From the Critical Illness, Brain Dysfunction, and Survivorship Center (C.G.H., J.C.J., A.S.H., B.T.P., O.M.O., R.R., J.L.S., A.L.K, M.B.P., N.E.B., T.D.G., R.S.D., G.R.B., E.W.E., P.P.P.), the Center for Health Services Research (C.G.H., J.C.J., R.R., M.B.P., T.D.G., R.S.D., E.W.E., P.P.P.), the Division of Anesthesiology Critical Care Medicine, Department of Anesthesiology (C.G.H., P.P.P.), the Division of Allergy, Pulmonary, and Critical Care Medicine (J.C.J., B.T.P., G.R.B., E.W.E.), and the Division of General Internal Medicine and Public Health (R.S.D.), Department of Medicine, the Departments of Biostatistics (O.M.O., R.R.) and Pharmaceutical Services (J.L.S.), and Division of Trauma and Surgical Critical Care, Department of Surgery (M.B.P.), Vanderbilt University Medical Center, and the Anesthesia Service (C.G.H., P.P.P.), Research Service (J.C.J.), Surgical Service (M.B.P.), and Geriatric Research, Education and Clinical Center (R.S.D., E.W.E.), Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System - both in Nashville; the Neuroscience Institute and Department of Critical Care Medicine, Maine Medical Center, Portland (P.T.M.); the Department of Pharmacy and Health Systems Sciences, Bouve College of Health Sciences, Northeastern University, Boston (J.W.D., M.S.D.); the Departments of Pharmacy (J.T.S., L.N.B.) and Surgery (J.T.S.) and the Center for Outcomes Research (J.T.S.), Houston Methodist, and the Pulmonary, Critical Care and Sleep Medicine Section, Ben Taub Hospital, Baylor College of Medicine (K.K.G.), Houston; the Division of Pulmonary/Critical Care Medicine, University of Texas Health, and the South Texas Veterans Health Care System, San Antonio (A.A.); and Texas Health Harris Methodist Hospital Fort Worth, Fort Worth (A.S.) - all in Texas; the University of Sydney, and the Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney, and the Department of Anesthesiology, University of Wisconsin, Madison (R.D.S.); Pulmonary and Critical Care Medicine, Baton Rouge General Medical Center and Our Lady of the Lake Regional Medical Center, Baton Rouge, LA (H.R.O.); the Department of Anesthesia and Perioperative Care, University of California, San Francisco, San Francisco (M.A.G.); Pulmonary and Critical Care, Mission Hospital, Asheville, NC (G.J.S.); the Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Ohio State University Wexner Medical Center, Columbus (N.E.B.); and Clinical Research, Investigation, and Systems Modeling of Acute Illness Center, Department of Critical Care Medicine, University of Pittsburgh School of Medicine, Pittsburgh (T.D.G.).
N Engl J Med. 2021 Apr 15;384(15):1424-1436. doi: 10.1056/NEJMoa2024922. Epub 2021 Feb 2.
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.).
目前的指南建议对接受机械通气的成年人采用右美托咪定或丙泊酚进行轻度镇静。这两种镇静剂在易激惹性、免疫和炎症方面存在差异。它们在接受机械通气且伴有脓毒症的轻度镇静的成年人中是否会产生不同的影响尚不清楚。
在一项多中心、双盲试验中，我们将患有脓毒症的机械通气成年人随机分配接受右美托咪定（0.2 至 1.5μg/公斤体重/小时）或丙泊酚（5 至 50μg/公斤/分钟），剂量由床边护士根据临床医生根据 Richmond 激惹-镇静量表（RASS，范围从-5[无反应]至+4[对抗性]）设定的目标镇静目标进行调整。主要终点是在 14 天干预期间无谵妄或昏迷的存活天数。次要终点是 28 天无呼吸机天数、90 天死亡率和 6 个月时 Telephone Interview for Cognitive Status 问卷（TICS-T；评分范围为 0 至 100，平均 50±10，得分越低表示认知越差）的年龄调整总评分。
在 432 名接受随机分组的患者中，422 名患者接受了试验药物治疗并纳入分析-214 名患者接受右美托咪定治疗，中位剂量为 0.27μg/公斤体重/小时，208 名患者接受丙泊酚治疗，中位剂量为 10.21μg/公斤体重/分钟。接受试验药物的中位持续时间为 3.0 天（四分位间距，2.0 至 6.0），中位 RASS 评分为-2.0（四分位间距，-3.0 至-1.0）。我们发现右美托咪定和丙泊酚在无谵妄或昏迷的存活天数方面没有差异（调整后的中位数，10.7 天 vs. 10.8 天；比值比，0.96；95%置信区间[CI]，0.74 至 1.26），无呼吸机天数（调整后的中位数，23.7 天 vs. 24.0 天；比值比，0.98；95%CI，0.63 至 1.51），90 天死亡率（38% vs. 39%；风险比，1.06；95%CI，0.74 至 1.52）或 6 个月时 TICS-T 评分（调整后的中位数评分，40.9 分 vs. 41.4 分；比值比，0.94；95%CI，0.66 至 1.33）。两组的安全性终点相似。
在接受推荐的轻度镇静方法治疗的患有脓毒症的机械通气成年人中，接受右美托咪定治疗的患者的结局与接受丙泊酚治疗的患者的结局没有差异。（由美国国立卫生研究院资助；临床试验.gov 编号，NCT01739933。）
