Pseudocholinesterase Deficiency

1
Pseudocholinesterase Deficiency

• Doctor, the patient is not waking up and
• can not breathe on their own
• What to do and what to think about
• Dorian Korz PGY-1

2
House of God

• Rule 4 The patient is the one with the disease
• Rule 8 They can always hurt you more
• Rule 13 The delivery of good medical care is to
  do as much nothing as possible

3
Case Presentation

• I.I. is a 47yo AA woman with a longstanding past
  hx of ventral hernia with progressive several
  week hx of abdominal pain and vomiting
• PMHx obese PSHx c-sections Rxsnone
• Allergies NKDA SHX married6 children
• 10/6/08 Ventral hernia repair with mesh
  uncomplicated recovery
• 10/30/08 Debridement of necrotic skin and sub
  cut. tissues with application of wound VAC 3
  hour recovery on vent support

4
Case Presentation

• Medical and cardiac clearance prior to first
  surgery, elevated BP and HR (130-140s)
• Fevers, tachycardia, elev. BP s/p first surgery
  with Neg cultures hyperthyroidism Dxed with
  benign thyroid nodule Bxed
• Anemia and pre-alb 5.3 poor nutritional state

5
Pseudocholinesterase Deficiency

• Background
• Pseudocholinesterase deficiency is an inherited
  enzyme abnormality that results in abnormally
  slow metabolic degradation of exogenous choline
  ester drugs
• Examples succinylcholine, mivacurium, procaine,
  and cocaine

6

• Background
• Condition is recognized most often when
  respiratory paralysis persists for a prolonged
  period of time following administration of
  succinylcholine
• Mainstay of treatment in these cases is
  respiratory support until passive diffusion of
  succ. choline from myoneural junction permits
  function of skeletal muscle

7
Pathophysiology

• Pseudocholinesterase is produced in the liver and
  found in plasma. It has no known physiologic
  function other than to hydrolyze exogenous
  choline esters
• Normal individuals hydrolyze 90-95 of IV succ.
  choline before it reaches the neuromuscular
  junction. 5-10 acts as Ach receptor agonist at
  N-M junction causing prolonged depolarization of
  the postsynaptic junction of the motor-end plate

8
Pathophysiology

• We see its succ. cholines effects as initial
  fasciculations of skeletal muscle.
• Flaccid paralysis develops within 1 minute
• Normal subjects, skeletal muscle function returns
  within 5 mins

9
Frequency

• The incidence of homozygous deficiency in the
  general population is 13,200
• Found most commonly in people of European descent
  and rare in Asians

10
Genetics

• Gene that codes for the pseudocholinesterase
  enzyme is located on Chromo 3 E1 locus on the Q
  arm
• 96 of the population is homozygous for the
  normal genotype designated EuEu
• Point Mutations Ea dibucaine resistant and Ef
  fluoride resistant
• Es frameshift silent variant

11
Other causes of Low enzyme activity

• Physiological States Neonates, elderly, and
  pregnant women
• Pathologic conditions Chronic infections,
  extensive burns, liver dz, malignancy,
  malnutrition, uremia, poisoning by
  organophosphates
• RXs Contraceptives, cyclophosphamide,
  glucocorticoids, metoclopramide, esmolol among
  others

12
Tests Plasma Assay and PCR

• Dibucaine inhibition of hydrolysis of benzyl
  choline lower the percent inhibition the less
  activity of enzyme there is. Normal is 80 EuEu
  mutant alleles 20 EaEa EuEa heterozygous in the
  middle
• Fluoride similar to Dibucaine but normal is 60
  and mutant allele is 36 EfEf

13
Tests

• Acholest test paper plasma drop to paper changes
  colorimetric rxn changes green to yellow the
  longer the change takes the less enz. activity
  there is
• PCR The Danish Cholinesterase Research Unit in
  Copenhagen, Denmark accepts outside patient
  samples for evaluation (Dr. Jørgen Viby-Mogensen)

14
Table 1                                         
                                                  
                               
15
Treatment

• Prophylactic transfusion of FFP, risk of
  iatrogenic infections
• Mechanical ventilatory support until patient
  recovers
• Administration of cholinesterase inhibitors, such
  as neostigmine, controversial and possibly short
  lived effects requiring re-intubation

16
Legal/Medical Pitfalls and Patient Education

• Cocaine use sudden cardiac death
• Patients should be tested and family alerted by
  the patient for the potential of anesthesia
  complications
• If confirmed, pt. may wear medic-alert bracelet
• Take an adequate history, monitor skeletal muscle
  paralysis by electrical stimulation
• Monitor the patient and provide support