Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.
Dexmedetomidine or Propofol for Sedation in Mechanically Ventilated Adults with Sepsis.
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DOI：
10.1056/nejmoa2024922
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发表时间：
2021-04-15
期刊：
影响因子：
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通讯作者：
MENDS2 Study Investigators
中科院分区：
文献类型：
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作者：
Hughes CG;Mailloux PT;Devlin JW;Swan JT;Sanders RD;Anzueto A;Jackson JC;Hoskins AS;Pun BT;Orun OM;Raman R;Stollings JL;Kiehl AL;Duprey MS;Bui LN;O'Neal HR Jr;Snyder A;Gropper MA;Guntupalli KK;Stashenko GJ;Patel MB;Brummel NE;Girard TD;Dittus RS;Bernard GR;Ely EW;Pandharipande PP;MENDS2 Study Investigators
目前指南建议接受机械通气的成人使用右美托咪定或异丙酚进行靶向轻度镇静。这些镇静剂在唤醒能力、免疫力和炎症方面存在差异。它们是否会对接受轻度镇静的机械通气成人败血症患者的预后产生不同的影响尚不清楚。在一项多中心双盲试验中，我们随机将接受机械通气的成年脓毒症患者分为两组，分别接受右美托咪定(每公斤体重每小时0.2至1.5μg)或异丙酚(每公斤每分钟5至50μg)，剂量由床边护士调整，以达到临床医生根据里士满激越-镇静评分(RASS)设定的目标镇静目标。评分范围从−5[无反应]到+4[好斗]。主要终点是在14天干预期内没有精神错乱或昏迷的存活天数。次要终点为28天无呼吸机天数，90天死亡天数，6个月时认知状态问卷电话访谈(TICS-T；得分范围0~100，平均50±10分，得分较低表明认知功能较差)。在接受随机分组的432名患者中，422名患者被分配接受一种试验药物，并被纳入分析-214名患者接受右美托咪定的中位剂量为每公斤每小时0.27μg，208名患者接受丙泊酚的中位剂量为每公斤每分钟10.21μg。接受试验药物的中位持续时间为3.0d(四分位数范围为2.0至6.0)，RASS评分中位数为−2.0(四分位数范围为−3.0至−1.0)。我们发现右旋美托咪定和异丙酚在无精神错乱或昏迷的存活天数(调整后的中位数，10.7天比10.8天；优势比，0.96；95%可信区间[CI]，0.74到1.26)、无呼吸机天数(调整后的中位数，23.7天比24.0天；优势比0.98；95%的可信区间，0.63到1.51)、90天的死亡率(38%比39%；风险比1.06；或6个月时的TICS-T评分(调整后的中位数得分，40.9比41.4；优势比0.94；95%可信区间0.66至1.33)。两组的安全终点相似。在接受推荐的光镇静方法治疗的机械通气成人脓毒症患者中，接受右美托咪定治疗的患者的结果与接受异丙酚的患者的结果没有差异。(由美国国立卫生研究院资助；ClinicalTrials.gov编号，NCT01739933。)
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. 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. 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. 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.)