米多君与安慰剂对重症监护病房持续性低血压患者停用血管加压素时间的影响：国际性随机临床试验

翻译：任文鑫  编辑：冯玉蓉  审校：曹莹

目的：ICU出院通常会因为需要静脉注射血管升压药以维持正常血压而延迟。我们假设口服米多君(一种α1肾上腺素能受体激动剂)作为标准治疗的辅助治疗可以缩短静脉注射加压素的持续时间。

方法：在这项多中心、随机、对照试验中，包括美国和澳大利亚的三家三级转诊医院，我们招募了需要单一静脉注射血管升压剂治疗≥24小时的低血压患者。受试者在标准护理的基础上每隔8小时口服米多君(20 mg)或安慰剂，直到停止静脉注射血管增压药、从ICU出院或发生不良事件。主要结果是血管加压素停止使用的时间。次要结果包括ICU出院准备时间、ICU和住院时间以及ICU再住院率。

结果：在2012年10月至2019年6月期间，136名参与者被随机抽样，其中132人接受了分配的干预，并纳入了分析(修改后的意向治疗方法)。米多君组和安慰剂组的升压药停药时间无差异(中位数[IQR], 23.5 [10–54] vs 22.5 [10.4–40] h; 差值为1 h; 95% CI −10.4~12.3 h; p=0.62)。次要指标未观察到差异。使用米多君后，心动过缓的发生率更高(5 [7.6%] vs 0 [0%], p=0.02)。

结论：米多君不能促进静脉升压药的释放，对危重症患者的低血压治疗无效。

原始文献来源：Peter S, Matthew HA, Maria DP, et al. Efect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.Intensive Care Med. 2020 Sep 3.  doi: 10.1007/s00134-020-06216-x.  

Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial

Abstract

Purpose: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α1-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.

Methods: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for≥24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.

Results: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modifed intention-to-treat approach). Time to vasopressor discontinuation was not diferent between midodrine and placebo groups (median [IQR], 23.5 [10–54] vs 22.5

[10.4–40] h; diference, 1 h; 95% CI−10.4 to 12.3 h; p=0.62). No diferences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p=0.02).

Conclusion: Midodrine did not accelerate liberation from intravenous vasopressors and was not efective for the treatment of hypotension in critically ill patients.