Response to mivacurium in patients carrying the k variant in the butyrylcholinesterase gene.
BACKGROUND
Mivacurium is hydrolyzed by the butyrylcholinesterase enzyme, and patients with hereditary changes of the enzyme often have prolonged duration of action of mivacurium. In this study, the authors investigated the significance of the most commonly occurring variant, the Kalow (K) variant, established using DNA analysis, for the response to mivacurium.


METHODS
A total of 58 patients carrying either the wild-type butyrylcholinesterase or different combinations of the atypical (A) variant and the K variant were included. Patients who were homozygous for the A variant were given 0.03 mg/kg mivacurium. All other patients received 0.2 mg/kg mivacurium. The neuromuscular block was measured using train-of-four nerve stimulation and mechanomyography. Genotyping was performed with complete nucleotide sequencing.


RESULTS
Heterozygosity of the K variant prolonged the time to train-of-four 0.70 from 26.6 to 34.5 min (30%; not significant) as compared with the wild type. Heterozygosity of the K variant linked to the A variant prolonged the corresponding time from 32 to 42.7 min (33%; P = 0.03) as compared with patients who were heterozygous for solely an A allele. For eight patients who were homozygous for both the A and K variants, the time to 25% recovery was 78-89 min as compared with 44-57 min in patients who were homozygous for the A variant or had only one linked K variant.


CONCLUSIONS
The K variant prolongs the duration of action of mivacurium. The current results indicate that the effect is modest when the K variant occurs heterozygously with the wild type or the A variant but is marked in patients who are homozygous for both the A and K variants.
Gätke
Mona R
MR
Danish Cholinesterase Research Unit, Department of Anesthesia and Intensive Care, Copenhagen University Hospital, Rigshospitalet, Denmark. mgatke@rh.dk
Viby-Mogensen
Jørgen
J
Ostergaard
Doris
D
Bundgaard
Jens R
JR
D000328:Adult; D000368:Aged; D002091:Butyrylcholinesterase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D000077590:Mivacurium; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology*; D017354:Point Mutation
D007546:Isoquinolines; D003473:Neuromuscular Nondepolarizing Agents; D000077590:Mivacurium; D002091:Butyrylcholinesterase