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) N 2 O is safe

Clinical presentation TimingClinical features Changes in monitors Changes in laboratory values Early  Rapid exhaustion of soda lime  Tachycardia  Tachypnoea  Masseter muscle spasm  Generalized muscle rigidity  Rising ETCO 2  Widened F i O 2 – ETO 2  Increased V m (spontaneous respiration)  ↑P a CO 2

Late  Cyanosis  Rising core temperature  ↓S p O 2  Peaked T waves  Ventricular ectopics  Metabolic acidosis  Increased lactate  Electrolyte disturbances (↑ K + )  ↓S p O 2, ↓pH  Rabdomyolysis (myoglobinurea, ↑ K +, ↑ phosphate, ↑CK)

DDx ConditionSimilarity with MH Sepsis Hyperthermia, hypercarcia, acidosis Hypoventilation Hypercarbia, acidosis Iatrogenic overheating Hyperthermia, tachycardia Thyrotoxicosis Hyperthermia, hypercarbia, tachycardia Pheochromocytoma Hypertension, tachycardia, fever Neurolept malignant syndrome Muscle rigidity, rhabdomyolysis, acidosis, fever Transfusion related reactions Hypercarbia, tachycardia, acidosis Anaphylaxis Shock, tachycardia, acidosis Defected anaesthetic breathing circuit Hypercarbia, tachycardia, acidosis

Treatment Call for help Halt the MH process  Remove trigger drugs - turn off vapouriser  High fresh gas flows (FiO 2 = 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% O 2, 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 management  Continue monitoring and symptomatic treatment  Give further dantrolene (recurrence possible up to 24 h) – 1mg/kg q4-8h IV x 36h Late management  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  No prophylactic dantrolene recommended  Ensure dantrolene present in theatre complex  Remove vapouriser on anaesthetic machine, new anaesthetic circuit and CO 2 absorber, flush anaesthetic machine with 10 l/min O 2 for 10 minutes Intra-operative monitoring Temperature, capnograph (ETCO 2 ), standard monitors Anaesthesia  Avoid triggers (suxamethonium and inhalants)  Use propofol TIVA