• Anne M Drewry, Nicholas M Mohr, Enyo A Ablordeppey, Catherine M Dalton, Rebecca J Doctor, Brian M Fuller, Marin H Kollef, and Richard S Hotchkiss.
• Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO.
• Crit. Care Med. 2022 Jun 1; 50 (6): 924934924-934.

ObjectivesTo test the hypothesis that forced-air warming of critically ill afebrile sepsis patients improves immune function compared to standard temperature management.DesignSingle-center, prospective, open-label, randomized controlled trial.SettingOne thousand two hundred-bed academic medical center.PatientsEligible patients were mechanically ventilated septic adults with: 1) a diagnosis of sepsis within 48 hours of enrollment; 2) anticipated need for mechanical ventilation of greater than 48 hours; and 3) a maximum temperature less than 38.3°C within the 24 hours prior to enrollment. Primary exclusion criteria included: immunologic diseases, immune-suppressing medications, and any existing condition sensitive to therapeutic hyperthermia (e.g., brain injury). The primary outcome was monocyte human leukocyte antigen (HLA)-DR expression, with secondary outcomes of CD3/CD28-induced interferon gamma (IFN-γ) production, mortality, and 28-day hospital-free days.InterventionsExternal warming using a forced-air warming blanket for 48 hours, with a goal temperature 1.5°C above the lowest temperature documented in the previous 24 hours.Measurements And Main ResultsWe enrolled 56 participants in the study. No differences were observed between the groups in HLA-DR expression (692 vs 2,002; p = 0.396) or IFN-γ production (31 vs 69; p = 0.678). Participants allocated to external warming had lower 28-day mortality (18% vs 43%; absolute risk reduction, 25%; 95% CI, 2-48%) and more 28-day hospital-free days (difference, 2.6 d; 95% CI, 0-11.6).ConclusionsParticipants randomized to external forced-air warming did not have a difference in HLA-DR expression or IFN-γ production. In this pilot study, however, 28-day mortality was lower in the intervention group. Future research should seek to better elucidate the impact of temperature modulation on immune and nonimmune organ failure pathways in sepsis.Copyright © 2022 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

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