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.