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.
Key Points:
- Study Objective: Investigate whether short-acting beta-blockers improve mortality outcomes in septic patients with persistent tachycardia.
- Included Trials: Seven RCTs, with patients randomized to beta-blockers (landiolol or esmolol) versus standard care or placebo.
- Mortality Outcomes: No significant reduction in 28-day, 90-day, or hospital mortality was observed with beta-blockers.
- Subgroup Analysis: Mortality outcomes did not differ based on patient age (<65 vs. ≥65 years) or initial cardiac rhythm (atrial fibrillation vs. sinus tachycardia).
- Heart Rate Control: Beta-blockers achieved target heart rates (80–94 bpm), which could have other clinical benefits not captured by mortality endpoints.
- Adverse Events: Serious adverse events, such as hypotension and bradycardia, were more common in beta-blocker groups, particularly with landiolol.
- Statistical Heterogeneity: Significant variability between studies (I² = 73%), suggesting differences in patient populations, methodologies, or treatment protocols.
- Limitations: Lack of uniformity in hemodynamic monitoring and patient selection criteria across studies; open-label designs may introduce bias.
- Future Directions: Emphasis on hemodynamic monitoring to identify patients likely to benefit from beta-blockers, and further investigation of esmolol and landiolol’s comparative efficacy.
- Clinical Implications: Beta-blocker use in septic patients should be approached cautiously, with consideration for individual hemodynamic status and potential adverse effects.
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