Abstract
BackgroundThe ProCESS, ARISE, and ProMISe trials have failed to show that early goal-directed therapy (EGDT) reduces mortality in patients with severe sepsis and septic shock. Although lactate-guided therapy (LGT) has been shown to result in significantly lower mortality, its use remains controversial. Therefore, we performed a meta-analysis to evaluate EGDT vs. LGT or usual care (UC) in adult patients with severe sepsis and septic shock.MethodsRelevant randomized controlled trials published from January 1, 2001 to March 30, 2017 were identified in PubMed, EMBASE, Web of Science, and the Cochrane Library. The primary outcome was mortality; secondary outcomes included red cell transfusions, dobutamine use, vasopressor infusion, and mechanical ventilation support within the first 6 h and Acute Physiology and Chronic Health Evaluation II (APACHE II) score.ResultsSixteen studies enrolling 5968 patients with 2956 in EGDT, 2547 in UC, and 465 in LGT were included in this meta-analysis. Compared with UC, EGDT was associated with a lower mortality (10 trials; RR 0.85, 95% CI 0.74–0.97, P = 0.01), and this difference was more pronounced in the subgroup of UC patients with mortality > 30%. In addition, EGDT patients received more red cell transfusions, dobutamine, and vasopressor infusions within the first 6 h. Compared with LGT, EGDT was associated with higher mortality (6 trials; RR 1.42, 95% CI 1.19–1.70, P = 0.0001) with no heterogeneity (P = 0.727, I2 = 0%).ConclusionEGDT seems to reduce mortality in adult patients with severe sepsis and septic shock, and the benefit may primarily be attributed to red cell transfusions, dobutamine administration, and vasopressor infusions within the first 6 h. However, LGT may result in a greater mortality benefit than EGDT.
Highlights
The ProCESS, ARISE, and ProMISe trials have failed to show that early goal-directed therapy (EGDT) reduces mortality in patients with severe sepsis and septic shock
Compared with lactate-guided therapy (LGT), EGDT was associated with higher mortality, with no heterogeneity (RR 1.42, 95% confidence interval (CI) 1.19-1.70, P = 0.0001; I2 = 0%, P = 0.73; Fig. 3)
Main findings EGDT vs. usual care (UC) This meta-analysis showed that EGDT resulted in a 15% reduction in all-cause mortality compared with UC in adult patients with severe sepsis and septic shock, and this difference was evident in the subgroup of UC patients with a mortality rate > 30%
Summary
The ProCESS, ARISE, and ProMISe trials have failed to show that early goal-directed therapy (EGDT) reduces mortality in patients with severe sepsis and septic shock. Three large multicentre RCTs, namely, the ProCESS [6], ARISE [7], and ProMISe [8] trials, failed to show that EGDT reduced mortality to a greater extent than UC in patients with severe sepsis and septic shock; no harm was associated with the intervention strategies. The patients in these trials [6,7,8] were less severely ill (lower baseline lactate levels, Scvo at or above the target value on admission, and lower mortality in the control group). EGDT cannot currently be recommended with the available evidence base, bedside clinicians still need guidance regarding how to approach this group of patients, who have significant mortality and morbidity [9], and the use of EGDT is still safe and may be considered
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