an academic health center network in Atlanta, GA.

PATIENTS: Adults greater than or equal to 18 years with coronavirus disease 2019 admitted to an ICU during the study period (i.e., Surge 1: March to April, Lull 1: May to June, Surge 2: July to August, Lull 2: September to November, Surge 3: December to January).

MEASUREMENTS AND MAIN RESULTS: Among 1,686 patients with coronavirus disease 2019 admitted to an ICU during the study period, all-cause hospital mortality was 29.7%.

Mortality differed significantly over time: 28.7% in Surge 1, 21.3% in Lull 1, 25.2% in Surge 2, 30.2% in Lull 2, 34.7% in Surge 3 (p = 0.007). Mortality was significantly associated with 1) preexisting risk factors (older age, race, ethnicity, lower body mass index, higher Elixhauser Comorbidity Index, admission from a nursing home); 2) clinical status at ICU admission (higher Sequential Organ Failure Assessment score, higher d-dimer, higher C-reactive protein); and 3) ICU interventions (receipt of mechanical ventilation, vasopressors, renal replacement therapy, inhaled vasodilators). After adjusting for baseline and clinical variables, there was a significantly increased risk of mortality associated with admission during Lull 2 (relative risk, 1.37 [95% CI = 1.03-1.81]) and Surge 3 (relative risk, 1.35 [95% CI = 1.04-1.77]) as compared to Surge 1.

CONCLUSIONS: Despite increased experience and evidence-based treatments, the risk of death for patients admitted to the ICU with coronavirus disease 2019 was highest during the fall and winter of 2020. Reasons for this increased mortality are not clear.

# 2019 年冠状病毒病 ICU 死亡率的趋势：三次高峰。

目的：确定 2019 年冠状病毒病重症成人患者住院时间段与住院死亡率之间的相关性。

设计：观察性队列研究，2020 年 3 月 6 日至 2021 年 1 月 31 日。

地点：美国国立卫生研究院学术中心网络内的 4 家医院的 ICU 佐治亚州亚特兰大。

患者：18 岁及以上伴有冠状病毒的成人 2019 年疾病在研究期间入住 ICU（即，Surge 1：3 月至 4 月，拉 1：5 月至 6 月，波动 2：7 月至 8 月，拉 2：9 月至 11 月，波动 3：12 月至 1 月）。

测量和主要结果：其中 1,686 例冠状病毒病患者 2019 例在研究期间入住 ICU 期间，全因死亡率为 29.7%。死亡率差异显著随时间推移：Surge 1 为 28.7%，Lull 1 为 21.3%，Surge 2 为 25.2%，Lull 2 为 30.2%，浪涌 3 中为 34.7%(p = 0.007)。死亡率与 1）显著相关既存风险因素（年龄较大、人种、种族、体重指数较低、 Elixhauser 合并症指数较高，入住养老院）；2）临床 ICU 入院时的状态（序贯器官衰竭评估评分较高，较高 d - 二聚体，C 反应蛋白较高）；和 3）ICU 干预（接受机械通气、血管加压药、肾脏替代治疗、吸入血管扩张剂）。校正基线和临床变量后，与 Lull 2 期间入院相关的死亡风险显著增加（相对风险，1.37 [95% CI = 1.03-1.81]）和浪涌 3（相对风险，1.35 [95% CI = 1.04-1.77]），相比浪涌 1. 结论：尽管增加经验和循证治疗，入院患者的死亡风险 2019 年秋冬季节冠状病毒病入住 ICU 的比例最高 of 2020. 死亡率增加的原因尚不清楚。关键词：Humans; Female; Male; Middle Aged; Time Factors; Aged; Critical Illness; Cohort Studies; Academic Medical Centers; *SARS-CoV-2; COVID-19/*mortality; Hospital Mortality/*trends; Hospitalization/*trends; Intensive Care Units/*trends

# Use of the Molecular Adsorbent Recirculating System in Acute Liver Failure: Results of a Multicenter Propensity Score-Matched Study., MacDonald, Andrew J.

2:286-295. DOI:10.1097/CCM.0000000000005194

Abstract:

OBJECTIVES: The molecular adsorbent recirculating system removes water-soluble and albumin-bound toxins and may be beneficial for acute liver failure patients. We compared the rates of 21-day transplant-free survival in acute liver failure patients receiving molecular adsorbent recirculating system therapy and patients receiving standard medical therapy.

DESIGN: Propensity score-matched retrospective cohort analysis.

SETTING: Tertiary North American liver transplant centers.

PATIENTS: Acute liver failure patients receiving molecular adsorbent recirculating system at three transplantation centers (n = 104; January 2009-2019) and controls from the U.S. Acute Liver Failure Study Group registry.

INTERVENTIONS: Molecular adsorbent recirculating system treatment versus standard medical therapy (control).

MEASUREMENTS AND MAIN RESULTS: One-hundred four molecular adsorbent recirculating system patients were propensity score-matched (4:1) to 416 controls. Using multivariable conditional logistic regression adjusting for acute liver failure etiology (acetaminophen: n = 248; vs nonacetaminophen: n = 272), age, vasopressor support, international normalized ratio, King's College Criteria, and propensity score (main model), molecular adsorbent recirculating system was significantly associated with increased 21-day transplant-free survival (odds ratio, 1.90; 95% CI, 1.07-3.39; p = 0.030). This association remained significant in several sensitivity analyses, including adjustment for acute liver failure etiology and propensity score alone ("model 2"; molecular adsorbent recirculating system odds ratio, 1.86; 95% CI, 1.05-3.31; p = 0.033), and further adjustment of the "main model" for mechanical ventilation, and grade 3/4 hepatic encephalopathy ("model 3"; molecular adsorbent recirculating system odds ratio, 1.91; 95% CI, 1.07-3.41; p = 0.029). In acetaminophen-acute liver failure (n = 51), molecular adsorbent recirculating system was associated with significant improvements (post vs pre) in mean arterial pressure (92.0 vs 78.0 mm Hg), creatinine (77.0 vs 128.2 ??mol/L), lactate (2.3 vs 4.3 mmol/L), and ammonia (98.0 vs 136.0 ??mol/L; p ?‰¤ 0.002 for all). In nonacetaminophen acute liver failure (n = 53), molecular adsorbent recirculating system was associated with significant improvements in bilirubin (205.2 vs 251.4 ??mol/L), creatinine (83.1 vs 133.5 ??mol/L), and ammonia (111.5 vs 140.0 ??mol/L; p ?‰¤ 0.022 for all).

CONCLUSIONS: Treatment with molecular adsorbent recirculating system is associated with increased 21-day transplant-free survival in acute liver failure and improves biochemical variables and hemodynamics, particularly in acetaminophen-acute liver failure.

# 分子吸附再循环系统在急性肝衰竭中的应用：一项多中心倾向评分匹配研究的结果。

目的：分子吸附再循环系统可去除水溶性和与白蛋白结合的毒素，可能对急性肝衰竭患者有益。我们比较了急性肝衰竭患者的 21 天无移植生存率接受分子吸附再循环系统治疗的患者和接受标准药物治疗。

设计：倾向得分匹配回顾性队列分析。

背景：第三期北美肝移植研究中心。

患者：接受分子吸附治疗的急性肝衰竭患者 3 个移植中心的再循环系统（n = 104；1 月 2009-2019）以及来自美国急性肝衰竭研究组登记研究的对照组。

干预：分子吸附再循环系统治疗 vs. 标准治疗药物治疗（对照）。

测量和主要结果：104 例分子吸附再循环系统患者倾向得分匹配 (4:1) 至 416 例对照。使用多变量条件性 logistic 回归校正急性肝衰竭病因（对乙酰氨基酚：n = 248；vs 非对乙酰氨基酚：n = 272），年龄，血管加压药支持，国际标准化比值、King's College 标准和倾向评分（主要模型），分子学吸附再循环系统与 21 天增加显著相关无移植生存期（比值比，1.90；95% CI，1.07-3.39；p = 0.030）。此在几项敏感性分析中，包括仅根据急性肝衰竭病因和倾向评分进行调整（“模型 2"；分子吸附再循环系统比值比，1.86；95% CI，1.05-3.31； p = 0.033），并且进一步调整了机械通风，和 3/4 级肝性脑病（“模型 3”；分子吸附剂再循环系统比值比，1.91；95% CI，1.07-3.41；p = 0.029）。In 对乙酰氨基酚 - 急性肝衰竭 (n = 51)，分子吸附再循环系统与平均值的显著改善（术后 vs 术前）相关动脉压 (92.0 vs 78.0 mmHg)、肌酐 (77.0 vs 128.2 μmol/L)，乳酸盐 (2.3 vs 4.3 mmol/L) 和氨（98.0 vs 136.0 μmol/L；p?‰?0.002，所有）。在非对乙酰氨基酚急性肝衰竭 (n = 53) 中，使用分子吸附剂循环系统与胆红素的显著改善相关（205.2 对比 251.4?mol/L）、肌酐（83.1 对比 133.5?mol/L）和氨（111.5 对比 251.4?mol/L）。 140.0 μmol/L；所有 p?‰?0.022）。

结论：分子吸附剂治疗再循环系统可提高 21 天无移植生存率在急性肝衰竭中，改善生化变量和血液动力学，尤其是对乙酰氨基酚 - 急性肝衰竭。关键词：Humans; Female; Male; Middle Aged; Adult; Cohort Studies; Propensity Score; Retrospective Studies; Logistic Models; Alberta/epidemiology; Tertiary Care Centers/organization & administration/statistics & numerical data; Liver Failure, Acute/epidemiology/*etiology/therapy; Liver Transplantation/methods/*statistics & numerical data; Models, Molecular

# Prone-Positioning for Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation., Petit, Matthieu

2:264-274. DOI:10.1097/CCM.0000000000005145

Abstract:

OBJECTIVES: To determine the characteristics and outcomes of patients prone-positioned during extracorporeal membrane oxygenation for severe acute respiratory distress syndrome and lung CT pattern associated with improved respiratory system static compliance after that intervention.

DESIGN: Retrospective, single-center study over 8 years.

SETTINGS: Twenty-six bed ICU in a tertiary center.

MEASUREMENTS AND MAIN RESULTS: A propensity score-matched analysis compared patients with prone-positioning during extracorporeal membrane oxygenation and those without. An increase of the static compliance greater than or equal to 3 mL/cm H2O after 16 hours of prone-positioning defined prone-positioning responders. The primary outcome was the time to successful extracorporeal membrane oxygenation weaning within 90 days of postextracorporeal membrane oxygenation start, with death as a competing risk. Among 298 venovenous extracorporeal membrane oxygenation-treated adults with severe acute respiratory distress syndrome, 64 were prone-positioning extracorporeal membrane oxygenation. Although both propensity score-matched groups had similar extracorporeal membrane oxygenation durations, prone-positioning extracorporeal membrane oxygenation patients' 90-day probability of being weaned-off extracorporeal membrane oxygenation and alive was higher (0.75 vs 0.54, p = 0.03; subdistribution hazard ratio [95% CI], 1.54 [1.05-2.58]) and 90-day mortality was lower (20% vs 42%, p < 0.01) than that for no prone-positioning extracorporeal membrane oxygenation patients. Extracorporeal membrane oxygenation-related complications were comparable for the two groups. Patients without improved static compliance had higher percentages of nonaerated or poorly aerated ventral and medial-ventral lung regions (p = 0.047).

CONCLUSIONS: Prone-positioning during venovenous extracorporeal membrane oxygenation was safe and effective and was associated with a higher probability of surviving and being weaned-off extracorporeal membrane oxygenation at 90 days. Patients with greater normally aerated lung tissue in the ventral and medial-ventral regions on quantitative lung CT-scan performed before prone-positioning are more likely to improve their static compliance after that procedure during extracorporeal membrane oxygenation.

# 需要体外膜肺氧合的重度急性呼吸窘迫综合征的俯卧位。

目的：确定重度急性呼吸窘迫综合征和肺 CT 模式（与干预后呼吸系统静态顺应性改善相关）体外膜肺氧合期间患者体位的特征和结局。

设计：8 年的回顾性、单中心研究。

背景：三级中心 ICU 的 26 张病床。

测量值和主要结果：倾向性评分匹配分析比较了体外膜肺氧合过程中俯卧位患者和无俯卧位患者。16 小时仰卧位后静态顺应性增加≥3 mL/cm H2O 定义为仰卧位应答者。主要结局为体外膜肺氧合开始后 90 天内至成功体外膜肺氧合撤机的时间，死亡为竞争风险。在 298 例静脉 - 静脉体外膜肺氧合治疗的成人重度急性呼吸窘迫综合征患者中，64 例为仰卧位体外膜肺氧合。尽管两个倾向性评分匹配组的体外膜氧合持续时间相似，但是单独定位体外膜氧合患者 90 天后脱离体外膜氧合和存活的概率更高（0.75 vs 0.54，p = 0.03；亚分布风险比 [95% CI]，1.54 [1.05-2.58]），90 天死亡率 (20% vs 42%，p < 0.01) 低于无体位体外膜肺氧合患者。两组的体外膜肺氧合相关并发症相当。无改善静态依从性的患者无通气或通气不良的腹侧和中 - 腹侧肺区百分比较高 (p = 0.047)。

结论：静脉 - 静脉体外膜氧合过程中的俯卧位安全有效，与 90 天时存活和脱离体外膜氧合的概率较高相关。在仰卧位前进行的定量肺 CT 扫描中，腹侧和中 - 腹侧区域通常充气肺组织较大的患者在体外膜肺氧合期间更可能改善该操作后的静态顺应性。关键词：Humans; Female; Male; Middle Aged; Adult; Retrospective Studies; Intensive Care Units/organization & administration/statistics & numerical data; Proportional Hazards Models; *Prone Position; Extracorporeal Membrane Oxygenation/methods/*standards/statistics & numerical data; Paris/epidemiology; Patient Positioning/methods; Respiratory Distress Syndrome/epidemiology/*therapy

# Phospholipid Screening Postcardiac Arrest Detects Decreased Plasma Lysophosphatidylcholine: Supplementation as a New Therapeutic Approach.

2:e199-e208. DOI:10.1097/CCM.0000000000005180

Abstract:

OBJECTIVES: Cardiac arrest and subsequent resuscitation have been shown to deplete plasma phospholipids. This depletion of phospholipids in circulating plasma may contribute to organ damage postresuscitation. Our aim was to identify the diminishment of essential phospholipids in postresuscitation plasma and develop a novel therapeutic approach of supplementing these depleted phospholipids that are required to prevent organ dysfunction postcardiac arrest, which may lead to improved survival.

DESIGN: Clinical case control study followed by translational laboratory study.

SETTING: Research institution. PATIENTS/SUBJECTS: Adult cardiac arrest patients and male Sprague-Dawley rats.

INTERVENTIONS: Resuscitated rats after 10-minute asphyxial cardiac arrest were randomized to be treated with lysophosphatidylcholine specie or vehicle.

MEASUREMENTS AND MAIN RESULTS: We first performed a phospholipid survey on human cardiac arrest and control plasma. Using mass spectrometry analysis followed by multivariable regression analyses, we found that plasma lysophosphatidylcholine levels were an independent discriminator of cardiac arrest. We also found that decreased plasma lysophosphatidylcholine was associated with poor patient outcomes. A similar association was observed in our rat model, with significantly greater depletion of plasma lysophosphatidylcholine with increased cardiac arrest time, suggesting an association of lysophosphatidylcholine levels with injury severity. Using a 10-minute cardiac arrest rat model, we tested supplementation of depleted lysophosphatidylcholine species, lysophosphatidylcholine(18:1), and lysophosphatidylcholine(22:6), which resulted in significantly increased survival compared with control. Furthermore, the survived rats treated with these lysophosphatidylcholine species exhibited significantly improved brain function. However, supplementing lysophosphatidylcholine(18:0), which did not decrease in the plasma after 10-minute cardiac arrest, had no beneficial effect.

CONCLUSIONS: Our data suggest that decreased plasma lysophosphatidylcholine is a major contributor to mortality and brain damage postcardiac arrest, and its supplementation may be a novel therapeutic approach.

