TIME TO SLOW DOWN: A DEEPER LOOK INTO REMDESIVIR-ASSOCIATED BRADYCARDIA

ABSTRACT

SESSION TITLE Drug-Induced and Associated Critical Care Cases Posters 1 SESSION TYPE Case Report Posters PRESENTED ON 10/19/2022 1245 pm - 0145 pm INTRODUCTION: The use of remdesivir in critical care setting has been utilized treatment of covid, but not without risk. Many cases have reported severe cardiac effects with bradycardia being the most common. CASE PRESENTATION The patient was a 15-year-old female with a history of asthma, hyperinsulinemia who required hospitalization for acute hypoxic respiratory failure secondary to COVID-19 pneumonia. She received ceftriaxone, azithromycin, and a 10-day course of remdesivir (RDV). On her third day of admission, the patient developed significant sinus bradycardic with heart rate nadir of 30-40 bpm but denied any symptoms. She completed her remdesivir course on day five of hospitalization and was discharged on day nine with a heart rate of 47 bpm. She later presented to ED the night of discharge following acute onset of lightheadedness and blurry vision at home secondary to orthostatic hypotension and bradycardia. Her pulse was 48 bpm, temperature 36.1 C, respirations 24/min, blood pressure 119/50 mmHg and SpO2 99% on room air. Her physical exam was unremarkable. EKG showed sinus bradycardia with a PR interval of 124 ms and QTc of 406 ms. Echocardiogram showed normal cardiac anatomy and function. Patient was diagnosed with persistent RDV-associated bradycardia and discharged home with a Holter monitor and cardiology follow-up. Bradycardia resolved by her follow-up visit two weeks later. DISCUSSION: According to the WHO pharmacovigilance database, bradycardia is a relatively new adverse effect and 3.6% of the 2,603 adverse effects reported since the onset of the pandemic, with 2 million RDV doses administered during this time [1]. The mechanism of RDV-associated bradycardia is proposed to be an effect of adenosine triphosphate, an active metabolite, which reduces SA node automaticity via stimulation of vagal nerve, as well as RDV cross-reactivity with mRNA polymerase, leading to cardiotoxicity that usually resolves within 24 hours of medication discontinuation. In our patient's case bradycardia did not resolve until eight days after discontinuation of medication [2]. Review of previously case reports does not identify any association with patient age but could be related to timing of when medication reaches therapeutic window, as many patients had onset of bradycardia on day 3 of treatment [3]. We report a pediatric case of severe acute COVID-19 who developed sinus bradycardia on day 3 of RDV treatment as previously described, but the bradycardia persisted long after the discontinuation of RDV. CONCLUSIONS: With over 50 thousand pediatric COVID-19 hospitalizations to date, this case serves as a timely reminder that medication side effects should be monitored closely, and that more research needs to be done into the effects of RDV on cardiac function in pediatric patients. Reference #1 Jung SY, Kim MS, Li H, Lee KH, Koyanagi A, Solmi M, Kronbichler A, Dragioti E, Tizaoui K, Cargnin S, Terrazzino S, Hong SH, Abou Ghayda R, Kim NK, Chung SK, Jacob L, Salem JE, Yon DK, Lee SW, Kostev K, Kim AY, Jung JW, Choi JY, Shin JS, Park SJ, Choi SW, Ban K, Moon SH, Go YY, Shin JI, Smith L. Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database. Clin Transl Sci. 2022 Feb;15(2)501-513. doi 10.1111/cts.13168. Epub 2021 Oct 31. PMID 34719115;PMCID PMC8841455. Reference #2 Touafchia A, Bagheri H, Carrié D, Durrieu G, Sommet A, Chouchana L, Montastruc F. Serious bradycardia and remdesivir for coronavirus 2019 (COVID-19) a new safety concerns. Clin Microbiol Infect. 2021 Feb 27;27(5)791.e5–8. doi 10.1016/j.cmi.2021.02.013. Epub ahead of print. PMID 33647441;PMCID PMC7910147. Reference #3 Rau, Cornelius MPhil;Apostolidou, Sofia MD;Singer, Dominique MD, PhD;Avataneo, Valeria PhD;Kobbe, Robin MD Remdesivir, Sinus Bradycardia and Therapeutic Drug Monitoring in Children With Severe CO