The Clinical Utility of Targeted Heart Rate Control in Septic Shock: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential Analysis

Objectives: Heart rate control using beta-blockers in sepsis has traditionally been avoided because of concerns with worsening cardiac index and organ perfusion. Recent studies has explored the possible beneficial effects of targeted heart rate control in patients with septic shock who have tachycardia despite initial resuscitation. We performed a systematic review and meta-analysis to explore the effects of heart rate control in septic shock patients. Methods: A systematic review and meta-analysis was conducted searching for studies from PubMed, Cochrane Central, and Embase registers for randomized controlled trials (RCTs) that compared the mortality of patients with sepsis and septic shock treated with targeted rate control. The literature search was done to include studies from January 2013 to December 2023. Two independent researchers independently assessed the studies and included RCTS in which adult patients (>18 years of age) with septic shock were treated with targeted heart rate control vs placebo after initial resuscitation due to persistent tachycardia. The study data was extracted by two independent researchers. A random effects model was used to present the results. A trial sequential analysis (TSA) was performed for the primary outcome of 28-day mortality. Results: A total of 9 studies with a pooled sample size of 807 participants were included in the analysis. Eight of the included studies with a pooled sample size of 766 reported 28-day mortality. Targeted heart rate control was associated with a trend toward lower 28-day mortality [risk ratio (RR): 0.78; 95% CI: 0.62-0.99; p = 0.04; I2 = 48%]. Trial sequential analysis showed the cumulative effect lying within the zone of uncertainty, with diversity-adjusted required information size of 1,756 and pooled effect size of the pooled RR 0.78 (alpha-spending adjusted 95% CI: 0.53-1.15). There was a statistically significant lower heart rate associated with rate control (MD: -16.66; 95% CI: -23.89 to -9.42; p-value < 0.001) but no difference in mean arterial pressure. cardiac index, lactate levels, norepinephrine (NE) requirements, and ICU length of stay (LOS) in between the groups. Conclusion: Targeted heart rate control in patients with septic shock may be tolerated from a hemodynamic standpoint. However, the beneficial effect on mortality is less certain than was reported in the initial studies.