Pseudocholinesterase Deficiency

Updated: Sep 26, 2016
  • Author: Daniel R Alexander, MD; Chief Editor: Karl S Roth, MD  more...
  • Print
Overview

Background

Pseudocholinesterase deficiency is an inherited enzyme abnormality that results in abnormally slow metabolic degradation of exogenous choline ester drugs such as succinylcholine and mivacurium. If there is a  deficiency in the plasma activity of pseudocholinesterase, prolonged muscular paralysis may occur, resulting in the extended need for mechanical ventilation.A variety of pathologic conditions, physiologic alterations, and medications also can lower plasma pseudocholinesterase activity. [1, 2, 3, 4, 5, 6, 7]

This condition is recognized most often when respiratory paralysis unexpectedly persists for a prolonged period of time following administration of standard doses of succinylcholine. [8] The mainstay of treatment in these cases is ventilatory support until diffusion of succinylcholine from the myoneural junction permits return of neuromuscular function of skeletal muscle. The diagnosis is confirmed by a laboratory assay demonstrating decreased plasma cholinesterase enzyme activity. See the image below.

Noninvasive ventilation. A bilevel positive airway Noninvasive ventilation. A bilevel positive airway pressure (BIPAP) prototype is shown here. Expiratory positive airway pressure is the expiratory pressure setting that determines the amount of positive end-expiratory pressure that is applied. The inspiratory positive airway pressure setting is the pressure support. The device can be used in spontaneous mode or timed mode (with a mandatory backup respiratory frequency).

Genetic analysis may demonstrate a number of allelic mutations in the pseudocholinesterase gene, including point mutations resulting in abnormal enzyme structure and function and frameshift or stop codon mutations resulting in absent enzyme synthesis. Partial deficiencies in inherited pseudocholinesterase enzyme activity may be clinically insignificant unless accompanied by a concomitant acquired cause of pseudocholinesterase deficiency. Clinically significant effects generally are not observed until the plasma cholinesterase activity is reduced to less than 75% of normal. [2]

Next:

Pathophysiology

Pseudocholinesterase is a glycoprotein enzyme, produced by the liver, circulating in the plasma. It specifically hydrolyzes exogenous choline esters; however, it has no known physiologic function.

Pseudocholinesterase deficiency results in delayed metabolism of only a few compounds of clinical significance, including the following: succinylcholine, mivacurium, procaine, and cocaine. [9] Of these, its most clinically important substrate is the depolarizing neuromuscular blocking agent, succinylcholine, which the pseudocholinesterase enzyme hydrolyzes to succinylmonocholine and then to succinic acid.

In individuals with normal plasma levels of normally functioning pseudocholinesterase enzyme, hydrolysis and inactivation of approximately 90-95% of an intravenous dose of succinylcholine occurs before it reaches the neuromuscular junction. The remaining 5-10% of the succinylcholine dose acts as an acetylcholine receptor agonist at the neuromuscular junction, causing prolonged depolarization of the postsynaptic junction of the motor-end plate. This depolarization initially triggers fasciculation of skeletal muscle. As a result of prolonged depolarization, endogenous acetylcholine released from the presynaptic membrane of the motor neuron does not produce any additional change in membrane potential after binding to its receptor on the myocyte. Flaccid paralysis of skeletal muscles develops within 1 minute.

In normal subjects, skeletal muscle function returns to normal approximately 5 minutes after a single bolus injection of succinylcholine as it passively diffuses away from the neuromuscular junction. Pseudocholinesterase deficiency can result in higher levels of intact succinylcholine molecules reaching receptors in the neuromuscular junction, causing the duration of paralytic effect to continue for as long as 8 hours.

This condition is recognized clinically when paralysis of the respiratory and other skeletal muscles fails to spontaneously resolve after succinylcholine is administered as an adjunctive paralytic agent during anesthesia procedures.

Previous
Next:

Epidemiology

Pseudocholinesterase deficiency is most common in people of European descent; it is rare in Asians.

Previous
Next:

Prognosis

Prognosis for recovery following administration of succinylcholine is excellent when medical support includes close monitoring and respiratory support measures. In nonmedical settings in which subjects with pseudocholinesterase deficiency are exposed to cocaine, sudden cardiac death can occur.

Previous
Next:

Patient Education

Patients with known pseudocholinesterase deficiency may wear a medic-alert bracelet that will notify healthcare workers of increased risk from administration of succinylcholine. These patients also may notify others in their family who may be at risk for carrying one or more abnormal pseudocholinesterase gene alleles.

Previous