Yonsei Med J.  2016 Sep;57(5):1260-1270. 10.3349/ymj.2016.57.5.1260.

Protocol-Based Resuscitation for Septic Shock: A Meta-Analysis of Randomized Trials and Observational Studies

• Lee WK
• Kim HY
• Lee J
• Koh SO
• Kim JM
• Na S

• KMID: 2374174
• DOI: http://doi.org/10.3349/ymj.2016.57.5.1260

Abstract

PURPOSE
Owing to the recommendations of the Surviving Sepsis Campaign guidelines, protocol-based resuscitation or goal-directed therapy (GDT) is broadly advocated for the treatment of septic shock. However, the most recently published trials showed no survival benefit from protocol-based resuscitation in septic shock patients. Hence, we aimed to assess the effect of GDT on clinical outcomes in such patients.
MATERIALS AND METHODS
We performed a systematic review that included a meta-analysis. We used electronic search engines including PubMed, Embase, and the Cochrane database to find studies comparing protocol-based GDT to common or standard care in patients with septic shock and severe sepsis.
RESULTS
A total of 13269 septic shock patients in 24 studies were included [12 randomized controlled trials (RCTs) and 12 observational studies]. The overall mortality odds ratio (OR) [95% confidence interval (CI)] for GDT versus conventional care was 0.746 (0.631-0.883). In RCTs only, the mortality OR (95% CI) for GDT versus conventional care in the meta-analysis was 0.93 (0.75-1.16). The beneficial effect of GDT decreased as more recent studies were added in an alternative, cumulative meta-analysis. No significant publication bias was found.
CONCLUSION
The result of this meta-analysis suggests that GDT reduces mortality in patients with severe sepsis or septic shock. However, our cumulative meta-analysis revealed that the reduction of mortality risk was diminished as more recent studies were added.

Keyword

Sepsis; septic shock; shock; meta-analysis

MeSH Terms

Humans
*Observational Studies as Topic
*Randomized Controlled Trials as Topic
Resuscitation/*methods
Shock, Septic/mortality/*therapy

Figure

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  Fig. 1 Flow diagram showing results of search and reasons for exclusion of studies.

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  Fig. 2 (A) Risk of bias summary of RCTs with Cochrane Collaboration tool. (B) Risk of bias summary of non-RCTs with Cochrane Collaboration tool. RCTs, randomized controlled trials.

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  Fig. 3 Forest plot of the effectiveness of goal-directed therapy on overall mortality including RCTs and non-RCTs. RCTs, randomized controlled trials; CI, confidence interval.

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  Fig. 4 Forest plot of the effectiveness of goal-directed therapy on overall mortality including only RCTs. RCTs, randomized controlled trials; CI, confidence interval.

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  Fig. 5 Cumulative forest plot of RCTs and non-RCTs published after 2001. RCTs, randomized controlled trials; CI, confidence interval.

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  Fig. 6 Subgroup analysis, forest plot by study initiation year (period 1, before 2003; period 2, 2004-2007; period 3, 2008-2015). CI, confidence interval.

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  Fig. 7 Funnel plot of overall trials, RCTs and non-RCTs (p-value=0.359). RCTs, randomized controlled trials.

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  Fig. 8 Funnel plot of RCTs (p-value=0.837). RCTs, randomized controlled trials.

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