Early goal-directed and lactate-guided therapy in adult patients with severe sepsis and septic shock: a meta-analysis of randomized controlled trials

Abstract

Background: 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. 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.

Methods: Relevant 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.

Results: Sixteen 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%).

Conclusion: EGDT 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.

Keywords: EGDT; Lactate-guided therapy; Meta-analysis; Sepsis; Usual care.

Fig. 1

Flow chart for the study selection

Fig. 2

Risk of bias summary reviewing authors’ evaluations of each risk of bias item for each included study. Green circles indicate low risk of bias, yellow circles indicate unclear risk of bias, and red circles indicate high risk of bias

Fig. 3

Forest plot showing the effect of EGDT vs. UC/LGT on mortality in patients with severe sepsis and septic shock. The analysis was stratified by UC or LGT. RR < 1.0 favours EGDT

Fig. 4

Forest plot showing EGDT vs. UC regarding mortality in patients with severe sepsis and septic shock. The analysis was stratified by publication year in relation to the SSC 2012 for UC. RR < 1.0 favours EGDT

Fig. 5

Forest plot showing EGDT vs. UC/LGT regarding mortality in patients with severe sepsis and septic shock. The analysis was stratified by UC or LGT, mortality > or < 30%. RR < 1.0 favours EGDT

Fig. 6

Forest plot showing EGDTvs. UC regarding red cell transfusions, dobutamine use, vasopressor infusion, and mechanical ventilation within the first 6 h and APACHE II score in patients with severe sepsis and septic shock. The severity of illness was reported in each study by the APACHE II score, and the data were presented as the mean ± SD. The distinction between higher and lower severity of illness was determined according to the mean APACHE II score in each study. APACHE II scores > or < 20 were reported in 3 trials. RR < 1.0 favours EGDT

Fig. 7

Forest plot showing EGDT vs. LGT regarding red cell transfusion, vasopressor infusion, dobutamine use, and mechanical ventilation within the first 6 h among patients with severe sepsis and septic shock. RR < 1.0 favours EGDT