"Far Reaching New Information Concerning the Diagnosis and Management of MH and Exertional Heat Stroke"

by Dr. Henry Rosenberg MD, CPE

Thursday, March 20, 2014

The views expressed in this posting are mine alone and do not necessarily represent the views of other professionals or Board Members of MHAUS.

A 'NEW' DANTROLENE?

In 1979 dantrolene was approved by the FDA for the treatment of Malignant Hyperthermia. Dantrium (dantrolene)  was developed by a small company  located in upstate New York called Norwich Eaton Pharmaceuticals.  Procter & Gamble Company (yes, the soap, detergent and household product company) acquired Norwich Eaton prior to the approval of the drug by the FDA. A major effort led by Mary Elizabeth Kolb, spearheaded the effort resulting in approval of the drug in record time.   Dantrolene  was instantly embraced by the anesthesia community as it was the only drug that was effective in treating and reversing MH. Many hundreds, if not thousands, of lives have been saved thanks to dantrolene.

EXERTIONAL HEAT STROKE AND MALIGNANT HYPERTHERMIA

I and others have often written about the possible relationship between exertional heat stroke (EHS) and MH.  There are isolated reports in the literature and presentations at meetings, (which often do not get published) demonstrating that some patients who develop exertional heat stroke harbor genetic changes that are found in MH susceptibles.  However, it has been difficult to identify  a significant number of patients who developed EHS and then were tested for MH susceptibility either by genetic tests or by the standard caffeine halothane contracture test.  A very recent publication in the journal Military Medicine by a group of French investigators associated with the French army who have been studying the problem of MH and heat stroke for several years, demonstrate that 138 of 295 patients (47%) who suffered heat stroke were determined to be MH susceptible, based on the European version of the caffeine halothane contracture test which has been shown to be both highly sensitive and specific in diagnosing MH susceptibility (Sagui et al. Military Medicine 179;342, 2014). Unfortunately, they did not report on the molecular genetics of these patients.  In addition, the muscle that was harvested for testing was not from the thigh, which is the agreed-upon standard site. However, several MH testing centers in Europe and the US have demonstrated, with a lesser number of patients, that  many who experienced  heat stroke also harbor MH related mutations in the ryanodine receptor gene.