Original Investigation

Effect of a Resuscitation Strategy Targeting Peripheral Perfusion Status vs Serum Lactate Levels on 28-Day Mortality Among Patients With Septic Shock： The ANDROMEDA-SHOCK Randomized Clinical Trial

Glenn Hernández, Gustavo A. Ospina-Tascón, Lucas Petri Damiani, et al

JAMA. Published online February 17, 2019. doi:10.1001/jama.2019.0071

Abstract

Importance  背景

Abnormal peripheral perfusion after septic shock resuscitation has been associated with organ dysfunction and mortality. The potential role of the clinical assessment of peripheral perfusion as a target during resuscitation in early septic shock has not been established.

感染性休克复苏后外周灌注异常常伴随器官功能障碍及死亡。临床评估外周灌注作为早期感染性休克复苏治疗目标的作用尚未明确。

Objective  目的

To determine if a peripheral perfusion–targeted resuscitation during early septic shock in adults is more effective than a lactate level–targeted resuscitation for reducing mortality.

对于早期感染性休克成年患者而言，与乳酸水平指导的复苏治疗相比，确定以外周灌注为目标的复苏治疗能够降低病死率。

Design, Setting, and Participants  设计，场景及研究对象

Multicenter, randomized trial conducted at 28 intensive care units in 5 countries. Four-hundred twenty-four patients with septic shock were included between March 2017 and March 2018. The last date of follow-up was June 12, 2018.

在5个国家28个ICU进行的多中心随机临床试验。2017年3月至2018年3月共入选424名感染性休克患者。最后随访日期为2018年6月12日。

Interventions  干预措施

Patients were randomized to a step-by-step resuscitation protocol aimed at either normalizing capillary refill time (n = 212) or normalizing or decreasing lactate levels at rates greater than 20% per 2 hours (n = 212), during an 8-hour intervention period.

患者接受随机分组，在8个小时的干预治疗期间，通过逐步复苏治疗方案分别使毛细血管再充盈时间正常 (n = 212) 或使乳酸水平恢复正常或下降(> 20%/2 h) (n = 212)。

Main Outcomes and Measures  主要预后指标

The primary outcome was all-cause mortality at 28 days. Secondary outcomes were organ dysfunction at 72 hours after randomization, as assessed by Sequential Organ Failure Assessment (SOFA) score (range, 0 [best] to 24 [worst]); death within 90 days; mechanical ventilation–, renal replacement therapy–, and vasopressor-free days within 28 days; intensive care unit and hospital length of stay.

主要预后指标为28天全因病死率。次要预后指标为随机分组后72小时器官功能障碍，通过SOFA评分进行评估（范围0 [最好] 至 24 [最差]）；90天病死率；28天内无机械通气天数，无肾脏替代治疗天数及无升压药物天数；ICU住院日及总住院日。

Results  结果

Among 424 patients randomized (mean age, 63 years; 226 [53%] women), 416 (98%) completed the trial. By day 28, 74 patients (34.9%) in the peripheral perfusion group and 92 patients (43.4%) in the lactate group had died (hazard ratio, 0.75 [95% CI, 0.55 to 1.02]; P = .06; risk difference, −8.5% [95% CI, −18.2% to 1.2%]). Peripheral perfusion–targeted resuscitation was associated with less organ dysfunction at 72 hours (mean SOFA score, 5.6 [SD, 4.3] vs 6.6 [SD, 4.7]; mean difference, −1.00 [95% CI, −1.97 to −0.02]; P = .045). There were no significant differences in the other 6 secondary outcomes. No protocol-related serious adverse reactions were confirmed.

共有424名患者接受随机分组（平均年龄63岁；226名 [53%] 女性），416名 (98%) 完成试验。至第28天时，外周关注组74名(34.9%)患者及乳酸组92名(43.4%)患者死亡（风险比，0.75 [95% CI, 0.55 to 1.02]; P = .06；风险差异，−8.5% [95% CI, −18.2% to 1.2%]）。外周关注为目标的复苏治疗患者72小时器官功能障碍更少（平均SOFA评分，5.6 [SD, 4.3] vs 6.6 [SD, 4.7]；平均差异，−1.00 [95% CI, −1.97 to −0.02]; P = .045）。其他6项次要预后指标没有显著差异。没有发现治疗方案相关的严重不良事件。

Conclusions and Relevance  结论与意义

Among patients with septic shock, a resuscitation strategy targeting normalization of capillary refill time, compared with a strategy targeting serum lactate levels, did not reduce all-cause 28-day mortality.

对于感染性休克患者，与血乳酸水平指导的复苏治疗策略相比，旨在恢复正常毛细血管充盈时间的复苏策略不能降低28天病死率。

Trial Registration  试验注册

ClinicalTrials.gov Identifier: NCT03078712