Mortality in septic patients treated with short-acting betablockers: a comprehensive meta-analysis of randomized controlled trials

Abstract

Treatment with short-acting betablockers in septic patients remains controversial. Two recent large multicenter trials have provided additional evidence on this therapeutic approach. We thus performed a meta-analysis, including the most recent data, to evaluate the potential impacts of treatment with short-acting betablockers on mortality in adult septic patients. The data search included PubMed, Web of Science, ClinicalTrials.gov and the Cochrane Library. A meta-analysis of all eligible peer-reviewed studies was performed in accordance with the PRISMA statement. Only randomized, controlled studies with valid classifications of sepsis and intravenous treatment with short-acting betablockers (landiolol or esmolol) were included. Short-term mortality served as the primary endpoint. Secondary endpoints included effects on short-term mortality regarding patient age and cardiac rhythm. A total of seven studies summarizing 854 patients fulfilled the predefined criteria and were included. Short-term mortality as well as pooled mortality (longest period of data on mortality) was not significantly impacted by treatment with short-acting betablockers when compared to the reference treatment (Risk difference, − 0.10 [95% CI, − 0.22 to 0.02]; p = 0.11; p for Cochran’s Q test = 0.001; I2 = 73%). No difference was seen when comparing patients aged < 65 versus ≥ 65 years (p = 0.11) or sinus tachycardia with atrial fibrillation (p = 0.27). Despite statistical heterogeneity, no significant publication bias was observed. Administration of short-acting betablockers did not reduce short-term mortality in septic patients with persistent tachycardia. Future studies should also provide extensive hemodynamic data to enable characterization of cardiac function before and during treatment.