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Overlapping Mechanisms of Exertional Heat Stroke and Malignant Hyperthermia: Evidence vs. Conjecture

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A Letter to the Editor to this article was published on 09 October 2021

A Letter to the Editor to this article was published on 09 October 2021

Abstract

Exertional heat stroke (EHS) and malignant hyperthermia (MH) are life-threatening conditions, triggered by different environmental stimuli that share several clinical symptoms and pathophysiological features. EHS manifests during physical activity normally, but not always, in hot and humid environments. MH manifests during exposure to haloalkane anesthetics or succinylcholine, which leads to a rapid, unregulated release of calcium (Ca2+) within the skeletal muscles inducing a positive-feedback loop within the excitation–contraction coupling mechanism that culminates in heat stroke-like symptoms, if not rapidly recognized and treated. Rare cases of awake MH, independent of anesthesia exposure, occur during exercise and heat stress. It has been suggested that EHS and MH are mediated by similar mechanisms, including mutations in Ca2+ regulatory channels within the skeletal muscle. Rapid cooling, which is the most effective treatment for EHS, is ineffective as an MH treatment; rather, a ryanodine receptor antagonist drug, dantrolene sodium (DS), is administered to the victim to prevent further muscle contractions and hyperthermia. Whether DS can be an effective treatment for EHS victims remains uncertain. In the last decade, multiple reports have suggested a number of mechanistic links between EHS and MH. Here, we discuss aspects related to the pathophysiology, incidence, diagnosis and treatment. Furthermore, we present evidence regarding potential overlapping mechanisms between EHS and MH and explore current knowledge to establish what is supported by evidence or a lack thereof (i.e. conjecture).

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Acknowledgements

We thank Mr. Lucas de Carvalho for technical contributions with the illustration.

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The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Army or the Department of Defense. Any citations of commercial organizations and trade names in this report do not constitute an official Department of the Army endorsement of approval of the products or services of these organizations.

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  1. Department of Applied Physiology and Kinesiology, College of Health and Human Performance, University of Florida, 1864 Stadium Road, Room 100, Gainesville, FL, USA

    Orlando Laitano & Kevin O. Murray

  2. Thermal and Mountain Medicine Division, US Army Research Institute for Environmental Medicine, Natick, MA, USA

    Lisa R. Leon

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Correspondence to Orlando Laitano.

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Orlando Laitano (OL), Kevin O. Murray (KOM) and Lisa R. Leon (LRL) declare that they have no conflicts of interest relevant to the content of this review.

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OL and LRL outlined and wrote the first draft of the manuscript. KOM analyzed, interpreted the literature and wrote the section on IVCT. OL, KOM and LRL revised the original manuscript. All authors read and approved the final version of the manuscript.

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Laitano, O., Murray, K.O. & Leon, L.R. Overlapping Mechanisms of Exertional Heat Stroke and Malignant Hyperthermia: Evidence vs. Conjecture. Sports Med 50, 1581–1592 (2020). https://doi.org/10.1007/s40279-020-01318-4

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