Malignant-Hyperthermia

Report
Malignant
Hyperthermia
Catherine Maw
24/10/2012
OUTLINE
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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
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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?
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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?
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Metabolic acidosis
Hyperkalaemia
Rhabdomyolysis
Renal failure
DIC
Liver failure
Death
Australian History
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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
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Anaesthetic complication
Ongoing patient care will always involve ICU
Insidious versus acute
True MH rare
Hyperthermia differentials more common
Epidemiology
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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
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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
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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
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Myoglobinuria
Myalgia
Grossly elevated CK
Coagulopathy
Cardiac arrest
Differential diagnosis
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Inadequate anaesthesia / machine issue / patient factor
Sepsis
Intracerebral infection or bleed
Recreational drugs
Neuroleptic malignant syndrome
Thyroid storm
Phaeochromocytoma
Management
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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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