# 心脏骤停后磷脂筛查检测血浆溶血磷脂酰胆碱降低：补充溶血磷脂酰胆碱作为一种新的治疗方法。

目的：已证实心脏骤停和随后的复苏可减少血浆磷脂。循环血浆中磷脂的耗竭可能导致复苏后器官损伤。我们的目的是确定复苏后血浆中必需磷脂的减少，并开发一种新的治疗方法，补充这些耗尽的磷脂，以预防心脏骤停后器官功能障碍（可能导致生存率改善）。

设计：临床病例对照研究后进行转化实验室研究。

单位：研究单位。患者 / 受试者：成年心脏骤停患者和雄性 Sprague-Dawley 大鼠。

干预：将 10 min 窒息性心脏骤停后复苏的大鼠随机分配至溶血磷脂酰胆碱组或溶媒组。

测量和主要结果：我们首先对人心脏骤停和对照血浆进行了磷脂调查。使用质谱分析后进行多变量回归分析，我们发现血浆溶血卵磷脂水平是心脏骤停的独立鉴别器。我们还发现血浆溶血磷脂酰胆碱降低与患者结局较差相关。在我们的大鼠模型中观察到了类似的关联，血浆溶血卵磷脂耗竭程度显著更大，心脏骤停时间增加，表明溶血卵磷脂水平与损伤严重程度相关。采用 10 min 心脏骤停大鼠模型，我们测试了补充耗尽的溶血磷脂酰胆碱、溶血磷脂酰胆碱 (18:1) 和溶血磷脂酰胆碱 (22:6)，与对照组相比，其导致存活率显著增加。此外，接受这些溶血卵磷脂物种治疗的存活大鼠表现出脑功能显著改善。然而，补充溶血卵磷脂 (18:0)（心脏骤停 10 min 后血浆中未减少）没有产生有益作用。

结论：我们的数据表明，血浆溶血磷脂酰胆碱降低是心脏骤停后死亡率和脑损伤的主要因素，补充溶血磷脂酰胆碱可能是一种新的治疗方法。关键词：Humans; Female; Male; Aged; Aged, 80 and over; Animals; Rats, Sprague-Dawley; Severity of Illness Index; Rats; Heart Arrest/blood/complications/*metabolism; Lysophosphatidylcholines/*analysis/blood; Mass Screening/methods/*standards/statistics & numerical data; Phospholipids/*analysis/blood

# Viral Micro-RNAs Are Detected in the Early Systemic Response to Injury and Are Associated With Outcomes in Polytrauma Patients., Vicente, Diego

2:296-306. DOI:10.1097/CCM.0000000000005181

Abstract:

OBJECTIVES: To evaluate early activation of latent viruses in polytrauma patients and consider prognostic value of viral micro-RNAs in these patients.

DESIGN: This was a subset analysis from a prospectively collected multicenter trauma database. Blood samples were obtained upon admission to the trauma bay (T0), and trauma metrics and recovery data were collected.

SETTING: Two civilian Level 1 Trauma Centers and one Military Treatment Facility.

PATIENTS: Adult polytrauma patients with Injury Severity Scores greater than or equal to 16 and available T0 plasma samples were included in this study. Patients with ICU admission greater than 14 days, mechanical ventilation greater than 7 days, or mortality within 28 days were considered to have a complicated recovery.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Polytrauma patients (n = 180) were identified, and complicated recovery was noted in 33%. Plasma samples from T0 underwent reverse transcriptase-quantitative polymerase chain reaction analysis for Kaposi's sarcoma-associated herpesvirus micro-RNAs (miR-K12_10b and miRK-12-12) and Epstein-Barr virus-associated micro-RNA (miR-BHRF-1), as well as Luminex multiplex array analysis for established mediators of inflammation. Ninety-eight percent of polytrauma patients were found to have detectable Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus micro-RNAs at T0, whereas healthy controls demonstrated 0% and 100% detection rate for Kaposi's sarcoma-associated herpesvirus and Epstein-Barr virus, respectively. Univariate analysis revealed associations between viral micro-RNAs and polytrauma patients' age, race, and postinjury complications. Multivariate least absolute shrinkage and selection operator analysis of clinical variables and systemic biomarkers at T0 revealed that interleukin-10 was the strongest predictor of all viral micro-RNAs. Multivariate least absolute shrinkage and selection operator analysis of systemic biomarkers as predictors of complicated recovery at T0 demonstrated that miR-BHRF-1, miR-K12-12, monocyte chemoattractant protein-1, and hepatocyte growth factor were independent predictors of complicated recovery with a model complicated recovery prediction area under the curve of 0.81.

CONCLUSIONS: Viral micro-RNAs were detected within hours of injury and correlated with poor outcomes in polytrauma patients. Our findings suggest that transcription of viral micro-RNAs occurs early in the response to trauma and may be associated with the biological processes involved in polytrauma-induced complicated recovery.

# 在对损伤的早期系统反应中检测到病毒 microrna，并与多发性创伤患者的结局相关。

目的：评估多创伤患者中潜伏病毒的早期激活，并考虑病毒 microrna 在这些患者中的预后价值。

设计：这是前瞻性收集的多中心创伤数据库的子集分析。在入住创伤室时 (T0) 采集血样，并收集创伤指标和恢复数据。

地点：两个一级二级二级二级创伤中心和一个军事治疗设施。

患者：损伤严重程度评分大于或等于 16 分的成人多发伤患者和可用的 T0 血浆样本纳入本研究。入住 ICU 超过 14 天、机械通气超过 7 天或 28 天内死亡的患者视为复杂的恢复。

干预：无。

测量和主要结果：确定了多发伤患者 (n = 180)，33% 的患者伴有并发症。从 T0 开始，对血浆样本进行 Kaposi 肉瘤相关疱疹病毒微 RNA（ΛK12_10b 和 ΛK-12-12）和 eb 病毒相关微 RNA (ΛBHRF-1) 的逆转录酶定量聚合酶链反应分析，以及建立炎症介质的 Luminex 多重阵列分析。发现 98% 的多发性创伤患者在 T0 时可检测到卡波西肉瘤相关疱疹病毒和 eb 病毒微 RNA，而健康对照显示对卡波西肉瘤相关疱疹病毒和 eb 病毒的检出率分别为 0% 和 100%。单变量分析显示病毒 microrna 与多发伤患者的年龄、人种和损伤后并发症之间存在相关性。T0 时临床变量和系统生物标志物的多变量最小绝对收缩和选择运算符分析显示，白介素 - 10 是所有病毒 microrna 的最强预测因子。在 T0 时，系统生物标志物作为复杂恢复预测因子的多变量最小绝对收缩和选择算子分析证明，综上所述，肝细胞生长因子是复杂恢复的独立预测因子，模型复杂恢复预测曲线下面积为 0.81。

结论：在受伤数小时内检测到病毒 microrna，并与多发伤患者的不良结局相关。我们的研究结果表明，病毒 microrna 的转录发生在创伤反应早期，可能与多种创伤诱导的复杂恢复相关的生物学过程有关。关键词：Humans; Female; Male; Middle Aged; Adult; Herpesvirus 4, Human/genetics/isolation & purification; Herpesvirus 8, Human/genetics/isolation & purification; MicroRNAs/*analysis/blood/genetics; Multiple Trauma/*immunology/*virology; Reverse Transcriptase Polymerase Chain Reaction/methods/statistics & numerical data; RNA, Viral/*analysis/blood/genetics

# Insights on Blood Product Transfusions on ICU-Acquired Infections in Septic Shock.

1:e102. DOI:10.1097/CCM.0000000000005254

# 对败血症性休克中 ICU 获得性感染血液制品输注的见解。

关键词：Humans; Intensive Care Units; Blood Transfusion; *Shock, Septic/therapy

# Bayesian Models for Therapeutic Monitoring of Vancomycin in the Critically Ill: What Should They Predict?, Briassoulis, Panagiotis

1:e100-e101. DOI:10.1097/CCM.0000000000005228

# 危重病患者中万古霉素治疗监测的贝叶斯模型：应预测什么？

关键词：Humans; Anti-Bacterial Agents/therapeutic use; *Vancomycin; *Critical Illness; Bayes Theorem; Drug Monitoring

# Hyperoxia on Venoarterial Extracorporeal Membrane Oxygenation: A Modifiable Risk?, Joyce, Christopher J.

1:e99-e100. DOI:10.1097/CCM.0000000000005252

# 静脉动脉体外膜氧合的高氧血症：可改变的风险？

关键词：Humans; Risk Factors; Retrospective Studies; *Hyperoxia; *Extracorporeal Membrane Oxygenation

# Possible Underestimation of Cerebral Hyperoxia in Patients With Left Ventricular Output Encountering With Extracorporeal Membrane Oxygenation Flow at the Aortic Arch.

1:e98-e99. DOI:10.1097/CCM.0000000000005249

# 伴有左室输出且主动脉弓处有体外膜肺氧合血流的患者，其脑氧饱和度可能被低估。

关键词：Humans; *Hyperoxia; *Extracorporeal Membrane Oxygenation; Heart Ventricles; Aorta, Thoracic/diagnostic imaging

# Potential Confounders in Evaluating the Impact of Hyperoxia on Neurological Outcomes in Patients Receiving Extracorporeal Membrane Oxygenation., Ishii, Junki

1:e97-e98. DOI:10.1097/CCM.0000000000005239

# 评价高氧血症对体外膜肺氧合患者神经系统结局影响的潜在混杂因素。

关键词：Humans; Retrospective Studies; *Hyperoxia; *Extracorporeal Membrane Oxygenation; *Cardiopulmonary Resuscitation

# The authors reply.

1:e91-e92. DOI:10.1097/CCM.0000000000005329

# 作者回复。

# Sedation, Neuromuscular Blockade, and Mortality in Acute Respiratory Distress Syndrome: Important Questions Remain., Train, Sarah E.

1:e89-e90. DOI:10.1097/CCM.0000000000005258

# 急性呼吸窘迫综合征中的镇静、神经肌肉阻滞和死亡率：仍然是重要的问题。

关键词：Humans; *Anesthetics; *Neuromuscular Blockade; *Anesthesia; *Neuromuscular Blocking Agents; *Respiratory Distress Syndrome/drug therapy

# The authors reply., Taylor, Stephanie Parks

1:e88-e89. DOI:10.1097/CCM.0000000000005339

# 作者回复。

# Concerning the Association Between Delayed Administration of Antibiotics and Mortality in Patients With Suspected Sepsis.

1:e87-e88. DOI:10.1097/CCM.0000000000005255

# 关于疑似败血症患者延迟抗生素给药与死亡率之间的相关性。

关键词：Humans; Anti-Bacterial Agents/therapeutic use; *Shock, Septic/drug therapy; *Sepsis/drug therapy

# Is Time-of-Flight Ready for Take Off to Measure Patient Self-Inflicted Lung Injury?, Kouch, Michael

1:168-170. DOI:10.1097/CCM.0000000000005237

# 准备好飞行时间测量患者自残肺损伤了吗？

关键词：Humans; Lung; *Lung Injury

# The Challenge of Conducting Research in the Neonatal and Pediatric Age and of Translating Results Into Clinical Practice., Marraro, Giuseppe A.

1:165-168. DOI:10.1097/CCM.0000000000005192

# 开展新生儿和儿科研究以及将结果转化为临床实践的挑战。

关键词：Humans; Child; Infant, Newborn; *Translating

# The ICU Liberation ABCDEF Bundle: Utilization Among Critically Ill Little Adults.

1:163-165. DOI:10.1097/CCM.0000000000005214

# ICU 自由 ABCDEF 束：在危重小成人中的应用。

关键词：Humans; Adult; Critical Care; *Intensive Care Units; *Critical Illness

# Why Predict What Time Will Tell? A Strategic Rationale for Predicting Prolonged Mechanical Ventilation After Subarachnoid Hemorrhage., Maas, Matthew B.

1:160-162. DOI:10.1097/CCM.0000000000005250

# 为什么预测什么时间会有结果？预测蛛网膜下腔出血后机械通气延长的策略原理。

关键词：Humans; Time Factors; Respiration, Artificial; *Subarachnoid Hemorrhage/therapy

# Chimeric Antigen Receptor T Cells, the Shock of the New.

1:157-160. DOI:10.1097/CCM.0000000000005153

# 嵌合抗原受体 T 细胞，新的休克。

关键词：T-Lymphocytes; *Receptors, Chimeric Antigen; Immunotherapy, Adoptive; Receptors, Antigen, T-Cell

# Renin Kinetics and Mortality-Same, Same But Different?, Khanna, Ashish K.

1:153-157. DOI:10.1097/CCM.0000000000005157

# 肾素动力学和死亡率 - 相同、相同但不同？

关键词：*Renin; Kinetics

# Preserving Equity and Quality in the Push to Increase Access to Critical Care Services.

1:150-153. DOI:10.1097/CCM.0000000000005161

# 在推动增加重症监护服务的准入方面，维护公平和质量。

关键词：Humans; Critical Care/*organization & administration/standards; Efficiency, Organizational; Health Equity/*organization & administration; Health Facility Planning/*organization & administration; Health Services Accessibility/*organization & administration; Quality of Health Care/*organization & administration/standards

# Sepsis Definitions: I Know It When I See It., Parker, Margaret M.

1:148-150. DOI:10.1097/CCM.0000000000005350

# 败血症定义：我看到时就知道了。

关键词：Humans; *Shock, Septic; *Sepsis/diagnosis

# Time for a New Approach Investigating and Eliminating Racial Inequities in the ICU.

1:144-147. DOI:10.1097/CCM.0000000000005280

# 在 ICU 探索和消除人种偏见的新方法的时机。

关键词：Humans; Intensive Care Units; *Racial Groups; *Racism

# Racial Disparities in ICU Outcomes: A Systematic Review.

1:1-20. DOI:10.1097/CCM.0000000000005269

Abstract:

OBJECTIVES: Racial disparities in the United States healthcare system are well described across a variety of clinical settings. The ICU is a clinical environment with a higher acuity and mortality rate, potentially compounding the impact of disparities on patients. We sought to systematically analyze the literature to assess the prevalence of racial disparities in the ICU.

DATA SOURCES: We conducted a comprehensive search of PubMed/MEDLINE, Scopus, CINAHL, and the Cochrane Library.

STUDY SELECTION: We identified articles that evaluated racial differences on outcomes among ICU patients in the United States. Two authors independently screened and selected articles for inclusion.

DATA EXTRACTION: We dual-extracted study characteristics and outcomes that assessed for disparities in care (e.g., in-hospital mortality, ICU length of stay). Studies were assessed for bias using the Newcastle-Ottawa Scale.

DATA SYNTHESIS: Of 1,325 articles screened, 25 articles were included (n = 751,796 patients). Studies demonstrated race-based differences in outcomes, including higher mortality rates for Black patients when compared with White patients. However, when controlling for confounding variables, such as severity of illness and hospital type, mortality differences based on race were no longer observed. Additionally, results revealed that Black patients experienced greater financial impacts during an ICU admission, were less likely to receive early tracheostomy, and were less likely to receive timely antibiotics than White patients. Many studies also observed differences in patients' end-of-life care, including lower rates on the quality of dying, less advanced care planning, and higher intensity of interventions at the end of life for Black patients.

CONCLUSIONS: This systematic review found significant differences in the care and outcomes among ICU patients of different races. Mortality differences were largely explained by accompanying demographic and patient factors, highlighting the effect of structural inequalities on racial differences in mortality in the ICU. This systematic review provides evidence that structural inequalities in care persist in the ICU, which contribute to racial disparities in care. Future research should evaluate interventions to address inequality in the ICU.

# ICU 结局中的种族差异：一项系统性综述。

目的：美国医疗保健系统中的人种差异在各种临床背景中均有很好的描述。ICU 是具有较高急性和死亡率的临床环境，可能加剧差异对患者的影响。我们试图系统分析文献，以评估 ICU 中人种差异的患病率。

数据来源：我们对 PubMed/MEDLINE、Scopus、CINAHL 和 Cochrane Library 进行了全面检索。

研究选择：我们确定了评价美国 ICU 患者结局的人种差异的文章。两位作者独立筛选并选择文章纳入。

数据提取：我们双重提取了研究特征和结局，评估护理差异（例如，住院死亡率、ICU 住院时间）。使用 Newcastle-Ottawa 量表评估研究的偏倚。

资料综合：在筛选的 1325 篇文献中，纳入 25 篇文献（n = 751796 例患者）。研究表明结局存在基于人种的差异，包括与白人患者相比，黑人患者的死亡率更高。但是，当控制混杂变量时，如疾病严重程度和医院类型，不再观察到基于人种的死亡率差异。此外，结果显示，与白人患者相比，黑人患者在入住 ICU 期间经历了更大的经济影响，不太可能接受早期气管造口术，也不太可能及时接受抗生素治疗。许多研究还观察到患者的临终关怀存在差异，包括黑人患者的死亡质量率较低、晚期护理计划较少和临终关怀干预强度较高。

结论：本系统综述发现不同人种 ICU 患者的护理和结局存在显著差异。死亡率差异在很大程度上可通过伴随的人口统计学和患者因素来解释，突出了结构性不平等对 ICU 中死亡率的人种差异的影响。这项系统性审查提供的证据表明，ICU 中护理的结构性不平等持续存在，这导致护理中的人种差异。未来的研究应评估干预措施，以解决 ICU 中的不均一性。关键词：Humans; Length of Stay; United States; Patient Acuity; Intensive Care Units/*statistics & numerical data; Healthcare Disparities/*ethnology; Hospital Mortality/ethnology; Terminal Care/standards

# Criteria for Pediatric Sepsis-A Systematic Review and Meta-Analysis by the Pediatric Sepsis Definition Taskforce., Menon, Kusum

1:21-36. DOI:10.1097/CCM.0000000000005294

Abstract:

OBJECTIVE: To determine the associations of demographic, clinical, laboratory, organ dysfunction, and illness severity variable values with: 1) sepsis, severe sepsis, or septic shock in children with infection and 2) multiple organ dysfunction or death in children with sepsis, severe sepsis, or septic shock.

