title: Genotyping the butyrylcholinesterase in patients with prolonged neuromuscular block after succinylcholine.
abstract: BACKGROUND
  Succinylcholine remains the standard neuromuscular blocking drug for tracheal intubation in emergency situations. The short duration of action is due to its rapid hydrolytic degradation by butyrylcholinesterase (plasmacholinesterase). Multiple variants of this enzyme are known (A, F, S, H, J, K variants) with different effects on enzyme activity. This study was undertaken to evaluate the use of molecular genetic methods in patients with clinically prolonged neuromuscular block.
  
  
  METHODS
  Nine patients with a neuromuscular block of 14 min to 5 h were selected. All four exons of the butyrylcholinesterase were amplified by polymerase chain reaction and analyzed by automated sequencing. Molecular genetic results were compared with clinical relaxation time and with biochemical test results (total butyrylcholinesterase activity, dibucaine and fluoride inhibition).
  
  
  RESULTS
  Seven of nine patients were mutation carriers. Five of these had more than one mutation. The A and K variants were the most frequent variations. Three of four patients who were homozygous for the A variant were also carriers of the K allele. The authors identified one novel mutation (G1294T) introducing a stop codon at amino acid position 432. The duration of neuromuscular block was substantially different between patients with identical butyrylcholinesterase genotypes.
  
  
  CONCLUSIONS
  Variations in the genetic sequence of butyrylcholinesterase are frequent in patients with prolonged duration of action of succinylcholine. Direct sequencing of the whole butyrylcholinesterase gene is an appropriate method for genotyping and, accordingly, should be used in future clinical studies with drugs metabolized by this enzyme (e.g., succinylcholine, mivacurium).
authors.affiliation: Department of Anesthesia, University of Basel, Switzerland.
authors.forename: Soledad
authors.initials: S
authors.lastname: Levano
authors.forename: Hans
authors.initials: H
authors.lastname: Ginz
authors.forename: Martin
authors.initials: M
authors.lastname: Siegemund
authors.forename: Miodrag
authors.initials: M
authors.lastname: Filipovic
authors.forename: Evgueni
authors.initials: E
authors.lastname: Voronkov
authors.forename: Albert
authors.initials: A
authors.lastname: Urwyler
authors.forename: Thierry
authors.initials: T
authors.lastname: Girard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002091:Butyrylcholinesterase / Q000235:genetics*; D002648:Child; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D019148:Neuromuscular Blockade; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D013390:Succinylcholine / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D009467:Neuromuscular Depolarizing Agents; D002091:Butyrylcholinesterase; D013390:Succinylcholine