UTILITY OF DANTROLENE FOR HYPERPYREXIA IN THE MANAGEMENT SARS-COV-2 INFECTION

Abstract

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Coronavirus Disease 2019 (COVID-19) continues to be a global pandemic with its management evolving as research continues to unveil innovative therapies. Dantrolene, approved in malignant hyperthermia, may have utility for hyperpyrexia in COVID-19 patients, given its cytoprotective effects (1). Here we present a COVID-19 case with persistent hyperpyrexia despite conventional antipyretic measures that abated after dantrolene administration. CASE PRESENTATION: A 57-year-old Hispanic male with no past medical history, presented with fever, palpitations, myalgias and worsening dyspnea. He denied other symptoms. His admission vitals were Temp 101.3F, BP 155/81, Pulse 106, Resp 22, SpO2 88% on RA and 98% on 50% Venturi Mask. Lung examination revealed decreased air entry throughout with scattered crackles. Laboratory investigations showed WBC of 5.61 with normal electrolytes. ABG showed pH 7.45, pCO2 36, pO2 59 with FiO2 0.35 which improved with increased oxygenation. CXR showed hallmark features for COVID-19 pneumonia. COVID-19 PCR was positive. Antibiotics and prophylactic anticoagulation were initiated. He was later admitted to the medical floor. His hospital course was unremarkable until day three when he developed acute hypoxic respiratory failure requiring high flow nasal cannula and intensive care transfer. Despite optimal oxygenation, PF ratio was 105F. Besides multiple positive COVID-19 tests, all other infectious investigations were negative. Antibiotics, antivirals and antifungals were started but pyrexia persisted. Intravenous dantrolene (2.5mg/kg then 1mg/kg) was given after which temperature abated. De-escalation of care ensued, with removal of antimicrobials, intubation and ECMO. Patient had an uneventful transfer from MICU and discharge from the hospital. DISCUSSION: Hyperpyrexia is an extreme elevation of core body temperature usually >106.7 °F due to an elevated hypothalamic thermo-regulatory threshold. It has been reported in COVID-19 patients and portends a poor outcome with up to 100% mortality. Proposed mechanisms include immune dysfunction, direct brain injury from SARS-CoV-2 and vascular thrombosis (2). Dantrolene has been shown to inhibit multiple cell damage induced by SARS-CoV-2 infection (1). In our index case, all conventional antipyretic measures failed, while dantrolene achieved normothermia. CONCLUSIONS: Our case had a favorable outcome juxtaposing those previously reported (1,2). The proposition that dantrolene can be repurposed in COVID-19 patients with hyperpyrexia is novel and hopefully will stimulate and unearth more research. REFERENCE #1: Jiang, B., Liang, S., Liang, G., & Wei, H. (2020). Could dantrolene be explored as a repurposed drug to treat COVID-19 patients by restoring intracellular calcium homeostasis?. European review for medical and pharmacological sciences, 24(19), 10228–10238. https://doi.org/10.26355/eurrev_202010_23247 REFERENCE #2: Suwanwongse, K., & Shabarek, N. (2020). Hyperpyrexia in patients with COVID-19. Journal of medical virology, 92(11), 2857–2862. https://doi.org/10.1002/jmv.26154 DISCLOSURES: No relevant relationships by Sneha Adidam, source=Web Response No relevant relationships by Sahai Donaldson, source=Web Response No relevant relationships by Lorenzo Leys, source=Web Response No relevant relationships by Alicia Thomas, source=Web Response