皮质类固醇对持续性急性呼吸窘迫综合征的疗效与安全性

Efficacy and safety of corticosteroids for persistent acute respiratory distress syndrome.

作者信息

Steinberg Kenneth P, Hudson Leonard D, Goodman Richard B, Hough Catherine Lee, Lanken Paul N, Hyzy Robert, Thompson B Taylor, Ancukiewicz Marek

机构信息

Division of Pulmonary and Critical Care Medicine, Harborview Medical Center, Box 359762, 325 Ninth Ave., Seattle, WA 98104, USA.

出版信息

N Engl J Med. 2006 Apr 20;354(16):1671-84. doi: 10.1056/NEJMoa051693.

DOI:10.1056/NEJMoa051693

PMID:16625008

Abstract

BACKGROUND

Persistent acute respiratory distress syndrome (ARDS) is characterized by excessive fibroproliferation, ongoing inflammation, prolonged mechanical ventilation, and a substantial risk of death. Because previous reports suggested that corticosteroids may improve survival, we performed a multicenter, randomized controlled trial of corticosteroids in patients with persistent ARDS.

METHODS

We randomly assigned 180 patients with ARDS of at least seven days' duration to receive either methylprednisolone or placebo in a double-blind fashion. The primary end point was mortality at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days, biochemical markers of inflammation and fibroproliferation, and infectious complications.

RESULTS

At 60 days, the hospital mortality rate was 28.6 percent in the placebo group (95 percent confidence interval, 20.3 to 38.6 percent) and 29.2 percent in the methylprednisolone group (95 percent confidence interval, 20.8 to 39.4 percent; P=1.0); at 180 days, the rates were 31.9 percent (95 percent confidence interval, 23.2 to 42.0 percent) and 31.5 percent (95 percent confidence interval, 22.8 to 41.7 percent; P=1.0), respectively. Methylprednisolone was associated with significantly increased 60- and 180-day mortality rates among patients enrolled at least 14 days after the onset of ARDS. Methylprednisolone increased the number of ventilator-free and shock-free days during the first 28 days in association with an improvement in oxygenation, respiratory-system compliance, and blood pressure with fewer days of vasopressor therapy. As compared with placebo, methylprednisolone did not increase the rate of infectious complications but was associated with a higher rate of neuromuscular weakness.

CONCLUSIONS

These results do not support the routine use of methylprednisolone for persistent ARDS despite the improvement in cardiopulmonary physiology. In addition, starting methylprednisolone therapy more than two weeks after the onset of ARDS may increase the risk of death. (ClinicalTrials.gov number, NCT00295269.).

摘要

背景

持续性急性呼吸窘迫综合征（ARDS）的特征为过度的纤维增生、持续的炎症反应、机械通气时间延长以及较高的死亡风险。由于既往报告提示皮质类固醇可能改善生存率，我们开展了一项针对持续性ARDS患者的皮质类固醇多中心随机对照试验。

方法

我们将180例ARDS病程至少7天的患者以双盲方式随机分组，分别给予甲泼尼龙或安慰剂。主要终点为60天时的死亡率。次要终点包括无呼吸机天数和无器官衰竭天数、炎症和纤维增生的生化标志物以及感染并发症。

结果

60天时，安慰剂组的医院死亡率为28.6%（95%置信区间为20.3%至38.6%），甲泼尼龙组为29.2%（95%置信区间为20.8%至39.4%；P = 1.0）；180天时，死亡率分别为31.9%（95%置信区间为23.2%至42.0%）和31.5%（95%置信区间为22.8%至41.7%；P = 1.0）。在ARDS发病至少14天后入组的患者中，甲泼尼龙与60天和180天死亡率显著增加相关。甲泼尼龙在最初28天内增加了无呼吸机天数和无休克天数，同时氧合、呼吸系统顺应性和血压得到改善，血管升压药治疗天数减少。与安慰剂相比，甲泼尼龙未增加感染并发症发生率，但与较高的神经肌肉无力发生率相关。