#VisualAbstract: Efficacy and safety of landiolol for treatment of sepsis-related tachyarrhythmia

1. Landiolol administration resulted in significantly more patients achieving target heart rates of 60-94 following sepsis-related tachyarrhythmia and was also associated with significantly reduced incidence of new onset arrhythmia

Evidence Rating: 1 (Excellent)

Sepsis associated tachyarrhythmias and atrial fibrillation are significant causes of mortality, with as many as a third of patients reaching fatal outcomes. In the context of sepsis, treatments traditionally used for tachyarrhythmias are often ineffective or contraindicated, leading to a small selection of effective treatment strategies. Retrospective studies have shown landiolol, an ultra-short-acting β1-blocker to be an effective rate control agent in the context of sepsis-related tachyarrhythmias, but no randomized controlled trials have been completed to further investigate its efficacy and safety. In this multicenter, open-label randomized controlled trial, 151 patients admitted to 54 different hospitals in Japan between 2018 to 2019 were recruited to address this knowledge gap. Patients included were 20 years of age or older, had been diagnosed with sepsis according to Third International Consensus Definitions for Sepsis and Septic Shock, and had developed either sinus tachycardia, atrial fibrillation, or atrial flutter without a change in catecholamine dose. Seventy-five patients were randomized to the standard therapy group (including respiratory and fluid resuscitation, antimicrobials, and catecholamines), and 76 to the treatment group, consisting of standard therapy and landiolol hydrochloride infusion at 1 μg/kg per min within 2h after randomization, with an option to increase the dose per study protocol to a maximum of 20 μg/kg per min. Compared to the control group, the group receiving landiolol had a significantly greater proportion of patients achieving target heart rate (60-94BPM) at 24 hours post randomization (55% versus 33%, between-group difference, 23.1%, 95% CI 7.1-37.5; p=.0031), with effects maintained until the end of the 96 hour treatment period. New-onset arrhythmia over 168 hours post randomization was also lower in the landiolol group that controls. landiolol appeared to be well tolerated in the treatment group, though few patients were reported to experience hypotension (4%), cardiac arrest (1%), bradycardia (1%), and reduction in ejection fraction (1%). This study represents the first randomized controlled trial investigating landiolol for administration in sepsis-related tachyarrhythmias, and evidence seems to support prior literature for the drug as an effective rate control agent.

Click to read the study in Lancet Respiratory Medicine