DATA SOURCES: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from January 1, 2004, and November 16, 2020.

STUDY SELECTION: Case-control studies, cohort studies, and randomized controlled trials in children greater than or equal to 37-week-old postconception to 18 years with suspected or confirmed infection, which included the terms "sepsis," "septicemia," or "septic shock" in the title or abstract.

DATA EXTRACTION: Study characteristics, patient demographics, clinical signs or interventions, laboratory values, organ dysfunction measures, and illness severity scores were extracted from eligible articles. Random-effects meta-analysis was performed.

DATA SYNTHESIS: One hundred and six studies met eligibility criteria of which 81 were included in the meta-analysis. Sixteen studies (9,629 patients) provided data for the sepsis, severe sepsis, or septic shock outcome and 71 studies (154,674 patients) for the mortality outcome. In children with infection, decreased level of consciousness and higher Pediatric Risk of Mortality scores were associated with sepsis/severe sepsis. In children with sepsis/severe sepsis/septic shock, chronic conditions, oncologic diagnosis, use of vasoactive/inotropic agents, mechanical ventilation, serum lactate, platelet count, fibrinogen, procalcitonin, multi-organ dysfunction syndrome, Pediatric Logistic Organ Dysfunction score, Pediatric Index of Mortality-3, and Pediatric Risk of Mortality score each demonstrated significant and consistent associations with mortality. Pooled mortality rates varied among high-, upper middle-, and lower middle-income countries for patients with sepsis, severe sepsis, and septic shock (p < 0.0001).

CONCLUSIONS: Strong associations of several markers of organ dysfunction with the outcomes of interest among infected and septic children support their inclusion in the data validation phase of the Pediatric Sepsis Definition Taskforce.

# 儿科败血症标准 - 儿科败血症定义 Taskforce 的系统审查和荟萃分析。

目的：确定人口统计学、临床、实验室、器官功能障碍和疾病严重程度变量值与以下指标的相关性：1）感染儿童中的败血症、重度败血症或感染性休克，和 2）败血症、重度败血症或感染性休克儿童中的多器官功能障碍或死亡。

资料来源：检索 2004 年 1 月 1 日至 2020 年 11 月 16 日 MEDLINE、Embase 和 Cochrane 临床对照试验中心注册数据库。

研究选择：在受孕后≥37 周、至 18 岁疑似或确诊感染的儿童中进行的病例对照研究、队列研究和随机对照试验，在标题或摘要中纳入术语 “败血症”、“败血症” 或 “感染性休克”。

数据提取：从合格文献中提取研究特征、患者人口统计学、临床体征或干预、实验室检查值、器官功能障碍指标和疾病严重程度评分。进行了随机效应荟萃分析。

数据综合：106 项研究符合合格标准，其中 81 项被纳入荟萃分析。16 项研究（9629 例患者）提供了败血症、重度败血症或感染性休克结局数据，71 项研究（154674 例患者）提供了死亡结局数据。在感染儿童中，意识水平下降和较高的儿科死亡风险评分与败血症 / 重度败血症相关。在伴有败血症 / 重度败血症 / 感染性休克、慢性疾病、肿瘤诊断、使用血管活性 / 正性肌力药、机械通气、血清乳酸盐、血小板计数、纤维蛋白原、降钙素原、多器官功能障碍综合征的儿童中，儿童 Logistic 器官功能障碍评分、儿童死亡率指数 - 3，儿科死亡风险评分均显示与死亡率显著且一致的相关性。对于脓毒症、重度脓毒症和脓毒性休克患者，不同高、中上、中下收入国家的汇总死亡率不同 (p < 0.0001)。

结论：在感染和败血症儿童中，器官功能障碍的几个标志物与关注结局的强相关性支持将其纳入儿科败血症定义工作组的数据验证阶段。关键词：Humans; Female; Male; Respiration, Artificial; Adolescent; Child; Infant; Infant, Newborn; Child, Preschool; Patient Acuity; Organ Dysfunction Scores; Clinical Laboratory Techniques; Consciousness; Global Health; Sepsis/*epidemiology/mortality/*physiopathology; Shock, Septic/epidemiology/physiopathology; Sociodemographic Factors

# The authors reply.

1:e94-e95. DOI:10.1097/CCM.0000000000005371

# 作者回复。

# Thrombocytopenia After Coronavirus Disease 2019 Vaccination: Remember to Put the Blame on Others Too., De Bruyne, Sander

1:e92-e93. DOI:10.1097/CCM.0000000000005327

# 2019 年接种冠状病毒病疫苗后发生血小板减少症：记住也要责备其他人。

关键词：Humans; *COVID-19; SARS-CoV-2; *Leukopenia; *Thrombocytopenia; Vaccination/adverse effects

# Physiological Assessment of Delirium Severity: The Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S)., van Sleuwen, Meike

1:e11-e19. DOI:10.1097/CCM.0000000000005224

Abstract:

OBJECTIVES: Delirium is a common and frequently underdiagnosed complication in acutely hospitalized patients, and its severity is associated with worse clinical outcomes.

We propose a physiologically based method to quantify delirium severity as a tool that can help close this diagnostic gap: the Electroencephalographic Confusion Assessment Method Severity Score (E-CAM-S).

DESIGN: Retrospective cohort study.

SETTING: Single-center tertiary academic medical center.

PATIENTS: Three-hundred seventy-three adult patients undergoing electroencephalography to evaluate altered mental status between August 2015 and December 2019.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We developed the E-CAM-S based on a learning-to-rank machine learning model of forehead electroencephalography signals. Clinical delirium severity was assessed using the Confusion Assessment Method Severity (CAM-S). We compared associations of E-CAM-S and CAM-S with hospital length of stay and inhospital mortality. E-CAM-S correlated with clinical CAM-S (R = 0.67; p < 0.0001). For the overall cohort, E-CAM-S and CAM-S were similar in their strength of association with hospital length of stay (correlation = 0.31 vs 0.41, respectively; p = 0.082) and inhospital mortality (area under the curve = 0.77 vs 0.81; p = 0.310). Even when restricted to noncomatose patients, E-CAM-S remained statistically similar to CAM-S in its association with length of stay (correlation = 0.37 vs 0.42, respectively; p = 0.188) and inhospital mortality (area under the curve = 0.83 vs 0.74; p = 0.112). In addition to previously appreciated spectral features, the machine learning framework identified variability in multiple measures over time as important features in electroencephalography-based prediction of delirium severity.

CONCLUSIONS: The E-CAM-S is an automated, physiologic measure of delirium severity that predicts clinical outcomes with a level of performance comparable to conventional interview-based clinical assessment.

# 谵妄严重程度的生理学评估：脑电图意识模糊评估方法严重程度评分 (E-CAM-S)。

目的：谵妄是急性住院患者中一种常见且经常被漏诊的并发症，其严重程度与较差的临床结局相关。我们提出一种基于生理学的方法，对谵妄严重程度进行定量，作为一种能够帮助填补该诊断空白的工具：脑电图意识模糊评估方法严重程度评分 (E-CAM-S)。

设计：回顾性队列研究。

单位：单中心三级学术医学中心。

患者：2015 年 8 月至 2019 年 12 月，373 例接受脑电图检查以评价精神状态改变的成人患者。

干预：无。

测量和主要结果：我们基于前额脑电图信号的学习秩机器学习模型开发了 E-CAM-S。采用意识模糊评估方法严重程度 (CAM-S) 评估临床谵妄严重程度。我们比较了 E-CAM-S 和 CAM-S 与住院时间和住院死亡率的相关性。E-CAM-S 与临床 CAM-S 相关 (R = 0.67；p < 0.0001)。对于总体队列，E-CAM-S 和 CAM-S 与住院时间（相关性分别为 0.31 vs 0.41；p = 0.082）和住院死亡率（曲线下面积 = 0.77 vs 0.81；p = 0.310）的相关性强度相似。即使仅限于非昏迷患者，E-CAM-S 与 CAM-S 在住院时间（相关性分别为 0.37 vs 0.42；p = 0.188）和住院死亡率（曲线下面积 = 0.83 vs 0.74；p = 0.112）方面仍然具有统计学相似性。除了以前认可的光谱特征外，机器学习框架还识别了多个指标随时间变化的变异性，作为基于脑电图预测谵妄严重程度的重要特征。

结论：E-CAM-S 是一种对谵妄严重程度的自动化、生理学测量，可预测临床结局，其性能水平与基于常规访谈的临床评估相当。关键词：Humans; Female; Male; Middle Aged; Prognosis; Aged; Adult; Retrospective Studies; Severity of Illness Index; Comorbidity; Patient Acuity; Length of Stay/statistics & numerical data; *Machine Learning; Academic Medical Centers/statistics & numerical data; Confusion/*diagnosis; Delirium/*diagnosis; Electroencephalography/*methods; Hospital Mortality/trends; Hospitals/statistics & numerical data; Image Processing, Computer-Assisted/*methods

# Molar Sodium Lactate Attenuates the Severity of Postcardiac Arrest Syndrome: A Preclinical Study., Stevic, Neven

1:e71-e79. DOI:10.1097/CCM.0000000000005233

Abstract:

OBJECTIVES: To determine whether continuous IV infusion of molar sodium lactate would limit cardiac arrest-induced neurologic injury and cardiovascular failure.

DESIGN: Randomized blinded study (animal model).

SETTING: University animal research facility.

SUBJECTS: Twenty-four adult male "New Zealand White" rabbits.

INTERVENTIONS: Anesthetized rabbits underwent 12.5 minutes of asphyxial cardiac arrest and were randomized to receive either normal saline (control group, n = 12) or molar sodium lactate (molar sodium lactate group, n = 12) at a rate of 5 mL/kg/hr during the whole 120-minute reperfusion period.

MEASUREMENTS AND MAIN RESULTS: Pupillary reactivity (primary outcome), levels of S100?? protein, in vitro brain mitochondria functions, cardiovascular function, and fluid balance were assessed. Molar sodium lactate reduced brain injury, with a higher proportion of animals exhibiting pupillary reactivity to light (83% vs 25% in the CTRL group, p = 0.01) and lower S100?? protein levels (189 ?± 42 vs 412 ?± 63 pg/mL, p < 0.01) at the end of the protocol. Molar sodium lactate significantly prevented cardiac arrest-induced decrease in oxidative phosphorylation and mitochondrial calcium-retention capacity compared with controls. At 120 minutes of reperfusion, survival did not significantly differ between the groups (10/12, 83% in the molar sodium lactate group vs nine of 12, 75% in the control group; p > 0.99), but hemodynamics were significantly improved in the molar sodium lactate group compared with the control group (higher mean arterial pressure [49 ?± 2 vs 29 ?± 3 mm Hg; p < 0.05], higher cardiac output [108 ?± 4 vs 58 ?± 9 mL/min; p < 0.05], higher left ventricle surface shortening fraction [38% ?± 3% vs 19% ?± 3%; p < 0.05], and lower left ventricular end-diastolic pressure [3 ?± 1 vs 8 ?± 2 mm Hg; p < 0.01]). While fluid intake was similar in both groups, fluid balance was higher in control animals (11 ?± 1 mL/kg) than that in molar sodium lactate-treated rabbits (1 ?± 3 mL/kg; p < 0.01) due to lower diuresis.

CONCLUSIONS: Molar sodium lactate was effective in limiting the severity of the postcardiac arrest syndrome. This preclinical study opens up new perspectives for the treatment of cardiac arrest.

# 乳酸钠摩尔降低心后停搏综合征的严重程度：一项临床前研究。

目的：确定持续 IV 输注摩尔乳酸钠是否会限制心脏骤停诱导的神经损伤和心血管衰竭。

设计：随机盲法研究（动物模型）。

单位：大学动物研究机构。

受试者：24 只成年雄性 “新西兰白兔”。

干预：麻醉家兔经历了 12.5 min 的窒息性心脏骤停，并在整个 120 min 再灌注期间随机接受生理盐水（对照组，n = 12）或摩尔乳酸钠（摩尔乳酸钠组，n = 12），速率为 5 mL/kg/hr。

测量和主要结果：评估瞳孔反应性（主要结局）、S100? 蛋白水平、体外脑线粒体功能、心血管功能和体液平衡。摩尔乳酸钠减少了脑损伤，在方案结束时，更高比例的动物表现出瞳孔对光的反应性（83% vs CTRL 组的 25%，p = 0.01），并且 s100nct014? 蛋白水平较低 (189?±42 vs 412Μ±63 pg/mL，p < 0.01)。与对照组相比，摩尔乳酸钠显著预防了心脏骤停诱导的氧化磷酸化和线粒体钙潴留能力下降。再灌注 120 min 时，各组间存活率无显著差异（10/12，摩尔乳酸钠组 83% vs 对照组 9/12，75%；p > 0.99），但与对照组相比，摩尔乳酸钠组的血流动力学显著改善（平均动脉压较高 [49?±2 vs 29?±3 mmHg；p < 0.05]、心输出量较高 [108?±4 vs 58?±9 mL/min；p < 0.05]、左心室表面缩短分数较高 [38%?±3% vs 19%?±3%；p < 0.05]，左室舒张末期压较低 ([mür±1 vs mür±2 mmHg；p < 0.01])。虽然两组的液体摄入量相似，但由于较低的利尿作用，对照动物 (11?±1 mL/kg) 的液体平衡高于摩尔乳酸钠处理的家兔 (1?±3 mL/kg；p < 0.01)。

结论：摩尔乳酸钠可有效限制心脏骤停后综合征的严重程度。本临床前研究为心脏骤停的治疗开辟了新的视角。关键词：Male; Animals; Disease Models, Animal; Random Allocation; Rabbits; Brain/drug effects; Hemodynamics/*drug effects; Post-Cardiac Arrest Syndrome/*physiopathology; Sodium Lactate/*pharmacology

1:e20-e30. DOI:10.1097/CCM.0000000000005230

Abstract:

OBJECTIVES: To evaluate which individual elements of health-related quality of life contribute most to decline in overall health-related quality of life status following pediatric critical care.

DESIGN: Retrospective cohort study.

SETTING: Seattle Children's Hospital.

PATIENTS: ICU patients age 1 month to 18 years admitted between December 2011 and February 2017.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: We assessed health-relatedquality of life decline from baseline to postdischarge (median, 6 wk) and determined the individual items of the Pediatric Quality of Life Inventory Infant Scales (< 2 yr) and Generic Core Scales (2-18 yr) with the highest prevalence of decline. We used multivariable regression to estimate the risk of decline in each of seven thematic categories by patient age, baseline health status, diagnosis, Pediatric Risk of Mortality score, and ICU length of stay. Decline from baseline health-related quality of life occurred in 22.5% of 539 patients. Items most commonly affected for infants less than 2 years were primarily emotional (cranky/crying, sleep, and self-soothing). Children 2-18 years most commonly experienced declines in physical functioning (play/exercise, lifting, and pain). Across the entire cohort, declines in categories of energy (31.5%), activity (31.0%), sleep (28.0%), and fear (24.7%) were most commonly endorsed. Risk of decline in each category varied with patient age, medical complexity, and diagnosis.

CONCLUSIONS: Deconditioning, sleep, fear, and pain are important targets for intervention to improve health-related quality of life outcomes for critically ill children.

