Early Neuromuscular Blockade in the Acute Respiratory Distress Syndrome
The National Heart, Lung, and Blood Institute PETAL Clinical Trials Network
N Engl J Med May 19, 2019
DOI: 10.1056/NEJMoa1901686
Abstract
BACKGROUND 背景
The benefits of early continuous neuromuscular blockade in patients with acute respiratory distress syndrome (ARDS) who are receiving mechanical ventilation remain unclear.
接受机械通气的ARDS患者早期使用神经肌肉阻滞剂的获益尚不清楚。
METHODS 方法
We randomly assigned patients with moderate-to-severe ARDS (defined by a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen of <150 mm Hg with a positive end-expiratory pressure [PEEP] of ≥8 cm of water) to a 48-hour continuous infusion of cisatracurium with concomitant deep sedation (intervention group) or to a usual-care approach without routine neuromuscular blockade and with lighter sedation targets (control group). The same mechanical-ventilation strategies were used in both groups, including a strategy involving a high PEEP. The primary end point was in-hospital death from any cause at 90 days.
我们将中重度ARDS（定义为PEEP ≥ 8 cmH2O时PaO2/FiO2 < 150 mmHg）患者随机分组，分别接受48小时持续输注顺式阿曲库胺，同时给予深度镇静（干预组），或常规组（不常规使用神经肌肉阻滞剂，轻度镇静为目标）（对照组）。两组患者机械通气策略相同，包括高PEEP。主要预后终点为90天全因住院病死率。
RESULTS 结果
The trial was stopped at the second interim analysis for futility. We enrolled 1006 patients early after the onset of moderate-to-severe ARDS (median, 7.6 hours after onset). During the first 48 hours after randomization, 488 of the 501 patients (97.4%) in the intervention group started a continuous infusion of cisatracurium (median duration of infusion, 47.8 hours; median dose, 1807 mg), and 86 of the 505 patients (17.0%) in the control group received a neuromuscular blocking agent (median dose, 38 mg). At 90 days, 213 patients (42.5%) in the intervention group and 216 (42.8%) in the control group had died before hospital discharge (between-group difference, −0.3 percentage points; 95% confidence interval, −6.4 to 5.9; P=0.93). While in the hospital, patients in the intervention group were less physically active and had more adverse cardiovascular events than patients in the control group. There were no consistent between-group differences in end points assessed at 3, 6, and 12 months.
试验因无效在第二次中期分析后结束。我们入选了1006名早期中重度ARDS患者（中位时间，发病后7.6小时）。在随机分组后最初48小时内，干预组501名患者中488名(97.4%)开始持续输注顺式阿曲库胺（输注中位时间47.8小时；中位剂量，1807 mg）；对照组505名患者中86名(17.0%)使用了神经肌肉阻滞剂（中位剂量38 mg）。90天时，干预组213名患者(42.5%)及对照组216名患者(42.8%)住院期间死亡（组间差异，-0.3百分点；95%可信区间-6.4 to 5.9；p=0.93）。在住院期间，干预组患者主动活动更少，心血管不良事件更多。在第3、6和12个月时，主要预后终点两组间没有差异。
CONCLUSIONS 结论
Among patients with moderate-to-severe ARDS who were treated with a strategy involving a high PEEP, there was no significant difference in mortality at 90 days between patients who received an early and continuous cisatracurium infusion and those who were treated with a usual-care approach with lighter sedation targets. (Funded by the National Heart, Lung, and Blood Institute; ROSE ClinicalTrials.gov number, NCT02509078.)
对于接受高PEEP的中重度ARDS患者，早期持续输注顺式阿曲库胺的患者与以浅镇静为目标的常规治疗患者间90天病死率无显著差异。
