What is the treatment for malignant hyperthermia (MH)?

From the Guidelines

Malignant hyperthermia requires immediate treatment with dantrolene sodium as the primary intervention, with an initial dose of 2-3 mg/kg IV given rapidly, repeated until symptoms resolve, as recommended by the most recent guidelines from the Association of Anaesthetists 1. The management of malignant hyperthermia involves a multi-faceted approach, including:

• Discontinuing all triggering agents, particularly volatile anesthetics and succinylcholine
• Hyperventilating with 100% oxygen
• Actively cooling the patient using ice packs, cold IV fluids, and lavage of body cavities if necessary
• Treating metabolic abnormalities, such as hyperkalemia, acidosis, and cardiac arrhythmias
• Monitoring core temperature, end-tidal CO2, electrolytes, blood gases, coagulation, and urine output The use of dantrolene is crucial in the treatment of malignant hyperthermia, as it works by inhibiting calcium release from the sarcoplasmic reticulum in skeletal muscle, interrupting the pathologic calcium cycling that causes sustained muscle contraction, hypermetabolism, and heat production 1. Some key points to consider in the management of malignant hyperthermia include:
• The importance of prompt recognition and treatment, as survival is highly dependent on early intervention 2
• The need for a high index of suspicion for malignant hyperthermia in patients with an unexplained and unexpected progressive increase in carbon dioxide production 1
• The importance of taking a personal and family history of anaesthetic problems as part of pre-operative assessment 1
• The need for genetic testing and counseling for patients and their family members after an acute episode of malignant hyperthermia 1 The most recent guidelines from the European Malignant Hyperthermia Group also recommend that dantrolene should be available at all locations where volatile anaesthetic drugs are used, and that the dosing of dantrolene should be based on actual body weight, up to a maximum initial dose of 300 mg 3, 4.

From the FDA Drug Label

The use of Dantrolene Sodium for Injection in the management of malignant hyperthermia crisis is not a substitute for previously known supportive measures These measures must be individualized, but it will usually be necessary to discontinue the suspect triggering agents, attend to increased oxygen requirements, manage the metabolic acidosis, institute cooling when necessary, monitor urinary output, and monitor for electrolyte imbalance Monitoring for early clinical and metabolic signs of malignant hyperthermia is indicated because attenuation of malignant hyperthermia, rather than prevention, is possible. These signs usually call for the administration of additional intravenous dantrolene.

Treating Malignant Hyperthermia:

• Dantrolene sodium is used in the management of malignant hyperthermia crisis.
• The treatment of malignant hyperthermia involves discontinuing suspect triggering agents, attending to increased oxygen requirements, managing metabolic acidosis, instituting cooling when necessary, monitoring urinary output, and monitoring for electrolyte imbalance.
• Administration of additional intravenous dantrolene may be necessary if early clinical and metabolic signs of malignant hyperthermia appear 5.
• Dantrolene sodium works by dissociating the excitation-contraction coupling in skeletal muscle, probably by interfering with the release of Ca++ from the sarcoplasmic reticulum, thereby reestablishing a normal level of ionized calcium in the myoplasm 6.

From the Research

Treatment of Malignant Hyperthermia

• The first-line treatment agent for malignant hyperthermia is dantrolene 7, 8, 9, 10, 11.
• Dantrolene acts by affecting calcium flux across the sarcoplasmic reticulum of skeletal muscle, leading to a decrease in intracellular calcium concentration 8, 11.
• The treatment of malignant hyperthermia also involves managing complications related to the hypermetabolic response, such as hyperkalemia and arrhythmias 7.
• Immediate discontinuation of triggering agents, oxygenation, and correction of acidosis and electrolyte abnormalities, cooling, and administration of dantrolene are essential for treatment of the syndrome 9, 10.

Efficacy of Dantrolene

• Dantrolene has been shown to be highly effective in the treatment of malignant hyperthermia, with a significant reduction in mortality rates 8, 9, 10, 11.
• The mortality rate from malignant hyperthermia has decreased from 80% to less than 5% with the introduction of dantrolene 9, 10.
• Dantrolene has also been used successfully in the treatment of other hypercatabolic syndromes, such as neuroleptic malignant syndrome and heat stroke 8.

Administration of Dantrolene

• Dantrolene should be available wherever general anesthesia is administered, due to the risk of malignant hyperthermia 10.
• The main disadvantage of dantrolene is its poor water solubility, which can make it difficult to rapidly prepare intravenous solutions in emergency situations 11.