Rapid Dantrolene Administration with Body Temperature Monitoring Is Associated with Decreased Mortality in Japanese Malignant Hyperthermia Events

Abstract

Purpose. Malignant hyperthermia (MH) is a rare genetic disorder but one of the most severe complications of general anesthesia. The mortality rate of MH has dropped from 70% in the 1960s to 15% because of dantrolene, the only currently accepted specific treatment for MH. In this study, we retrospectively identified the optimal dantrolene administration conditions to reduce MH mortality further. Methods. Our database performed a retrospective analysis of patients with MH clinical grading scale (CGS) grade 5 (very likely) or 6 (almost certain) between 1995 and 2020. We examined whether dantrolene administration affected mortality and compared the clinical variables associated with improved prognosis. Furthermore, a multivariable logistic regression analysis was used to identify specific variables associated with improved prognosis. Results. 128 patients met the inclusion criteria. 115 patients were administered dantrolene; 104 survived, and 11 died. The mortality rate of patients who were not administered dantrolene was 30.8%, which was significantly higher than those of patients who were administered dantrolene ( P = 0.047 ). Among patients administered dantrolene, the interval from the first sign of MH to the start of dantrolene administration was significantly longer in the deceased than in the survivors (100 min vs. 45.0 min, P < 0.001 ), and the temperature at the start of dantrolene administration was also significantly higher in the deceased (41.6°C vs. 39.1°C, P < 0.001 ). There was no significant difference in the rate of increase in temperature between the two, but there was a substantial difference in the maximum temperature ( P < 0.001 ). The multivariable analysis also showed that the patient’s temperature at dantrolene administration and interval from the first MH sign to dantrolene administration was significantly associated with improved prognosis. Conclusions. Dantrolene should be given as rapidly as possible once MH has been diagnosed. Beginning treatment at a more normal body temperature can prevent critical elevations associated with a worse prognosis.

Real Evidence and Misconceptions about Malignant Hyperthermia in Children: A Narrative Review

“…A significant drawback of dantrolene sodium is related to its classical pharmaceutical formulation: Dantrium/Revonto/dantrolene sodium 20 mg of lyophilized orange powder needs to be diluted in 60 mL of sterile water (the drug will not completely dissolve in crystalloid-containing solutions) with a filter, leading to a final concentration of 0.32 mg/mL and a preparation time of about 3 min per vial. The water for diluting dantrolene should not be stored in a refrigerator; it may be stored in a warming cabinet designed to maintain fluid temperatures between 35 °C and 40 °C [ 82 ]. The number of vials varies widely according to the patient’s weight: while for a 10 kg infant, a single vial can provide the correct amount for the first bolus in 3 min, for a 50 kg pediatric patient, five vials and potentially 15 min are needed for the initial bolus to be administered.…”

Effects of Remimazolam on Intracellular Calcium Dynamics in Myotubes Derived from Patients with Malignant Hyperthermia and Functional Analysis of Type 1 Ryanodine Receptor Gene Variants

“…However, MH can still be a fatal complication as there is a possibility of death even when dantrolene is used at the time of onset [3,4]. Early administration of dantrolene is essential in the management of MH, and it is also important to avoid exposure in provoking anesthetics in patients predisposed to MH [5]. Thus, it is important to detect carriers with a genetic predisposition to MH prior to anesthesia, and to use anesthetics that do not induce MH in this population [6].…”