Effect of early goal directed therapy in the treatment of severe sepsis and/or septic shock: A meta-Analysis

Background: Many studies showed a dramatic mortality reduction after the use of early goal directed therapy (EGDT) in patients with severe sepsis and/or septic shock. Three large RCTs got neutral results for its usage compared with usual care group. So the debate whether EGDT could help in the management of severe sepsis and/or septic shock was a dilemma. Objectives: To determine the effect of EGDT in the treatment of severe sepsis and/or septic shock. Methods: A systematic review and meta-analysis of RCTs and prospective studies were performed, which extracted studies from Pubmed, Elsevier ScienceDirect, Cochrane, Clinicaltrials.gov, Google Scholar, China Knowledge Resource Integrated Database, and Wanfang Database. The mortality trend in the control group from included studies was analyzed. Results: Seven RCTs and twelve prospective studies were included, enrolling 3502 EGDT participants and 3791 usual care participants. EGDT could reduce overall mortality compared with usual care group. This reduction was resulted from the prospective studies and studies before 2010. There was a mortality reduction trend in the severe sepsis and/or septic shock patients received usual care. Limitations: This conclusion was limited by the small size of some selected studies, and the long time range of the studies selected. The bias in some included studies would also affect the overall result. Conclusions: EGDT helped in the mortality reduction in patients with severe sepsis and/or septic shock in the past years. With the progression in the management of this disease and mortality reduction in this disease, especially that some EGDT ingredients have been involved in usual care, the benefit of EGDT on overall mortality reduced to the comparable level as the usual care for sepsis patients. A more strict RCT is need to confirm the role of EGDT in the current clinical practice.

背景：多项研究显示，对重症脓毒症（severe sepsis）和/或脓毒性休克（septic shock）患者采用早期目标导向治疗（early goal directed therapy, EGDT）后，死亡率可显著降低。但三项大型随机对照试验（Randomized Controlled Trial, RCT）对比其与常规治疗的效果时得到了中性结果。因此，关于EGDT是否有助于重症脓毒症和/或脓毒性休克的临床管理，学界始终存在争议。
研究目标：明确EGDT在重症脓毒症和/或脓毒性休克治疗中的疗效。
研究方法：本研究针对随机对照试验与前瞻性研究（prospective study）开展系统综述（systematic review）与荟萃分析（meta-analysis），文献检索范围涵盖PubMed、Elsevier ScienceDirect、Cochrane图书馆、Clinicaltrials.gov、Google Scholar、中国知识资源总库（China Knowledge Resource Integrated Database）及万方数据库（Wanfang Database），同时对纳入研究中对照组的死亡率变化趋势进行了分析。
研究结果：共纳入7项随机对照试验与12项前瞻性研究，合计纳入EGDT组受试者3502例、常规治疗组受试者3791例。与常规治疗组相比，EGDT可降低患者总死亡率；该获益仅见于前瞻性研究以及2010年之前发表的研究。此外，接受常规治疗的重症脓毒症和/或脓毒性休克患者存在死亡率下降趋势。
研究局限性：本研究结论受到部分纳入研究样本量较小、纳入研究时间跨度较大的限制；部分纳入研究存在的偏倚也会对整体研究结果产生影响。
研究结论：既往研究显示，EGDT可降低重症脓毒症和/或脓毒性休克患者的死亡率。随着该疾病临床管理方案的优化及患者死亡率的下降，加之EGDT的部分治疗组分已被纳入常规治疗方案，如今EGDT相较于常规治疗在降低总死亡率方面的获益已降至与常规治疗相当的水平。未来需开展更为严谨的随机对照试验，以明确EGDT在当前临床实践中的作用。