# 健康相关生活质量的组分在儿童危重疾病后受影响最大。

目的：评价在儿科重症监护后，健康相关生活质量的个体因素对总体健康相关生活质量状态下降的贡献最大。

设计：回顾性队列研究。

单位：西雅图儿童医院。

患者：2011 年 12 月至 2017 年 2 月期间收治的 1 月龄至 18 岁的 ICU 患者。

干预：无。

测量和主要结果：我们评估了出院后健康相关生活质量自基线（中位数，6 周）的下降，并确定了下降患病率最高的儿科生活质量调查表婴儿量表（<2 年）和通用核心量表（2-18 年）的单项。我们使用多变量回归来估计按患者年龄、基线健康状况、诊断、儿科死亡风险评分和 ICU 住院时间划分的 7 个主题类别中每一个类别的下降风险。539 例患者中，22.5% 的患者的健康相关生活质量较基线下降。2 岁以下婴儿最常受累的项目主要为情绪（烦躁 / 哭闹、睡眠和自我舒缓）。2-18 岁儿童最常发生身体功能下降（游戏 / 运动、举起和疼痛）。在整个队列中，能量 (31.5%)、活动 (31.0%)、睡眠 (28.0%) 和恐惧 (24.7%) 类别下降最常见。各类别中的下降风险因患者年龄、医学复杂性和诊断而异。

结论：失调、睡眠、恐惧和疼痛是改善危重儿童健康相关生活质量结局的重要干预目标。关键词：Humans; Female; Male; Length of Stay; Adolescent; Retrospective Studies; Child; Infant; Severity of Illness Index; Child, Preschool; Exercise; Age Factors; *Quality of Life; *Critical Illness; *Intensive Care Units, Pediatric; Health Status; Hospitals, Pediatric; Play and Playthings; Sleep Quality; Surveys and Questionnaires/*standards

# Coronavirus Disease-Induced Blurred Judgment.

1:e95-e96. DOI:10.1097/CCM.0000000000005248

# 冠状病毒病引起的判断模糊。

关键词：Humans; *Coronavirus; *Coronavirus Infections; Diagnostic Tests, Routine; Judgment

# Characterization and Outcomes of Hospitalized Children With Coronavirus Disease 2019: A Report From a Multicenter, Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) Registry., Bhalala, Utpal S.

1:e40-e51. DOI:10.1097/CCM.0000000000005232

Abstract:

OBJECTIVES: Multicenter data on the characteristics and outcomes of children hospitalized with coronavirus disease 2019 are limited. Our objective was to describe the characteristics, ICU admissions, and outcomes among children hospitalized with coronavirus disease 2019 using Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: Coronavirus Disease 2019 registry.

DESIGN: Retrospective study.

SETTING: Society of Critical Care Medicine Viral Infection and Respiratory Illness Universal Study (Coronavirus Disease 2019) registry.

PATIENTS: Children (< 18 yr) hospitalized with coronavirus disease 2019 at participating hospitals from February 2020 to January 2021.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The primary outcome was ICU admission. Secondary outcomes included hospital and ICU duration of stay and ICU, hospital, and 28-day mortality. A total of 874 children with coronavirus disease 2019 were reported to Viral Infection and Respiratory Illness Universal Study registry from 51 participating centers, majority in the United States. Median age was 8 years (interquartile range, 1.25-14 yr) with a male:female ratio of 1:2. A majority were non-Hispanic (492/874; 62.9%). Median body mass index (n = 817) was 19.4 kg/m2 (16-25.8 kg/m2), with 110 (13.4%) overweight and 300 (36.6%) obese. A majority (67%) presented with fever, and 43.2% had comorbidities. A total of 238 of 838 (28.2%) met the Centers for Disease Control and Prevention criteria for multisystem inflammatory syndrome in children, and 404 of 874 (46.2%) were admitted to the ICU. In multivariate logistic regression, age, fever, multisystem inflammatory syndrome in children, and pre-existing seizure disorder were independently associated with a greater odds of ICU admission. Hospital mortality was 16 of 874 (1.8%). Median (interquartile range) duration of ICU (n = 379) and hospital (n = 857) stay were 3.9 days (2-7.7 d) and 4 days (1.9-7.5 d), respectively. For patients with 28-day data, survival was 679 of 787, 86.3% with 13.4% lost to follow-up, and 0.3% deceased.

CONCLUSIONS: In this observational, multicenter registry of children with coronavirus disease 2019, ICU admission was common. Older age, fever, multisystem inflammatory syndrome in children, and seizure disorder were independently associated with ICU admission, and mortality was lower among children than mortality reported in adults.

# 2019 年冠状病毒病住院儿童的特征和结局：一项多中心、病毒感染和呼吸系统疾病的报告通用研究 (Coronavirus Disease 2019) 登记研究。

目的：有关 2019 年因冠状病毒病住院的儿童的特征和结局的多中心数据有限。我们的目标是描述儿童的特征、ICU 收治和结局 2019 年重症协会评估的冠状病毒病导致住院医学发现病毒感染和呼吸系统疾病的普遍研究： 2019 年冠状病毒病登记研究。

设计：回顾性研究。

单位：学会重症医学病毒感染与呼吸系统疾病的普遍研究 (Coronavirus Disease 2019) 登记研究。

患者：儿童（< 18 岁）住院伴随冠状病毒病 2019 年 2020 年 2 月 2 月在参与医院 2021 年 1 月。

干预：无。

测量和主要结果：主要结局为入住 ICU。次要结局包括住院和 ICU 持续时间住院和 ICU、住院和 28 天死亡率。共有 874 例儿童发生 2019 年将冠状病毒病报告至病毒感染和呼吸系统疾病来自 51 家参与研究中心的通用研究登记，大多数在美国状态。中位年龄为 8 岁（四分位距：1.25-14 岁），男性：女性比例为 1:2。大多数为非西班牙裔 (492/874；62.9%)。中位数体重指数 (n = 817) 为 19.4 kg/m2 (16-25.8 kg/m2)，其中 110 (13.4%) 超重和肥胖患者 300 例 (36.6%)。大多数 (67%) 表现为发热，以及 43.2% 有合并症。共计 238/838 名患者 (28.2%) 符合我国多系统炎症综合征的疾病防治标准儿童，404/874 (46.2%) 例患者进入 ICU。多变量 logistic 回归、年龄、发热、儿童多系统炎症综合征，既存癫痫发作性疾病与以下因素独立相关：入住 ICU 的几率。住院死亡率为 874 例中的 16 例 (1.8%)。中位数（四分位距）ICU (n = 379) 和住院 (n = 857) 时间 3.9 天（2-7.7 天）和 4 天（1.9-7.5 d）。对于 28 天患者数据，生存率为 679/787，86.3%，13.4% 失访，0.3% 死亡。

结论：在这项观察性、儿童多中心登记研究中 2019 年，患者因冠状病毒病入住 ICU。高龄、发热、儿童多系统炎症综合征和癫痫发作与入住 ICU 独立相关，且死亡率较低儿童死亡率高于成人死亡率。关键词：Humans; Female; Male; Adolescent; Retrospective Studies; Child; Infant; Child, Preschool; Age Factors; Comorbidity; SARS-CoV-2; Intensive Care Units/statistics & numerical data; Body Mass Index; Logistic Models; Hospital Mortality/trends; Child, Hospitalized/*statistics & numerical data; COVID-19/*complications/*epidemiology/mortality/*physiopathology; Systemic Inflammatory Response Syndrome/*epidemiology/mortality/*physiopathology

# Mortality Among Noncoronavirus Disease 2019 Critically Ill Patients Attributable to the Pandemic in France.

1:138-143. DOI:10.1097/CCM.0000000000005215

Abstract:

OBJECTIVES: We investigated whether the risk of death among noncoronavirus disease 2019 critically ill patients increased when numerous coronavirus disease 2019 cases were admitted concomitantly to the same hospital units.

DESIGN: We performed a nationwide observational study based on the medical information system from all public and private hospitals in France.

SETTING: Information pertaining to every adult admitted to ICUs or intermediate care units from 641 hospitals between January 1, 2020, and June 30, 2020 was analyzed.

PATIENTS: A total of 454,502 patients (428,687 noncoronavirus disease 2019 and 25,815 coronavirus disease 2019 patients) were included.

INTERVENTIONS: For each noncoronavirus disease 2019 patient, pandemic exposure during their stay was calculated per day using the proportion of coronavirus disease 2019 patients among all patients treated in ICU.

MEASUREMENTS AND MAIN RESULTS: We computed a multivariable logistic regression model to estimate the influence of pandemic exposure (low, moderate, and high exposure) on noncoronavirus disease 2019 patient mortality during ICU stay. We adjusted on patient and hospital confounders. The risk of death among noncoronavirus disease 2019 critically ill patients increased in case of moderate (adjusted odds ratio, 1.12; 95% CI, 1.05-1.19; p < 0.001) and high pandemic exposures (1.52; 95% CI, 1.33-1.74; p < 0.001).

CONCLUSIONS: In hospital units with moderate or high levels of coronavirus disease 2019 critically ill patients, noncoronavirus disease deaths were at higher levels.

# 2019 年法国大流行导致的非冠状病毒疾病危重患者的死亡率

目的：我们研究了在 2019 例重症患者中，当许多冠状病毒疾病发生时，非冠状病毒疾病的死亡风险是否升高 2019 例病例在同一医院住院。

设计：我们基于医学信息开展一项全国观察性研究来自法国所有公立和私立医院的系统。

设置：信息与 641 年入住 ICU 或中间监护病房的每一位成人有关分析了 2020 年 1 月 1 日至 2020 年 6 月 30 日期间的医院。

患者：A 共 454,502 例患者（428,687 例非冠状病毒病 2019 和 25,815 例）冠状病毒病 2019 例患者）。

干预：针对每种非冠状病毒病 2019 例患者，住院期间大流行暴露使用 2019 例患者中的冠状病毒病比例计算 ICU 治疗的所有患者中。

测量和主要结果：我们计算了用于估计大流行影响的多变量 logistic 回归模型 2019 年非冠状病毒疾病暴露（低、中、高暴露）患者在 ICU 住院期间的死亡率。我们根据患者和医院进行了调整混杂因素。2019 年重症非冠状病毒病死亡风险分析中度患者增加（调整比值比，1.12；95% CI， 1.05-1.19；p <0.001）和大流行暴露（1.52；95% CI，1.33-1.74；p < 0.001). 结论：在医院病房中，中度或高度冠状病毒病 2019 例重症患者，非冠状病毒病死亡均处于较高水平。关键词：Humans; Female; Male; Middle Aged; Aged; Aged, 80 and over; Pandemics; SARS-CoV-2; Logistic Models; COVID-19/*epidemiology; Intensive Care Units/*statistics & numerical data; Critical Illness/*mortality; France/epidemiology; Mortality/*trends

# Body Mass Index and Mortality in Coronavirus Disease 2019 and Other Diseases: A Cohort Study in 35,506 ICU Patients.

1:e1-e10. DOI:10.1097/CCM.0000000000005216

Abstract:

OBJECTIVES: Obesity is a risk factor for severe coronavirus disease 2019 and might play a role in its pathophysiology. It is unknown whether body mass index is related to clinical outcome following ICU admission, as observed in various other categories of critically ill patients. We investigated the relationship between body mass index and inhospital mortality in critically ill coronavirus disease 2019 patients and in cohorts of ICU patients with non-severe acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and multiple trauma.

DESIGN: Multicenter observational cohort study.

SETTING: Eighty-two Dutch ICUs participating in the Dutch National Intensive Care Evaluation quality registry.

PATIENTS: Thirty-five-thousand five-hundred six critically ill patients.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Patient characteristics and clinical outcomes were compared between four cohorts (coronavirus disease 2019, nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and multiple trauma patients) and between body mass index categories within cohorts. Adjusted analyses of the relationship between body mass index and inhospital mortality within each cohort were performed using multivariable logistic regression. Coronavirus disease 2019 patients were more likely male, had a higher body mass index, lower Pao2/Fio2 ratio, and were more likely mechanically ventilated during the first 24 hours in the ICU compared with the other cohorts. Coronavirus disease 2019 patients had longer ICU and hospital length of stay, and higher inhospital mortality. Odds ratios for inhospital mortality for patients with body mass index greater than or equal to 35 kg/m2 compared with normal weight in the coronavirus disease 2019, nonsevere acute respiratory syndrome coronavirus 2 viral pneumonia, bacterial pneumonia, and trauma cohorts were 1.15 (0.79-1.67), 0.64 (0.43-0.95), 0.73 (0.61-0.87), and 0.81 (0.57-1.15), respectively.

CONCLUSIONS: The obesity paradox, which is the inverse association between body mass index and mortality in critically ill patients, is not present in ICU patients with coronavirus disease 2019-related respiratory failure, in contrast to nonsevere acute respiratory syndrome coronavirus 2 viral and bacterial respiratory infections.

# 2019 年冠状病毒病和其他疾病患者的体重指数和死亡率：一项纳入 35,506 例 ICU 患者的队列研究。

目的：肥胖是 2019 年严重冠状病毒疾病的风险因素，可能在其病理生理学中发挥作用。体重指数是否未知与 ICU 入院后的临床结局相关，如在各种其他类别的重症患者。我们研究了关系危重冠状病毒患者体重指数与住院死亡率的关系 2019 例患者和 ICU 非重度急性发作患者队列呼吸道综合征冠状病毒 2 型病毒性肺炎、细菌性肺炎和多发性创伤。

设计：多中心观察性队列研究。

设置： 82 间荷兰 ICU 参与荷兰国家重症监护评价质量登记。

患者：355006 重症患者。

干预：无。

测量和主要结果：比较了 4 个队列之间的患者特征和临床结局（冠状病毒病 2019、非严重急性呼吸综合征冠状病毒 2 病毒性肺炎、细菌性肺炎和多发性创伤患者）以及队列内的体重指数类别。相关性的校正分析每个队列中体重指数与住院死亡率之间的关系为使用多变量 logistic 回归进行。冠状病毒病 2019 患者更可能为男性，体重指数更高，Pao2/Fio2 更低比值，并且更可能在入组后 24 小时内进行机械通气 ICU 与其他队列相比。冠状病毒病 2019 例患者 ICU 和住院时间更长，住院死亡率更高。几率体重指数大于或等于在 2019 年，与正常体重相比，等于 35 kg/m2，非严重急性呼吸综合征冠状病毒 2 型细菌性病毒性肺炎肺炎和创伤队列分别为 1.15 (0.79-1.67)、0.64 (0.43-0.95) 和 0.73 (0.61-0.87), 和 0.81（0.57-1.15）。

结论：肥胖反常，即体重指数与死亡率之间的负相关重症患者中，ICU 患者中不存在冠状病毒 2019 年相关疾病呼吸衰竭，与非重度急性相反呼吸道综合征冠状病毒 2 型病毒性和细菌性呼吸道感染。关键词：Humans; Female; Male; Middle Aged; Aged; Critical Illness; Intensive Care Units; Length of Stay; SARS-CoV-2; Netherlands/epidemiology; Patient Acuity; Hospital Mortality/*trends; *Body Mass Index; COVID-19/*epidemiology/mortality; Multiple Trauma/epidemiology; Obesity/*epidemiology; Pneumonia, Bacterial/epidemiology

# Dielectric Blood Coagulometry for the Early Detection of Sepsis-Induced Disseminated Intravascular Coagulation: A Prospective Observational Study., Takayama, Wataru

1:e31-e39. DOI:10.1097/CCM.0000000000005231

Abstract:

OBJECTIVES: To evaluate the utility of dielectric blood coagulometry for early sepsis-induced disseminated intravascular coagulation diagnosis.

DESIGN: Single-center, prospective observational study.

SETTING: Patients with sepsis or septic shock at the Tokyo Medical and Dental University Hospital of Medicine between September 2019 and September 2020.

PATIENTS: The patients were divided into three groups according to the timing of disseminated intravascular coagulation diagnosis based on the Disseminated Intravascular Coagulation score by the Japanese Association for Acute Medicine: 1) no disseminated intravascular coagulation group, 2) late-diagnosed disseminated intravascular coagulation group: not diagnosed with disseminated intravascular coagulation on day 1 but diagnosed within 48 hours after admission, and 3) disseminated intravascular coagulation group: diagnosed with disseminated intravascular coagulation on day 1. The study evaluated 80 patients (no disseminated intravascular coagulation, 31 [38.8%]; late-diagnosed disseminated intravascular coagulation, 34 (42.5%); disseminated intravascular coagulation, 15 [18.8%]).

MEASUREMENTS AND MAIN RESULTS: We compared the clinical severity scores and mortality of the groups and assessed the correlation between the dielectric blood coagulometry-derived coagulation marker, thrombin levels, and Disseminated Intravascular Coagulation score using Spearman rank correlation. The mortality rate was 0% (0/31) in the no disseminated intravascular coagulation group, 35.3% (12/34) in the late-diagnosed disseminated intravascular coagulation group, and 33.3% (5/15) in the disseminated intravascular coagulation group. Although the Disseminated Intravascular Coagulation score on day 1 did not reflect disseminated intravascular coagulation in approximately 70% of patients who developed disseminated intravascular coagulation by day 2, dielectric clot strength measured by dielectric blood coagulometry on day 1 strongly correlated with disseminated intravascular coagulation development by day 2 (Spearman ρ = 0.824; p < 0.05) and with thrombin level on day 1 (Spearman ρ = 0.844; p < 0.05).

