法国南特大学医院Karim Asehnoune团队研究了大剂量巴氯芬对接受机械通气的不健康饮酒患者躁动相关事件的影响。2021年2月23日，《美国医学会杂志》报道了该成果。
在重症监护病房（ICU），不健康的饮酒会导致躁动。
为了评价在接受机械通气的不健康饮酒患者中，与安慰剂相比，使用大剂量巴氯芬是否能减少躁动相关事件，2016年6月至2019年5月，研究组在法国18个ICU进行了一项3期、双盲、安慰剂对照、随机临床试验，招募符合不健康饮酒标准的接受机械通气的成年人。将其随机分组，其中159名接受巴氯芬治疗（根据肾小球滤过率调整最大剂量），155名接受安慰剂治疗。主要终点为治疗期间出现至少1次躁动相关事件的患者百分比。次要终点包括机械通气持续时间、ICU住院时间和28天死亡率。
314名患者的平均年龄为57岁，女性占17.2%，313名（99.7%）完成了试验。巴氯芬组至少经历过1次躁动相关事件的患者百分比为19.7%，显著低于安慰剂组（29.7%）。在18个预先指定的次要终点中，14个没有显著差异。巴氯芬组的中位机械通气时间为9天，显著长于安慰剂组（8天）；中位ICU停留时间为14天，显著长于安慰剂组（11天）。巴氯芬组与安慰剂组的28天死亡率无显著差异。巴氯芬组有14名患者（8.9%）出现苏醒延迟（停止使用镇静剂和镇痛剂72小时后没有睁眼），安慰剂组有3名（1.9%）。
研究结果表明，对于接受机械通气的不健康饮酒患者，与安慰剂相比，使用大剂量巴氯芬治疗可显著减少躁动相关事件的发生，但仍需结合不良事件来综合权衡剂量。
附：英文原文
Title: Effect of High-Dose Baclofen on Agitation-Related Events Among Patients With Unhealthy Alcohol Use Receiving Mechanical Ventilation: A Randomized Clinical Trial
Author: Mickael Vourc’h, Charlotte Garret, Arnaud Gacouin, Jean-Claude Lacherade, Maud Jonas, Kada Klouche, Martine Ferrandiere, Samir Jaber, Laurent Flet, Eric Dailly, Caroline Pouplet, Adel Maamar, Jean Reignier, Antoine Roquilly, Fanny Feuillet, Pierre-Joachim Mahe, Karim Asehnoune, BACLOREA study group
Issue&Volume: 2021/02/23
Abstract:
Importance Unhealthy alcohol use can lead to agitation in the intensive care unit (ICU).
Objective To assess whether high-dose baclofen reduces agitation-related events compared with placebo in patients with unhealthy alcohol use receiving mechanical ventilation.
Design, Settings, and Participants This phase 3, double-blind, placebo-controlled, randomized clinical trial conducted in 18 ICUs in France recruited adults receiving mechanical ventilation who met criteria for unhealthy alcohol use. Patients were enrolled from June 2016 to February 2018; the last follow-up was in May 2019.
Interventions Baclofen (n=159), adjusted from 50 to 150 mg per day based on estimated glomerular filtration rate, or placebo (n=155) during mechanical ventilation up to a maximum of 15 days before gradual dose reduction over 3 to 6 days.
Main Outcomes and Measures The primary end point was the percentage of patients with at least 1 agitation-related event over the treatment period. Secondary outcomes included duration of mechanical ventilation, length of ICU stay, and 28-day mortality.
Results Among 314 patients who were randomized (mean age, 57 years; 60 [17.2%] women), 313 (99.7%) completed the trial. There was a statistically significant decrease in the percentage of patients who experienced at least 1 agitation-related event in the baclofen group vs the placebo group (31 [19.7%] vs 46 [29.7%]; difference, 9.93% [95% CI, –19.45% to –0.42%]; adjusted odds ratio, 0.59 [95% CI, 0.35-0.99]). Of 18 prespecified secondary end points, 14 were not significantly different. Compared with the placebo group, the baclofen group had a significantly longer median length of mechanical ventilation (9 vs 8 days; difference, 2.00 [95% CI, 0.00-3.00]; hazard ratio [HR] for extubation, 0.76 [95% CI, 0.60-0.97]) and stay in the ICU (14 vs 11 days; difference, 2.00 [95% CI, 0.00-4.00]; HR for discharge, 0.70 [95% CI, 0.54-0.90]). At 28 days, there was no significant difference in mortality in the baclofen vs placebo group (25.3% vs 21.6%; adjusted odds ratio, 1.24 [95% CI, 0.72-2.13]). Delayed awakening (no eye opening at 72 hours after cessation of sedatives and analgesics) occurred in 14 patients (8.9%) in the baclofen group vs 3 (1.9%) in the placebo group.
Conclusions and Relevance Among patients with unhealthy alcohol use receiving mechanical ventilation, treatment with high-dose baclofen, compared with placebo, resulted in a statistically significant reduction in agitation-related events. However, considering the modest effect and the totality of findings for the secondary end points and adverse events, further research is needed to determine the possible role of baclofen in this setting and to potentially optimize dosing.
DOI: 10.1001/jama.2021.0658
Source: https://jamanetwork.com/journals/jama/article-abstract/2776690
JAMA-Journal of The American Medical Association：《美国医学会杂志》，创刊于1883年。隶属于美国医学协会，最新IF：157.335
官方网址：https://jamanetwork.com/
投稿链接：http://manuscripts.jama.com/cgi-bin/main.plex
本期文章：《美国医学会杂志》：Vol 325 No 8
