Malignant hyperthermia is a life-threatening reaction triggered by exposure to certain anesthetic agents, most commonly the volatile anesthetics sevoflurane and desflurane as well as the depolarizing muscle relaxant succinylcholine. In susceptible individuals, these drugs provoke an uncontrolled release of calcium ions from the sarcoplasmic reticulum, the intracellular storage compartment that normally regulates muscle contraction. The result is sustained, rigid contraction of skeletal muscle fibers, a massively accelerated metabolic rate, and a cascade of physiological derangements that can quickly become fatal. The cardinal signs include so-called lead pipe muscle rigidity, tachycardia, hyperthermia at or above 38.5 degrees Celsius, and a striking elevation of end-tidal carbon dioxide, the concentration of carbon dioxide measured in exhaled breath during mechanical ventilation. As the crisis progresses, muscle breakdown releases creatine kinase into the bloodstream, and patients may develop altered mental status, hypertension, and profuse sweating.

The patient in this case had been brought to the emergency department by ambulance after a rollover crash that left him with a right midshaft femur fracture, a right distal tibia and fibula fracture, and a right talar fracture. He had a remote history of childhood asthma treated with albuterol, no prior surgical history, and, crucially, no family history of adverse reactions to anesthesia. His preoperative examination documented a Mallampati class III airway, normal cardiovascular and pulmonary findings, and obesity, with functional capacity limited to less than four metabolic equivalents by his acute injuries. Nothing in his history flagged him as being at risk for malignant hyperthermia, which is precisely the point the authors emphasize: many susceptible individuals carry no warning signs until their first exposure to a triggering agent.

One day after his injury, the patient underwent open reduction and internal fixation of his fractures using a trochanteric femoral nail and an intramedullary rod for the tibia. Because he was a recent polytrauma patient with a presumed full stomach and elevated aspiration risk, the team used a rapid sequence induction strategy. He received midazolam, fentanyl, etomidate, esmolol, and succinylcholine, the latter chosen specifically to achieve rapid intubating conditions. Rocuronium was also administered for ongoing neuromuscular blockade, and sevoflurane maintained general anesthesia throughout the procedure. The operation began uneventfully, but approximately three hours after induction the surgical team noticed something alarming: the patient’s skin temperature had climbed to 39.4 degrees Celsius, or 103 degrees Fahrenheit, his end-tidal carbon dioxide had risen to 58.5 millimeters of mercury, and his heart rate was running between 120 and 130 beats per minute.

The anesthesiology team recognized an impending malignant hyperthermia crisis and immediately activated the standard protocol. Sevoflurane was discontinued, and the anesthetic was switched to total intravenous anesthesia using a propofol infusion. The patient received 100 percent oxygen, external cooling measures including ice packs, and intravenous acetaminophen. Most critically, he was given 260 milligrams of intravenous dantrolene, corresponding to approximately 2.3 milligrams per kilogram based on his perioperative weight of 113 kilograms. Within 15 minutes of the initial dantrolene bolus, the patient’s temperature began to fall and his end-tidal carbon dioxide levels normalized. The surgical team completed the operation, and the patient was transported to the intensive care unit intubated and sedated. Intraoperative records show that by 17:15, roughly 45 minutes after the crisis began, his end-tidal carbon dioxide had dropped to 37.3 millimeters of mercury and his temperature had returned to 36.7 degrees Celsius.

In the intensive care unit, the patient remained persistently tachycardic at 130 to 140 beats per minute and hypertensive despite an intravenous fluid bolus and a unit of packed red blood cells. Following recommendations from the Malignant Hyperthermia Association of the United States hotline, he received two additional doses of dantrolene at 1 milligram per kilogram every six hours. Laboratory results showed an elevated creatine kinase peaking at 6,397 units per liter, a level likely attributable to both the malignant hyperthermia episode and the up-trending muscle damage from his recent trauma, with kidney function remaining normal. He was extubated the following day and transitioned to the trauma surgery service for continued management. Three days later, he underwent a second operation to fix his talar neck fracture using total intravenous anesthesia and regional techniques, and he experienced no recurrence of malignant hyperthermia symptoms.

Before discharge, the patient and his family were counseled about suspected malignant hyperthermia susceptibility and the need to avoid future exposure to volatile anesthetics and succinylcholine unless evaluated by a malignant hyperthermia specialist. The event was communicated to his primary care provider, and referral for confirmatory testing was recommended, including consideration of genetic testing for the RYR1 and CACNA1S genes and possibly caffeine-halothane contracture testing. Family counseling and screening were also advised given the inherited nature of the condition. Notably, the authors point out that the absence of any family history in this case underscores the importance of vigilance in all patients, because de novo mutations in RYR1 or CACNA1S can produce malignant hyperthermia susceptibility in individuals with no prior warning.

