Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial showing lower mortality by warming afebrile sepsis patients in the intensive care unit. The objective of this prospective single-site randomized controlled trial was to determine if core warming improves respiratory physiology of mechanically ventilated patients with COVID-19, allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean BMI 34.5 (±5.9) kg/m2 with COVID-19 requiring mechanical ventilation were enrolled from September 2020 through February 2022. Patients were randomized 1:1 to standard-of-care or to receive core warming for 72 hours via an esophageal heat exchanger commonly utilized in critical care and surgical patients. The maximum target temperature was 39.8 °C. A total of 10 patients received usual care and 9 patients received esophageal core warming. After 72 hours of warming, PaO2/FiO2 ratios were 197 (±32) and 134 (±13.4), Cycle Thresholds were 30.8 (±6.4) and 31.4 (±3.2), ICU mortality was 40% and 44%, 30-day mortality was 30% and 22%, and mean 30-day ventilator-free days were 11.9 (±12.6) and 6.8 (±10.2) for standard-of-care and warmed patients, respectively (p=NS). This pilot study suggests that core warming of patients with COVID-19 undergoing mechanical ventilation is feasible and appears safe. Optimizing time to achieve febrile-range temperature may require a multimodal temperature management strategy to further evaluate effects on outcome.

Dr. Willms, disclosures limited to: i.Speaker Bureau, La Jolla Pharmaceutical Company ii.Board of Directors & Investor, Octet Medical, Inc iii.Investor and Medical Advisor, InVent Respiratory and Connected Rock Ventures Dr. Bedimo, disclosures limited to: i.Research support from Merck & Co. ii.Scientific advisory board for Merck & Co., Shionogi, Gilead, and Theratechnologies Dr. Kulstad, disclosure limited to equity and employment in Attune Medical

NCT04494867

This did not receive any external funding.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

IRB of Sharp Memorial Hospital gave ethical approval for this work. IRB # 2007901; approved August 17, 2020

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All data produced in the present study are available upon reasonable request to the authors.