Malignant Hyperthermia Catherine Maw - PowerPoint Presentation

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Malignant Hyperthermia

Catherine Maw

24/10/2012

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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

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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

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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)

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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)

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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

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Why?

Metabolic acidosis

Hyperkalaemia

Rhabdomyolysis

Renal failure

DIC

Liver failure

Death

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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

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Definition and Aetiology

Pharmacological disease of skeletal muscle

Hypermetabolic

crisis

Induced by exposure to volatile anaesthetic agents or

S

uxamethonium

Loss of normal calcium homeostasis

Unregulated release of Calcium form the sarcoplasmic reticulum

Myocyte

hypermetabolism

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Relevance

Anaesthetic complication

Ongoing patient care will always involve ICU

Insidious versus acute

True MH rare

Hyperthermia differentials more common

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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

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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

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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

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Risk Factors

Positive family history

Previous exposure to Suxamethonium or volatiles

Exertional heat stroke

Exercise induced rhabdomyolysis

Central core disease

Scoliosis

Strabismus surgery

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Diagnosis

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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

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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

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Late

Myoglobinuria

Myalgia

Grossly elevated CK

Coagulopathy

Cardiac arrest

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Differential diagnosis

Inadequate anaesthesia / machine issue / patient factor

Sepsis

Intracerebral

infection or bleed

Recreational drugs

Neuroleptic malignant syndrome

Thyroid storm

Phaeochromocytoma

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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

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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

D

antrolene

every 6 hours for 48 hours

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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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