Remembering the Classics: MH
Henry Rosenberg MD
Before his untimely death, Ron Litman was very involved with the Malignant Hyperthermia Association of the United States (MHAUS). When he started the PAAD, there was a weekly or biweekly MH article that he reviewed or he recounted his many experiences with the MH hotline. In his honor and memory, I (Myron Yaster) asked Dr. Henry Rosenberg, President Emeritus and cofounder of MHAUS, to pick a malignant hyperthermia themed paper for today’s PAAD.
Pawar S, Rosenberg H, Adamson R, LaRosa J, Chamberlain R. Dantrolene in the Treatment of Refractory Hyperthermic Conditions in Critical Care: A Multicenter Retrospective Study Open Journal of Anesthesiology Vol.05 No.04(2015) DOI: 10.4236/ojanes.2015.54013
The package insert for dantrolene, approved in 1979, clearly states that the drug is to be used for the treatment of malignant hyperthermia (MH) syndrome. However many calls to the MHAUS hotline seek advice on how to handle situations where MH is suspected but not proven. We examined the frequency of dantrolene use outside the operating room in the St. Barnabas Medical System and whether it would be effective in reducing high temperature due to causes other than MH. With IRB approval, temperature, muscle rigidity, creatine kinase levels, and mortality were assessed in association with dantrolene use outside of the operating room. At the time of the study, the first author, Dr. Pawar, was a first year resident in general surgery at Saint Barnabas Medical Center. She subsequently completed training in Anesthesiology at Temple University Hospital in Philadelphia and a fellowship in Cardiac Anesthesia.
With the help of the data from Saint Barnabas’ Pharmacy, we were able to identify patients receiving intravenous dantrolene sodium who were found to have a diagnosis of neuroleptic malignant syndrome (NMS)(36%), sepsis (32%), sepsis and NMS (16%), malignant hyperthermia (8%), cocaine toxicity (4%), and diabetic ketoacidosis (8%). Not unexpectedly only two patients showed signs of MH in the ICU, the others related to sepsis, NMS, and a variety of other diagnoses. Dantrolene was effective in reducing rigidity, temperature, and lowering Creatinine kinase levels in 9 out of 9 NMS cases, 2 out 2 MH cases, 1 out of 1 cocaine toxicity case, 3 out of 8 sepsis cases, and 2 out 3 cases with NMS/sepsis diagnosis. Dantrolene was found to be partially effective in 3 out of 8 sepsis and 1 out of 3 NMS/sepsis case. The drug was ineffective in 2 out of 8 sepsis cases. Overall 8 among the 25 cases treated with dantrolene died.
Dantrolene continues to be used for treatment of elevated body temperature outside the operating room for a variety of indications. We learned that a positive response to dantrolene in the critical care unit is not necessarily indicative that the causative diagnosis was malignant hyperthermia but the drug is useful in the treatment of hyperthermia. Dantrolene reduces intracellular calcium levels by inhibiting calcium release from the SR. Elevated intracellular calcium levels may lead to increased muscle tone and hyperthermia, signs that are common in MH and a variety of other disorders such as NMS. Dantrolene is a relatively clean drug that is free of significant toxicity.
The study was done prior to the current understanding of the genetics of MH so the patients were not tested for genetic changes typical for MH. Other studies now employ genetic characterization to determine the likelihood that a specific patient might be MH susceptible. (See: Biesecker LB, Dirksen R, Girard T, Hopkins P,Riazi S, Rosenberg H, Stowell K, weber J, Genomic Screening for Malignant Hyperthermia Susceptibility .Anesthesiology.2020,133(6):1277–1282)
Henry Rosenberg MD
PS: After completing my Pediatric residency and starting my Anesthesia residency at UPenn, Henry was one of the first attending anesthesiologists I worked with. I was incredibly fortunate to have him as a teacher and role model. We’ve kept in contact, usually at ASA meetings, over the following 40 years! MY