Outline the diagnostic features, complications and treatment of patients with malignant hyperpyrexia.

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College Answer

Malignant hyperpyrexia is a rare genetic disorder, usually autosomal dominant inheritance, with mutations of the calcium channel (ryanodine) found in the sarcoplasmic reticulum of skeletal muscle.  When triggered by drugs (esp. suxamethonium and volatile anaesthetic agents), usually within 1 hour, uncontrolled calcium efflux results in tetany, and markedly increased skeletal muscle metabolism. 

 

 Diagnostic features include susceptible patient (may be unknown), exposed to triggering agent, with signs of increased metabolic rate (early tachycardia, increased muscle tone, increased oxygen consumption, increased CO2 production [e.g. ETCO2], and later marked hyperthermia).    Complications include rhabdomyolyis, shock, disseminated intravascular coagulation, and a mixed metabolic (lactic) and respiratory acidosis.  

 

The mainstay of treatment is the removal of triggering agents and administration of the specific antidote (dantrolene 20 mg/vial, diluted to 60 mL with water, dosage e.g. 2 mg/kg every 5 minutes up to 10 mg/kg, repeated every
10 to 15 hours, and continued for three days).  Other treatment is supportive initially with active cooling, and detection and treatment of the potential complications listed above. Confirmation of diagnosis (muscle biopsy) and family screening may be necessary.

 

Discussion

The European Malignant Hyperthermia Group has published some nice guidelines in 2010, which offer an excellent overview of this topic.

 

General features

  • Follows suxamethonium or volatile agent administration
  • Develops during anaesthesia
  • Body temperature rises by 1 degree every 10 minutes

 

Clinical features

  • Hyperthermia
  • Jaw rigidity persists after sux has worn off
  • Tachycardia and tachypnoea
  • Increased EtCO2
  • Increased O2 consumption
  • Profuse sweating
  • Hyperkalemia
  • Cyanosis
  • Generalised rigidity, increased muscle tone
  • Prolonged bleeding

 

Complications

  • DIC
  • Rhabdomyolysis
  • Hypotension
  • Lactic and respiratory acidosis

 

Management

  • Abort the procedure
  • Stop the anaesthetic
  • Give 100% FiO2 and hyperventilate
  • Start active cooling
  • Administer dantrolene: 20mg as a rapid infusion
  • Keep giving dantrolene until features of resolution begin to manifest
  • Give steroids; eg. 2g of methylprednisolone
  • Maintain high urine output to avoid renal damage from rhabodomyolysis
  • Correct coagulopathy

 

 

References

References

Hopkins, P. M. "Malignant hyperthermia: advances in clinical management and diagnosis." British journal of Anaesthesia 85.1 (2000): 118-128.

 

Glahn, K. P. E., et al. "Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group." British journal of anaesthesia 105.4 (2010): 417-420.