One of the most instructive aspects of the case is the differential diagnosis it forced the team to work through. Hypermetabolic crises in the perioperative setting can mimic one another, and several conditions share the overlapping features of hyperthermia, tachycardia, muscle rigidity, and autonomic dysfunction. Neuroleptic malignant syndrome, caused by dopamine receptor blockade from antipsychotic drugs, produces similar findings but typically evolves over 24 to 72 hours rather than minutes, and it responds to dopamine agonists such as bromocriptine in addition to dantrolene. Thyroid storm, a life-threatening exacerbation of thyrotoxicosis, presents with tachycardia, hypertension, hyperthermia, and widened pulse pressure, but it can be distinguished by low thyroid-stimulating hormone and elevated T3 and T4 levels. Paroxysmal sympathetic hyperactivity, a feared complication after traumatic brain injury, produces episodic hypertension, fever, and dystonia through abnormal autonomic regulation rather than calcium release in skeletal muscle. Sympathomimetic toxicity from drugs such as cocaine can also cause rhabdomyolysis with hyperthermia and rigidity, but it is associated with stimulant use rather than anesthetic exposure.

In this patient, the acute intraoperative timeline, the exposure to known triggering agents, and the rapid response to dantrolene aligned strongly with malignant hyperthermia. Thyroid storm was excluded based on the absence of thyroid disease and normal thyroid function tests. Neuroleptic malignant syndrome was unlikely given no neuroleptic medication use, and paroxysmal sympathetic hyperactivity was ruled out by the lack of neurological injury. Although a formal Malignant Hyperthermia Clinical Grading Scale score was not calculated during clinical care, the combination of triggering agent exposure, acute hypercarbia, hyperthermia, tachycardia, creatine kinase elevation, and dramatic improvement after dantrolene would support a high clinical probability of the diagnosis. The authors acknowledge that confirmatory in vitro contracture testing or genetic analysis was not performed, so the event is best characterized as clinically suspected rather than definitively confirmed malignant hyperthermia.

The case also highlights the pharmacology of dantrolene, the only specific antidote for malignant hyperthermia. Dantrolene works by antagonizing ryanodine receptors within the sarcoplasmic reticulum, inhibiting the release of calcium ions and thereby dampening the overactive muscle contraction that drives the crisis. A Japanese study of 128 patients with very likely or almost certain malignant hyperthermia found that mortality dropped from 30.8 percent in those who did not receive dantrolene to 9.6 percent in those who did, a statistically significant difference. The same study found that timing mattered enormously: patients given dantrolene at an average interval of 100 minutes from the first sign of crisis had a significantly higher mortality rate than those treated within an average of 45 minutes, and higher body temperature at the time of administration was also associated with greater mortality. Since dantrolene entered clinical use, the overall mortality rate for malignant hyperthermia has fallen from roughly 70 percent in the 1960s to about 15 percent today. The most common first sign of the crisis in that study was end-tidal carbon dioxide elevation, seen in 55.8 percent of patients, followed by temperature abnormality at 19.5 percent, a finding that reinforces the value of continuous capnography in every anesthetized patient.

Ultimately, this case serves as a reminder that malignant hyperthermia diagnosis rests on early suspicion rather than absolute confirmation against a differential diagnosis, and that immediate intervention is required to prevent morbidity and death. The authors note that malignant hyperthermia remains difficult to quantify globally due to inconsistent reporting systems, but that improved data collection could inform guidelines for better preparedness. For the patient in this report, the combination of perioperative vigilance, protocol-driven intervention, and prompt dantrolene administration transformed what could have been a fatal hypermetabolic crisis into a full recovery, and his subsequent uneventful surgery under total intravenous and regional anesthesia demonstrates how susceptible patients can be safely anesthetized once the risk is recognized.

Subject of Research: A case report of suspected malignant hyperthermia during orthopedic surgery, its differential diagnosis, and the role of rapid dantrolene treatment

Article Title: Unmasking malignant hyperthermia: a rapid response to a hypermetabolic crisis: case report

Article References: Chang, E., Nalchajyan, H., Fisler, D. A., Lee, C., Cintron, L. L., & Nathan, N. (2026). Unmasking malignant hyperthermia: a rapid response to a hypermetabolic crisis: case report. Frontiers in Anesthesiology, 5, Article 1829469. https://doi.org/10.3389/fanes.2026.1829469

Image Credits: AI Generated

DOI: 10.3389/fanes.2026.1829469

Keywords: malignant hyperthermia, dantrolene, anesthesia, succinylcholine, sevoflurane, hypermetabolic crisis, RYR1, case report, perioperative medicine, hypercarbia, rhabdomyolysis, differential diagnosis