Evaluating the efficacy of esmolol in septic shock: a systematic review and meta-analysis

Persistent tachycardia in septic shock is associated with adverse outcomes, yet optimal management remains uncertain. Esmolol, a short-acting β1-selective blocker, has been investigated as a strategy to control heart rate and attenuate excessive sympathetic activation. This systematic review and meta-analysis evaluated the efficacy of esmolol in adult patients with septic shock.

A comprehensive search of PubMed/MEDLINE, Cochrane Central, and Google Scholar was conducted from database inception to March 28, 2025. Reference lists and clinical trial registries were also screened. Randomized controlled trials comparing esmolol plus standard care with standard care alone in adults with septic shock were included. The primary outcome was 28-day mortality. Secondary outcomes included heart rate, mean arterial pressure (MAP), and lactate.

Three randomized controlled trials involving 314 patients were included. Esmolol was associated with a significant reduction in 28-day mortality (OR 0.33, 95% CI 0.20-0.53; I2 = 0%). Heart rate was significantly reduced at both 24 h (day 1) (MD - 8.50 bpm, 95% CI - 10.82 to - 6.17) and 48 h (day 2) (MD - 16.60 bpm, 95% CI - 20.03 to - 13.17). No statistically significant difference in MAP was observed between groups (MD 0.10 mmHg, 95% CI - 3.46 to 3.66; I2 = 53%). Although the included studies did not report clinically meaningful differences in lactate levels, differences in outcome reporting precluded quantitative synthesis.

Esmolol therapy may improve heart rate control and reduce 28-day mortality in carefully selected patients with septic shock without adversely affecting MAP. However, these findings should be interpreted cautiously because they are based on a limited number of randomized trials and are subject to clinical heterogeneity and potential risk of bias. Larger, high-quality randomized controlled trials are needed to confirm these findings and define the optimal use of esmolol in septic shock.

The review protocol was registered with PROSPERO (CRD42024584599).