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Meta-Analysis
. 2024 Nov 27;28(1):392.
doi: 10.1186/s13054-024-05174-w.

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

Mihai-Gabriel Alexandru  1 , Patrick Niewald  2 , Stefan Krüger  2 , Rainer Borgstedt  2 , Tony Whitehouse  3 , Mervyn Singer  4 , Sebastian Rehberg  2 , Sean S Scholz  2
Affiliations
Meta-Analysis

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

Mihai-Gabriel Alexandru et al. Crit Care. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Betablocker; Esmolol; Landiolol; Mortality; Sepsis; Septic shock.

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Conflict of interest statement

Declarations. Human ethics and consent to participate: Not applicable. Consent for publication: All authors have read and approved the submission of this manuscript. Competing interests: M.A., P.N., S.K., R.B., and S.S.S. report no competing interests. S. R. served as a speaker for AOP Health. T.W. was the Chief Investigator for STRESS‐L which was funded by the National Institute for Health Research (NIHR) Efficacy and Mechanism Evaluation (Project Number: EME‐14/150/85) and during the conduct of the study, he received personal fees and non‐financial support from AOP Orphan, manufacturer of landiolol. M.S. (or Institution) receives funding for studies, advisory board or speaker fees from the NIHR, Medical Research Council, AOP Pharma, Aptarion, Biomerieux, Biotest, deePull, Deltex Medical, Gentian, Matisse, Roche Diagnostics, Safeguard Biosystems, Volition. Singer is Sepsis Topic Advisor for NICE and sits on the council of the International Sepsis Forum.

Figures

Fig. 1
Fig. 1
PRISMA flow diagram showing search and selection strategies
Fig. 2
Fig. 2
Short-term mortality. Risk difference, short-acting betablocker treatment versus Control; M–H, Mantel–Haenszel; CI, confidence interval
Fig. 3
Fig. 3
Short-term mortality. Subgroup analysis comparing atrial fibrillation with sinus tachycardia. M–H, Mantel–Haenszel; CI, confidence interval
Fig. 4
Fig. 4
Risk of Bias assessment
See this image and copyright information in PMC

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