Fit for Duty: Malignant Hyperthermia Susceptibility

Research Paper Title

Malignant Hyperthermia Susceptibility and Fitness for Duty.


Malignant hyperthermia (MH) is an inherited hypermetabolic condition characterised by uncontrolled calcium release from the sarcoplasmic reticulum of skeletal muscle, usually from exposure to inhaled general anesthetics and/or the depolarising neuromuscular blocking agent succinylcholine. Multiple case reports now reveal that crises may be precipitated by environmental factors such as exercise or high ambient temperatures. Common signs of an MH crisis include life-threatening hyperthermia, metabolic acidosis, muscle rigidity, and tachycardia. Treatment consists of stopping triggering agents, administering dantrolene, and actively cooling the patient. MH is a medically disqualifying condition for service in the US Armed Forces. However, patients with MH-causative mutations may never have experienced an MH episode. If they previously have had an event concerning for MH, details are often sparse and a formal evaluation is absent.


The researchers present 2 case reports with military service implications, one as a formal applicant to the service academies and the other as the father of an active duty Navy chief. Both patients experienced prior MH-like reactions to anesthesia but had not undergone testing with a caffeine-halothane contracture test (CHCT) or genetic analysis. Both patients underwent skeletal muscle biopsies of the left vastus lateralis with nontriggering anesthetics at Children’s National Medical Center in Washington, DC, and MH diagnostic CHCT at the Uniformed Services University of the Health Sciences (USUHS) in Bethesda, Maryland. The CHCT was performed according to the North American MH Registry Protocol. With USUHS Institutional Review Board approval, ryanodine receptor type 1 gene (RYR1) and L-type calcium channel α-1 subunit gene (CACNA1S) sequencing was performed on the remaining muscle at USUHS.


Each subject was CHCT positive, confirming a diagnosis of MH. One was found to have a known MH-causative gene mutation. The applicant to the service academy was therefore determined unfit for military service. The active duty son of the MH-positive patient underwent muscle biopsy and CHCT in order to continue his military career.


A personal or familial history concerning for MH raises important questions on fitness for duty in the U.S. Armed Forces. Department of Defense regulation uniformly defines MH as a disqualifying condition; however, screening for a history of anesthetic complications during accession into the military is inconsistent.

Medical standards across the services are also variable in the context of a familial history of MH. These case reports highlight the need for clinicians to seek expert consultation about how to proceed with MH-related issues. They also stress the importance of applying current understanding of heritable conditions to our fitness for duty determinations.

Further investigation is also recommended to establish an MH-susceptible individual’s propensity for exercise or heat-related injury outside the operating room. Department of Defense policy may thereafter be updated to reflect a quantitative assessment of MH’s relative risk during inherently strenuous military operations.


Lee, M.A., McGlinch, E.B., McGlinch, M,C. & Capacchione, J.F. (2017) Malignant Hyperthermia Susceptibility and Fitness for Duty. Military Medicine. 182(3):e1854-e1857. doi: 10.7205/MILMED-D-16-00186.


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