malignant hyperthermia/hyperthermia of anesthesia

Etiology

• inhalation anesthetics or muscle relaxants such as succinylcholine

Pathology

• inherited abnormality of skeletal muscle sarcoplasmic reticulum
• rapid increase in intracellular Ca+2 levels in response to inhalation anesthetics or muscle relaxants

Genetics

• heterogeneous disorder
• type 1 associated with mutation in RYR1 gene ryanodine receptor 1 (at least 25%) (autosomal dominant)
• type 2 associated with mutation in gene for voltage-dependent sodium channel of skeletal muscle on chromosome 17q11.2-q24
• type 3 associated with unidentified gene on chromosome 7q21-q22
• type 4 associated with unidentified gene on chromosome 3q13.1
• type 5 (autosomal dominant) associated with defect in CACNA1S (1%)

Clinical manifestations

• hyperthermia
• muscle rigidity
  • masseter rigidity
  • rigor mortis-like
• hyporeflexia
• accelerated muscle metabolism
• rhabdomyolysis
• tachycardia
• tachypnea, increased minute ventilation
• hypertension
• cardiovascular instability
  • hyperkalemia-induced rhythms
  • premature ventricular contractions
  • ventricular tachycardia, ventricular fibrillation
• agitation
• skin mottling
• pupils normal
• hypoactive bowel sounds
• brown urine (myoglobinuria)
• metabolic acidosis
• rapid development of signs/symptoms (1/2 hour - 24 hours)

Laboratory

• arterial blood gas:
  • metabolic acidosis (lactic acidosis)
  • increased arterial pCO2
• elevated serum creatine kinase
• serum K+: hyperkalemia
• urinalysis
  • myoglobinuria
• abnormal coagulation tests
• molecular diagnostic testing
  • CACNA1S gene mutation

Differential diagnosis

• parkinsonian hyperpyrexia syndrome
• neuroleptic malignant syndrome

Management

• cessation of anesthesia
• 100% O2
• dantrolene
• supportive measures
  • treat hyperkalemia
  • treat hypercarbia
• patients who require surgery
  • regional anesthesia
    • spinal, epidural or peripheral nerve block
  • local anesthetics in combination with (a)
  • general anesthesia with non-triggering agents
    • barbiturates, benzodiazepines, opioids, propofol, etomidate, ketamins, nitrous oxide
    • non-depolarizing neuromuscular blockers

More general terms

• pharmacogenetic disease
• muscular disease; myopathy

Additional terms

• adenylate kinase-1 (AK1, ATP/AMP phosphotransferase, myokinase)
• hyperthermia (pyrexia)
• ryanodine receptor (RyR)

Database

• OMIM: https://mirror.omim.org/entry/102990
• OMIM: https://mirror.omim.org/entry/145600
• OMIM: https://mirror.omim.org/entry/601887