Extensively Long Recovery after Mivacurium Caused by Rare “Silent” Gene Mutations. Gätke et al. (page 600)

In patients who have the butyrylcholinesterase gene (BChE ), mivacurium is rapidly hydrolyzed in plasma, and duration of action is short. An estimated 24% of the white population carries a genetic variant allele of the BChE enzyme, which can result in slow hydrolysis of mivacurium and prolonged neuromuscular block. In this article, Gätke et al.  describe the anesthetic course of a healthy 30-yr-old man undergoing a correction of the inner nose who received a single dose of 10 mg mivacurium to facilitate tracheal intubation.

Ninety minutes after administration of mivacurium, at completion of surgery, the patient had no response either to train-of-four or to tetanic stimulation. The patient was transferred to the intensive care unit, where neuromuscular blockade was continuously monitored until a train-of-four ratio of 0.75 was obtained—nearly 8 h (469 min) after injection of mivacurium. While the patient was in the intensive care unit, venous blood samples were collected at 12 regular intervals (from 134 to 494 min after mivacurium administration). A blood sample drawn when the patient arrived in the intensive care unit was analyzed to determine BChE activity, phenotype, and genotype. The patient’s BChE activity was zero, indicating that he was homozygous for silent mutations. Subsequent to the patient’s discharge from the hospital, the researchers obtained permission to perform complete nucleotide sequencing of the BchE gene of not only the patient, but also of his parents and siblings.

DNA analysis revealed two point mutations, the known S7 variant and an undescribed mutation, which introduced a stop codon at amino acid residue 172 of the 574 amino acid residues of normal BChE. Biochemical data supported the finding that the patient was compound heterozygous for two silent mutations. Pedigree analysis showed that S7 was inherited from the patient’s mother and the novel mutation was inherited from his father, proving that both alleles are affected in the patient. Screening for abnormal BChE genotypes is not practical or cost-effective in daily clinical practice, but it could be used, according to the authors, to supplement equivocal results obtained by biochemical methods and in clinical situations such as the one described in this article.