Oseltamivir-Associated Bradycardia in Critically Ill Patients

Abstract

Background: Oseltamivir is frequently administered to critically ill patients with presumed influenza. It may modulate Na+, K+, and Ca2+ channels to produce bradycardia. Objective: To evaluate the association between oseltamivir and bradycardia in critically ill patients and assess parameters associated with bradycardia. Methods: This was a retrospective audit of 203 critically ill adults with presumed influenza receiving at least 2 doses of oseltamivir. The primary outcome was the occurrence of bradycardia, defined as a heart rate (HR) ≤59 beats per minute (BPM) while receiving oseltamivir or a decrease of ≥20 BPM compared with the lowest HR before initiating oseltamivir. Results: A total of 88 (43.4%) patients manifested bradycardia, 59 with HR ≤59 BPM, 19 with HR decrease of ≥20 BPM, and 10 with both. The time from first dose to bradycardia was 51.4 ± 43 hours. In all, 48 (54.6%) patients received therapies for bradycardia, including increased inotropic/vasopressor dose, electrolyte replacement, electrocardiogram, discontinuation of other medications, cardiology consult, discontinuation of oseltamivir, and pacer placement. There were no significant differences between groups with bradycardia versus without in terms of demographics, laboratory values, hospital characteristics, or oseltamivir dosing. Multivariate logistic regression showed that bradycardia was associated with baseline HR, age, past medical history of neurological issues, and positive influenza status. Between hours 6 through 126, significant differences existed between groups in actual and lowest HR. Conclusion and Relevance: Oseltamivir was associated with clinically relevant bradycardia in critically ill patients. Clinicians should closely monitor HR in critically ill patients receiving oseltamivir.