Relative efficacy and safety of early lactate clearance-guided therapy resuscitation in patients with sepsis: A meta-analysis

OBJECTIVE: Compelling evidence has shown that aggressive resuscitation bundles are one of the cornerstones of the successful treatment of patients with sepsis. Recent studies suggest that lactate normalization during resuscitation is a more powerful indicator of resuscitative adequacy; however, early lactate clearance-guided therapy is still not recommended. We performed this meta-analysis to evaluate the effect of early lactate clearance-directed therapy as a potentially more effective resuscitation target. METHODS: Studies were identified using PubMed, Embase, and the Cochrane Library without region, publication type, or language restrictions. Randomized trials were included when they compared the efficacy and safety of lactate clearance-guided resuscitation versus central venous oxygen saturation (ScvO(2))-guided therapy. The primary outcome was mortality, and the secondary outcomes were intensive care unit (ICU) stay, length of hospital stay, mechanical ventilation time, Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score, and Sepsis-related Organ Failure Assessment (SOFA) score. RESULTS: Seven randomized controlled trials encompassing 1301 cases were reviewed. Compared with guided ScvO(2) therapy, early lactate clearance-directed therapy was associated with decreased in-hospital mortality (relative ratio [RR] 0.68, 95% confidence interval [CI] 0.56 to 0.82), shorter ICU stay (mean difference [MD] −1.64 days, 95% CI −3.23 to −0.05), shorter mechanical ventilation time (MD −10.22 hours, 95% CI −15.94 to −4.5), and lower APACHE-II scores (MD −4.47, 95% CI −7.25 to −1.69). However, patients undergoing early lactate clearance-guided therapy had similar lengths of hospital stay and similar SOFA scores. CONCLUSIONS: As a specific indicator of resuscitation outcome, lactate clearance alone is superior to ScvO(2) alone during a standard resuscitation paradigm. The optimal or desired rate of lactate clearance is still a contentious area. To guide resuscitation and normalize lactate levels in patients, repeating lactate measurements every 2 hours until the patient has met a lactate clearance of 10% or greater may be helpful. TRIAL REGISTRATION NUMBER: PROSPERO CRD42018100515.