Malignant hyperthermia Dr S Spijkerman Pathogenesis 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 re-uptake 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 Timin Clinical g features
Early Changes in monitors Rapid Rising ETCO2 exhaustion Widened Fi O2 of soda lime ETO2 Tachycardia Increased Vm Tachypnoea (spontaneous Masseter respiration) 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 Sepsis Hypoventilation Iatrogenic overheating Thyrotoxicosis Similarity with MH Hyperthermia, hypercarcia, acidosis Hypercarbia, acidosis Hyperthermia, tachycardia Hyperthermia, hypercarbia, tachycardia Hypertension, tachycardia, fever Muscle rigidity, rhabdomyolysis,
acidosis, fever Hypercarbia, tachycardia, acidosis Pheochromocytoma Neurolept malignant syndrome Transfusion related reactions Anaphylaxis Shock, tachycardia, acidosis Defected anaesthetic Hypercarbia, tachycardia, acidosis breathing circuit Treatment Call for help Halt the MH process
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 Hypoxaemia 100% O2,
hyperventilate complications 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 manageme nt Late manageme
nt 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 Intra-operative monitoring Anaesthesia No prophylactic dantrolene recommended Ensure dantrolene present in theatre complex
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 Avoid triggers (suxamethonium and inhalants) Use propofol TIVA
