Update on Dantrolene in the Treatment of Anesthetic Induced Malignant Hyperthermia

Abstract

Adverse Metabolic/Muscular Reaction to Anesthesia Reports (AMRAs) received after January 1, 2007 and before December 31, 2013 in the North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States were examined with the goal of describing any changes in the administration of dantrolene, complications associated with dantrolene or with the Malignant Hyperthermia (MH) episode itself that might contribute to increased morbidity. Greater age of the patient, longer time from the beginning of the anesthetic to the first sign of MH and longer time from the first sign of MH to the administration of dantrolene were all found to be associated with increased risk of complications due to MH. There was no significant change in the side effect profile of dantrolene from the previous report of AMRAs prior to 2007. Patients in whom Pulmonary Edema (PE) was reported received about twice as much intravenous fluid during the initial treatment of MH than did those in whom PE was not reported. than it had been previously [2]. Using reports of MH cases Adverse Metabolic/Muscular Reaction to Anesthesia reports (AMRAs) voluntarily submitted to the North American Malignant Hyperthermia Registry (NAMHR) Visoiu et al. observed that time to the first sign of MH differed between anesthetic agents. Anesthetics utilizing halothane and succinylcholine produced the first sign of MH the fastest. In the presence of isoflurane or desflurane the first sign of MH more often occurred in the second or third hour of the anesthetic [2]. However, the MH deaths known to the NAMHR after 2006 suggest that the death rate from MH due to anesthetic exposure has increased [10]. Therefore, AMRAs reporting anesthetic induced MH occurring after January 1, 2007 and before December 31, 2013, were examined. The goal of this review is to describe the complications that were reported as a result of the MH episode and to examine the hypothesis that the time to administration of dantrolene after the first sign of MH and other details of the administration of dantrolene are associated with increased morbidity following anesthetic induced MH episodes. Complications associated with the administration of dantrolene were described in a review of AMRAs reporting MH events between 1987 and 2006 [9]. A secondary purpose of the present review is to determine if the complications associated with administration of dantrolene have changed in recent years. Methods The University of Pittsburgh IRB judged this study exempt, #PRO14040208. In the NAMHR 152 AMRAs reported signs of MH in events that occurred in the US or Canada between January 1, 2007 and December 31, 2013, with at least one anesthetic drug and dantrolene given at some point during the event (Figure 1). Patient outcomes after the MH episode were documented in the AMRA reports as checkboxes. These complications included: cardiac dysfunction, change in consciousness level and/or coma, disseminated intravascular coagulation, hepatic dysfunction, pulmonary edema, and renal dysfunction. Patient survival was documented as a separate checkbox option. For this study, serious complications associated with the MH episode were