成人脓毒症机械通气应用右美托咪定还是丙泊酚镇静

原文

Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis

Hughes CG, Mailloux PT, Devlin JW, et al. Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis. N Engl J Med. 2021;384(15):1424-1436. doi:10.1056/NEJMoa2024922

摘要

背景：指南目前推荐成人机械通气使用右美托咪定或者丙泊酚镇静，目标为轻度镇定。两药在唤醒、免疫、炎症方面有差别。它们对脓毒症机械通气轻度镇静患者预后的影响是否有差别尚不清楚。

原文

Background:Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown.

方法：这是一项多中心、双盲研究，将成人脓毒症机械通气患者随机分为右美托咪定（0.2 - 1.5 μg・kg^-1·h^-1）或丙泊酚（5 - 50 μg・kg^-1·min^-1）组，床旁护士调节剂量维持医生设定的 RASS（评分范围从 -5 分没有反应到 +4 分好斗）镇静目标。主要终点是 14 天治疗中无谵妄或昏迷的存活天数。次要终点是 28 天的撤呼吸机天数、90 天的病死率、以及 6 个月的年龄矫正后的电话随访认知状况问卷得分（TICS-T，范围是 0 -100，小于等于平均分 50 ± 10 分为认知有问题）。

原文

METHOD：In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation–Sedation Scale (RASS, on which scores range from −5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months.

结果：共 432 例患者随机分组，其中 422 例使用了试验药物并纳入统计分析，214 例患者应用右美托咪定剂量的中位数为 0.27 μg・kg^-1·h^-1，208 例患者应用丙泊酚剂量的中位数为 10.21 μg・kg^-1·min^-1。实验药物使用时间的中位数为 3.0 天（四分位间距，2.0 - 6.0），RASS 评分中位数为 -2.0（四分位间距，-3.0 - -1.0）。无谵妄或昏迷存活时间（校正后的中位数为 10.7 比 10.8 天；比值比（OR）：0.96；95% CI：0.74 -1.26）、呼吸机撤机时间（校正后的中位数为 23.7 比 24.0 天；OR：0.98；95% CI：0.63 - 1.51）、90 天病死率（38% 比 39%；风险比（HR）：1.06；95% CI 0.74 -1.52）、或者 6 个月 TICS-T 评分（得分校正后中位数为 40.9 比 14.4；OR：0.94；95% CI 0.66 -1.33）右美托咪定和丙泊酚之间没有差异。两组安全性终点相同。

原文

RESULTS: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses — 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups.

结论：按推荐实施轻度镇静方案的机械通气成人脓毒症患者，应用右美托咪定与丙泊酚相比患者的预后没有差别。

原文

CONCLUSIONS : Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933. opens in new tab (opens new window).)