Dibucaine Number and Atypical Butyrylcholinesterase
Succinylcholine-induced neuromuscular blockade can be significantly
prolonged if the patient has an abnormal genetic variant of butyrylcholinesterase.
The variant was found by Kalow and Genest[88]
to
respond to dibucaine differently than normal butyrylcholinesterase does. Dibucaine
inhibits normal butyrylcholinesterase to a far greater extent than it does the abnormal
enzyme. This observation led
*The
dibucaine number indicates the percentage of enzyme inhibited.
Figure 13-6
Correlation between the duration of succinylcholine neuromuscular
blockade and butyrylcholinesterase activity. The normal range of activity lies between
the arrows. (From Viby-Mogensen J: Correlation
of succinylcholine duration of action with plasma cholinesterase activity in subjects
with the genotypically normal enzyme. Anesthesiology 53:517–520, 1980.)
to development of the test for dibucaine number. Under standardized test conditions,
dibucaine inhibits the normal enzyme about 80% and the abnormal enzyme about 20%
( Table 13-2
). Subsequently,
many other genetic variants of butyrylcholinesterase have been identified, although
dibucaine-resistant variants are the most important. Reviews by Pantuck[89]
and by Jensen and Viby-Mogensen[90]
can be consulted
for more detailed information on this topic.
Although the dibucaine number indicates the genetic makeup of
an individual with respect to butyrylcholinesterase, it does not measure the concentration
of the enzyme in plasma, nor does it indicate the efficiency of the enzyme in hydrolyzing
a substrate such as succinylcholine or mivacurium. Both the latter factors are determined
by measuring butyrylcholinesterase activity—which may be influenced by genotype.
The molecular biology of butyrylcholinesterase is well understood.
The amino acid sequence of the enzyme is known, and the coding errors responsible
for most genetic variations have been identified.[89]
[90]
Most variants are due to a single amino acid
substitution error or sequencing error at or near the active site of the enzyme.
For example, in the case of the "atypical" dibucaine-resistant (A) gene, a mutation
occurs at nucleotide 209, where guanine is substituted for adenine. The resultant
change in
this codon causes substitution of glycine for aspartic acid at position 70 in the
enzyme. In the case of the fluoride-resistant (F) gene, two amino acid substitutions
are possible, namely, methionine for threonine at position 243 and valine for glycine
at position 390. Table 13-2
summarizes many of the known genetic variants of butyrylcholinesterase: the amino
acid substitution at position 70 is written as Asp Ø Gly. New variants of
butyrylcholinesterase genotypes continue to be discovered.[91]
[92]
