The efficacy of steroids in reducing morbidity and mortality from extreme hyperthermia and heatstroke—A systematic review

Abstract

Hyperthermia induces deleterious effects at the cellular, organ, and whole-body level, 1 and has a variety of causes, which include sepsis, classical and exertional heat illness, and drug-induced hyperthermia. While there is a survival benefit to a mild pyrexia in sepsis, 2,3 mortality increases as the core temperature (T CORE) exceeds 40°C, 2 suggesting that at higher temperatures, the deleterious effects on organ and cellular function outweigh any benefit conferred from pyrexia. In noninfective hyperthermia, however, a T CORE of 38.5°C or greater, is associated with a worse outcome. 3 Heatstroke represents the most severe form of heat illness with significant morbidity and mortality, including long-term multiorgan dysfunction and susceptibility to further heat illness. Exertional heatstroke (EHS) occurs in individuals undergoing strenuous physical activity, especially in hot and humid conditions, and is defined

Exercise hyperthermia induces greater changes in gastrointestinal permeability than equivalent passive hyperthermia

“…Future work should seek to quantify these responses against baseline/control L:R and data from a normothermic exercise trial, and investigate pharmacological and nutritional-or hydration-related interventions to mitigate against heat stress. Strategies to reduce GI permeability, endotoxemia, and/or organ dysfunction have shown promising results via prior-exercise glutamine ingestion (Pugh et al, 2017); mid-exercise carbohydrate and protein intake (Snipe et al, 2017), and in animals, the administration of steroid (Walter & Gibson, 2020a) and antibiotics (Walter & Gibson, 2020b) following the development of exertional heat stress. This work should extend to a heterogeneous cohort of participants likely to be exposed to passive heat or EHI across a spectrum of thermal and exercise stressors.…”

Heatstroke-induced coagulopathy: Biomarkers, mechanistic insights, and patient management

“…The survival benefit was most significant when steroid administration preceded heat stress. 69 As for antipyretics, there is no evidence supporting the use of nonsteroidal antiinflammatory drugs in heatstroke. 70 Neural injury is a significant issue in heatstroke, and mesenchymal stem cell transplantation has been reported to improve neurological function, and its efficacy and molecular mechanisms have been intensively investigated.…”

Drug-Induced Hyperthermia Review

“…Nonsteroidal anti-inflammatory drugs (NSAIDs), aspirin, and acetaminophen are ineffective and could exacerbate end-organ damage [ 46 , 67 , 69 ]. Dantrolene is not routinely effective, although small studies suggest benefits in combination with cooling [ 46 , 70 ]. Corticosteroids may reduce pro-inflammatory cytokines.…”

“…A recent meta-analysis of animal studies found that they reduced morbidity and mortality. However, applying this steroid data to humans remains controversial [ 70 ]. Older animal trials evaluated the efficacy of oral prophylactic antibiotics.…”

“…Kanamycin reduced endotoxemia and cardiac dysfunction without an overall reduction in mortality. Another study found a reduction in mortality with neomycin and tetracycline in combination with laxatives [ 70 ].…”