Abstract
Landiolol is being investigated for its potential to manage septic shock (SS) and sepsis-related tachyarrhythmias (TA). We performed a systematic review and meta-analysis of three randomized controlled trials (RCTs) involving 473 patients with sepsis or SS, including those with TA, comparing landiolol to standard therapy-controlled (STC) groups. Standard therapy consisted of usual sepsis care ± placebo but excluded β-blockers in the control arms. MEDLINE, Embase, and Cochrane databases were searched for trial data extracted from published reports up to November 2024, excluding non-English reports. Quality assessment was performed per Cochrane recommendations. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were pooled across trials to evaluate the outcomes. The primary endpoints included heart rate (HR) at 96 hours, chosen because all three trials consistently recorded HR at this time point, allowing for uniform comparison despite additional time points being reported, and 28-day mortality. Secondary outcomes included atrial fibrillation (AF), hypotension, changes in Sequential Organ Failure Assessment score, and norepinephrine dose. Of the three RCTs, 473 patients were included, with an intervention-to-control arm ratio of approximately 1:1. A lower HR (MD: -6.36; 95% CI: -9.25, -3.47; p < 0.0001; I² = 0%) was observed in the landiolol group compared to the STC. Hypotension (RR: 3.62, 95% CI: 1.37, 9.58; p = 0.010; I² = 5%) was significantly increased in patients who received landiolol when compared to STC, and 28-day mortality showed no significant difference between the groups (RR: 1.07; 95% CI: 0.72, 1.58; p = 0.74; I² = 44%), as did AF (RR: 0.63; 95% CI: 0.25, 1.59; p = 0.33; I² = 8%). Landiolol, a highly selective ultrashort-acting β1-blocker with distinct pharmacokinetic properties from esmolol, reduces HR in patients with sepsis-related TA without significantly affecting 28-day mortality. However, careful monitoring for hypotension is advised, given the absolute risk increase of 8.4% observed in treated patients. However, results should be interpreted cautiously as only three small trials underpin these results. To our knowledge, this is the first MA to focus exclusively on landiolol in this setting, offering drug-specific insights for critical care management.