Copyright @ 200 by the American College of Sports Medicine. Unauthorized reproduction of this article is prohibited. 8 Exertional Heat Illness, Exertional Rhabdomyolysis, and Malignant Hyperthermia: Is There a Link? Sheila Muldoon, 1,2 Patricia Deuster, 3 Maria Voelkel, 1 John Capacchione, 1 and Rolf Bunger 4 1 Department of Anesthesiology, 2 Malignant Hyperthermia Biopsy Center, 3 Department of Military and Emergency Medicine, and 4 Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD MULDOON, S., P. DEUSTER, M. VOELKEL, J. CAPACCHIONE, and R. BUNGER. Exertional heat illness, exertional rhabdomyolysis, and malignant hyperthermia: Is there a link? Curr. Sports Med. Rep. Vol. 7, No. 2, pp. 74Y80, 2008. This short review discusses possible links between exertional heat illness (EHI), malignant hyperthermia (MH), and exertional rhabdomyolysis (ER). Evidence on clinical, genetic, and functional aspects, though limited, is compared through individual case reports and a small number of clinical studies. Typically, MH occurs during anesthesia and surgery, EHI during strenuous exercise in hot and humid environments, and ER unrelated to heat and humidity after strenuous exercise. Genetic analysis of the RYR1 gene has identified various mutations, especially in MH, but also in some cases of EHI and in number of ER cases as well. Pathophysiologically, loss of intracellular calcium control appears to be a common feature. Recommendations for treatment and recovery include cooling and administration of dantrolene for MH, cooling and aggressive fluid administration for EHI, and physical rest and aggressive intravenous fluid administration for ER. INTRODUCTION Previously, malignant hyperthermia (MH), exertional heat illness (EHI), and exertional rhabdomyolysis (ER) have been considered related syndromes. However, the current literature regarding this relationship is not exten- sive. Hopkins stated in a recent article, ‘‘there is a link between MH and exertional heat illness,’’ but the nature of this link and the relationship between these events was not enumerated (1). To provide a comprehensive discussion, this review will include publications over a broad period of time to address several questions: 1) Can EHI and ER be pathophysiologically (i.e., mechanistically) linked to MH? Conversely, can MH be mechanistically linked to EHI and ER? 2) What are the appropriate functional and genetic tests to differentiate between MH, EHI, and ER? And 3) When should individuals who suffer from MH, EHI, or ER resume strenuous physical activity? THE CLINICAL ENTITIES Malignant Hyperthermia MH is an uncommon, autosomal, dominantly inherited disorder of calcium handling in skeletal muscle, mainly caused by mutations in the gene coding for the type one ryanodine receptor (RyR1). RyR1 functions as a calcium ion channel in the sarcoplasmic reticulum (SR) membrane regulating the release of calcium from the SR. Until challenged by ‘‘triggering’’ inhalational anesthetics and/or succinylcholine, patients with MH, many of whom are physically fit, are asymptomatic. Triggering anesthetics can cause a life-threatening, fulminant episode of MH. Such episodes are characterized by hypermetabolism with variable signs and symptoms including tachycardia, hypercarbia, metabolic acidosis, generalized or localized muscle rigidity, rhabdomyolysis, hyperthermia, and if untreated, death. Dantrolene, a compound that blocks release of calcium from the SR via the RyR1, can provide effective treatment of such episodes. Without treatment, mortality from ‘‘fulminant’’ 74 CHEST CONDITIONS Address for correspondence: Sheila Muldoon, M.D., Department of Anesthesiology, Director of Malignant Hyperthermia Biopsy Center, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814 (E-mail: smuldoon@usuhs.mil). 1537-890X/0702/74Y80 Current Sports Medicine Reports Copyright * 2008 by the American College of Sports Medicine