Differential Mortality Benefit of Beta-blockers in Septic Shock: A Subgroup Meta-analysis

Tachycardia in septic shock is a typical physiological response driven by sympathetic activation and vasopressor use. While initially compensatory, excessive heart rates (HRs) can compromise myocardial efficiency and lead to worse outcomes. Targeted HR control has been proposed to mitigate these effects, although the evidence remains inconclusive.

To evaluate drug-specific effects of HR control agents on 28-day all-cause mortality in patients with septic shock requiring vasopressor support.

A subgroup meta-analysis and meta-regression were performed using randomized controlled trials (RCTs) included in a recent systematic review. Relative risk (RR) estimates and heterogeneity (I²) were calculated using R. Subgroup analyses compared outcomes across drugs, and a meta-regression assessed the impact of Landiolol (vs non-Landiolol agents) as a binary moderator.

Esmolol (n = 5; 431 participants) was associated with a significant mortality benefit (RR: 0.73; 95% CI: 0.56-0.95; I² = 29.4%), whereas Landiolol (n = 3) showed insignificant effect (RR: 1.08; 95% CI: 0.45-2.62; I² = 43.2%). Meta-regression revealed a nonsignificant trend toward increased mortality with Landiolol (β = 0.42; p = 0.21).

Esmolol appears beneficial, while Ivabradine and Landiolol show no clear mortality advantage. Further head-to-head trials are warranted.

Karim HMR, Khandelwal A, Baidya DK, Ravikumar RH. Differential Mortality Benefit of Beta-blockers in Septic Shock: A Subgroup Meta-analysis. Indian J Crit Care Med 2025;29(8):704-707.