Comparison Between the European and North American Protocols for Diagnosis of Malignant Hyperthermia Susceptibility in Humans

Abstract

We compared the two major protocols for investigating malignant hyperthermia susceptibility. There was 87% accordance in diagnostic outcome. The diverging outcomes were seen in individuals with less reproducible test results near the cutoff limits. In scientific studies, such results should be considered as unknown.

Suspected Malignant Hyperthermia Reactions in New Zealand

“…The MHE category represents a "grey" area under permanent review and some MHE diagnoses most likely are normal variants 38 . This group contains both true positive and true negative results 39 of replacing IVCT with a DNA-based test for susceptibility to MH, DNA and RNA samples from families with MHS members have been used for genetic screening. As a causative factor in MH, the ryanodine receptor gene (RYR1) has been the most widely studied and to date 15 mutations in the RYR1 gene which result in altered amino acid residues in the skeletal muscle ryanodine receptor have been shown to be causative of MH 41,42 .…”

Confirmation of Nonanesthetic-induced Malignant Hyperthermia

“…They observed diverging outcomes in subjects with less reproducible test results near the cutoff limits of their respective protocols. 6 Because case 1's results markedly exceeded North American diagnostic thresholds by an order of magnitude in five of five tested muscle strips to both halothane and caffeine exposures, we contend that this patient should be designated by both North Americans and Europeans to be MH susceptible and not equivocal and thus, a suitable genetic research subject.…”

In Reply

“…These confounding factors may be responsible for a lack of difference in the amount of postoperative opioid consumption between the controls and the threemethadone groups. 2 A randomized prospective pediatric study 3 and another study on posterior spinal fusion surgery patients 4 found a beneficial effect of methadone administration on postoperative opioid consumption and pain scores. This observational study may not have the power and design to look at the clinical effects of methadone in the postoperative period.…”

“…The most important differences are bolus versus incremental halothane exposure and the European designation of an equivocal research diagnostic category for subjects demonstrating positive contracture responses only to halothane or only to caffeine exposures. 3,5 Islander and Twetman have studied the concordance of the North American and European biopsy protocols. Although Islander and Twetman's excellent study found an accordance in diagnostic outcome between the European and North American protocols of 87%, they noted a 100% accordance for individuals with contractures exceeding thresholds in at least five of six tested muscle strips.…”

“…However, Islander and Twetman differentiate between inclusion and exclusion of the MH equivocal results. 3 Simply put, 9 of 74 MH-susceptible results according to the North American protocol using 3% halothane were MH equivocal according to the European protocol using 2% halothane as trigger; that is 12%. Therefore, the in vitro contracture test of the boy could very well be considered MH equivocal by European standards.…”