CONCLUSIONS: Dielectric blood coagulometry can be used to detect early-phase disseminated intravascular coagulation in patients with sepsis and is strongly correlated with thrombin levels. Larger studies are needed to verify our results for developing clinical applications.

# 使用电介质血液凝固法早期检测败血症诱导的弥散性血管内凝血：一项前瞻性观察性研究。

目的：评价电介质血液凝固法用于早期败血症诱导的弥散性血管内凝血的诊断。

设计：单中心、前瞻性观察性研究。

设置：脓毒症或东京医科齿科大学医学院脓毒性休克 2019 年 9 月至 2020 年 9 月。

患者：将患者分为根据弥散性血管内基于弥散性血管内凝血评分的凝血诊断日本急性医学协会：1）无弥漫性血管内凝血组，2）晚期确诊的弥漫性血管内凝血组：第 1 天未诊断为弥散性血管内凝血，但入院后 48 小时内确诊，和 3）弥散性血管内凝血组：当天确诊弥散性血管内凝血 1. 研究评估了 80 名患者（无弥散性血管内凝血，31 [38.8%]；晚期诊断的弥散性血管内凝血，34 (42.5%)；弥散性血管内凝血，15 [18.8%]）。测量和主要结果：我们比较了各组的临床严重程度评分和死亡率评估了电介质血凝仪测得的凝血标志物、凝血酶水平和弥散性血管内凝血使用 Spearman 等级相关进行评分。无并发症组的死亡率为 0%(0/31) 弥散性血管内凝血组，晚期诊断患者中 35.3%(12/34) 弥散性血管内凝血组，33.3%(5/15) 弥散性血管内凝血组。尽管已传播第 1 天血管内凝血评分未反映弥散性约 70% 发生血管内凝血的患者第 2 天弥散性血管内凝血，电介质凝块强度第 1 天通过电介质血凝测定法测量的结果与第 2 天出现弥散性血管内凝血（Spearman ρ =0.824； p<0.05），第 1 天的凝血酶水平 (Spearman ρ =0.844；p<0.05)。

结论：介电血凝仪可用于检测早期脓毒症患者弥散性血管内凝血，强烈与凝血酶水平相关。需要更大规模的研究来验证我们的结果用于开发临床应用。关键词：Humans; Female; Male; Middle Aged; Prospective Studies; Aged; Aged, 80 and over; Early Diagnosis; Patient Acuity; Blood Coagulation Tests/*methods; Disseminated Intravascular Coagulation/*diagnosis/*etiology; Sepsis/*complications/mortality; Shock, Septic/complications/mortality

# Cardiac Output Measurement in Neonates and Children Using Noninvasive Electrical Bioimpedance Compared With Standard Methods: A Systematic Review and Meta-Analysis., Mansfield, Roshni C.

1:126-137. DOI:10.1097/CCM.0000000000005144

Abstract:

OBJECTIVE: To systematically review and meta-analyze the validity of electrical bioimpedance-based noninvasive cardiac output monitoring in pediatrics compared with standard methods such as thermodilution and echocardiography.

DATA SOURCES: Systematic searches were conducted in MEDLINE and EMBASE (2000-2019).

STUDY SELECTION: Method-comparison studies of transthoracic electrical velocimetry or whole body electrical bioimpedance versus standard cardiac output monitoring methods in children (0-18 yr old) were included.

DATA EXTRACTION: Two reviewers independently performed study selection, data extraction, and risk of bias assessment. Mean differences of cardiac output, stroke volume, or cardiac index measurements were pooled using a random-effects model (R Core Team, R Foundation for Statistical Computing, Vienna, Austria, 2019). Bland-Altman statistics assessing agreement between devices and author conclusions about inferiority/noninferiority were extracted.

DATA SYNTHESIS: Twenty-nine of 649 identified studies were included in the qualitative analysis, and 25 studies in the meta-analyses. No significant difference was found between means of cardiac output, stroke volume, and cardiac index measurements, except in exclusively neonatal/infant studies reporting stroke volume (mean difference, 1.00 mL; 95% CI, 0.23-1.77). Median percentage error in child/adolescent studies approached acceptability (percentage error less than or equal to 30%) for cardiac output in L/min (31%; range, 13-158%) and stroke volume in mL (26%; range, 14-27%), but not in neonatal/infant studies (45%; range, 29-53% and 45%; range, 28-70%, respectively). Twenty of 29 studies concluded that transthoracic electrical velocimetry/whole body electrical bioimpedance was noninferior. Transthoracic electrical velocimetry was considered inferior in six of nine studies with heterogeneous congenital heart disease populations.

CONCLUSIONS: The meta-analyses demonstrated no significant difference between means of compared devices (except in neonatal stroke volume studies). The wide range of percentage error reported may be due to heterogeneity of study designs, devices, and populations included. Transthoracic electrical velocimetry/whole body electrical bioimpedance may be acceptable for use in child/adolescent populations, but validity in neonates and congenital heart disease patients remains uncertain. Larger studies in specific clinical contexts with standardized methodologies are required.

# 无创生物电阻抗法测量新生儿和儿童心输出量与标准方法的比较：一项系统回顾和荟萃分析。

目的：对基于电生物阻抗的无创心输出量监测在儿科中应用的有效性进行系统回顾和荟萃分析使用标准方法，如热稀释法和超声心动图。

数据来源：在 MEDLINE 和 EMBASE (2000-2019) 中进行了系统检索。研究选择：经胸廓电测速或全身电生物阻抗与标准心输出量监测纳入儿童（0-18 岁）方法。

数据提取：两名审查员独立进行研究选择、数据提取和偏倚风险评估。心输出量、每搏输出量或心脏指数的平均差异使用随机效应模型 (R Core Team,R Foundation) 汇总测量值统计计算，Vienna,Austria,2019）。Bland-Altman 统计量评估器械之间的一致性以及作者的结论提取劣效性 / 非劣效性。

数据综合：29/649 确定的研究纳入定性分析，25 项研究纳入荟萃分析。心脏参数平均值之间无显著差异输出量、每搏输出量和心脏指数测量值，除外报告每搏输出量的新生儿 / 婴儿研究（平均差异，1.00 mL；95% CI, 0.23-1.77). 接近儿童 / 青少年研究的中位误差百分比心输出量的可接受性（误差百分比≤30%） L/min（31%；范围：13-158%）和每搏输出量 (mL)（26%；范围：14-27%），但不是新生儿 / 婴儿研究（45%；范围：29-53% 和 45%；范围：28-70%，分别）。29 项研究中有 20 项得出的结论是，经胸廓电速度测量 / 全身电生物阻抗非劣效。经胸在 9 项研究的 6 项中，电测速被认为劣于异质性先天性心脏病人群。

结论：荟萃分析显示，比较的平均值之间无显著差异器械（新生儿每搏输出量研究除外）。百分比范围宽报告的错误可能是由于研究设计、器械和纳入的人群。经胸廓电测速 / 全身电生物阻抗可用于儿童 / 青少年人群，但在新生儿和先天性心脏病患者中的有效性仍不确定。在特定临床背景中使用标准化方法的更大型研究为要求。关键词：Humans; Female; Male; Adolescent; Child; Infant; Infant, Newborn; Child, Preschool; Cardiac Output/*physiology; Cardiography, Impedance/*standards; Echocardiography/standards; Monitoring, Physiologic/*methods; Stroke Volume/physiology; Thermodilution/standards

# Noninvasive Tidal Volume Measurements, Using a Time-of-Flight Camera, Under High-Flow Nasal Cannula-A Physiological Evaluation, in Healthy Volunteers., Le Moigne, Guillaume

1:e61-e70. DOI:10.1097/CCM.0000000000005183

Abstract:

OBJECTIVES: The mechanisms of high-flow nasal cannula are still debated but may be mediated by the generation of low positive end-expiratory pressure and a washout of the airway dead space. The aims of this study were to assess the effects of high-flow nasal cannula on tidal volume using a noninvasive method using a time-of-flight camera, under various conditions.

DESIGN: A physiologic evaluation in healthy volunteers.

SETTING: An university hospital ICU.

SUBJECTS: Ten healthy volunteers were included in a physiologic study (CamOpt study, ClinicalTrials.gov identifier: NCT04096183).

INTERVENTIONS: All volunteers were submitted to 12 different conditions (i.e., gas flow [baseline = 0; 30-60 L/min]; mouth [open/closed]; respiratory rate [baseline; baseline + 10 breaths/min]). Tidal volume measurements were performed every minute, during a 6-minute recording period. In all combinations, reference respiratory rate was measured by using chronometric evaluation, over a 30-second period (RRREF), and by using the time-of-flight camera (RRTOF).

MEASUREMENTS AND MAIN RESULTS: Tidal volume increased while increasing gas flow whatever the respiratory rate and mouth condition (p < 0.001). Similar results were observed whatever the experimental conditions (p < 0.01), except one (baseline respiratory rate + 10 breaths/min and mouth closed). Tidal volume increased while decreasing respiratory rate (p < 0.001) and mouth closing (p < 0.05). Proportion of tidal volume greater than 10, 15, and 20 mL/kg changed while increasing the flow. RRTOF was in agreement with RRREF (intraclass correlation coefficient, 0.96), with a low mean bias (0.55 breaths/min) and acceptable deviation.

CONCLUSIONS: Time-of-flight enables to detect tidal volume changes under various conditions of high-flow nasal cannula application. Tidal volume increased significantly while increasing gas flow and mouth closing. Such technique might be useful to monitor the risk of patient self-inflicted lung injury or under assistance.

# 在健康志愿者中，使用飞行时间相机在高流量鼻插管 - a 生理评估下进行非侵入性潮气量测量。

目的：高流量鼻插管的机制仍有争议，但可能是通过产生低呼气末正压和冲洗气道死腔。本研究的目的是评估非侵入性方法评价高流量鼻导管对潮气量的影响在各种条件下使用飞行时间相机。

设计：生理学在健康志愿者中的评价。

单位：大学医院 ICU。

受试者： 10 例健康志愿者被纳入一项生理学研究（CamOpt 研究，临床试验。gov 标识符：NCT04096183）。

干预：所有志愿者均为提交至 12 种不同的条件（即，气体流量 [基线 = 0；30-60 L/min]；口腔 [打开 / 关闭]；呼吸率 [基线；基线 + 10 次 / 分]）。6 min 内，每分钟进行一次潮气量测量记录周期。在所有组合中，参考呼吸率通过以下指标测量使用时间计时评估，在 30 秒期间 (RRREF)，并通过使用飞行时间相机 (RRTOF)。

测量和主要结果：潮气量无论呼吸频率和口腔如何，随着气体流量增加而增加条件 (p < 0.001)。无论实验结果如何，均观察到相似结果疾病 (p < 0.01)，除了 1 项（基线呼吸速率 + 10 次 / 分钟和闭口）。潮气量随呼吸频率降低而增加（p < 0.001）和闭口 (p < 0.05)。潮气量大于 10 的比例， 15 和 20 mL/kg 随流速增加而变化。RRTOF 与 RRREF（组内相关系数，0.96），平均偏倚较低 (0.55) 次 / 分）和可接受的偏差。

结论：飞行时间能够检测高流量鼻导管不同条件下的潮气量变化申请。潮气量随着气体流量增加而显著增加，闭口。这种技术可能有助于监测患者自身造成的肺损伤风险或辅助治疗。关键词：Humans; Female; Male; Time Factors; Intensive Care Units; Adult; Healthy Volunteers; *Cannula; Oxygen Inhalation Therapy/*methods; Tidal Volume/*physiology

# Recognizing Vaccine-Induced Immune Thrombotic Thrombocytopenia.

1:e80-e86. DOI:10.1097/CCM.0000000000005211

Abstract:

OBJECTIVES: Vaccine-induced immune thrombotic thrombocytopenia is an unexpected consequence of the coronavirus disease 2019 pandemic era. We reviewed the pathogenesis, clinical presentation, diagnosis, and treatment of this rare side effect.

DATA SOURCES: Online search of published medical literature through PubMed, Scopus, Web of Science, and Google Scholar using the terms "COVID-19," "vaccine," "thrombosis" was performed.

STUDY SELECTION: Articles were chosen for inclusion based on their relevance to coronavirus disease 2019, vaccine, and thrombosis.

DATA SYNTHESIS: Vaccine-induced immune thrombotic thrombocytopenia manifests most often as unusual thromboses (cerebral venous sinus thrombosis, splanchnic vein thrombosis) but sometimes also "usual" thromboses (arterial stroke, pulmonary embolism, deep-vein thrombosis), with oftentimes severe thrombocytopenia, that becomes clinically evident 5-30 days after adenovirus-vectored coronavirus disease 2019 vaccine administration. Most patients have disseminated intravascular coagulation. These features are the result of vaccine-triggered formation of anti-platelet factor 4 immunoglobulin G that activate platelets, clinically mimicking autoimmune heparin-induced thrombocytopenia. Early recognition based on thrombosis (sometimes, hemorrhage), thrombocytopenia, and d-dimer elevation within the day 5-30 postvaccine "window" is important given treatment with high-dose IV immunoglobulin plus nonheparin anticoagulation.

CONCLUSIONS: Vaccine-induced immune thrombotic thrombocytopenia is a serious complication of vaccination that is not feasible to anticipate or prevent. When the patient presents with sustained headache, neurologic symptoms/signs, abdominal pain, dyspnea, or limb pain/swelling beginning 5-30 days post vaccination, platelet count and d-dimer must be measured, and imaging for thrombosis performed. Confirmation of vaccine-induced immune thrombotic thrombocytopenia diagnosis should be ordered (platelet factor 4/polyanion enzyme-linked immunosorbent assay; platelet factor 4-enhanced platelet activation testing) as treatment is initiated (nonheparin anticoagulation, IV immunoglobulin).

# 认识疫苗诱导的免疫性血栓性血小板减少症。

目的：疫苗诱导的免疫血栓性血小板减少症是 2019 年冠状病毒病大流行时代的非预期结果。我们对这种罕见副作用的发病机制、临床表现、诊断和治疗进行了综述。

数据来源：使用术语 “COVID-19”、“疫苗”、“血栓形成” 在线检索 PubMed、Scopus、Web of Science 和 Google Scholar 中已发表的医学文献。

研究选择：根据文章与 2019 年冠状病毒疾病、疫苗和血栓形成的相关性选择文章纳入。

资料综合：疫苗诱导的免疫性血栓性血小板减少症最常表现为不寻常的血栓形成（脑静脉窦血栓形成、内脏静脉血栓形成），但有时也表现为 “常见” 血栓形成（动脉卒中、肺栓塞、深静脉血栓形成），通常伴有重度血小板减少症，在 2019 年腺病毒载体冠状病毒病疫苗接种后 5-30 天出现临床症状。大多数患者有弥散性血管内凝血。这些特征是疫苗触发的活化血小板的抗血小板因子 4 免疫球蛋白 G 形成的结果，临床上类似自身免疫性肝素诱导的血小板减少症。在疫苗接种后第 5-30 天的 “窗口期” 内，根据血栓形成（有时是出血）、血小板减少症和 d - 二聚体升高进行早期识别很重要，给予高剂量 IV 免疫球蛋白加非肝素抗凝治疗。

结论：疫苗诱导的免疫性血栓性血小板减少症是疫苗接种的一种严重并发症，不能进行预测或预防。疫苗接种后 5-30 天，患者出现持续性头痛、神经系统症状 / 体征、腹痛、呼吸困难或肢体疼痛 / 肿胀时，必须测量血小板计数和 d - 二聚体，并对血栓形成进行影像学检查。随着治疗的开始（非肝素抗凝，IV 免疫球蛋白），应进行疫苗诱导的免疫性血栓形成性血小板减少症的确诊（血小板因子 4 / 聚阴离子酶联免疫吸附试验；血小板因子 4 增强的血小板活化试验）。关键词：Humans; Age Factors; Sex Factors; SARS-CoV-2; COVID-19 Vaccines/administration & dosage/*adverse effects; COVID-19/prevention & control; Enzyme-Linked Immunosorbent Assay; Thrombocytopenia/*chemically induced/immunology; Thrombosis/*chemically induced/immunology

# ABCDEF Bundle Practices for Critically Ill Children: An International Survey of 161 PICUs in 18 Countries., Ista, Erwin

1:114-125. DOI:10.1097/CCM.0000000000005168

Abstract:

OBJECTIVES: To evaluate current international practice in PICUs regarding components of the "Assessing Pain, Both Spontaneous Awakening and Breathing Trials, Choice of Sedation, Delirium Monitoring/Management, Early Exercise/Mobility, and Family Engagement/Empowerment" (ABCDEF) bundle.

DESIGN: Online surveys conducted between 2017 and 2019.

