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Meta-Analysis
. 2016 Sep;57(5):1260-70.
doi: 10.3349/ymj.2016.57.5.1260.

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

Woo Kyung Lee  1 , Ha Yeon Kim  1 , Jinae Lee  2 , Shin Ok Koh  3 , Jeong Min Kim  1   4 , Sungwon Na  1   5
Affiliations
Meta-Analysis

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

Woo Kyung Lee et al. Yonsei Med J. 2016 Sep.

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.

Keywords: Sepsis; meta-analysis; septic shock; shock.

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Conflict of interest statement

The authors have no financial conflicts of interest.

Figures

Fig. 1
Fig. 1. Flow diagram showing results of search and reasons for exclusion of studies.
Fig. 2
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.
Fig. 3
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.
Fig. 4
Fig. 4. Forest plot of the effectiveness of goal-directed therapy on overall mortality including only RCTs. RCTs, randomized controlled trials; CI, confidence interval.
Fig. 5
Fig. 5. Cumulative forest plot of RCTs and non-RCTs published after 2001. RCTs, randomized controlled trials; CI, confidence interval.
Fig. 6
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.
Fig. 7
Fig. 7. Funnel plot of overall trials, RCTs and non-RCTs (p-value=0.359). RCTs, randomized controlled trials.
Fig. 8
Fig. 8. Funnel plot of RCTs (p-value=0.837). RCTs, randomized controlled trials.
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