Malignant Hyperthermia: Rising Cases in Medical Literature

Malignant hyperthermia is a rare but life-threatening disorder triggered by specific anesthetic agents. It causes a rapid rise in body temperature and severe muscle contractions, which can lead to serious complications or death if not treated promptly. Although it can affect any patient during the perioperative period, children are particularly vulnerable, with a five-fold higher incidence compared to adults.

Recently, the DrugCard platform has discovered several cases of malignant hyperthermia in the medical literature. This raises the question: could the “unknown” frequency mentioned in SmPCs be more common than previously thought?

The History and Incidence of Malignant Hyperthermia

Since the early 20th century, reports have linked increased body temperature during general anesthesia (GA) to complications and deaths often described as “ether convulsions.” 1962, a notable case involved a 21-year-old student who was admitted to the Royal Melbourne Hospital in Australia for a leg fracture. The student was more concerned about receiving GA than his fracture because ten of his family members had died during or after GA, typically administered for minor procedures. This case highlighted the familial nature of the condition.

The exact incidence of malignant hyperthermia is unknown. Studies demonstrate that malignant hyperthermia occurs in about 1 in 100,000 adults and 1 in 30,000 in children. The incidence of malignant hyperthermia varies based on geographic region.

Risk Factors and Genetic Basis of Malignant Hyperthermia

The most well-known risk factor for malignant hyperthermia is the use of volatile anesthetic agents, such as halothane, isoflurane, sevoflurane, desflurane, and the depolarizing skeletal muscle relaxant succinylcholine. Halothane-induced MH seems to cause most MH crises; however, sevoflurane has the highest prevalence of MH among all volatile anesthetics. MH is primarily caused by a genetic mutation in the RYR1 gene, which encodes the ryanodine receptor, a critical component of skeletal muscle calcium release. When susceptible individuals are exposed to triggering agents like volatile anesthetics or depolarizing muscle relaxants, abnormal calcium release occurs, leading to sustained muscle contraction and hypermetabolism.

Case Studies and Lessons Learned

Analyzing case studies of MH incidents can provide valuable insights into best practices and areas for improvement in pharmacovigilance. Below are a few cases recently identified by the DrugCard platform during literature monitoring.

First Reported Case of Malignant Hyperthermia Following Electroconvulsive Therapy (ECT)

Recently, the DrugCard platform uncovered the first case of potentially deadly malignant hyperthermia following electroconvulsive therapy (ECT). Despite the frequent use of succinylcholine with ECT, no previous cases of potentially lethal MH have been reported.

The case involves a 79-year-old woman with severe depression who experienced MH after succinylcholine administration during an ECT session. She developed a high fever of 40.2°C, tachycardia, hypertension, significant muscle rigidity, and impaired consciousness. These symptoms appeared two hours after ECT, which was conducted in a psychiatric ward rather than an operating room and peaked within 24 hours.

She received 60 mg of dantrolene, which quickly reduced her muscle rigidity. She then received two additional doses of 20 mg and 60 mg of dantrolene, which lowered her fever to 36.2°C and completely relieved her muscle rigidity within two days.

Key Point: Monitoring and Management of Malignant Hyperthermia Following ECT

What does finding this case in the medical literature mean for us? Since malignant hyperthermia following ECT can be deadly, psychiatrists need to carefully monitor vital signs and physical symptoms both during and after the procedure. Early detection and prompt treatment with dantrolene are crucial for managing this condition.

Case Report: Malignant Hyperthermia in a 13-Year-Old Following Laparoscopic Appendectomy

In another case report, a 13-year-old undergoing a laparoscopic appendectomy developed malignant hyperthermia (MH) after using inhalational anesthetics. The patient’s temperature soared to an alarming 44.2°C, accompanied by muscle rigidity, tachycardia, hypercapnia, malignant arrhythmias, cardiogenic shock, hyperkalemia, and metabolic and respiratory acidosis. Early recognition, multidisciplinary management, and the administration of dantrolene led to a successful treatment. Exome sequencing revealed a point mutation (amino acid change) in the RYR1 gene: c.12700G>C(p.Val4234Leu).

Key Point: Genetic Basis of Malignant Hyperthermia and Inheritance Risk

In this case, genetic testing revealed the mutation responsible for the patient’s malignant hyperthermia. Studies show that most cases of (MH) are due to abnormalities in the ryanodine receptor type 1 gene (RYR1). A mutation in this gene causes excessive calcium release in muscle cells when exposed to triggers like inhalation anesthetics, leading to continuous muscle contractions. MH is an autosomal dominant disorder, meaning children of MH patients have a 50% chance of inheriting the condition.

Case Report: Successful Management of Malignant Hyperthermia Without Dantrolene

Managing malignant hyperthermia typically involves stopping the trigger agent, providing symptomatic treatment, and administering dantrolene. However, another case found by the DrugCard platform describes a case of MH successfully treated without dantrolene. An 8-year-old boy developed classic MH symptoms after general anesthesia with isoflurane. The team stopped isoflurane, gave acetaminophen, hyperventilated him with a new circuit, started propofol for maintenance, and cooled him with ice packs, cold Ringer’s lactate, and cold saline irrigation. Active cooling was stopped once his temperature dropped to 38°C. The patient improved over three days in the ICU, was transferred to the postoperative ward, and later discharged. His family was briefed and counselled about the incident and condition.

Key Point: Importance of Timely Diagnosis and Management of Malignant Hyperthermia

Malignant hyperthermia can be fatal if not treated quickly and correctly, making accurate diagnosis and prompt treatment crucial. Operating room staff must understand the seriousness of MH and receive training in its diagnosis and management. Dantrolene is not available in many countries, as was the case here. Therefore, it’s important to advocate for better access to dantrolene and improved laboratory facilities to confirm diagnoses, ensuring better management of MH in the future.

Conclusion

Malignant hyperthermia is a rare but potentially deadly condition triggered by certain anesthetics, leading to a rapid rise in body temperature and severe muscle contractions. Children are particularly vulnerable, experiencing MH five times more often than adults. Recent cases identified by the DrugCard platform suggest that MH may be more common.

Key risk factors include using volatile anesthetics and specific genetic mutations in the RYR1 gene. Effective management typically involves prompt treatment with dantrolene. However, alternative methods like cooling and supportive care have proven successful in its absence.

To improve outcomes, healthcare providers must be vigilant, enhance access to dantrolene, and advance diagnostic capabilities. Early detection and swift intervention remain critical in managing this potentially fatal condition.