Succinylcholine


Succinylcholine is a synthetic short-acting muscle relaxant that is made up of two molecules of acetylcholine linked through the acetate methyl groups. It is a depolarizing muscle relaxant; similar to acetylcholine, it stimulates cholinergic receptors at the neuromuscular junction. The usual duration of action for succinylcholine is 5 to 10 min. This patient has prolonged paralysis because she has a genetic variant of the enzyme that metabolizes both mivacurium and succinylcholine, pseudocholinesterase. Both of these paralytic drugs are rapidly hydrolyzed by pseudocholinesterase, an enzyme in the liver and plasma. Pseudocholinesterase influences the duration of succinylcholine and mivacurium by its effect on the rate of hydrolysis. Prolonged paralysis by these two drugs therefore occurs when there is a reduced quantity of the normal pseudocholinesterase enzyme or there is an atypical form of the enzyme.

The quantity of the normal enzyme is reduced when there is profound liver disease, pregnancy, or cancer. Drugs can decrease the quantity of this enzyme; drugs noted to do this include tetrahydroaminacrine, acetylcholinesterase inhibitors, metoclopramide, echothiophate, phenelzine, hexafluorenium, and certain cytotoxic drugs. Investigations have shown that the usual dose of succinylcholine or mivacurium is only modestly increased when the quantity of normal pseudocholinesterase is decreased.

In contrast, genetic variations that cause amino acid substitutions at or near the active site of the enzyme lead to severe prolongation of the effects of these drugs. Individuals with these variations are identified by activities of the enzyme below 1,700 U/L (normal: 2,900 to 7,100 U/L). They can also be identified by their dibucaine number; dibucaine, a local anesthetic, inhibits normal pseudocholinesterase to a far greater extent than it inhibits the abnormal pseudocholinesterase enzyme. In the standard test, dibucaine inhibits the normal enzyme inhibition 80% and the abnormal enzyme inhibition 20%. Investigations have shown that patients with genetic variants of pseudocholinesterase enzymes that have dibucaine numbers of 20 to 30% of enzyme inhibition have the most prolonged response to succinylcholine and mivacurium.


Pathogenesis


Diagnosis

Electromyography and peripheral nerve stimulators would document that this patient is paralyzed due to neuromuscular blockade but would not determine the cause of the paralysis. Muscle biopsy would not reveal abnormalities in this condition, and creatine phosphokinase concentrations are normal in these patients.


Treatment


References