In adults with septic shock, esmolol may be the most effective beta blocker for reducing mortality and improving clinical outcomes, compared with landiolol or standard care. Compared with landiolol, esmolol significantly reduced 28-day mortality, ICU mortality, heart rate, and serum lactate levels, and was associated with a shorter ICU stay.
Septic shock, involving circulatory and metabolic dysfunction, has a high death rate. Excessive sympathetic activation increases cardiac strain, immune dysregulation, and metabolic imbalance.
Beta blockers, such as esmolol and landiolol, have been studied for their potential to modulate excessive sympathetic activation and improve septic shock outcomes.
To compare the effectiveness of beta blockers on mortality and key clinical outcomes in adults with septic shock, the researchers conducted a Bayesian network meta-analysis. They queried standard medical research databases for randomized controlled trials that compared esmolol or landiolol to standard care. Eight trials, with 916 participants, met their inclusion criteria.
Esmolol Outperformed Landiolol
They calculated hazard ratios (HRs) with 95% credible intervals (CrIs) for dichotomous outcomes, adjusting for follow-up time, and mean differences (MDs) for continuous outcomes compared to control.
After applying a random-effects model to account for between-study variability and Surface Under the Cumulative Ranking Curve (SUCRA) to rank the beta blockers’ performance, they found the following:
- Primary outcome: 28-day mortality, esmolol ranked highest (HR, 0.47; 95% CrI, 0.29 to 0.72; SUCRA, 99.16%), followed by control (SUCRA, 33.75%), then landiolol (HR, 1.14; 95% CrI, 0.63 to 1.83; SUCRA, 17.09%).
- ICU mortality: Esmolol showed the greatest reduction (HR, 0.54; 95% CrI, 0.16 to 1.51; SUCRA, 91.35%), followed by control (SUCRA, 31.53%), then landiolol (HR, 1.20, 95% CrI, 0.37 to 3.00; SUCRA, 27.11%).
- ICU stay duration: Esmolol was associated with the greatest decrease in number of days (MD, -1.25, 95% CrI, -3.66 to 1.71; SUCRA, 67.06%), vs landiolol (MD, -1.15; 95% CrI, -5.01 to 3.04; SUCRA, 60.6%).
- Hospital stay duration: Landiolol was associated with slightly fewer days (MD, -0.25; 95% CrI, -7.68 to 7.15; SUCRA, 56.67%), while esmolol showed a minor increase (MD, 0.84; 95% CrI, -2.20 to 3.66; SUCRA, 32.45%).
- Heart rate reduction: Esmolol had the most significant effect on beats per minute (MD, -18.35; 95% CrI, -22.45 to -12.40; SUCRA, 99.11%), followed by landiolol (MD, -7.50; 95% CrI, -14.54 to -0.46; SUCRA, 49.83%).
- Serum lactate levels (mmol/L): Esmolol was the most effective in reducing lactate (MD, -0.38; 95% CrI, -1.40 to 0.67; SUCRA, 81.77%), and landiolol showed a slight increase (MD, 0.57; 95% CrI, -1.19 to 2.31; SUCRA, 19.76%).
Further studies to assess esmolol’s safety and efficacy in septic shock treatment are needed, the researchers noted.
Reference
Khalil I, Sayed A, Sultana N, et al. Comparative Effectiveness of Beta Blockers on Mortality and Clinical Outcomes in Adults With Septic Shock: A Comprehensive Systematic Review and Bayesian Network Meta-Analysis. Presented at: CHEST 2025, October 19-22, 2025; Chicago.
