- Clinical science
Malignant hyperthermia (MH) is a subclinical myopathy in which general anesthesia triggers an uncontrollable contraction of skeletal muscle that leads to a life-threatening hypercatabolic state and increase in body temperature. The disease is primarily autosomal dominant; mutations in receptors (especially ryanodine receptor type 1) predispose to volatile anesthetic agents or succinylcholine causing an accumulation of intracellular calcium in skeletal muscle that leads to its overactivation and hypermetabolism. In the acute setting, diagnosis is based mainly on clinical presentation and end-tidal capnography, which reveals an increase in end-tidal CO2. Immediate treatment measures involve stopping the triggering agent and administration of dantrolene. In non-acute settings, there are specific diagnostic tools (e.g., caffeine halothane contracture test) to confirm suspected cases. MH is a lethal disease and has a high mortality rate if left untreated.
- Sex: ♂ > ♀ (2:1)
- Incidence: ∼ 700 per year in the US, or 1:5,000 to 1:100,000 in individuals undergoing anesthesia.
Epidemiological data refers to the US, unless otherwise specified.
- Inherited susceptibility: primarily autosomal dominant with reduced penetrance
- Triggering agents
Administration of triggering substances → calcium release from intercellular compartments or delay in its reuptake → ↑ calcium in muscle cells → ↑ contractility of the skeletal muscle → ↑ metabolism → ↑ oxygen consumption in addition to ↑ CO2 production, heat, and lactate (malignant hyperthermia) → mixed respiratory and metabolic acidosis → uncoupled oxidative phosphorylation → breakdown of the cell's energy supply → cell death
- Early signs
- Late signs
Although the rise in body temperature is usually a late sign in malignant hyperthermia, it may occur as an early sign in severe cases! References:
The diagnosis is based on clinical presentation (e.g., muscle and jaw rigidity, hyperthermia) with an increase in end-tidal CO2 and signs of muscle breakdown. Confirmatory tests are reserved for stabilized patients and to prophylactically investigate those with a positive family history.
- Respiratory parameters: continuous increase in end-tidal CO2
- Blood tests
- Urine: myoglobinuria
- Confirmatory studies
- Indication: stabilized MH patients; patients with a positive family history (before receiving anesthetics)
- Gold standard: caffeine halothane contracture test
- Molecular genetic testing: low sensitivity, but highly specific, and less expensive and invasive than the muscle contracture test
- See differential diagnosis of drug-induced hyperthermia.
- Acute porphyria crisis
- Levodopa withdrawal syndrome
The differential diagnoses listed here are not exhaustive.
Immediate administration of dantrolene (ryanodine receptor antagonist)
- Dantrolene prevents the release of calcium from the sarcoplasmic reticulum of striated muscle → reduced muscular activity
- Stop administration of potential triggering agents!
- Further steps:
- Increase respiratory minute volume by at least 3-fold.
- Ventilation with 100% O2
- Rapid completion of surgery
- Forced diuresis
- Low-dose heparin
- Extended postoperative monitoring in intensive care