Early goal-directed resuscitation for patients with severe sepsis and septic shock: a meta-analysis and trial sequential analysis

Abstract

Background: The aim of this study was to explore whether early goal-directed therapy (EGDT) was associated with a lower mortality rate in comparison to usual care in patients with severe sepsis and septic shock.

Methods: PubMed, EMBASE, Cochrane library and a Chinese database (SinoMed) were searched systematically to identify randomized controlled trials (RCTs) comparing standard EGDT with usual care in resuscitation of patients with severe sepsis and septic shock and the search time could date back to the publication of the study by Rivers in 2001. The study selection, data extraction and methodological evaluation were performed by two investigators independently. The primary outcome was all-cause mortality. The present meta-analysis had been registered in PROSPERO (CRD42015017667).

Results: Our meta-analysis identified 6 studies and enrolling 4336 patients. There was no significant difference in mortality between the two groups, and the pooled odds ratio (OR) was 0.83 (95 % confident interval, CI, 0.64-1.08) with significant heterogeneity (p = 0.02, I(2) = 64%). However, the pooled OR of 3 multicenter RCTs was 1.03 (95% CI, 0.89-1.21) with no heterogeneity (p = 0.78, I(2) = 0%). The effects of EGDT on length of stay in the emergency department and intensive care unit were uncertain, and there was no effect of EGDT on hospital length of stay. There were no differences of mechanical ventilation rate and renal replacement therapy rate between the two groups, and patients in the EGDT group were more admitted in ICU than patients in the control group. During the early 6-h intervention period, patients in the EGDT group received more intravenous fluids, had a higher vasopressor usage rate, higher dobutamine usage rate and higher blood transfusion rate, than patients in the control group. Finally, there was no difference in the incidence of adverse events between the two groups, and the pooled OR was 1.06 (95%CI 0.80-1.39) with moderate heterogeneity (I(2) = 62%, p = 0.07).

Discussion: Our meta-analysis showed that the application of EGDT was not associated with lower mortality rate currently. However it does not mean that it is useless of EGDT in patients with sever sepsis and septic shock. On the contrary, there was no difference in mortality rate between the two groups may be due to the improvement of therapeutic strategies in these patients. And the results may be related to the different compliance rate of EGDT resuscitation bundle.

Conclusions: The current evidence does not support the significant advantage of Early goal-directed therapy (EGDT) in the resuscitation of patients with severe sepsis and septic shock.

Fig. 1

Flow chart for study selection

Fig. 2

Risk of bias summary

Fig. 3

Forest plot showing the effects of early goal-direced therapy on all-cause mortality in patients with severe sepsis and septic shock

Fig. 4

Trial sequential analysis of all-cause mortality in patients with severe sepsis and septic shock. Trial sequential analyses assessing the effect of early goal-direced therapy on all-cause mortality in 6 studies. The diversity-adjusted required information size was based on a relative risk reduction of 20; an alpha of 5; a beta of 2 and an event proportion of 25.7 % in the control arm. The blue cumulative z curve was constructed using a random effects model

Fig. 5

Trial sequential analysis of all-cause mortality in patients with severe sepsis and septic shock of ProCESS, ARISE and ProMISe. Trial sequential analyses assessing the effect of early goal-direced therapy on all-cause mortality in 3 multicenter harmonious studies. The diversity-adjusted required information size was based on a relative risk reduction of 20; an alpha of 5; a beta of 2 and an event proportion of 22.2 %in the control arm. The blue cumulative z curve was constructed using a random effects model