Plasma cholinesterase and abnormal reaction to succinylcholine: twenty years' experience with the Danish Cholinesterase Research Unit

Abstract

For more than 20 years, the Danish Cholinesterase Research Unit (DCRU) has collected information about patients showing an abnormal response to succinylcholine. The purpose of this study was, on the basis of the 20 years' experiences with the Unit, to evaluate our clinical findings in patients referred because of prolonged response following succinylcholine. Also, we wanted to evaluate the results of our prospective controlled studies of the effect of succinylcholine in patients with normal and abnormal plasma cholinesterase genotypes. An explanation for the apparent abnormal response to succinylcholine was found in 61.1% of the 1,247 patients referred to the Unit. Of the 1,247 patients, 28.5% were genotypically normal and 46.5% had an abnormal genotype. In the remaining 24.9% of the patients, the genotype could not be established. The time to sufficient recovery of neuromuscular function following succinylcholine 1.0-1.5 mg kg-1 was 15-30 min in patients heterozygous for one abnormal gene, 35-45 min in patients heterozygous for two abnormal genes and 90-180 min in patients homozygous for the atypical gene. Patients with two newly discovered genotypes (AK (5 patients) and AH (1 patient) showed slightly prolonged (20 min) and markedly prolonged (90 min) duration of action of succinylcholine, respectively. Our results indicate that it is a problem for many anaesthetists to correctly diagnose a prolonged response to succinylcholine. We therefore urge the anaesthetist always to use a peripheral nerve stimulator when faced with a case of apparent abnormal response to succinylcholine.

Pharmacogenetics, Drug-Metabolizing Enzymes, and Clinical Practice

“…In one series of 1247 patients, inhibition studies revealed a genetic cause in 47% of patients, whereas low activity of the usual enzyme due to other factors such as pregnancy was identified in ϳ7% of patients. Most of the remaining patients (39%) did not have a clearly identifiable cause, largely because of equivocal "genotyping" (inhibition studies) (Jensen and Viby-Mogensen, 1995). In another study, 52 (80%) of 65 patients with a history of suxamethonium apnea had reduced BChE activity caused by variations in the BCHE gene (Yen et al, 2003).…”

Effect of normal and pre-eclamptic pregnancies on plasma cholinesterase in Nigerian women

“…In such patients there is a wide variability in the neuromuscular blocking effect, onset and duration of paralysis caused by succinylcholine (16,17). The mechanisms by which normal and eclamptic pregnancies cause a reduction in plasma cholinesterase activity are not fully known.…”

Selective reversal of muscle relaxation in general anesthesia: focus on sugammadex

“…17,18 Human BChE has been sequenced, and has been shown to contain four identical subunits (tetramer); each subunit contains 574 amino acids, and the tetramer has a total weight of 342,000 Da. 19 BChE is synthesized in the liver.…”