Transcript Malignant hyperthermia

Malignant
hyperthermia
Dr S Spijkerman
Pathogenesis
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Pharmacogenetic disorder
Autosomal dominant inheritance
Patients inherit a defected ryanodine 1 (RYR1) receptor.
This receptor is responsible for regulating the calcium
flow from the sarcoplasmic reticulum (SR) to the
cytoplasm.
When a MH susceptible patient is exposed to a
triggering anaesthetic agent (suxamethonium or
inhalants), continuous activation of the Ryanodine 1
(RY1) receptor occurs, resulting in supraphysiological
levels of sarcoplasmic reticulum calcium release with a
compensatory increase in activity of the SR calcium reuptake pump (an ATP dependent pump).
The increase in utilization of ATP stimulates metabolism,
resulting in increased oxygen consumption, increased
carbon dioxide production, thermogenesis and
sympathetic stimulation (tachycardia and arrhythmias)
As ATP demand exceeds supply, muscle rigidity is seen
with subsequent rhabdomyolysis, with release of
potassium and myoglobin
This is followed by multi-organ failure and death.
MH triggers
Suxamethonium (scoline)
Volatile anaesthetic agents
(halothane, sevoflurane,
isoflurane, desflurane, enflurane)
N2O is safe
Clinical presentation
Timing Clinical features
Changes in
monitors
Early
 Rising ETCO2
 Widened Fi O2 –
ETO2
 Increased Vm
(spontaneous
respiration)
 Rapid
exhaustion
of soda lime
 Tachycardia
 Tachypnoea
 Masseter
muscle spasm
 Generalized
muscle rigidity
Changes in
laboratory
values
 ↑PaCO2
Late
 Cyanosis  Rising core
temperature
 ↓SpO2
 Peaked
T waves
 Ventricular
ectopics
 Metabolic acidosis
 Increased lactate
 Electrolyte
disturbances (↑ K+)
 ↓SpO2, ↓pH
 Rabdomyolysis
(myoglobinurea,
↑ K+, ↑ phosphate, ↑CK)
DDx
Condition
Similarity with MH
Sepsis
Hypoventilation
Hyperthermia, hypercarcia,
acidosis
Hypercarbia, acidosis
Iatrogenic overheating
Hyperthermia, tachycardia
Thyrotoxicosis
Hyperthermia, hypercarbia,
tachycardia
Hypertension, tachycardia, fever
Pheochromocytoma
Neurolept malignant
syndrome
Transfusion related
reactions
Anaphylaxis
Muscle rigidity, rhabdomyolysis,
acidosis, fever
Hypercarbia, tachycardia, acidosis
Defected anaesthetic
breathing circuit
Hypercarbia, tachycardia, acidosis
Shock, tachycardia, acidosis
Treatment
Call for help
Halt the MH
process
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Remove trigger drugs - turn off vapouriser
High fresh gas flows (FiO2 = 1)
New breathing circuit (no residual vapour)
Maintain anaesthesia with TIVA (propofol)
Dantrolene 2.5 mg/kg IV q 5 minutes (max
dose = 10 mg/kg). Mix with 60 ml sterile water,
not saline. Poorly soluble in water, thus
administer through blood administration set to
filter precipitants)
Active body cooling: cold IV fluids, cold
lavages (bladder, gastric), ice packs over
central blood vessels (groin, axillae)
Treatment (cont)
Treat
complications
 Hypoxaemia – 100% O2, hyperventilate
 Acidosis – sodium bicarbonate
 Hyperkalaemia – glucose and insulin,
sodium bicarbonate, hyperventilate
 Myoglobinaemia – forced alkaline
diuresis (furosemide, mannitol and fluid)
 DIC – FFP, cryoprecipitate, platelets
 Cardiac arrhythmias
Treatment (cont)
ICU
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management
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Late
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management
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Continue monitoring and symptomatic
treatment
Give further dantrolene (recurrence possible
up to 24 h) – 1mg/kg q4-8h IV x 36h
Counsel patient and family regarding
implications of MH
Refer patient to tertiary center for confirmation
of MH susceptibility by :
- halothane/caffeine contraction tests done on
a fresh muscle biopsy (gold standard)
- genetic studies done on blood samples (lower
sensitivity because tests can only be done for
known mutations) (not done in RSA)
Anaesthesia for MH sensitive
patient
Preparation
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No prophylactic dantrolene recommended
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Ensure dantrolene present in theatre
complex
Intra-operative
monitoring
Remove vapouriser on anaesthetic machine,
new anaesthetic circuit and CO2 absorber,
flush anaesthetic machine with 10 l/min O2
for 10 minutes
Temperature, capnograph (ETCO2), standard
monitors
Anaesthesia
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Avoid triggers (suxamethonium and
inhalants)
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Use propofol TIVA
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