Intensive Care National Audit and Research Centre, London, United Kingdom
University of Pittsburgh School of Medicine, Pittsburgh
N Engl J Med. 2017 Jun 8;376(23):2223-2234. doi: 10.1056/NEJMoa1701380. Epub 2017 Mar 21.
After a single-center trial and observational studies suggesting that early, goal-directed therapy (EGDT) reduced mortality from septic shock, three multicenter trials (ProCESS, ARISE, and ProMISe) showed no benefit. This meta-analysis of individual patient data from the three recent trials was designed prospectively to improve statistical power and explore heterogeneity of treatment effect of EGDT.
We harmonized entry criteria, intervention protocols, outcomes, resource-use measures, and data collection across the trials and specified all analyses before unblinding. After completion of the trials, we pooled data, excluding the protocol-based standard-therapy group from the ProCESS trial, and resolved residual differences. The primary outcome was 90-day mortality. Secondary outcomes included 1-year survival, organ support, and hospitalization costs. We tested for treatment-by-subgroup interactions for 16 patient characteristics and 6 care-delivery characteristics.
We studied 3723 patients at 138 hospitals in seven countries. Mortality at 90 days was similar for EGDT (462 of 1852 patients [24.9%]) and usual care (475 of 1871 patients [25.4%]); the adjusted odds ratio was 0.97 (95% confidence interval, 0.82 to 1.14; P=0.68). EGDT was associated with greater mean (±SD) use of intensive care (5.3±7.1 vs. 4.9±7.0 days, P=0.04) and cardiovascular support (1.9±3.7 vs. 1.6±2.9 days, P=0.01) than was usual care; other outcomes did not differ significantly, although average costs were higher with EGDT. Subgroup analyses showed no benefit from EGDT for patients with worse shock (higher serum lactate level, combined hypotension and hyperlactatemia, or higher predicted risk of death) or for hospitals with a lower propensity to use vasopressors or fluids during usual resuscitation.
In this meta-analysis of individual patient data, EGDT did not result in better outcomes than usual care and was associated with higher hospitalization costs across a broad range of patient and hospital characteristics. (Funded by the National Institute of General Medical Sciences and others; PRISM ClinicalTrials.gov number, NCT02030158 .).
一项单中心试验和观察性研究表明，早期目标导向治疗（EGDT）可降低脓毒性休克患者的死亡率，随后三项多中心试验（ProCESS、ARISE 和 ProMISe）并未显示出获益。本项对这三项最新试验的个体患者数据进行的荟萃分析旨在前瞻性地提高统计学效能，并探讨 EGDT 治疗效果的异质性。
我们协调了试验之间的入组标准、干预方案、结局、资源使用措施和数据收集，并在揭盲前指定了所有分析。在试验完成后，我们汇总数据，并排除 ProCESS 试验中基于方案的标准治疗组，解决剩余差异。主要结局为 90 天死亡率。次要结局包括 1 年生存率、器官支持和住院费用。我们针对 16 项患者特征和 6 项护理提供特征进行了治疗组间交互作用检验。
我们研究了来自 7 个国家的 138 家医院的 3723 名患者。90 天死亡率在 EGDT 组（1852 例患者中有 462 例[24.9%]）和常规治疗组（1871 例患者中有 475 例[25.4%]）中相似；调整后的比值比为 0.97（95%置信区间，0.82 至 1.14；P=0.68）。与常规治疗相比，EGDT 更可能导致 ICU 入住时间（5.3±7.1 天 vs. 4.9±7.0 天，P=0.04）和心血管支持时间（1.9±3.7 天 vs. 1.6±2.9 天，P=0.01）更长；其他结局无显著差异，尽管 EGDT 组的平均费用更高。亚组分析显示，在休克更严重（血清乳酸水平更高、低血压合并高乳酸血症或预测死亡率更高）或常规复苏期间使用升压药或液体可能性较低的医院中，EGDT 并未带来获益。
在这项针对个体患者数据的荟萃分析中，EGDT 并未带来优于常规治疗的结局，且与广泛的患者和医院特征相关联的住院费用更高。（由美国国立卫生研究院综合医学科学研究所等资助；PRISM ClinicalTrials.gov 注册号：NCT02030158）。
