Administration of Ondansetron Is Associated With Lethal Outcome

Abstract

We report here the case of a child with a known muscular abnormality and susceptibility to malignant hyperthermia who abruptly died after receiving a therapeutic dose of ondansetron. Also, we discuss the pharmacodynamic relationship of ondansetron to malignant hyperthermia in a susceptible host.

RYR1-related rhabdomyolysis: A common but probably underdiagnosed manifestation of skeletal muscle ryanodine receptor dysfunction

“…Family counselling is vital to identify potentially MH-susceptible relatives [1] We performed a systematic literature review (including the patients in the studies mentioned above), based on a Pubmed search with "RYR1" and "rhabdomyolysis". This resulted in identification of several case report and small series [1,8,[21][22][23][24][25][26], and two review article [27,28] Subsequently, we also included cases from references of these articles [20,26,[29][30][31][32][33][34] and added our recent letter by Snoeck et al [35]. Finally, we added two patients from our paper on the spectrum of RYR1 related myopathies by Snoeck et al who were not included in any other publication (patients 14 and 52 [1]).…”

“…physical exercise and hot ambient temperatures, or viral infection or exercise and medication. Gener et al reported the case of a child who had suffered a sevoflurane-triggered MH episode treated with dantrolene during an orchidopexy procedure (at the age of 3 years 5 months), a common operation during which MH episodes have been observed [32]. He died at the age of 5 and a half years when he developed muscle rigidity and became hyperthermic and asystolic after receiving ondansetron because of vomiting and abdominal pain [32].…”

“…Gener et al reported the case of a child who had suffered a sevoflurane-triggered MH episode treated with dantrolene during an orchidopexy procedure (at the age of 3 years 5 months), a common operation during which MH episodes have been observed [32]. He died at the age of 5 and a half years when he developed muscle rigidity and became hyperthermic and asystolic after receiving ondansetron because of vomiting and abdominal pain [32]. A recent case published by Russell et al illustrates a similar point: a 20-year-old woman who developed RM, disseminated intravascular coagulopathy and multi-organ failure induced by MDMA.…”

“…The children reported by Gener and Lavezzi also had a fatal outcome of their heat illness. [32,33] This clinical overlap has implications for some MHsusceptible patients and their capacity to exercise, as well as for clinicians treating and anesthetizing patients with histories of unexplained exertional heat and exercise illnesses [25]. [15,25,37] Exertional heat illness, ERM, and MH have similar pathophysiology: all three are hypermetabolic states that include high demand for adenosine triphosphate, accelerated oxidative, chemical, and mechanical stress of muscle, and uncontrolled increase in intracellular calcium.…”

Fatal Cardiac Arrest in 2 Children

“…Rarely, even deaths have been reported in adults and children. [3][4][5] Here, we report 2 cases of refractory cardiac arrest and death after administration of ondansetron in pediatric patients.…”