Comparison of Esmolol Versus Landiolol on Mortality in Adult Patients With Sepsis: A Systematic Review and Network Meta-Analysis

Objectives: The clinical efficacy of short-acting β-blockers in the management of sepsis remains uncertain. In particular, the comparative effects of two commonly used agents—esmolol and landiolol—have not been clearly established. This network meta-analysis aims to systematically evaluate and compare the effects of esmolol, landiolol, and standard of care (SOC) on mortality in patients with sepsis. Data Sources: A systematic search of PubMed, Web of Science, Embase, MEDLINE, CENTRAL, ClinicalTrials.gov, preprints, and citation searching was conducted before April 15, 2025. Study Selection: Randomized controlled trials that enrolled adult patients (≥ 18 yr) diagnosed with sepsis or septic shock and treated with β-blockers and conducted in ICUs. Data Extraction: Data were extracted on study characteristics, enrolled patients’ characteristics, administration strategies of drugs, and key clinical outcomes (including 28-d mortality, ICU length of stay, and other relevant endpoints). Data Synthesis: A total of 1165 records were identified through searches of five databases, registries, and relevant references up to April 15, 2025. Ten studies involving 1035 patients were included, after screening and eligibility assessment. Compared with esmolol, landiolol was associated with increased 28-day mortality (relative risk [RR], 1.57; 95% CI, 1.08–2.30; low certainty) and higher norepinephrine requirements (mean difference [MD], 0.17 μg/kg/min; 95% CI, 0.02–0.32; low certainty). Esmolol significantly reduced 28-day mortality (RR, 0.69; 95% CI, 0.56–0.85; moderate certainty) and 24-hour heart rate (MD, –16.92 beats/min; 95% CI, –23.49 to –10.36; moderate certainty) compared with SOC. In contrast, landiolol increased norepinephrine use compared with SOC (MD, 0.09 μg/kg/min; 95% CI, 0.01–0.18; moderate certainty). Conclusions: Among patients with sepsis treated with β-blockers, esmolol probably improves clinical outcomes compared with SOC. However, the effect of landiolol remains uncertain due to the low certainty of evidence. Esmolol may confer a relative clinical advantage over landiolol, but further studies are needed to confirm this finding and elucidate the underlying mechanisms.