Effect of Ultrashort-Acting Β-Blocker on the Mortality of Patients with Sepsis or Septic Shock: A Systematic Review and Trial Sequential Meta-Analysis of Randomized Controlled Trials

Importance: Sepsis poses a significant global health burden, with high morbidity and mortality rates, despite advances in evidence-based management. Adrenergic responses, particularly tachycardia, play a role in sepsis-related complications. Ultrashort-acting β-blockers, such as esmolol and landiolol, have been evaluated in randomized controlled trials (RCTs) for their impact on sepsis outcomes, but conflicting results have been reported. Objective: This systematic review and meta-analysis aim to provide an updated perspective on the impact of ultrashort-acting β-blockers on the clinical outcomes of sepsis. Data Sources: A comprehensive search of PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, and ClinicalTrials.gov was conducted from inception to January 12, 2024. Study Selection: RCTs investigating the clinical effects and safety of ultrashort-acting β-blockers in sepsis or septic shock were included. Out of 1034 initially identified records, 27 RCTs met the eligibility criteria. Data Extraction and Synthesis: Two investigators independently screened, extracted, and assessed the risk of bias in the included studies. Meta-analyses were performed using random-effects models, and trial sequential analysis (TSA) was conducted to evaluate the reliability of cumulative evidence. Main outcome and measures: The primary outcome was 28-day mortality rate. Results: A total of 2253 patients involved in 27 RCTs were included. Overall, ultrashort-acting β-blockers significantly reduced the 28-day mortality rate (31.6% versus 48.4%; risk ratio [RR] 0.66; 95% CI 0.56–0.78). TSA provided robust evidence for the 28-day and in-hospital mortality benefit. The survival benefit remains evident in subgroups of patients with septic tachycardia (RR, 0.66; 95% CI, 0.47–0.93), septic cardiomyopathy (RR, 0.61; 95% CI, 0.44–0.83), Chinese populations (RR, 0.64; 95% CI, 0.54–0.76), and those treated with esmolol (RR, 0.64; 95% CI, 0.56–0.73). For patients with septic shock, only those with tachycardia demonstrated a statistically significant difference in mortality rates (RR, 0.70; 95% CI, 0.55–0.88). Conclusions and relevance: Adjuvant ultrashort-acting β-blocker therapy demonstrated potential benefits in improving survival for patients with sepsis or septic shock. The findings support the consideration of β-blockers, particularly esmolol, as a valuable adjunctive treatment in sepsis, emphasizing the need for further research to confirm efficacy in diverse populations and optimize dosage regimen.Funding: None to declare. Declaration of Interest: None to declare.