From the Guidelines
Malignant hyperthermia is a life-threatening medical emergency that requires immediate treatment with discontinuation of triggering agents, administration of intravenous dantrolene, and active body cooling to prevent morbidity and mortality. The condition is triggered by certain anesthetic agents, causing rapid temperature elevation and muscle rigidity, and can occur in patients with a genetic predisposition, particularly those with a mutation in the ryanodine receptor gene 1. The incidence of malignant hyperthermia is estimated to be around 1:100,000 general anaesthetics in the UK, with a higher incidence in pediatric populations and men 2.
Key Management Principles
- Discontinue triggering agents immediately
- Administer intravenous dantrolene (initial dose 2-3 mg/kg) and repeat as necessary until symptoms resolve 1
- Implement active body cooling measures
- Provide hyperventilation with 100% oxygen
- Monitor core temperature, arterial blood gases, electrolytes, creatine kinase, coagulation studies, and urine output closely
Prevention and Precautions
- Take a personal and family history of anaesthetic problems as part of pre-operative assessment 1
- Avoid exposure to potent inhalation anaesthetics or suxamethonium in patients at increased risk of developing malignant hyperthermia
- Ensure availability of activated charcoal filters at all locations where general anaesthesia is administered 1
Post-Event Management
- Refer patients who survive an acute episode for genetic testing
- Inform patients and their GPs about the suspected diagnosis of malignant hyperthermia and its implications for them and their family 1
- Advise susceptible individuals to wear medical alert identification and inform all healthcare providers about their condition to avoid triggering agents during future procedures.
From the FDA Drug Label
In the anesthetic-induced malignant hyperthermia syndrome, evidence points to an intrinsic abnormality of skeletal muscle tissue. It is hypothesized that addition of dantrolene sodium to the "triggered" malignant hyperthermic muscle cell reestablishes a normal level of ionized calcium in the myoplasm. The efficacy of intravenous dantrolene in the treatment of human and porcine malignant hyperthermia crisis, when considered along with prophylactic experiments in malignant hyperthermia susceptible swine, lends support to prophylactic use of oral or intravenous dantrolene in malignant hyperthermia susceptible humans Clinical experience has shown that early vital sign and/or blood gas changes characteristic of malignant hyperthermia may appear during or after anesthesia and surgery despite the prophylactic use of dantrolene and adherence to currently accepted patient management practices These signs are compatible with attenuated malignant hyperthermia and respond to the administration of additional intravenous dantrolene
Malignant Hyperthermia Treatment and Prevention:
- Dantrolene sodium is used to treat malignant hyperthermia crisis.
- It is also used prophylactically in malignant hyperthermia susceptible humans.
- The administration of additional intravenous dantrolene may be necessary if signs of malignant hyperthermia appear despite prophylactic use.
- Monitoring for early clinical and metabolic signs of malignant hyperthermia is indicated, as attenuation rather than prevention is possible 3.
- Supportive measures, such as discontinuing triggering agents and managing metabolic acidosis, are also necessary in the management of malignant hyperthermia crisis 4.
From the Research
Definition and Causes of Malignant Hyperthermia
- Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases and depolarizing muscle relaxants 5.
- It is caused by a genetic disorder of the skeletal muscle that induces a hypermetabolic response when patients are exposed to a triggering agent such as volatile inhaled anesthetics or depolarizing neuromuscular blockers 6.
- The ryanodine receptor, the calcium-release channel of the sarcoplasmic reticulum, is the primary locus for malignant hyperthermia susceptibility, with multiple mutations in the gene for the ryanodine receptor protein being causative 7.
Symptoms and Diagnosis of Malignant Hyperthermia
- Symptoms of MH include increased carbon dioxide production, hyperthermia, muscle rigidity, tachypnea, tachycardia, acidosis, hyperkalemia, and rhabdomyolysis 6, 5.
- An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue 5.
- Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centers ryanodine and 4-chloro-m-cresol, as well as DNA testing for susceptibility to MH 5.
Treatment and Management of Malignant Hyperthermia
- The first-line treatment agent for an MH response is dantrolene, which acts primarily by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle 8.
- Further treatment includes managing complications related to a hypermetabolic response such as hyperkalemia and arrhythmias, as well as active cooling and hyperventilation 6, 9.
- Immediate discontinuation of triggering agents, oxygenation, and correction of acidosis and electrolyte abnormalities are also essential for treatment of the syndrome 7.
Prognosis and Prevention of Malignant Hyperthermia
- Mortality from MH has decreased from 80% thirty years ago to <5% in 2006, thanks to increased understanding of the clinical manifestation and pathophysiology of the syndrome, as well as the introduction of dantrolene sodium 5.
- Prophylactic treatment with dantrolene prior to anesthesia can prevent the syndrome from occurring in most cases, especially in patients with a family history or previous episodes of malignant hyperthermia 8.
- Suspected MH reactions have important implications for future anesthetic exposure for both the patient and their family, and should be followed up at a specialized MH testing center using muscle contracture and genetic testing 9.