Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trial

Abstract Background Accidental hypothermia is associated with high morbidity and mortality. Research on treatment strategies for accidental hypothermia is complicated by the low incidence and heterogeneous patient population. We have developed a new method for clinical trials of experimental hypothe...

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Main Authors: Ane M. Helland, Sigurd Mydske, Jörg Assmus, Guttorm Brattebø, Øystein Wiggen, Haakon K. Kvidaland, Øyvind Thomassen
Format: Article
Language:English
Published: BMC 2025-01-01
Series:Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
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Online Access:https://doi.org/10.1186/s13049-025-01331-4
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author Ane M. Helland
Sigurd Mydske
Jörg Assmus
Guttorm Brattebø
Øystein Wiggen
Haakon K. Kvidaland
Øyvind Thomassen
author_facet Ane M. Helland
Sigurd Mydske
Jörg Assmus
Guttorm Brattebø
Øystein Wiggen
Haakon K. Kvidaland
Øyvind Thomassen
author_sort Ane M. Helland
collection DOAJ
description Abstract Background Accidental hypothermia is associated with high morbidity and mortality. Research on treatment strategies for accidental hypothermia is complicated by the low incidence and heterogeneous patient population. We have developed a new method for clinical trials of experimental hypothermia, to enable further studies of active rewarming. If cold ambient air is effective as a cooling method, this would mimic the most frequent clinical setting of hypothermic patients and provide a feasible cooling method for field studies. We aimed to induce mild hypothermia in healthy volunteers by exposure to cold ambient air, and tested the hypothesis that drug-induced suppression of endogenous thermoregulation would be required. Methods In a randomized, double-blind, crossover design, 15 healthy volunteers wearing wet clothes were put in a windy climate chamber set to 5 °C. Each participant completed the experimental procedure twice, once receiving active drugs (meperidine and buspirone) and once receiving placebo. The experiments were separated by a one-week wash-out period. Primary outcome was core temperature at termination, defined as 3 h of exposure or 35 °C. The between-groups difference was assessed using analysis of covariance (ANCOVA) with left censoring (Tobit model) and individual random intercept. Secondary outcomes were trajectory of core temperature and reduction of shivering. Results At termination, the active drug vs placebo group differed in temperature by 1.4 °C. With adjustment for the removal of participants reaching 35 °C, the estimated mean difference was 1.7 °C (1.4–2.0, p < 0.001). Shivering was effectively reduced, but not completely inhibited by the drug regimen, and core temperature declined at a rate of − 0.82 °C per hour. Conclusion The novel protocol utilizing cold air as a cooling method and drug-induced suppression of endogenous thermoregulation, is effective and enables future research projects. We have provided suggestions for minor alterations. Trial registration: EudraCT ID 2023–506020-81–00.
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series Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
spelling doaj-art-2ec7dd3047d547c88affe501b2eb6f7e2025-02-02T12:40:10ZengBMCScandinavian Journal of Trauma, Resuscitation and Emergency Medicine1757-72412025-01-0133111110.1186/s13049-025-01331-4Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trialAne M. Helland0Sigurd Mydske1Jörg Assmus2Guttorm Brattebø3Øystein Wiggen4Haakon K. Kvidaland5Øyvind Thomassen6Department of Clinical Medicine, University of BergenDepartment of Clinical Medicine, University of BergenMountain Medicine Research Group, The Norwegian Air Ambulance FoundationDepartment of Clinical Medicine, University of BergenMountain Medicine Research Group, The Norwegian Air Ambulance FoundationDepartment of Pediatrics, Haukeland University HospitalDepartment of Clinical Medicine, University of BergenAbstract Background Accidental hypothermia is associated with high morbidity and mortality. Research on treatment strategies for accidental hypothermia is complicated by the low incidence and heterogeneous patient population. We have developed a new method for clinical trials of experimental hypothermia, to enable further studies of active rewarming. If cold ambient air is effective as a cooling method, this would mimic the most frequent clinical setting of hypothermic patients and provide a feasible cooling method for field studies. We aimed to induce mild hypothermia in healthy volunteers by exposure to cold ambient air, and tested the hypothesis that drug-induced suppression of endogenous thermoregulation would be required. Methods In a randomized, double-blind, crossover design, 15 healthy volunteers wearing wet clothes were put in a windy climate chamber set to 5 °C. Each participant completed the experimental procedure twice, once receiving active drugs (meperidine and buspirone) and once receiving placebo. The experiments were separated by a one-week wash-out period. Primary outcome was core temperature at termination, defined as 3 h of exposure or 35 °C. The between-groups difference was assessed using analysis of covariance (ANCOVA) with left censoring (Tobit model) and individual random intercept. Secondary outcomes were trajectory of core temperature and reduction of shivering. Results At termination, the active drug vs placebo group differed in temperature by 1.4 °C. With adjustment for the removal of participants reaching 35 °C, the estimated mean difference was 1.7 °C (1.4–2.0, p < 0.001). Shivering was effectively reduced, but not completely inhibited by the drug regimen, and core temperature declined at a rate of − 0.82 °C per hour. Conclusion The novel protocol utilizing cold air as a cooling method and drug-induced suppression of endogenous thermoregulation, is effective and enables future research projects. We have provided suggestions for minor alterations. Trial registration: EudraCT ID 2023–506020-81–00.https://doi.org/10.1186/s13049-025-01331-4Accidental hypothermiaThermoregulationShiveringProtocolPrehospitalEmergency medicine
spellingShingle Ane M. Helland
Sigurd Mydske
Jörg Assmus
Guttorm Brattebø
Øystein Wiggen
Haakon K. Kvidaland
Øyvind Thomassen
Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trial
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine
Accidental hypothermia
Thermoregulation
Shivering
Protocol
Prehospital
Emergency medicine
title Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trial
title_full Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trial
title_fullStr Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trial
title_full_unstemmed Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trial
title_short Experimental hypothermia by cold air: a randomized, double-blind, placebo-controlled crossover trial
title_sort experimental hypothermia by cold air a randomized double blind placebo controlled crossover trial
topic Accidental hypothermia
Thermoregulation
Shivering
Protocol
Prehospital
Emergency medicine
url https://doi.org/10.1186/s13049-025-01331-4
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