SETTING: One-hundred sixty-one PICUs across the United States (n = 82), Canada (n = 14), Brazil (n = 27), and Europe (n = 38) participating in the Prevalence of Acute Rehabilitation for Kids in the PICU study.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Of the 161 participating PICUs, 83% were in academic teaching hospitals and 42% were in free-standing children's hospitals. Median size was 16 beds (interquartile range, 10-24 beds). Only 15 PICUs (9%) had incorporated all six ABCDEF bundle components into routine practice. Standardized pain assessment (A) was the most common (91%), followed by family engagement (F, 88%) and routine sedation assessment (C) with validated scales (84%). Protocols for testing extubation readiness or conducting spontaneous breathing trials (B) were reported in 57%, with 34% reporting a ventilator weaning protocol. Routine delirium monitoring with a validated screening tool (D) was reported by 44% of PICUs, and 26% had a guideline, protocol, or policy for early exercise/mobility (E). Practices for spontaneous breathing trials were variable in 29% of Canadian PICUs versus greater than 50% in the other regions. Delirium monitoring was lowest in Brazilian PICUs (18%) versus greater than 40% in other regions, and family engagement was reported in 55% of European PICUs versus greater than 90% in other regions.

CONCLUSIONS: ABCDEF bundle components have been adopted with substantial variability across regions. Additional research must rigorously evaluate the efficacy of specific elements with a focus on B, D, E, and full ABCDEF bundle implementation. Implementation science is needed to facilitate an understanding of the barriers to ABCDEF implementation and sustainability with a focus on specific cultural and regional differences.

# ABCDEF 危重儿童捆绑措施：18 个国家 161 家 PICU 的国际调查。

目的：评价 PICU 中有关 “评估疼痛、自发觉醒和呼吸试验、镇静选择、谵妄监测 / 管理、早期运动 / 活动和家庭参与 / 增强”(ABCDEF) 组合组成部分的当前国际实践。

设计：2017 年至 2019 年进行在线调查。

设置：美国 (n = 82)、加拿大 (n = 14)、巴西 (n = 27) 和欧洲 (n = 38) 的 161 家 PICU 参与了 PICU 研究中儿童急性康复的患病率。

干预：无。

测量和主要结果：在 161 家参与的 PICU 中，83% 在教学医院，42% 在独立儿童医院。中位尺寸为 16 个床位（四分位距，10-24 个床位）。仅 15 家 PICU (9%) 将 ABCDEF 束支所有 6 个组成部分整合到常规实践中。标准化疼痛评估 (A) 最常见 (91%)，其次是家庭参与 (F，88%) 和使用经验证的量表进行的常规镇静评估 (C)(84%)。57% 报告了测试拔管准备或进行自主呼吸试验 (B) 的方案，34% 报告了呼吸机撤机方案。44% 的 PICU 报告了采用经验证的筛选工具 (D) 进行的常规谵妄监测，26% 的 PICU 有指南、方案或早期运动 / 运动 (E) 政策。29% 的加拿大 PICU 患者的自主呼吸试验实践不同，而其他地区则超过 50%。谵妄监测在巴西 PICU 中最低 (18%)，在其他地区高于 40%，55% 的欧洲 PICU 报告了家庭参与，在其他地区高于 90%。

结论：采用了 ABCDEF 束支成分，不同地区存在相当大的变异性。额外的研究必须严格评价特定要素的疗效，重点是 B、D、E 和完整的 ABCDEF 集束化实施。需要实施科学来促进理解 ABCDEF 实施和可持续性的障碍，重点关注特定的文化和地区差异。关键词：Humans; Clinical Protocols; Critical Illness/*therapy; Anesthesia/standards; Delirium/diagnosis/prevention & control/therapy; Family; Intensive Care Units, Pediatric/standards/*statistics & numerical data; Pain Measurement/standards/statistics & numerical data; Patient Care Bundles/standards/*statistics & numerical data; Ventilator Weaning/standards

# Regionalization of Critical Care in the United States: Current State and Proposed Framework From the Academic Leaders in Critical Care Medicine Task Force of the Society of Critical Care Medicine., Leung, Sharon

1:37-49. DOI:10.1097/CCM.0000000000005147

Abstract:

OBJECTIVES: The Society of Critical Care Medicine convened its Academic Leaders in Critical Care Medicine taskforce on February 22, 2016, during the 45th Critical Care Congress to develop a series of consensus papers with toolkits for advancing critical care organizations in North America. The goal of this article is to propose a framework based on the expert opinions of critical care organization leaders and their responses to a survey, for current and future critical care organizations, and their leadership in the health system to design and implement successful regionalization for critical care in their regions.

DATA SOURCES AND STUDY SELECTION: Members of the workgroup convened monthly via teleconference with the following objectives: to 1) develop and analyze a regionalization survey tool for 23 identified critical care organizations in the United States, 2) assemble relevant medical literature accessed using Medline search, 3) use a consensus of expert opinions to propose the framework, and 4) create groups to write the subsections and assemble the final product.

DATA EXTRACTION AND SYNTHESIS: The most prevalent challenges for regionalization in critical care organizations remain a lack of a strong central authority to regulate and manage the system as well as a lack of necessary infrastructure, as described more than a decade ago. We provide a framework and outline a nontechnical approach that the health system and their critical care medicine leadership can adopt after considering their own structure, complexity, business operations, culture, and the relationships among their individual hospitals. Transforming the current state of regionalization into a coordinated, accountable system requires a critical assessment of administrative and clinical challenges and barriers. Systems thinking, business planning and control, and essential infrastructure development are critical for assisting critical care organizations.

CONCLUSIONS: Under the value-based paradigm, the goals are operational efficiency and patient outcomes. Health systems that can align strategy and operations to assist the referral hospitals with implementing regionalization will be better positioned to regionalize critical care effectively.

# 美国重症监护的区域化：重症医学协会重症医学学术领袖工作组的当前状态和拟定框架。

目的：2016 年 2 月 22 日，在第 45 届重症监护大会期间，重症监护医学协会召集了其重症监护医学学术领袖工作组，使用工具包开发了一系列共识文件，以推进北美的重症监护组织。本文的目的是根据重症监护组织领导的专家意见及其对调查的答复，为当前和未来的重症监护组织及其在卫生系统的领导设计并实施其所在地区成功的重症监护区域化，提出一个框架。

数据来源和研究选择：工作组成员每月通过电话会议召开会议，目的如下：1）为美国确定的 23 家重症监护组织开发和分析区域化调查工具，2）收集使用 Medline 检索访问的相关医学文献，3）运用专家共识意见提出框架，4）创建小组撰写小节汇编最终产品。

数据提取和综合：正如 10 多年前所描述的，重症监护组织中区域化最普遍的挑战仍然是缺乏监管和管理系统的强大中央权力机构以及缺乏必要的基础设施。我们提供了一个框架，概述了卫生系统及其重症监护医学领导在考虑了自身结构、复杂性、业务运营、文化及其个体医院之间的关系后可以采用的非技术方法。将目前的区域化状态转变为一个协调、负责的系统，需要对行政和临床挑战和障碍进行严格评估。系统思考、业务规划和控制以及基本基础设施开发对于帮助重症监护组织至关重要。

结论：在基于价值的模式下，目标是操作效率和患者结局。卫生系统可以使战略和运作一致，以帮助转诊医院实施区域化，将更好地定位，以有效地对重症监护进行区域化。关键词：Humans; Treatment Outcome; United States; Efficiency, Organizational; Health Facility Planning/*organization & administration; Critical Care/*organization & administration; Leadership; Referral and Consultation/organization & administration; Systems Analysis; Telemedicine/organization & administration

# Left Ventricular Function Changes Induced by Moderate Hypothermia Are Rapidly Reversed After Rewarming-A Clinical Study.

1:e52-e60. DOI:10.1097/CCM.0000000000005170

Abstract:

OBJECTIVES: Targeted temperature management (32-36?°C) is used for neuroprotection in cardiac arrest survivors. The isolated effects of hypothermia on myocardial function, as used in clinical practice, remain unclear. Based on experimental results, we hypothesized that hypothermia would reversibly impair diastolic function with less tolerance to increased heart rate in patients with uninsulted hearts.

DESIGN: Prospective clinical study, from June 2015 to May 2018.

SETTING: Cardiothoracic surgery operation room, Oslo University Hospital.

PATIENTS: Twenty patients with left ventricular ejection fraction greater than 55%, undergoing ascending aorta graft-replacement connected to cardiopulmonary bypass were included.

INTERVENTIONS: Left ventricular function was assessed during reduced cardiopulmonary bypass support at 36?°C, 32?°C prior to graft-replacement, and at 36?°C postsurgery. Electrocardiogram, hemodynamic, and echocardiographic recordings were made at spontaneous heart rate and 90 beats per minute at comparable loading conditions.

MEASUREMENTS AND MAIN RESULTS: Hypothermia decreased spontaneous heart rate, and R-R interval was prolonged (862 ?± 170 to 1,156 ?± 254 ms, p < 0.001). Although systolic and diastolic fractions of R-R interval were preserved (0.43 ?± 0.07 and 0.57 ?± 0.07), isovolumic relaxation time increased and diastolic filling time was shortened. Filling pattern changed from early to late filling. Systolic function was preserved with unchanged myocardial strain and stroke volume index, but cardiac index was reduced with maintained mixed venous oxygen saturation. At increased heart rate, systolic fraction exceeded diastolic fraction (0.53 ?± 0.05 and 0.47 ?± 0.05) with diastolic impairment. Strain and stroke volume index were reduced, the latter to 65% of stroke volume index at spontaneous heart rate. Cardiac index decreased, but mixed venous oxygen saturation was maintained. After rewarming, myocardial function was restored.

CONCLUSIONS: In patients with normal left ventricular function, hypothermia impaired diastolic function. At increased heart rate, systolic function was subsequently reduced due to impeded filling. Changes in left ventricular function were rapidly reversed after rewarming.

# 中度低温诱导的左心室功能变化在再次提醒后迅速逆转 - 一项临床研究。

目的：目标温度管理 (32-36 ℃) 用于心脏骤停幸存者的神经保护。临床实践中使用的低温对心肌功能的孤立效应尚不清楚。根据实验结果，我们假设低体温可逆性损害心脏舒张功能，对未受损心脏患者心率增加的耐受性较低。

设计：前瞻性临床研究，2015 年 6 月至 2018 年 5 月。

单位：奥斯陆大学医院心胸外科手术室。

患者：20 例左室射血分数大于 55%，接受与心肺转流相连的升主动脉移植物置换的患者被纳入。

干预：在移植物置换前和术后 36 ℃下，在减少心肺转流支持期间评估左心室功能。在相当负荷条件下，以自主心率和每分钟 90 次搏动记录心电图、血液动力学和超声心动图。

测量值和主要结果：低温降低了自发性心率，并且 R-R 间期延长（862?±170 至 1,156?±254 ms，p < 0.001）。虽然 R-R 间期的收缩和舒张分数保持不变（0.43?±0.07 和 0.57?±0.07），但等容舒张时间延长，舒张充盈时间缩短。灌装模式从早期变更为晚期灌装。在心肌应变和每搏量指数不变的情况下，保留了收缩功能，但在维持混合静脉血氧饱和度的情况下，心脏指数降低。心率增加时，收缩分数超过舒张分数（0.53?±0.05 和 0.47?±0.05），出现舒张损害。应变和每搏量指数降低，后者降至自主心率时每搏量指数的 65%。心脏指数下降，但混合静脉血氧饱和度保持不变。复温后心肌功能恢复。

结论：在左心室功能正常的患者中，低温会损害舒张功能。心率加快时，由于充盈受阻，收缩功能随后降低。复温后左心室功能变化迅速逆转。关键词：Hemodynamics; Humans; Female; Male; Middle Aged; Prospective Studies; Aged; *Rewarming; Electrocardiography; Heart Arrest/*therapy; Hypothermia, Induced/*methods; Hypothermia/*physiopathology; Ventricular Function, Left/*physiology

1:81-92. DOI:10.1097/CCM.0000000000005149

Abstract:

OBJECTIVES: To report the epidemiology, treatments, and outcomes of adult patients admitted to the ICU after cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome.

DESIGN: Retrospective cohort study.

SETTING: Nine centers across the U.S. part of the chimeric antigen receptor-ICU initiative.

PATIENTS: Adult patients treated with chimeric antigen receptor T-cell therapy who required ICU admission between November 2017 and May 2019.

INTERVENTIONS: Demographics, toxicities, specific interventions, and outcomes were collected.

RESULTS: One-hundred five patients treated with axicabtagene ciloleucel required ICU admission for cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome during the study period. At the time of ICU admission, the majority of patients had grade 3-4 toxicities (66.7%); 15.2% had grade 3-4 cytokine release syndrome and 64% grade 3-4 immune effector cell-associated neurotoxicity syndrome. During ICU stay, cytokine release syndrome was observed in 77.1% patients and immune effector cell-associated neurotoxicity syndrome in 84.8% of patients; 61.9% patients experienced both toxicities. Seventy-nine percent of patients developed greater than or equal to grade 3 toxicities during ICU stay, however, need for vasopressors (18.1%), mechanical ventilation (10.5%), and dialysis (2.9%) was uncommon. Immune Effector Cell-Associated Encephalopathy score less than 3 (69.7%), seizures (20.2%), status epilepticus (5.7%), motor deficits (12.4%), and cerebral edema (7.9%) were more prevalent. ICU mortality was 8.6%, with only three deaths related to cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. Median overall survival time was 10.4 months (95% CI, 6.64-not available mo). Toxicity grade or organ support had no impact on overall survival; higher cumulative corticosteroid doses were associated to decreased overall and progression-free survival.

CONCLUSIONS: This is the first study to describe a multicenter cohort of patients requiring ICU admission with cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome after chimeric antigen receptor T-cell therapy. Despite severe toxicities, organ support and in-hospital mortality were low in this patient population.

# 治疗嵌合抗原受体相关毒性的危重患者：一项多中心研究。

目的：报告细胞因子释放综合征或免疫效应细胞相关神经毒性综合征后入住 ICU 的成人患者的流行病学、治疗和结局。

设计：回顾性队列研究。

设置：美国嵌合抗原受体 ICU 倡议的 9 个中心。

患者：2017 年 11 月至 2019 年 5 月期间需要入住 ICU 接受嵌合抗原受体 T 细胞治疗的成人患者。

干预：收集人口统计学、毒性、特殊干预和结局数据。

结果：105 例接受 axicabtagene ciloleucel 治疗的患者在研究期间因细胞因子释放综合征或免疫效应细胞相关神经毒性综合征需要入住 ICU。入住 ICU 时，大多数患者发生 3-4 级毒性 (66.7%)；15.2% 发生 3-4 级细胞因子释放综合征，64% 发生 3-4 级免疫效应细胞相关神经毒性综合征。在 ICU 住院期间，77.1% 的患者观察到细胞因子释放综合征，84.8% 的患者观察到免疫效应细胞相关神经毒性综合征；61.9% 的患者发生两种毒性。79% 的患者在 ICU 住院期间发生≥3 级毒性，然而，血管加压素 (18.1%)、机械通气 (10.5%) 和透析 (2.9%) 的需求并不常见。免疫效应细胞相关性脑病评分小于 3 (69.7%)、癫痫发作 (20.2%)、癫痫持续状态 (5.7%)、运动缺陷 (12.4%) 和脑水肿 (7.9%) 更常见。ICU 死亡率为 8.6%，仅 3 例死亡与细胞因子释放综合征或免疫效应细胞相关的神经毒性综合征相关。中位总生存时间为 10.4 个月（95% CI，6.64 - 不可用月）。毒性分级或器官支持对总生存期无影响；更高的糖皮质激素累积剂量与总生存期和无进展生存期下降相关。

结论：这是首次描述一个多中心队列患者的研究，该队列患者在接受嵌合抗原受体 T 细胞治疗后出现细胞因子释放综合征或免疫效应细胞相关神经毒性综合征，需要入住 ICU。尽管存在重度毒性，但该患者人群的器官支持和住院死亡率较低。关键词：Humans; Female; Male; Middle Aged; Aged; Adult; Retrospective Studies; Comorbidity; United States; Intensive Care Units/statistics & numerical data; *Critical Illness; Patient Acuity; *Receptors, Chimeric Antigen; Sociodemographic Factors; Biological Products/*toxicity; Cytokine Release Syndrome/*chemically induced/mortality/therapy; Immunotherapy, Adoptive/*adverse effects; Neurotoxicity Syndromes/*etiology/mortality/therapy

# Factors Associated With Prolonged Mechanical Ventilation in Patients With Subarachnoid Hemorrhage-The RAISE Score., Rass, Verena

1:103-113. DOI:10.1097/CCM.0000000000005189

Abstract:

OBJECTIVES: Patients suffering from spontaneous subarachnoid hemorrhage frequently require mechanical ventilation. Here, we aimed to identify factors associated with prolonged mechanical ventilation in subarachnoid hemorrhage patients and to create a new predictive score for prolonged mechanical ventilation.

