Early, Goal-Directed Therapy for Septic Shock — A Patient-Level Meta-Analysis

In reporting the results of their meta-analysis of individual patient data from three trials, the Protocolized Resuscitation in Sepsis Meta-Analysis (PRISM) investigators (June 8 issue)1 conclude that early, goal-directed therapy (EGDT) did not result in better outcomes than usual care in the resuscitation of patients with septic shock. I was hoping that the meta-analysis would answer an important question — what is usual care? EGDT is a well-defined intervention to guide hemodynamic resuscitation according to targets for central venous pressure, mean arterial blood pressure, urinary output, and central venous oxygen saturation.

在报告3项临床试验患者个体数据的meta分析结果时，PRISM研究者（6月8日刊）得出结论，即与感染性休克患者的常规复苏治疗相比，早期目标指导治疗(EGDT)不能改善预后。我希望这个meta分析能够回答一个重要的问题—什么是常规治疗？EGDT是有明确定义的治疗措施，根据中心静脉压、平均动脉压、尿量和中心静脉血氧饱和度指导血流动力学复苏治疗。

Which monitoring tools and hemodynamic targets (other than central venous pressure, mean arterial blood pressure, and urinary output) were used by the physicians in the usual-care groups in the three trials to guide their decision to administer or withhold fluids, vasopressors, and blood products? Such data are very important to guide recommendations for therapy, as well as to clarify how usual care was associated with a significant increase in the rate of serious adverse events as compared with EGDT in the Australasian Resuscitation in Sepsis Evaluation (ARISE) trial2 (1.8% vs. 0.5%; absolute risk difference, 1.3 percentage points; 95% confidence interval, 0.18 to 2.54; P=0.03; number needed to harm [i.e., the number of patients needed for one adverse event to occur], 76.9).

在3项临床试验的常规治疗组中，临床医生采用什么监测手段及血流动力学目标（除中心静脉压、平均动脉压和尿量外）治疗液体治疗、升压药物及血液制品使用的决策？这些数据对于指导治疗非常重要，同时对于理解ARISE研究中常规治疗组较EGDT组严重不良事件显著增加也至关重要（1.8% vs. 0.5%; 绝对风险差异, 1.3%; 95%可信区间, 0.18 to 2.54; P=0.03; 造成危害需病例数 [即，一个不良事件发生所需患者数], 76.9)。

Ahmad S. Saleh, M.B., B.Ch., M.Sc.

Okba Ben Nafee Hospital, Alexandria, Egypt

sabryccm@gmail.com

In the patient-level meta-analysis of the ARISE, Protocolized Care for Early Septic Shock (ProCESS), and Protocolised Management in Sepsis (ProMISe) trials, the authors conclude that EGDT did not result in better outcomes than usual care. Their findings contradict the findings of Rivers et al.1

在ARISE，ProCESS和ProMISe试验的患者水平meta分析中，作者得出结论，与常规治疗相比，EGDT不能改善预后。这一发现与Rivers研究的结果相反。

The key to the divergent findings between these trials and the trial conducted by Rivers and colleagues lies mainly in the medical management in the usual-care group.2,3 In the trial by Rivers et al., the amount of fluids administered and the mean central venous pressure achieved in the first 6 hours of treatment were significantly lower in the usual-care group (the standard-therapy group) than in the early-therapy group. In contrast, in the recent trials, early, aggressive, and targeted resuscitation, the hallmark of EGDT, was achieved even in the usual-care group. Thus, the differences between the usual-care groups and the early-therapy groups in the recent trials were limited to the monitoring of central venous oxygen saturation and the use of dobutamine and blood transfusions toward predefined central venous oxygen saturation targets.

上述3项临床试验与Rivers研究得到不同结果的关键在于常规治疗组的治疗。在Rivers研究中，常规治疗（标准治疗组）最初6小时内输注的液体量及达到的中心静脉压显著低于早期治疗组。相反，在近期的临床试验中，EGDT的标志性措施（即早期、积极、目标指导的复苏治疗）在常规治疗组也达到（与EGDT组）相同比例。因此，近期临床试验中，常规治疗组与早期治疗组的差异仅限于监测中心静脉血氧饱和度，使用多巴酚丁胺及输血达到既定的中心静脉血氧饱和度目标。

After the trial by Rivers et al., early, goal-directed, protocol-based resuscitation of patients with septic shock became the norm. If “usual care” has now evolved to involve early, targeted administration of antibiotics, fluids, and vasopressors, it is to the credit of EGDT.

在Rivers的试验之后，感染性休克患者的早期、目标指导、基于方案的复苏治疗成为常规。如果目前的“常规治疗”已经包括早期针对性使用抗生素、液体和升压药物，这就是EGDT。

Sahajal Dhooria, M.D., D.M.

Inderpaul S. Sehgal, M.D., D.M.

Ritesh Agarwal, M.D., D.M.

Postgraduate Institute of Medical Education and Research, Chandigarh, India

sahajal@gmail.com