近日，苏格兰爱丁堡皇家医院Timothy S. Walsh团队比较了右美托咪啶或可乐定的镇静与丙泊酚在危重患者中的效果与安全性。2025年5月19日出版的《美国医学会杂志》发表了这项成果。

与异丙酚镇静相比，α - 2肾上腺素能受体激动剂镇静是否能减少重症监护病房（ICU）机械通气患者拔管时间尚不确定。

为了评估以右美托咪定或可乐定为基础的镇静与以异丙酚为基础的镇静（常规护理）相比是否能缩短机械通气持续时间，研究组在英国的41个ICU中进行了一项实用的、开放标签的随机临床试验，包括在开始机械通气48小时内接受异丙酚加阿片类药物镇静和镇痛的成年人，预计需要机械通气48小时或更长时间。从插管到随机化的中位时间为21.0小时（IQR, 13.2-31.3）。招募时间为2018年12月至2023年10月；最后一次随访发生在2023年12月10日。

使用的床边算法的目标是里士满激动-镇静量表得分为- 2到1（除非临床医生要求更深的镇静）。算法支持以右美托咪定和可乐定为基础的镇静干预组的升滴，支持以异丙酚为基础的镇静的降滴，然后主要使用分配的镇静（右美托咪定或可乐定）进行镇静。如果需要，允许补充使用异丙酚。主要观察指标是从随机分组到成功拔管的时间。次要结局包括死亡率、镇静质量、谵妄率和心血管不良事件。

分析人群中1404例患者(平均年龄59.2 [SD， 14.9]岁；男性901例，占64%；平均APACHE II评分为20.3 [SD, 8.2])，拔管成功时间的亚分布风险比（HR）为1.09 (95% CI, 0.96-1.25；右美托咪定（n = 457）与异丙酚（n = 471）的差异P = 0.20，为1.05 (95% CI, 0.95-1.17；可乐定（n=476）和异丙酚（n=471）的P= 34)。右美托咪定从随机分配到成功拔管的中位时间为136 （95% CI, 117-150）小时，可乐定为146 （95% CI, 124-168）小时，异丙酚为162 （95% CI, 136-170）小时。

在预定义的亚组分析中，没有与年龄、脓毒症状态、顺序器官衰竭评估中位数评分或谵妄风险中位数评分的相互作用。在次要结局中，右美托咪定与异丙酚组激越发生率较高（风险比[RR]， 1.54），可乐定与异丙酚组激越发生率较高（RR, 1.55）。与异丙酚相比，右美托咪定（RR, 1.62）和可乐定（RR, 1.58）的严重心动过缓（心率<；50/min）发生率更高。与异丙酚相比，右美托咪定（HR, 0.98）和可乐定（HR, 1.04） 180天内的死亡率相似。

研究结果表明，在危重患者中，右美托咪定和可乐定在缩短成功拔管时间方面都不优于异丙酚。

附：英文原文

Title: Dexmedetomidine- or Clonidine-Based Sedation Compared With Propofol in Critically Ill Patients: The A2B Randomized Clinical Trial

Author: Timothy S. Walsh, Richard A. Parker, Leanne M. Aitken, Cathrine A. McKenzie, Lydia Emerson, Julia Boyd, Alix Macdonald, Gayle Beveridge, Annabel Giddings, David Hope, San Irvine, Sharon Tuck, Nazir I. Lone, Kalliopi Kydonaki, John Norrie, David Brealey, David Antcliffe, Michael Reay, Alan Williams, Jeremy Bewley, Benedict Creagh-Brown, Daniel F. McAuley, Paul Dark, Matt P. Wise, Anthony C. Gordon, Gavin D. Perkins, Michael C. Reade, Bronagh Blackwood, Alasdair MacLullich, Robert Glen, Valerie J. Page, Christopher J. Weir, AB Trial Investigators, Natalie Pattison, Barry Williams, Louise Rose, Paul Mouncey, John Prowle, David Wellsted, Tim Walsh, Stephen Brett, Heather Charles, Christoper Weir, John Norrie, Julian Bion, Graeme McLennan, Matt Stevenson, Alistair Nichol, Timothy Walsh, Maria Amamio, Lucy Barclay, Sophie Birch, Kate Briton, Sarah Clark, Jessica Crossan, Katherine Doverman, David Hope, Lucy Macdonald, Corrienne McCulloch, Nicola Rae, Scott Simpson, Jo Singleton, Maggie Wishart, Ruth Thompson, Neill Aitken, Rachel Fairlie, Nabeel Salim, Sam Talbot, Sarah Ackroyd, Valeria Alicino, Euan Allan, Thomas Anderson, Rosemary Andrew, Andrew Baigey

