Pseudocholinesterase Deficiency

Pseudocholinesterase (plasma cholinesterase, butyrylcholinesterase) deficiency is reduced quantity or abnormal function of the enzyme that hydrolyses succinylcholine and mivacurium. It causes prolonged paralysis after normal doses of these drugs. It may be inherited or acquired.

Epidemiology. Heterozygous atypical variants occur in about 1 in 25 people of European descent, and homozygous atypical in about 1 in 2500. Genetic prevalence varies by population. Acquired reduction is common in critical illness.

Genetics. The BCHE gene on chromosome 3 has variants: atypical (dibucaine resistant, Asp70Gly), fluoride resistant, silent, and K-variant. Inheritance is autosomal recessive for the clinically significant states.

Acquired causes. Liver disease, pregnancy and the puerperium, malnutrition, chronic kidney disease, burns, malignancy, cardiac failure, plasmapheresis and cardiopulmonary bypass. Drugs include organophosphates, neostigmine, pancuronium, oral contraceptives, ecothiopate and cytotoxics.

Pathophysiology.

Succinylcholine is normally hydrolysed in plasma within minutes, and only a small fraction reaches the neuromuscular junction. With reduced enzyme activity, more drug persists and phase II block develops.

Normal duration of block is 5 to 10 minutes. Heterozygotes have 20 to 30 minutes, and homozygous atypical patients 4 to 8 hours (sometimes longer).

Prolonged apnoea and flaccid paralysis after succinylcholine or mivacurium, with failure of spontaneous ventilation. The patient may be awake and paralysed, so awareness is a danger. Sedation is essential.

Use a nerve stimulator to confirm persistent block: absent or fading train-of-four, with a phase II pattern. Exclude other causes: residual non-depolarising drug, hypothermia, electrolyte disturbance, magnesium excess and neuromuscular disease.

Laboratory tests (after recovery, at least 1 to 2 weeks after any plasma transfusion). Measure plasma cholinesterase activity (low in quantitative deficiency) and the dibucaine number (percentage inhibition by dibucaine). Normal is about 80%, heterozygous about 40% to 70%, and homozygous atypical about 20% or lower. The fluoride number adds specificity. Genotyping confirms the variant.

Differential diagnosis.

• Residual non-depolarising block.
• Phase II block from overdose of succinylcholine.
• Myasthenic or Lambert-Eaton syndrome.
• Hypermagnesaemia.
• Electrolyte disturbance.
• Hypothermia.

Immediate. Maintain airway, oxygenation and ventilation. Keep the patient sedated and given analgesia until neuromuscular function returns. Do not wake the patient while paralysed.

• Propofol infusion: 1 to 3 mg/kg/h IV; continue until train-of-four ratio is 0.9 or more, usually within 8 hours; maximum 4 mg/kg/h and keep under 48 hours; monitor blood pressure, triglycerides if prolonged and depth of sedation; reduce in older adults and haemodynamic instability.

Reversal. Sugammadex does not reverse succinylcholine. Neostigmine is usually avoided because it inhibits any remaining enzyme. Fresh frozen plasma 10 to 15 mL/kg or purified human butyrylcholinesterase concentrate (where available) can shorten block, but supportive ventilation until spontaneous recovery is the usual practice and is safe.

Documentation and follow up. Test patient and, when a variant is found, first degree relatives. Issue an alert card or bracelet. Record in the notes that succinylcholine and mivacurium must be avoided in homozygotes and used with a nerve stimulator in heterozygotes.

Future anaesthesia. Use rocuronium 0.6 to 1.2 mg/kg IV with sugammadex available; maximum sugammadex 16 mg/kg; avoid if creatinine clearance is under 30 mL/min. Local anaesthetic esters (chloroprocaine, procaine, tetracaine) also depend on this enzyme, so use amide agents when deficiency is known.

Monitoring. Train-of-four every 5 to 15 minutes, sedation depth, oxygenation and temperature.

Referral and escalation. Anaesthetic consultant involvement and referral to a clinical genetics or anaesthetic allergy service for testing and counselling. Notify relatives.