2002B05 Outline the possible reasons for prolongation of paralysis
induced by an intravenous dose of 1mg/kg suxamethonium.
Briefly indicated the consequences of such a prolonged block.

 

List:

·      Phase 2 blockade

·      Plasma cholinesterase inhibition (drug)

·      Plasma cholinesterase deficiency (phys, path)

·      Plasma cholinesterase abnormality (sux apnoea)

 

Phase 2 blockade:

Cause

·   If total >3-5mg/kg (i.e. recent dose)

Features

·   Train-of-four ratio <0.3

·   Fade with tetanic stimulation

·   Post-tetanic potentiation

·   Antagonised by acetylcholinesterase inhibitors

Pathophysiology

·   Continuous agonist binding

·   Large ion flux (Na+, K+, Ca2+)

·   Phosphorylation of tyrosine residue

·   Conformational change

·   Dysfunction of receptor and membrane

·   Flux between resting and desensitized state

·   Does not adopt active state

·   Impervious to agonist binding

Solution

·   Time

 

Pseudocholinesterase inhibitors:

·         Acetylcholinesterase inhibitors e.g. neostigmine

·         Metoclopramide

·         Ketamine

·         Oral contraceptive

·         Lithium

·         Lignocaine

·         Ester local anaesthetics

·         Cyclophosphamide

 

Relative pseudocholinesterase deficiency: (rarely significant)

Physiological causes

·   Neonate -> ↓production

·   Pregnancy -> ↑ECF water -> same amount but ↓concentration

Pathological causes

·   Heart failure

·   Liver failure

·   Renal failure

·   Thyrotoxicosis

·   Cancer

 

Pseudocholinesterase mutation = suxamethonium apnoea

Genetics

·   Two copies

·   Four described alleles:

o Normal (N)

o Dibucaine-resistance (DR)

o Chloride-resistant (CR)

o Absent (A)

 

Alleles

% population

Dibucaine number

Duration

N-N

96%

80

5-10mins

N-DR

<4%

60

15-30mins

DR-DR

0.03%

20

8-12 hours

 

 

Test

·   Patient’s plasma + dibucaine + 10-5 benzylcholine

·   Dibucaine number = % inhibition of benzylcholine metabolism

·   Normal-normal -> 80% inhibition (as above)

Management

·   If no reversal after 30 mins

·   Prolonged ventilation and sedation in ICU

·   Monitor with nerve stimulator

·   +/- FFP

Follow up

·   Counsel +/- test family

·   Avoid suxamethonium/mivacurium/ester local anaesthetic in future

 

 

 

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