Effect of ultrashort-acting β-blocker on the mortality of patients with sepsis or septic shock: A systematic review and trial sequential meta-analysis of randomized controlled trials.

Summary

Across 27 randomized trials (n=2253), ultrashort-acting beta-blockers significantly reduced 28-day mortality (RR 0.66, 95% CI 0.56–0.78). Trial sequential analysis supported robustness, with benefits notable in septic tachycardia, septic cardiomyopathy, and with esmolol use.

Key Findings

• Pooled 28-day mortality reduction with ultrashort-acting beta-blockers (RR 0.66; 95% CI 0.56–0.78).
• Trial sequential analysis confirmed sufficient information size for mortality benefit.
• Benefits persisted in subgroups: septic tachycardia (RR 0.66), septic cardiomyopathy (RR 0.61), Chinese cohorts, and esmolol-treated patients.
• Mortality benefit in septic shock was significant only in patients with tachycardia.

Clinical Implications

Consider esmolol or landiolol as adjuncts for septic tachycardia under hemodynamic monitoring, with protocols emphasizing patient selection (e.g., persistent tachycardia), titration, and safety surveillance.

Limitations

• Heterogeneity in populations, dosing strategies, and co-interventions across trials
• Potential geographic concentration (e.g., many trials from China) limiting generalizability

Future Directions

Large pragmatic multicenter RCTs with standardized protocols and hemodynamic targets to define indications, dosing, and safety in diverse sepsis populations.