Malignant hyperthermiaDr 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 triggersSuxamethonium (scoline)

Volatile anaesthetic agents (halothane, sevoflurane, isoflurane, desflurane, enflurane)

N2O is safe

Clinical presentationTiming

Clinical features

Changes in monitors

Changes in laboratory values

Early Rapid exhaustion

of soda lime Tachycardia Tachypnoea Masseter

muscle spasm Generalized

muscle rigidity

Rising ETCO2 Widened Fi O2 –

ETO2 Increased Vm

(spontaneous respiration)

 

↑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)

DDxCondition Similarity with MH

Sepsis Hyperthermia, hypercarcia, acidosis

Hypoventilation Hypercarbia, acidosisIatrogenic overheating

Hyperthermia, tachycardia

Thyrotoxicosis Hyperthermia, hypercarbia, tachycardia

Pheochromocytoma Hypertension, tachycardia, feverNeurolept malignant syndrome

Muscle rigidity, rhabdomyolysis, acidosis, fever

Transfusion related reactions

Hypercarbia, tachycardia, acidosis

Anaphylaxis Shock, tachycardia, acidosisDefected anaesthetic breathing circuit

Hypercarbia, tachycardia, acidosis

TreatmentCall 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 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 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 CO2 absorber, flush anaesthetic machine with 10 l/min O2 for 10 minutes

Intra-operative monitoring

Temperature, capnograph (ETCO2), standard monitors

Anaesthesia Avoid triggers (suxamethonium and inhalants)

Use propofol TIVA