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Succinylcholine apnoea is usually the result of a delay in hydrolysis of the injected muscle relaxant due to the presence of an inherited defect in the enzyme cholinesterase. This report presents a Nova Scotia family in whom several members had "difficulty in breathing" following anaesthesia. Subsequent investigations revealed the presence of several phenotypes of the enzyme cholinesterase including individuals who were homozygous for the atypical cholinesterase genes. The frequency of occurrence and significance of the various phenotypes are discussed, together with their management and recommendations for family screening.

Investigations of the serum cholinesterase of individuals known to be excessively sensitive to succinylcholine have resulted in the recognition of many variants. These have been identified by the use of various esterase inhibitors of widely differing chemical structures. Subsequent family studies have shown that these variants are genetically determined by four allelic genes functioning at the same locus. More recent studies using sodium chloride, n-butyl alcohol and formaldehyde to inhibit serum cholinesterase differentially have indicated the probable existence of more phenotypes. These will have to be confirmed by family studies and more extensive screening of random populations. The existence of these new phenotypes may help to resolve the unexpectedly high proportion of succinylcholine-sensitive individuals typed as “normal” phenotype by established methods.

A patient who received succinylcholine chloride developed the signs of cerebral death as a result of dysfunction of succinylcholine metabolism by the enzyme, pseudocholinesterase. However, the electroencephalogram was only moderately abnormal and the patient recovered fully in eight hours, emphasizing the importance of the EEG in the evaluation of cerebral death.

Increased sensitivity to succylcholine may be due to inherited variants of serum cholinesterase (acylcholine-acylhydrolase, E.C.3.1.1.8). Four different allelic genes at locus E1 controlling human serum cholinesterase have been identified: the normal gene Eu1, the atypical gene Ea1, the fluoride-resistant gene Ef1, and the silent gene Es1. These 4 genes give rise to 10 possible genotype combinations. The sensitivity of some of these genotypes to succinylcholine, as, for instance, homozygotes for the atypical enzyme Ea1 Ea1, is well documented. However, the relation between some of the rarer genotypes and the sensitivity to succinylcholine is less well clarified. The present report represents the 1st case in which a peripheral nerve stimulator has been used to substantiate the increased succinylcholine sensitivity of a patient heterozygous for the silent and the fluoride-resistant gene, and the 2nd published case of prolonged apnea following succinylcholine in a patient carrying the Ef1 Es1 genotype for abnormal serum cholinesterase.

Cocaine was stable (93.6 +/- 5.0 (SD)% remaining after 120 minutes) when incubated in plasma from six patients with histories of succinylcholine sensitivity and low dibucaine numbers (phenotype A), but was rapidly hydrolyzed (40.6 +/- 6.6% remaining after 120 minutes) when incubated in plasma obtained from normal subjects (phenotype U). Intermediate decay (69.4 +/- 9.0% remaining) occurred in three heterozygous offspring of the succinylcholine-sensitive patients. Since serum cholinesterase has recently been implicated in the human metabolism of cocaine, patients who are homozygous for the atypical enzyme may be at greater risk for a toxic reaction when administered this drug. We recommend caution in using cocaine for topical anesthesia in patients with histories of succinylcholine sensitivity or low dibucaine numbers.

This automated spectrophotometric method for determination of cholinesterase activity in erythrocytes and plasma is based on measurement of the choline produced at 30 degrees C by the hydrolysis of acetyl-, butyryl-, or succinylcholine. Blanks, standards, and samples are prepared by a Gilson robotic unit. Use of flow-injection analysis for detection allows use of smaller volumes of reagent and sample. We applied this method to the study of 91 healthy subjects and members of two families with succinylcholine sensitivity. Results with use of the three different substrates for determination of activity in plasma correlated well (r greater than 0.94). Results for plasma and erythrocytes from healthy subjects are lower in women less than 50 years old than in women greater than 50 years or men. Values for plasma obtained with succinylcholine substrate (range: 31 to 100 U/L) allow detection of very sensitive subjects--AA phenotypes (less than 10 U/L)--but do not distinguish the UA from the UU phenotype.

The proposed method is based on routine reagents and equipment, and gives reliable results. The three inhibitors are suited to decide, if a low CHE activity is inherited or acquired and to estimate the degree of succinylcholine sensitivity of its carrier.