Among nonanesthesiologists, there is a lack of familiarity with dantrolene and its uses and indications. (Image source: Thinkstock)

Among nonanesthesiologists, there is a lack of familiarity with dantrolene and its uses and indications. (Image source: Thinkstock)

Most anesthesiologists realize that rhabdomyolysis is an expected consequence of malignant hyperthermia.  In addition to treating the malignant hyperthermia event with dantrolene, rhabdomyolysis must also be treated to avoid such complications as renal failure.  In susceptible individuals malignant hyperthermia can be triggered by volatile anesthetics and succinylcholine. What is less appreciated is that in  susceptible individuals exposure to heat and exercise can also trigger malignant hyperthermia.  Many physicians, particularly nonanesthesiologists, do not realize that anesthetics are not required to trigger the syndrome.  Dr. John F. Capacchione, Department of Anesthesiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, and colleagues describe this conundrum in their article published in a recent issue of A & A Case Reports titled “Improving Awareness of Nonanesthesia-Related Malignant Hyperthermia Presentations: A Tale of Two Brothers.”

The case involves a 30-year-old twin who presented to an emergency department (ED) with chest pain after working outside on a hot summer day, whereupon rhabdomyolysis was diagnosed.  The patient was treated with intravenous hydration, discharged home, but it was not until two months after the event that his creatine kinase decreased from 3900 U/L (normal < 200 U/L) to 1000 U/L.  The workup for common genetic causes of myopathies was negative.  Ultimately, a muscle biopsy was performed and the caffeine halothane contracture test was positive for malignant hyperthermia.  The RYR1 gene was positive for an Arg2454Cys mutation, which has been shown to cause MH. Two months later, the brother’s twin was found to have the same mutation while undergoing testing for upcoming surgery.  He reported two episodes of cardiac arrest as a child while undergoing surgery for ptosis.  Also, CK values during two unexplained episodes of exertional rhabdomyolysis were both > 18,000 U/L.  The twins’ mother also had the same RYR1 mutation.  Each brother was prescribed dantrolene for muscle cramping and fatigue, which decreased their symptoms.

The brothers both moved to another state, where their primary care physician was unfamiliar with the malignant hyperthermia susceptibility and stopped treatment with dantrolene. Their symptoms subsequently recurred.  The second twin reported to an ED with incapacitating muscle pain without exercise, was ultimately admitted to the hospital, and by day 2 of his hospital stay, his CK had increased to 10,000 U/L.  When the patient told the hospitalist about his mutation, the Malignant Hyperthermia Association of the United States (MHAUS) and a MH testing center director were independently contacted. Both advised ICU admission and treatment with dantrolene.  Neither the anesthesiologist nor the pharmacist was aware that MH symptomatology, e.g., rhabdomyolysis, could occur in an awake patient.  The patient was transferred to larger city hospital, though neither the MHAUS hotline consultant nor the director of the MH testing center was informed of this transfer, and the receiving physician did not immediately contact them for advice.  After 2 days, the hospitalist contacted the MH testing center director for advice, dantrolene therapy was advised, but again, it was not administered.  Two weeks later, the second twin returned to the ED with muscle pain that had not resolved.  His CK was 3500 U/L.  A different hospitalist contacted the MH testing center director and followed the recommendation of ICU admission with dantrolene therapy, whereupon the patient’s pain decreased and his CK decreased to 900 U/L after 1 dosage of dantrolene and 1 day in the ICU.

Many individuals have the RYR1 mutation, and the number of MH susceptible patients based on RYR1 mutations may be much greater than develop MH during anesthesia. The presentation of these individuals may be muscle pain during heat or exercise.   As aptly stated by Dr. Henry Rosenberg, Department of Medical Education and Clinical Research, Saint Barnabas Medical Center, Livingston, New Jersey, in his Editorial Comment: Improving Awareness of Nonanesthesia-Related Malignant Hyperthermia Presentations: A Tale of Two Brothers, “among nonanesthesiologists, there is a lack of familiarity with dantrolene and its uses and indications,” and “the understanding of the role of molecular genetics in relation to diagnosis of many disorders, drug action, and cell function needs to be included in the education of anesthesiologists and other anesthesia providers.”