DESIGN: Prospective cohort study with retrospective data analysis.

SETTING: Neurocritical care unit at a tertiary academic medical center.

PATIENTS: Two hundred ninety-seven consecutive nontraumatic adult subarachnoid hemorrhage patients.

METHODS: In patients with mechanical ventilation, we identified factors associated with mechanical ventilation greater than 48 hours, greater than 7 days, and greater than 14 days compared with mechanical ventilation less than or equal to 48 hours, less than or equal to 7 days, or less than or equal to 14 days in multivariable generalized linear models. Ventilated patients who died before 48 hours, 7 days, or 14 days and those never ventilated were excluded from the respective analysis. We incorporated those factors into a new prognostic score (the RAISE score) to predict prolonged mechanical ventilation greater than 7 days. The calculation was based on a random dataset of 60% of subarachnoid hemorrhage patients and was internally validated.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Patients were 57 years old (interquartile range, 47-68 yr) and presented with a median Hunt and Hess grade of 3 (1-5). Two hundred forty-two patients (82%) required mechanical ventilation for 9 days (2-20 d). In multivariable analysis, a higher Acute Physiology Score was associated with mechanical ventilation greater than 48 hours, greater than 7 days, and greater than 14 days, a higher Hunt and Hess grade with greater than 7 days and greater than 14 days. Early neuroimaging findings were associated with mechanical ventilation greater than 48 hours (hydrocephalus; high-grade Subarachnoid Hemorrhage Early Brain Edema Score), greater than 7 days (high-grade Subarachnoid Hemorrhage Early Brain Edema Score, co-occurrence of intracerebral bleeding) but not with prolonged mechanical ventilation greater than 14 days. The RAISE score, including age, Acute Physiology Score, Hunt and Hess grade, Subarachnoid Hemorrhage Early Brain Edema Score, and the co-occurrence of intracerebral hemorrhage accurately stratified patients by prolonged mechanical ventilation greater than 7 days (C-statistic 0.932). A RAISE score of 12 predicted 60% likelihood of mechanical ventilation greater than 7 days.

CONCLUSIONS: Initial disease severity and neuroimaging findings detected within 24 hours after ICU admission were associated with the need for prolonged mechanical ventilation in patients with subarachnoid hemorrhage. These results may be helpful for patient families and caregivers to better anticipate the course of therapy.

# 蛛网膜下腔出血患者机械通气延长的相关因素 - RAISE 评分。

目的：自发性蛛网膜下腔出血患者经常需要机械通气。在此，我们旨在确定蛛网膜下腔出血患者中与长期机械通气相关的因素，并创建一个新的长期机械通气预测评分。

设计：回顾性数据分析的前瞻性队列研究。

设置：三级学术医学中心的神经重症监护室。

患者：297 例连续非创伤性成人蛛网膜下腔出血患者。

方法：在机械通气患者中，与小于或等于 48 小时，小于或等于 7 天的机械通气相比，我们确定了大于 48 小时，大于 7 天，大于 14 天的机械通气相关因素。或在多变量广义线性模型中≤14 天。在 48 小时、7 天或 14 天前死亡的通气患者以及从未通气的患者被排除在各自的分析之外。我们将这些因素纳入新的预后评分（RAISE 评分），以预测超过 7 天的长期机械通气。该计算基于 60% 蛛网膜下腔出血患者的随机数据集，并进行了内部验证。

干预：无。

测量和主要结果：患者 57 岁（四分位距，47-68 岁），中位 Hunt 和 Hess 分级为 3 级 (1-5)。242 例患者 (82%) 需要机械通气 9 天（2-20 天）。在多变量分析中，较高的急性生理学评分与超过 48 小时、超过 7 天和超过 14 天的机械通气、超过 7 天和超过 14 天的 Hunt and Hess 分级较高相关。早期神经影像学检查结果与大于 48 小时（脑积水；高级别蛛网膜下腔出血早期脑水肿评分）、大于 7 天（高级别蛛网膜下腔出血早期脑水肿评分，同时发生脑出血）的机械通气相关，但与超过 14 天的机械通气不相关。RAISE 评分，包括年龄、急性生理学评分、Hunt and Hess 分级、蛛网膜下腔出血早期脑水肿评分和同时发生脑出血通过长期机械通气大于 7 天对患者进行准确分层（C - 统计量 0.932）。12 分的 RAISE 评分预测机械通气超过 7 天的可能性为 60%。

结论：入 ICU 24 小时内检测到的初始疾病严重程度和神经影像学结果与蛛网膜下腔出血患者需要延长机械通气相关。这些结果可能有助于患者家属和护理人员更好地预测治疗过程。关键词：Humans; Female; Male; Middle Aged; Prognosis; Time Factors; Aged; APACHE; Adult; Retrospective Studies; Severity of Illness Index; Comorbidity; Academic Medical Centers/statistics & numerical data; Brain Edema/etiology; Respiration, Artificial/*statistics & numerical data; Subarachnoid Hemorrhage/complications/*therapy

# Renin Kinetics Are Superior to Lactate Kinetics for Predicting In-Hospital Mortality in Hypotensive Critically Ill Patients.

1:50-60. DOI:10.1097/CCM.0000000000005143

Abstract:

OBJECTIVES: Whole blood lactate concentration is widely used in shock states to assess perfusion. We aimed to determine if the change in plasma renin concentration over time would be superior to the change in lactate concentration for predicting in-hospital mortality in hypotensive patients on vasopressors.

DESIGN: Prospective, observational cohort study.

SETTING: Tertiary academic ICU.

PATIENTS: Adult patients on vasopressors for greater than 6 hours to maintain a mean arterial pressure greater than or equal to 65 mm Hg during January 2020.

INTERVENTIONS: Plasma renin concentrations were measured at enrollment and at 24, 48, and 72 hours. Whole blood lactate measurements were performed according to normal standard of care. Logistic regression was performed to evaluate whether the change in renin or lactate concentration could predict in-hospital mortality. Generalized estimating equations were used to analyze the association between renin and lactate concentration and in-hospital mortality. The area under the receiver operating characteristics curve was performed to measure the discriminative ability of initial and peak renin and lactate concentration to predict mortality. The association between renin and lactate concentration above the upper limit of normal at each timepoint with in-hospital mortality was also examined.

MEASUREMENTS AND MAIN RESULTS: The study included 197 renin and 148 lactate samples obtained from 53 patients. The slope of the natural log (ln) of renin concentration was independently associated with mortality (adjusted odds ratio, 10.35; 95% CI, 1.40-76.34; p = 0.022), but the slope of ln-lactate concentration was not (adjusted odds ratio, 4.78; 95% CI, 0.03-772.64; p = 0.55). The generalized estimating equation models found that both ln-renin (adjusted odds ratio, 1.18; 95% CI, 1.02-1.37; p = 0.025) and ln-lactate (adjusted odds ratio, 2.38; 95% CI, 1.05-5.37; p = 0.037) were associated with mortality. Area under the receiver operating characteristics curve analysis demonstrated that initial renin could predict in-hospital mortality with fair discrimination (area under the receiver operating characteristics curve, 0.682; 95% CI, 0.503-0.836; p = 0.05), but initial lactate could not (area under the receiver operating characteristics curve, 0.615; 95% CI, 0.413-0.803; p = 0.27). Peak renin (area under the receiver operating characteristics curve, 0.728; 95% CI, 0.547-0.888; p = 0.01) and peak lactate (area under the receiver operating characteristics curve, 0.746; 95% CI, 0.584-0.876; p = 0.01) demonstrated moderate discrimination. There was no significant difference in discriminative ability between initial or peak renin and lactate concentration. At each study time point, a higher proportion of renin values exceeded the threshold of normal (40 pg/mL) in nonsurvivors than in survivors, but this association was not significant for lactate.

CONCLUSIONS: Although there was no significant difference in the performance of renin and lactate when examining the absolute values of each laboratory, a positive rate of change in renin concentration, but not lactate concentration, over 72 hours was associated with in-hospital mortality. For each one-unit increase in the slope of ln-renin, the odds of mortality increased 10-fold. Renin levels greater than 40 pg/mL, but not lactate levels greater than 2 mmol/L, were associated with in-hospital mortality. These findings suggest that plasma renin kinetics may be superior to lactate kinetics in predicting mortality of hypotensive, critically ill patients.

# 肾素动力学在预测低血压危重患者院内死亡率方面优于乳酸盐动力学。

目的：全血乳酸盐浓度被广泛用于休克状态，以评估灌注。我们的目的是确定在预测接受血管加压药的低血压患者住院期间死亡率时，血浆肾素浓度随时间的变化是否优于乳酸盐浓度的变化。

设计：前瞻性、观察性队列研究。

单位：三级学术 ICU。

患者：2020 年 1 月期间，接受血管加压药治疗 6 小时以上，以维持平均动脉压≥65 mmHg 的成人患者。

干预：在入组时和 24、48 和 72 小时测量血浆肾素浓度。根据正常护理标准进行全血乳酸盐测量。进行 Logistic 回归，以评价肾素或乳酸盐浓度的变化是否可预测住院死亡率。使用广义估计方程分析肾素和乳酸盐浓度与住院死亡率之间的相关性。受试者工作特征曲线下面积用于测量初始和峰值肾素和乳酸盐浓度预测死亡率的鉴别能力。还检查了每个时间点高于正常上限的肾素和乳酸盐浓度与住院死亡率之间的相关性。

测量和主要结果：研究包括从 53 例患者中获得的 197 份肾素和 148 份乳酸盐样本。肾素浓度的自然对数 (ln) 斜率与死亡率独立相关（校正后比值比为 10.35；95% CI，1.40-76.34；p = 0.022），但 ln - 乳酸盐浓度的斜率则与死亡率不相关（校正后比值比为 4.78；95% CI，0.03-772.64；p = 0.55）。广义估计方程模型发现，肾素（校正比值比，1.18；95% CI，1.02-1.37；p = 0.025）和乳酸（校正比值比，2.38；95% CI，1.05-5.37；p = 0.037）均与死亡率相关。受试者工作特征曲线下面积分析表明，初始肾素可以在公平判别下预测住院死亡率（受试者工作特征曲线下面积，0.682；95% CI，0.503-0.836；p = 0.05），但初始乳酸盐不能（受试者工作特征曲线下面积，0.615；95% CI，0.413-0.803；p = 0.27）。肾素峰值（受试者工作特征曲线下面积，0.728；95% CI，0.547-0.888；p = 0.01）和乳酸盐峰值（受试者工作特征曲线下面积，0.746；95% CI，0.584-0.876；p = 0.01）表现出中度区分度。初始或峰值肾素和乳酸盐浓度之间的区分能力无显著差异。在每个研究时间点，非存活者中肾素值超过正常阈值 (40 pg/mL) 的比例高于存活者，但乳酸盐的这种相关性不显著。

结论：尽管在检查每个实验室的绝对值时，肾素和乳酸盐的性能没有显著差异，但是 72 小时内肾素浓度（而不是乳酸盐浓度）变化的阳性率与住院死亡率相关。肾素斜率每增加 1 个单位，死亡率增加 10 倍。肾素水平大于 40 pg/mL，但乳酸盐水平不大于 2 mmol/L 与住院死亡率相关。这些结果表明，在预测低血压重症患者的死亡率方面，血浆肾素动力学可能优于乳酸盐动力学。关键词：Humans; Female; Male; Middle Aged; Prospective Studies; Aged; Adult; Retrospective Studies; Academic Medical Centers; ROC Curve; Intensive Care Units/statistics & numerical data; Critical Illness/*mortality; Hospital Mortality/*trends; Hypotension/*mortality; Lactic Acid/*blood/metabolism; Renin/*blood/metabolism

# Association of Proximity to a Long-Term Acute Care Hospital With Hospital Tracheostomy Practices., Mehta, Anuj B.

1:93-102. DOI:10.1097/CCM.0000000000005146

Abstract:

OBJECTIVES: Availability of long-term acute care hospitals has been associated with hospital discharge practices. It is unclear if long-term acute care hospital availability can influence patient care decisions. We sought to determine the association of long-term acute care hospital availability at different hospitals with the likelihood of tracheostomy.

DESIGN: Retrospective cohort study.

SETTING: California Patient Discharge Database, 2016-2018.

PATIENTS: Adult patients receiving mechanical ventilation for respiratory failure.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Using the California Patient Discharge Database 2016-2018, we identified all mechanically ventilated patients and those who received tracheostomy. We determine the association between tracheostomy and the distance between each hospital and the nearest long-term acute care hospital and the number of long-term acute care hospital beds within 20 miles of each hospital. Among 281,502 hospitalizations where a patient received mechanical ventilation, 22,899 (8.1%) received a tracheostomy. Patients admitted to a hospital closer to a long-term acute care hospital compared with those furthest from a long-term acute care hospital had 38.9% (95% CI, 33.3-44.6%) higher odds of tracheostomy (closest hospitals 8.7% vs furthest hospitals 6.3%, adjusted odds ratio = 1.65; 95% CI, 1.40-1.95). Patients had a 32.4% (95% CI, 27.6-37.3%) higher risk of tracheostomy when admitted to a hospital with more long-term acute care hospital beds in the immediate vicinity (most long-term acute care hospital beds within 20 miles 8.9% vs fewest long-term acute care hospital beds 6.7%, adjusted odds ratio = 1.54; 95% CI, 1.31-1.80). Distance to the nearest long-term acute care hospital was inversely correlated with hospital risk-adjusted tracheostomy rates (ρ = -0.25; p < 0.0001). The number of long-term acute care hospital beds within 20 miles was positively correlated with hospital risk-adjusted tracheostomy rates (ρ = 0.22; p < 0.0001).

CONCLUSIONS: Proximity and availability of long-term acute care hospital beds were associated with patient odds of tracheostomy and hospital tracheostomy practices. These findings suggest a hospital effect on tracheostomy decision-making over and above patient case-mix. Future studies focusing on shared decision-making for tracheostomy are needed to ensure goal-concordant care for prolonged mechanical ventilation.

# 长期急症医院与医院气管造口术实践的关联。

目的：长期急症护理医院的可用性与出院实践相关。目前尚不清楚长期急症护理医院的可用性是否会影响患者的护理决策。我们试图确定不同医院的长期急症护理医院可用性与气管造口术可能性的相关性。

设计：回顾性队列研究。

设置：加利福尼亚州患者出院数据库，2016-2018。

患者：接受机械通气治疗呼吸衰竭的成人患者。

干预：无。

测量和主要结果：使用加利福尼亚州患者出院数据库 2016-2018，我们确定了所有机械通气患者和接受气管造口术的患者。我们确定了气管造口术与每家医院与最近的长期急症医院之间的距离以及每家医院 20 英里内长期急症医院床位数量之间的相关性。在 281,502 例接受机械通气的住院患者中，22,899 例 (8.1%) 接受了气管造口术。与长期急症医院距离最远的患者相比，入住距离长期急症医院较近的医院的患者接受气管造口术的几率高 38.9%(95% CI，33.3-44.6%)（距离最近的医院 8.7% vs 距离最远的医院 6.3%，调整后的比值比 = 1.65；95% CI，1.40-1.95）。当患者入住附近有较多长期急症护理医院床位的医院时，气管造口术的风险高 32.4%(95% CI，27.6-37.3%)（大部分长期急症护理医院床位在 20 英里内为 8.9% vs 长期急症护理医院床位最少为 6.7%，调整后比值比 = 1.54；95% CI，1.31-1.80）。距离最近的长期急症护理医院的距离与医院风险调整的气管切开率呈负相关 (ρ =-0.25；p<0.0001)。20 英里内的长期急症护理医院床位数量与医院风险调整的气管切开率呈正相关 (ρ =0.22；p<0.0001)。

结论：长期急症护理医院床位的接近和可用性与气管造口术和医院气管造口术实践的患者几率相关。这些结果表明，在患者病例组合中以上，医院对气管造口术的决策有影响。需要重点关注气管造口术共同决策制定的未来研究，以确保长时间机械通气的目标一致护理。关键词：Humans; Female; Male; Middle Aged; Aged; Adult; Aged, 80 and over; Retrospective Studies; Hospital Mortality; Comorbidity; Sociodemographic Factors; Respiration, Artificial/*statistics & numerical data; California; Hospitals/*statistics & numerical data/*supply & distribution; Long-Term Care/statistics & numerical data; Respiratory Insufficiency/*therapy; Tracheostomy/*statistics & numerical data; Transportation

# Long-Term Functional Outcome and Quality of Life Following In-Hospital Cardiac Arrest-A Longitudinal Cohort Study.

1:61-71. DOI:10.1097/CCM.0000000000005118

Abstract:

OBJECTIVES: To evaluate the functional outcome and health-related quality of life of in-hospital cardiac arrest survivors at 6 and 12 months.

