Pseudocholinesterase deficiency + MH genetics

Pseudocholinesterase (butyrylcholinesterase, plasma cholinesterase) is the enzyme that breaks down succinylcholine in plasma BEFORE it reaches the NMJ. Normal half-life of succ = 3-5 min. Heterozygous atypical → 20-30 min block. Homozygous atypical → 4-8 HOURS of paralysis after a normal 1 mg/kg dose. Also affects mivacurium and ester local anesthetics. Acquired causes: pregnancy, liver disease, malnutrition, chemo, organophosphate poisoning.

Dibucaine is a local anesthetic that inhibits normal pseudocholinesterase by ~80% but only inhibits the atypical enzyme by ~20%. The dibucaine number is the percent inhibition. Normal homozygote = 80. Heterozygote = 50-60. Atypical homozygote = 20. This is a QUALITATIVE test — it tells you enzyme TYPE, not amount. Useful for family screening after an unexpected prolonged block.

MH is a hypermetabolic crisis triggered by volatile anesthetics (sevo, des, iso, halothane) or succinylcholine. The defect is in the ryanodine receptor (RYR1, ~70% of cases) or the voltage-gated calcium channel (CACNA1S, ~1%) — both control sarcoplasmic reticulum calcium release in skeletal muscle. Trigger exposure → uncontrolled Ca²⁺ release → sustained muscle contraction → hypermetabolism, hypercarbia, tachycardia, hyperthermia, rhabdomyolysis, hyperkalemia.

Gold standard: in-vitro caffeine-halothane contracture test (CHCT). Sensitivity ~99%, specificity ~78-94%. Only at a few centers. Genetic testing for RYR1 / CACNA1S is increasingly used. If susceptibility confirmed: avoid ALL volatile anesthetics and succinylcholine. Use TIVA. Machine must be MH-prepared — vaporizers removed, fresh CO₂ absorbent, flushed with high-flow O₂ for 90+ minutes. Dantrolene immediately available. First-degree relatives should be tested.