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Chapter: Clinical Cases in Anesthesia : Depolarizing Neuromuscular Blockade

What factors may decrease the normal metabolism of succinylcholine?

Succinylcholine is metabolized by plasma cholinesterase at an estimated rate of 0.1 mg/kg per minute.

What factors may decrease the normal metabolism of succinylcholine?

 

Succinylcholine is metabolized by plasma cholinesterase at an estimated rate of 0.1 mg/kg per minute. A decrease in enzyme concentration from many causes may decrease this rate. However, rarely does this have a significant clinical effect. A decrease in enzyme levels of 20% will prolong the duration of 1 mg/kg of succinylcholine by approximately 5 minutes.

 

During pregnancy, plasma cholinesterase activity can fall by 20–30%. It is lowest at 3 days postpartum and returns to normal by 2–6 weeks. The newborn has about 50% activity, reaching normal levels by 3–4 years of age.

 

Many pathologic states are associated with reduced plasma cholinesterase activity. They include hepatitis, cir-rhosis, acute infections, carcinomas (particularly gastro-intestinal), chronic debilitating disease, uremia, burns, renal failure, and others. Rarely do these cause clinically significant prolonged blockade.

 

Plasma cholinesterase may be inhibited by a number of drugs, both reversibly and irreversibly. Irreversible inhibition of the enzyme from echothiophate eye drops (used to treat glaucoma) has been reported to decrease plasma cholinesterase activity to nearly zero. Organophosphate pesticides and certain antineoplastic drugs (thiotepa and cyclophosphamide) may cause similar inhibition. Reversible inhibition decreases activity transiently and to a lesser degree. This is seen with neostigmine, pyridostigmine, and edrophonium. Other reversible inhibitors include monoamine oxidase inhibitors (MAOIs), oral contraceptives, local anesthetics, and pancuronium.

Variants of plasma cholinesterase have been recognized. Four alleles for the production of cholinesterase have been described; the normal gene EU, the atypical gene EA, the silent gene ES, and the fluoride-resistant gene EF. Abbreviations may be simplified by calling homozygotes UU, AA, SS, and FF, and heterozygotes can be abbreviated in a similar fashion (e.g., UA). These variants of the usual enzyme have an amino acid substitution that alters the hydrolytic activity of the protein. The homozygote abnor-mality will demonstrate prolonged apnea after succinyl-choline that usually lasts from 1 to 2 hours. In the heterozygotes (UA, UF, and US), apnea is prolonged by only 10 or 15 minutes. The AF heterozygote may take 30 minutes to recover from succinylcholine.

 

The incidence of plasma cholinesterase variants differs among the population groups. The AA variant is found most commonly in Iranian Jews (1:175) and is rarest among Asians and Africans (1:25,000). The SS variant is most common in Alaskan Eskimos (1:58) and rare in Europeans (1:10,000). Incidence data are not available for the FF variant. The heterozygote state is common (esti-mated at 1:25), but the clinical response of these patients is rarely significant (or recognized). Variants are associated with quantitative decreases in enzymatic activity (H, J, and K), which are indistinguishable clinically in the hetero-zygote state. The H variant is extremely rare, found in only two families, and has a 90% decreased activity. The J vari-ant is found in 1:150,000 and has a 66% decrease in activ-ity. The K variant has a frequency of 1:100 and has a 33% decrease in activity.

 

When a patient has a prolonged response to succinyl-choline, the plasma cholinesterase activity can be meas-ured, and the qualitative function may be assessed in the presence of inhibitors. Inhibitors can be used to differenti-ate the responses of the qualitative variants A, F, and S. The usual (U) protein is markedly inhibited by dibucaine, while the atypical (A) is moderately inhibited, and the fluoride-resistant (F) and the silent (S) enzymes are mildly inhib-ited. Fluoride is used to differentiate the fluoride-resistant variant.

 

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Clinical Cases in Anesthesia : Depolarizing Neuromuscular Blockade : What factors may decrease the normal metabolism of succinylcholine? |


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