DESIGN: A longitudinal cohort study.

SETTING: Seven metropolitan hospitals in Australia.

PATIENTS: Data were collected for hospitalized adults (?‰? 18 yr) who experienced in-hospital cardiac arrest, defined as "a period of unresponsiveness, with no observed respiratory effort and the commencement of external cardiac compressions." INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: Prior to hospital discharge, patients were approached for consent to participate in 6-month and 12-month telephone interviews. Outcomes included the modified Rankin Scale, Barthel Index, Euro-Quality of Life 5 Dimension 5 Level, return to work and hospital readmissions. Forty-eight patients (80%) consented to follow-up interviews. The mean age of participants was 67.2 (?± 15.3) years, and 33 of 48 (68.8%) were male. Good functional outcome (modified Rankin Scale score ?‰¤ 3) was reported by 31 of 37 participants (83.8%) at 6 months and 30 of 33 (90.9%) at 12 months. The median Euro-Quality of Life-5D index value was 0.73 (0.33-0.84) at 6 months and 0.76 (0.47-0.88) at 12 months. The median Euro-Quality of Life-Visual Analogue Scale score at 6 months was 70 (55-80) and 75 (50-87.5) at 12 months. Problems in all Euro-Quality of Life-5D-5 L dimension were reported frequently at both time points. Hospital readmission was reported by 23 of 37 patients (62.2%) at 6 months and 16 of 33 (48.5%) at 12 months. Less than half of previously working participants had returned to work by 12 months.

CONCLUSIONS: The majority of in-hospital cardiac arrest survivors had a good functional outcome and health-related quality of life at 6 months, and this was largely unchanged at 12 months. Despite this, many reported problems with mobility, self-care, usual activities, pain, and anxiety/depression. Return to work rates was low, and hospital readmissions were common.

# 院内心脏骤停后的长期功能结局和生活质量 - 一项纵向队列研究。

目的：评价 6 个月和 12 个月时院内心脏骤停幸存者的功能结局和健康相关生活质量。

设计：纵向队列研究。

设置：澳大利亚的 7 家大都市医院。

患者：收集发生院内心脏骤停的成年住院患者（ ≥ 18 岁）的数据，定义为 “无反应，没有观察到呼吸努力，开始外部心脏按压的时间段”。

干预：无。

测量和主要结果：在出院前，患者被要求同意参加 6 个月和 12 个月的电话访谈。结局包括改良 Rankin 量表、Barthel 指数、欧洲生活质量 5 维度 5 水平、恢复工作和再次入院。48 例患者 (80%) 同意进行随访访谈。受试者的平均年龄为 67.2 (?±15.3) 岁，48 例受试者中 33 例 (68.8%) 为男性。在 6 个月时 37 名参与者中有 31 名 (83.8%) 报告了良好的功能结局（改良 Rankin 量表评分？‰?3），在 12 个月时 33 名参与者中有 30 名 (90.9%) 报告了良好的功能结局。6 个月时中位欧洲生活质量 - 5D 指数值为 0.73 (0.33-0.84)，12 个月时为 0.76 (0.47-0.88)。6 个月时的中位欧洲生活质量 - 视觉模拟量表评分为 70 (55-80)，12 个月时为 75 (50-87.5)。在两个时间点频繁报告了所有欧洲生活质量 - 5D-5l 维度的问题。在 6 个月时 37 例患者中的 23 例 (62.2%) 和 12 个月时 33 例患者中的 16 例 (48.5%) 报告了再次入院。之前参加工作的受试者中不到一半在 12 个月内返回工作。

结论：6 个月时，大多数院内心脏骤停幸存者的功能结局和健康相关生活质量良好，12 个月时基本没有变化。尽管如此，许多报告了运动、自理、日常活动、疼痛和焦虑 / 抑郁问题。恢复工作的比率较低，再次入院很常见。关键词：Humans; Female; Male; Middle Aged; Aged; Aged, 80 and over; Activities of Daily Living; *Quality of Life; Survivors/*statistics & numerical data; *Functional Status; Heart Arrest/*epidemiology; Patient Readmission/statistics & numerical data; Return to Work/statistics & numerical data

# Trends in Endotracheal Intubation During In-Hospital Cardiac Arrests: 2001-2018., Schwab, Kristin

1:72-80. DOI:10.1097/CCM.0000000000005120

Abstract:

OBJECTIVES: Airway management during in-hospital cardiac arrest represents a fundamental component of resuscitative efforts, yet little is known about temporal trends in intubation during in-hospital cardiac arrest. Our objective was to investigate changes in in-hospital cardiac arrest airway management over time and in response to national guideline updates.

DESIGN: Observational cohort study of a prospectively collected database.

SETTING: Multicenter study of hospitals participating in the "Get With The Guidelines-Resuscitation" registry from January 1, 2001, to December 31, 2018.

SUBJECTS: Adult patients who experienced an in-hospital cardiac arrest and did not have an invasive airway in place prior to the arrest.

INTERVENTIONS: The primary outcome was the rate of intra-arrest intubation from 2001 to 2018. We constructed multivariable regression models with generalized estimating equations to determine the annual adjusted odds of intubation. We also assessed the timing of intubation relative to the onset of pulselessness and other arrest measures. We used an interrupted time-series analysis to assess the association between the 2010 Advanced Cardiac Life Support guideline update and intubation rates.

MEASUREMENTS AND MAIN RESULTS: One thousand sixty-six eight hundred patients from 797 hospitals were included. From 2001 to 2018, the percentage of patients intubated during an arrest decreased from 69% to 55% for all rhythms, 73% to 60% for nonshockable rhythms, and 58% to 36% for shockable rhythms (p < 0.001 for trend for all 3 groups). The median time from onset of pulselessness to intubation increased from 5 minutes in 2001 (interquartile range, 2-8 min) to 6 minutes in 2018 (interquartile range, 4-10 min) (p < 0.001 for trend). Following the 2010 guideline update, there was a downward step change and a steeper decrease over time in the rate of intubation as compared to the preintervention period (p < 0.001).

CONCLUSIONS: Endotracheal intubation rates during in-hospital cardiac arrest have decreased significantly over time, with a more substantial decline following the updated 2010 guideline that prioritized chest compressions over airway management.

# 院内心脏骤停期间气管插管的趋势：2001-2018。

目的：院内心脏骤停期间的气道管理是复苏努力的基本组成部分，但对于院内心脏骤停期间插管的时间趋势知之甚少。我们的目的是调查院内心脏骤停气道管理随时间推移的变化，并对国家指南更新作出回应。

设计：前瞻性收集数据库的观察性队列研究。

设置：从 2001 年 1 月 1 日至 2018 年 12 月 31 日，参加 “遵循指南 - 复苏” 登记的医院的多中心研究。

受试者：发生院内心脏骤停且在心脏骤停前未放置侵入性气道的成人患者。

干预：主要结局是 2001 年至 2018 年的停搏内插管率。我们用广义估计方程构建了多变量回归模型，以确定每年调整的插管几率。我们还评估了相对于无脉性发作和其他停搏措施的插管时间。我们使用了间断时间序列分析来评估 2010 年高级心脏生命支持指南更新和插管率之间的相关性。

测量和主要结果：797 家医院的 166800 名患者被纳入。从 2001 年至 2018 年，所有节律时心脏骤停期间插管的患者百分比从 69% 降至 55%，不可电击节律时从 73% 降至 60%，可电击节律时从 58% 降至 36%（所有 3 组趋势 p <0.001）。从出现无脉症到插管的中位时间从 2001 年的 5 min（四分位距，2-8 min）增加到 2018 年的 6 min（四分位距，4-10 min）（趋势 p < 0.001）。2010 年指南更新后，与干预前阶段相比，插管率随时间推移发生了向下的阶跃变化，并且下降幅度更大 (p < 0.001)。

结论：院内心脏骤停期间的气管插管率随时间推移显著下降，在 2010 年更新指南中将胸外按压优先于气道管理后，气管插管率显著下降。关键词：Humans; Female; Male; Middle Aged; Prospective Studies; Time Factors; Aged; Aged, 80 and over; Heart Arrest/*therapy; Cardiopulmonary Resuscitation/statistics & numerical data; Hospitals/*statistics & numerical data; Interrupted Time Series Analysis; Intubation, Intratracheal/*statistics & numerical data

编辑

上次更新: 2022/08/20, 10:56:49

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期刊题录 -- 2022 Critical Care Medicine

# 期刊题录 -- 2022 Critical Care Medicine.

# Stability of Spo2/Fio2 and Respiratory Rate-Oxygenation Indexes in Critical Respiratory Disorders.

# 严重呼吸疾病中 Spo2/Fio2 和呼吸频率 - 氧合指数的稳定性。

# Therapeutic Hyperthermia Is Associated With Improved Survival in Afebrile Critically Ill Patients With Sepsis: A Pilot Randomized Trial., Kula, Roman

# 治疗性高热与发热危重症脓毒症患者的生存率改善相关：一项初探性随机化试验。

# The authors reply.

# 作者回复。

# Fragility Index and Trial Sequential Analysis for Randomized Controlled Studies Testing IV Vitamin C in Critically Ill Patients.

# 在危重病患者中评估 IV 维生素 C 的随机对照研究的脆性指数和试验序列分析。

# The authors reply.

# 作者回复。

# Cerebral Tissue Oxygenation Monitoring for Guiding RBC Transfusion in Neurocritical Patients.

# 神经重症患者指导 RBC 输注的脑组织氧合监测。

# The authors reply.

# 作者回复。

# Hyperbaric Oxygenation Therapy Alone for Carbon Monoxide Poisoning: Time for Reinforcements?

# 一氧化碳中毒的单独高压氧合治疗：强化时间？

# The authors reply., Rass, Verena

# 作者回复。

# Factors Associated With Prolonged Mechanical Ventilation in Nontraumatic Subarachnoid Hemorrhage., Siddiqui, Suhail Sarwar

# 非创伤性蛛网膜下腔出血机械通气延长的相关因素。

# Home-Ward Bound?, Rampon, Garrett

# 家庭病房界限？

# Is "Set It and Forget It" Bad Medicine for Sedation and Analgesia for Intubated Emergency Department Patients?, Winkle, Julie

# “设置它，遗忘它” 是否有损急诊插管患者的镇静和镇痛的良药？

# A Call for a Consensus Approach to the Design, Implementation, and Evaluation of Early Warning Systems., Bhavani, Sivasubramanium V.

# 呼吁对预警系统的设计、实施和评估采取共识方法。

# Sepsis Awareness Is Good, Please Do Not Let It Be Misunderstood.

# 败血症意识良好，请不要误解。

# Probiotics in Critical Illness: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

# 益生菌在危重症中的应用：一项随机对照试验的系统评价和荟萃分析。

# Electrical Impedance Tomography in Acute Respiratory Distress Syndrome Management.

# 急性呼吸窘迫综合征管理中的电阻抗断层成像。

# Patient, Public, and Healthcare Professionals' Sepsis Awareness, Knowledge, and Information Seeking Behaviors: A Scoping Review., Fiest, Kirsten M.

# 患者、公众和医疗保健专业人员的败血症意识、知识和寻求信息的行为：一项应对审查。

# The Impact of Health Information Technology for Early Detection of Patient Deterioration on Mortality and Length of Stay in the Hospital Acute Care Setting: Systematic Review and Meta-Analysis.

# 早期检测患者病情恶化的健康信息技术对医院急性护理环境中死亡率和住院时间的影响： 系统评价和荟萃分析。

# The Feasibility of Implementing Targeted SEDation in Mechanically Ventilated Emergency Department Patients: The ED-SED Pilot Trial.

# 在机械通气的急诊科患者中实施靶向镇静的可行性：ED-SED 初探性试验。

# Outcomes After Direct Discharge Home From Critical Care Units: A Population-Based Cohort Analysis., Martin, Claudio M.

# 从重症监护室直接出院回家后的结局：基于人群的队列分析。

# Acquired von Willebrand Syndrome and Desmopressin Resistance During Venovenous Extracorporeal Membrane Oxygenation in Patients With COVID-19: A Prospective Observational Study.

# COVID-19 患者静脉 - 静脉体外膜肺氧合期间获得性血管性血友病综合征和去氨加压素抵抗的前瞻性观察研究。

# Relative Hypoglycemia and Lower Hemoglobin A1c-Adjusted Time in Band Are Strongly Associated With Increased Mortality in Critically Ill Patients., Krinsley, James S.

# 在危重患者中，相对低血糖和较低的血红蛋白 A1c - 调整时间与死亡率增加明显相关。

# Neurologic Outcomes of Survivors of COVID-19-Associated Acute Respiratory Distress Syndrome Requiring Intubation., Jaquet, Pierre

# 需要插管的 COVID-19 相关急性呼吸窘迫综合征生存者的神经系统结局。

# Platelet Phenotype and Function Changes With Increasing Duration of Extracorporeal Membrane Oxygenation.

# 血小板表型和功能随着体外膜氧合持续时间的增加而变化。

# Does Interrupting Self-Induced Lung Injury and Respiratory Drive Expedite Early Spontaneous Breathing in the Setting of Early Severe Diffuse Acute Respiratory Distress Syndrome?, Petitjeans, Fabrice

# 在早期重度弥漫性急性呼吸系统疾病背景下，阻断自身诱发的肺损伤和呼吸驱动是否会加速早期自主呼吸 窘迫综合征？

# Can We Always Trust the Wisdom of the Body?, Marini, John J.

# 我们能否始终相信身体的智慧？

# Emergency Department ICUs Add Value.

# 急诊科 ICU 附加值。

# Incidence and Outcomes of Cardiopulmonary Resuscitation in ICUs: Retrospective Cohort Analysis.

# ICU 中心肺复苏的发生率和结局：回顾性队列分析。

# Persistent But Not Transient Acute Kidney Injury Was Associated With Lower Transplant-Free Survival in Patients With Acute Liver Failure: A Multicenter Cohort Study., Cardoso, Filipe S.

# 急性肝衰竭患者中持续性但非一过性急性肾损伤与无移植生存率降低相关：一项多中心研究 队列研究。

# The Comparative Effectiveness of Vasoactive Treatments for Hepatorenal Syndrome: A Systematic Review and Network Meta-Analysis.

# 血管活性药物治疗肝肾综合征的有效性比较：一项系统评价和网络荟萃分析。

# The authors reply., Kleinpell, Ruth M.

# 作者回复。

# Omission of Dietitian as Integral Member of Critical Care Team.

# 遗漏营养师作为重症监护团队的成员。

# The Role of Registered Dietitian Nutritionists on the Critical Care Interdisciplinary Team., Sauer, Kevin L.

# 注册营养师在重症监护跨学科团队中的作用。

# Dietitians' Role in Critical Care Interdisciplinary Team Needs Better Recognition.

# 营养师在重症监护跨学科团队中的角色需要得到更好的认可。

# The authors reply.

# 作者回复。

# "RAISE"ing a Score to Predict Prolonged Mechanical Ventilation Following Subarachnoid Hemorrhage.

# 预测蛛网膜下腔出血后机械通气延长的 “RAISE” 评分。

# The authors reply., Shanahan, Kristen H.

# 作者回复。

# Abandon Noninvasive Ventilation in Bronchiolitis? How Unrecognized Bias Can Lead to Problematic Conclusions., Keim, Garrett

# The authors reply., Seeliger, Benjamin

# 作者回复。

# Symptomatic and Asymptomatic Intracranial Hemorrhage in Patients Receiving Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Distress Syndrome: Are We Missing an Opportunity for Early Intervention?, Clarke, Jonathan

# 早期检测患者病情恶化的健康信息技术对医院急性护理环境中死亡率和住院时间的影响：系统评价和荟萃分析。

# 在早期重度弥漫性急性呼吸系统疾病背景下，阻断自身诱发的肺损伤和呼吸驱动是否会加速早期自主呼吸窘迫综合征？

# 急性肝衰竭患者中持续性但非一过性急性肾损伤与无移植生存率降低相关：一项多中心研究队列研究。

# 接受静脉 - 静脉体外膜肺氧合治疗急性呼吸窘迫的患者的症状性和无症状性颅内出血综合征：我们是否错过了早期干预的机会？

# 肺部超声和电阻抗作为急性呼吸衰竭的长期监测工具：有时没有数字比好（或令人困惑）编号。

# 药剂师对改善危重病患者治疗的影响：一项使用有意义的指标及给药方案的大型多中心分析复杂性 - ICU (MRC-ICU)。