Prolonged Apnoea after Suxamethonium: An Analysis of the First 225 Cases Reported to the Danish Cholinesterase Research Unit

Abstract

During the last 4 years, 225 patients have been referred to the Danish Cholinesterase Research Unit following an episode of prolonged apnoea after suxamethonium. Fourteen patients (6.2%) were found to have a low serum cholinesterase activity due to an acquired deficiency (for instance, liver disease, chronic debilitating disease or carcinoma). One hundred and forty-eight patients (65.8%) had an inherited abnormal serum cholinesterase, and 105 of these patients (46.7%) were homozygous for the atypical enzyme (E1 Ea1). The mean period of apnoea in this latter group was 92 min (range: 25--240). Seventeen patients (7.6%) were heterozygous for the normal and the atypical enzyme (Eu1 Ea1), with a mean apnoea period of 25 min (range: 7--60 min). Twelve patients were found to be heterozygous for the atypical and the silent gene (E(a)1 E(s)1). The mean period of apnoea was 126 min (range: 45--210 min). Fourteen patients had other rare genotypes. The longest mean period of apnoea (170 min, range: 70--330) was found in patients homozygous for the silent gene (Es1 Es1). The silent gene and the fluoride-resistant gene were found in 8.9% and 2.7% of the patients, respectively. In 63 patients (28.1%) both the type and quantity of serum cholinesterase were normal. In 34 of these patients (15.2%), the prolonged apnoea was due to other causes; for example, suxamethonium overdose, hyperventilation and central as well as peripheral respiratory depression. However, in the other 29 patients (12.9%), the reason for the prolonged apnoea could not be established. The possibility therefore exists that these cases represent unknown genotypes.

Butyrylcholinesterase (BCHE) Genotyping for Post-Succinylcholine Apnea in an Australian Population

“…As early as 1978, the Danish Cholinesterase Research Unit reported that 13% of individuals with abnormal SC responses were unable to be typed by inhibitor-identified alleles (2 ), an observation reinforced 4 years later by Morgan (4 ), who suggested that up to 8 -10% of patients were potentially misdiagnosed because of difficulties with phenotyping. Phenotype studies are prone to inaccuracy when enzyme amounts are low, but additional problems of variable enzyme response in different substrates and a diagnostic range of 10 phenotypes contribute to difficulties with identification.…”

“…cases) (2 ). Hence, the identification of individuals with inherited BChE variants remains within the province of the laboratory because the demonstration of low plasma cholinesterase activity (BChE) and abnormal enzyme phenotype (defined by responses to dibucaine and fluoride inhibitors) quantify the degree of impairment and confirm its hereditary basis.…”

Acquired pseudocholinesterase deficiency after high-dose cyclophosphamide

“…8 However, respiratory depression due to PSC deficiency rarely exceeds 240 min. 2,4 Al-Jafari et al 9 suggested that the CY effect on PSC is reversible, after demonstrating inhibition did not vary according to the length of preincubation in vitro. Walker et al 8 showed that CY inhibits PSC in a concentration-dependent manner.…”

“…3,11 Other coexisting factors such as abnormal enzyme genotype might account for the prolonged neuromuscular blockade in some of the cases reported previously. 2,4 Prolonged apnea after anesthesia is extremely rare in patients receiving CY despite its extensive use. In the case described, the complication developed 9 h after the completion of high-dose CY.…”

“…1,2 As a result, prolonged apnea and cardiac arrythmia after general anesthesia have been reported. [1][2][3][4][5][6] Conditions associated with reduced PSC activity include hereditary enzyme deficiency 3,4 and acquired disease states such as disseminated cancer, chronic debilitating illnesses and malnutrition. 2,5,7 Kaniaris et al 7 showed that cancer patients with PSC activity of less than 40% of normal had delayed recovery after succinylcholine administration.…”