Succinylcholine, a commonly used neuromuscular blocker, is hydrolyzed by the pseudocholinesterase (also known as butyrylcholinesterase) enzyme in the plasma to inactive metabolites. Individuals who have inherited genetic variants in the BCHE gene that result in decreased or no pseudocholinesterase enzyme activity are at increased risk of prolonged neuromuscular blockade with succinylcholine. Although succinylcholine/BCHE is one of the earliest identified pharmacogenomic drug/gene associations, clinical implementation remains the exception rather than the norm today. This review will explore the historical roots of pseudocholinesterase deficiency, its therapeutic implications for succinylcholine use, and future considerations for BCHE genetic testing to minimize the occurrence of prolonged neuromuscular blockade that can cause serious physical (i.e., apnea) and psychological (i.e., post-traumatic stress) consequences for patients. A summary and critical examination of the published literature that includes BCHE genetic testing in relation to succinylcholine response is also provided. Prolonged paralysis with succinylcholine may be prevented with preemptive BCHE genetic testing.

This report outlines a case of pseudocholinesterase deficiency in a pediatric patient, whose autosomal recessive condition is caused by two different pathologic variants of the butyrylcholinesterase gene, resulting in a rare case of functional homozygosity. A healthy 4-year-old girl of Northern European descent underwent general anesthesia for tonsillotomy, adenoidectomy, and bilateral tympanocentesis. Previously unknown pseudocholinesterase deficiency presented as delayed emergence with sustained apnea and paralysis following administration of mivacurium, necessitating transfer to the pediatric intensive care unit for prolonged post-operative ventilatory support and monitoring. Extubation was safely performed 8 hours later. No long-term sequelae were noted. Genetic testing identified compound heterozygosity in the butyrylcholinesterase gene. Thus, a diagnosis of autosomal recessive hereditary pseudocholinesterase deficiency was made. Pseudocholinesterase deficiency will almost always present unexpectedly and must be included in the differential diagnosis of delayed emergence. Once suspected, a clinical diagnosis can be supported using a peripheral nerve stimulator, and confirmed using laboratory tests. Genetic testing can help determine the etiology of disease.

Serum butyrylcholinesterase (BChE) levels are positively correlated with serum albumin levels and are influenced by inflammation. Heterozygous BChE deficiency in patients on dialysis may be overlooked as malnutrition owing to dialysis-associated low BChE and albumin levels. In this study, we aimed to clarify a method for identifying low BChE levels due to hereditary causes. This single-center, retrospective, observational study included 1,104 patients undergoing dialysis and 1,716 patients not undergoing dialysis. Patients on dialysis with available data of high-sensitivity C-reactive protein (hsCRP) levels were divided into three groups according to the hsCRP level: low (< 1 mg/L), average (1-3 mg/L), and high (> 3 mg/L), and the association of serum hsCRP level with BChE and albumin levels was investigated. We compared intercept values (y value at x = 0) of the regression formula obtained from repeated measurements between patients on dialysis and those with a known hereditary heterozygous BChE deficiency. Serum BChE and albumin levels in patients on dialysis were significantly lower, and a positive correlation was observed. The hsCRP level and the BChE and albumin levels were negatively correlated. BChE and albumin levels were highest in the low hsCRP group and lowest in the high hsCRP group, and a significant positive correlation was observed in all groups. The intercept values of the regression formula obtained from repeated measurements of BChE and albumin levels in patients on dialysis and a patient with hereditary heterozygous BChE deficiency were 0.383 and ---102.730, respectively, which may be useful in distinguishing hereditary causes.

Serum levels of butyrylcholinesterase (BChE) are commonly used to assess liver function. Its levels have been reported to be significantly lower in patients undergoing dialysis. To the best of our knowledge, this is the first report of hereditary heterozygous BChE deficiency in a patient undergoing dialysis. Medical staff involved in the care of patients with BChE deficiency should be aware of anesthetic usage, because prolonged neuromuscular paralysis following the administration of succinylcholine or mivacurium may occur. However, in the heterozygotes, BChE activity is not completely absent. Therefore, differentiating patients undergoing dialysis is challenging. A 52-year-old man underwent living-related kidney transplantation for focal segmental glomerulosclerosis at 22 years of age. As the renal function gradually worsened, the patient began to receive combined hemodialysis and peritoneal dialysis therapy. No problems with anesthesia were observed in past surgeries. The patient's BChE levels fluctuated between 76 and 170 U/L (reference range: 198-495 U/L); however, they had never been previously investigated. We suspected hereditary heterozygous BChE deficiency because the patient's sister was also diagnosed with it. DNA sequencing revealed a heterozygous missense mutation (Gly365Arg) and a K-variant (Ala539Thr). Patients on dialysis with low serum BChE levels often present with low albumin levels which may be overlooked as malnutrition. Thus, BChE deficiency should be suspected in patients on dialysis with unexplained low serum BChE levels. In the case of heterozygous BChE deficiency, the reference value is low, and continuous monitoring is crucial.

Inherited pseudocholinesterase deficiency refers to an uncommon defect in the butyrylcholinesterase enzyme which can result in prolonged muscle paralysis due to delayed breakdown of choline ester paralytic anaesthetic agents. We describe a 25-year-old woman receiving electroconvulsive therapy (ECT) for treatment of depression in whom motor function did not recover adequately after administration of succinylcholine. Investigated post-ECT, she was found to have severe pseudocholinesterase deficiency. Implications of pseudocholinesterase deficiency for ECT treatment and anaesthetic strategies are discussed.