Malignant HyperthermiaCatherine Maw24/10/2012

OUTLINE• Define and discuss aetiology of thermal disorders• Relevance to ICU• Clinical Presentation of MH• Differential diagnosis and pitfalls• Treatment in theatre and ICU• Subsequent management

Thermoregulation• Balance between heat production and loss• Hypothalamic thermoregulatory centre• “Pyrexia” = resetting of thermoregulatory set point to a higher

level by activation of heat conserving mechanisms• “Hyperthermia” = failure of effector mechanisms to maintain

the normal set point

Fever in the ICU• Regulated hyperthermia• Endogenous pyrogens (IL6 and PGE2) act on the hypothalamus• Reset the thermoregulatory set point to higher temp• Effector organs prevent heat loss• May be protective • When pyrogens decrease, set point decreases• Deleterious effects (↑CO, O2 consumption, CO2 production)

Hyperthermia• Failure of effector mechanisms to maintain the hypothalamic

set point (core ≥ 40°C)• Heat stroke • Drug induced hyperthermias (MH, NMS, Serotonin syndrome,

sympathomimetic syndrome, anticholinergic syndrome)• Heat injury is the insult• Protein denaturation and lipid dissolution at 42°C (core)

Why is it fatal?• Direct cellular damage• Increases membrane permeability• Activation of Na-K-ATPase pump• ATP depletion• Tissue oedema• Cytokine activation, coagulation cascade activation • Cellular death (lactate, hyperkalaemia, acidosis)• Similar picture to sepsis

Why?• Metabolic acidosis• Hyperkalaemia• Rhabdomyolysis• Renal failure• DIC• Liver failure• Death

Australian History• 1960: Dr Jim Villiers at Royal Melbourne Hospital• Patient with 10 family members who died under GA• Patient had malignant hyperthermia (MH)• Villiers presented the successful anaesthetic outcome• 1972: Lancet. Denborough and Lovell.• Royal Melbourne (one of 3) centres for MH

Definition and Aetiology• Pharmacological disease of skeletal muscle• Hypermetabolic crisis• Induced by exposure to volatile anaesthetic agents or

Suxamethonium• Loss of normal calcium homeostasis• Unregulated release of Calcium form the sarcoplasmic

reticulum• Myocyte hypermetabolism

Relevance • Anaesthetic complication• Ongoing patient care will always involve ICU• Insidious versus acute• True MH rare• Hyperthermia differentials more common

Epidemiology• 1 in 10,000 to 1 in 30,000 anaesthetics• Young adults (45-55% of cases in <19 years)• More frequent in minor ops• Male > Female 2:1• Mortality previously 70-80%• Reduced to 2-3% now

Genetics of MH• Majority of MH susceptible patients have mutations on RYR1

or DHP genes• Inherited or spontaneous• 50% Autosomal Dominant• 200 mutations identified• 29 have causality

Pathophysiology ctd• Sustained muscle contraction due to high levels of myoplasmic

calcium• Heat generated (initial insult)• Cascade similar to sepsis/systemic inflammation• Initial aerobic metabolism generating CO2 and → cellular

acidosis• Then Oxygen and ATP depletion → worsening acidosis and

lactate production• Depleted energy → muscle death and rhabdomyolysis

Risk Factors• Positive family history• Previous exposure to Suxamethonium or volatiles• Exertional heat stroke • Exercise induced rhabdomyolysis• Central core disease• Scoliosis• Strabismus surgery

Diagnosis

Early• Prolonged masseter muscle spasm after Suxamethonium• Inappropriately ↑ ETCO2 or tachypnoea during

spontaneous respiration (ETCO2 >60)• Inappropriately ↑ ETCO2 (ETCO2 >55) during controlled

ventilation• Inappropriate tachycardia• Cardiac arrhythmias, especially ventricular ectopics

Developing• Developing rise in temperature (0.5 ◦C per 15 mins)• Progressive respiratory and later metabolic acidosis• Hyperkalaemia• Profuse sweating• Cardiovascular instability• Desaturation• Generalised muscle rigidity

Late• Myoglobinuria• Myalgia• Grossly elevated CK• Coagulopathy• Cardiac arrest

Differential diagnosis• Inadequate anaesthesia / machine issue / patient factor• Sepsis• Intracerebral infection or bleed• Recreational drugs• Neuroleptic malignant syndrome• Thyroid storm• Phaeochromocytoma

Management• ANZCA suggest MH Resource kit• Link to mhanz• Task cards based on the aviation safety model• If diagnosis is suspected:• Declare Emergency• Call for HELP and send for MH resource kit• Turn off the volatile and remove vaporisers• Hyperventilate on >15l/min fresh gas flows with 100% O2• TIVA

Ongoing Care• ICU for ventilatory support, haemodynamic monitoring, renal

support• CK peaks at 14 hours• Dantrolene does not effect cardiac or smooth muscle• Recrudescence in 25%• 1mg/kg Dantrolene every 6 hours for 48 hours

MH Susceptibility Testing• Gold standard is the contracture test• In vitro response of a fresh sample of muscle tissue to Caffeine

or Halothane• Muscle strip in physiological solution is attached to a strain

gauge and electrically stimulated to measure baseline tension• Repeat in Halothane and Caffeine• High sensitivity and specificity• Expensive and specialist referral needed• Genetic testing cheaper but sensitivity 30-50%

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