A CASE OF DEXMEDETOMIDINE-INDUCED DRUG FEVER: AN IMPORTANT AND PRESS-EDEX-ING ISSUE

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Dexmedetomidine has revolutionized the field of critical care medicine, providing clinicians a short-acting, well-tolerated sedative. Cardiovascular adverse effects are well described with this agent (1). Less common adverse effects such as fever are increasingly being reported (2). Previous studies demonstrated no appreciable rate of dexmedetomidine-related fever (1, 3). Here we report a case of high-grade fever in the intensive care unit (ICU) after initiation of dexmedetomidine, with resolution after discontinuation. CASE PRESENTATION: A 34-year-old male with a past medical history of alcohol abuse and asthma was admitted to the general ward with Coronavirus disease 2019 (COVID-19) pneumonia. His course was complicated by severe hypoxia and subsequent pulseless electrical activity (PEA) arrest, requiring ICU transfer after achieving return of circulation and undergoing mechanical ventilation. On hospital day 7, after improvement in respiratory status with COVID-19 management including corticosteroids, as well as treatment with ceftriaxone and azithromycin given concern for superimposed bacterial pneumonia, he was transitioned to dexmedetomidine in preparation for a ventilator weaning trial. He developed fevers over the following 12 hours, initially to 39.4 C (102.9 F) prompting empiric sepsis management with intravenous fluids and broad-spectrum antibiotics (see figure-1). Despite this, he continued to have fevers to a maximum core temperature of 41.1 C (106 F). Blood, fungal, and respiratory cultures were unremarkable. With no clear infectious source or alternative explanation for severe hyperthermia, the decision was made to wean off dexmedetomidine given suspicion for drug-induced fever, upon which core temperature returned to 37.8 C (100.1 F). He remained afebrile, and eventually extubated and discharged in stable condition. DISCUSSION: We present a case of severe hyperthermia corresponding to, with a probable association using the Naranjo Adverse Drug Reaction Probability Scale, dexmedetomidine initiation, followed by resolution of fever after discontinuation. Antimicrobial therapy had no observable effect on the fever, and extensive infectious work-up was unremarkable. Completely attributing a febrile episode in the ICU setting to a medication is a difficult task. Furthermore, adequately powering studies to identify rare medication adverse effects in the ICU is a challenge, which may explain the absence of fever as a documented adverse effect of dexmedetomidine (1,2,4). In this case, no alternate diagnoses were evident, thus management was focused on discontinuing the presumed inciting agent. CONCLUSIONS: Recognizing dexmedetomidine as an etiology of severe hyperthermia in the ICU may help mitigate excessive therapies and improve outcomes. Further research is warranted to describe risk factors and proper recognition for when fevers occur with dexmedetomidine. REFERENCE #1: Hospira (2014) Precedex® (dexmedetomidine hydrochloride) [package insert]. Lake Forest, IL: Hospira, Inc. REFERENCE #2: Peterson J, Thomas W, Michaud C, et al. Incidence of Fever Associated With Dexmedetomidine in the Adult Intensive Care Unit. J Pharm Pract. 2021 Apr 5:8971900211004828. REFERENCE #3: Jakob SM, Ruokonen E, Grounds RM, et al. Dexmedetomidine for Long-Term Sedation Investigators. JAMA. 2012 Mar 21;307(11):1151-60. DISCLOSURES: No relevant relationships by Raef Fadel, source=Web Response No relevant relationships by Sara Hegab, source=Web Response No relevant relationships by Michael Reaume, source=Web Response No relevant relationships by Zachary Smith, source=Web Response