Issue&Volume: 2025-05-19

Abstract:

Importance  Whether α2-adrenergic receptor agonist–based sedation, compared with propofol-based sedation, reduces time to extubation in patients receiving mechanical ventilation in the intensive care unit (ICU) is uncertain.

Objective  To evaluate whether dexmedetomidine- or clonidine-based sedation reduces duration of mechanical ventilation compared with propofol-based sedation (usual care).

Design, Setting, and Participants  Pragmatic, open-label randomized clinical trial conducted at 41 ICUs in the UK including adults who were within 48 hours of starting mechanical ventilation, were receiving propofol plus an opioid for sedation and analgesia, and were expected to require mechanical ventilation for 48 hours or longer. The median time from intubation to randomization was 21.0 (IQR, 13.2-31.3) hours. Recruitment occurred from December 2018 to October 2023; the last follow-up occurred on December 10, 2023.

Interventions  The bedside algorithms used targeted a Richmond Agitation-Sedation Scale score of 2 to 1 (unless clinicians requested deeper sedation). The algorithms supported uptitration in the dexmedetomidine- and clonidine-based sedation intervention groups and supported downtitration for propofol-based sedation followed by sedation primarily with the allocated sedation (dexmedetomidine or clonidine). If required, supplemental use of propofol was permitted.

Main Outcomes and Measures  The primary outcome was time from randomization to successful extubation. The secondary outcomes included mortality, sedation quality, rates of delirium, and cardiovascular adverse events.

Results  Among the 1404 patients in the analysis population (mean age, 59.2 [SD, 14.9] years; 901 [64%] were male; and the mean APACHE II score was 20.3 [SD, 8.2]), the subdistribution hazard ratio (HR) for time to successful extubation was 1.09 (95% CI, 0.96-1.25; P=.20) for dexmedetomidine (n=457) vs propofol (n=471) and was 1.05 (95% CI, 0.95-1.17; P=.34) for clonidine (n=476) vs propofol (n=471). The median time from randomization to successful extubation was 136 (95% CI, 117-150) hours for dexmedetomidine, 146 (95% CI, 124-168) hours for clonidine, and 162 (95% CI, 136-170) hours for propofol. In the predefined subgroup analyses, there were no interactions with age, sepsis status, median Sequential Organ Failure Assessment score, or median delirium risk score. Among the secondary outcomes, agitation occurred at a higher rate with dexmedetomidine vs propofol (risk ratio [RR], 1.54 [95% CI, 1.21-1.97]) and with clonidine vs propofol (RR, 1.55 [95% CI, 1.22-1.97]). Compared with propofol, the rates of severe bradycardia (heart rate <50/min) were higher with dexmedetomidine (RR, 1.62 [95% CI, 1.36-1.93]) and clonidine (RR, 1.58 [95% CI, 1.33-1.88]). Compared with propofol, mortality was similar over 180 days for dexmedetomidine (HR, 0.98 [95% CI, 0.77-1.24]) and clonidine (HR, 1.04 [95% CI, 0.82-1.31]).

Conclusions and Relevance  In critically ill patients, neither dexmedetomidine nor clonidine was superior to propofol in reducing time to successful extubation.

DOI: 10.1001/jama.2025.7200

Source: https://jamanetwork.com/journals/jama/fullarticle/2834276