1. Succinylcholine and Plasma cholinesterase deficiency
Is there more we didn’t see?
2018/11/11
Liu, Chih-Min

2. Case 2004/5/6 馬X珮 Female 39/1 3927666 05A -11-01 Uterine myoma
No any special medical history
2018/11/11
Liu, Chih-Min

3. Case Induction agent Maintain Reverse
Atropine, fentanyl, propofol, SCC
Maintain
Cisatracurium, volatile agent
Reverse
Atropine, Enlon
2018/11/11
Liu, Chih-Min

4. Case Total operation time Recovery time About 90 minutes 2018/11/11
Liu, Chih-Min

5. Case At the beginning of recovery Suction with reflex
Reverse with atropine and Enlon
Peripheral muscle weakness
No respiration movement
No eye opening
2018/11/11
Liu, Chih-Min

6. Case Keep ventilator support for 30 minutes Eye opening
Muscle weakness
Can not head elevation
Hand elevation for 2 seconds
Recovery of respiratory muscle with small tidal volume
50ml- 100ml
2018/11/11
Liu, Chih-Min

7. Case Keep ET tube for another 30 minutes with assistance
Remove ET tube for another 30 minutes with mask assistance
Send patient to POR for close observation about 2 hours
2018/11/11
Liu, Chih-Min

8. Case Patient recall Recovery of consciousness
Can hear our talking and discussion
Can not move and open her eyes when she awake
Know we are trying to help her
2018/11/11
Liu, Chih-Min

9. Discussion
2018/11/11
Liu, Chih-Min

10. What happened to her?
2018/11/11
Liu, Chih-Min

11. Myasthenia Gravis or Plasma cholinesterase deficiency
2018/11/11
Liu, Chih-Min

12. Is Myasthenia Gravis possible?
No history of MG
The incidence is about 1:10,000
Clinical course not likely
The patient did not recovery with reverse agent
Edrophonium test (-)
Muscle power recovery with time and did not decrease with the metabolism of recovery agent
MG is not likely
2018/11/11
Liu, Chih-Min

13. Plasma cholinesterase deficiency?
What is plasma cholinesterase?
a glycoprotein enzyme
Produced by liver
Metabolize SCC, ester local anesthetics and mivacurium (NMB)
2018/11/11
Liu, Chih-Min

14. Plasma cholinesterase deficiency
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 SCC dose acts as an acetylcholine receptor agonist at the neuromuscular junction, causing prolonged depolarization of the postsynaptic junction of the motor-end plate.
2018/11/11
Liu, Chih-Min

15. Plasma cholinesterase deficiency
Heterozygous atypical Plasma cholinesterase
EuEa
1/50 to 1/480
Lengthened by about %
Longer than 5 minutes but shorter than 1 hour
Homozygous atypicalPlasma cholinesterase
EaEa
1/3000 to 1/3200
Prolonged to 4-8 hours
2018/11/11
Liu, Chih-Min

16. Plasma cholinesterase deficiency
The most severe form
occurs in only 1 in 100,000 individuals who are homozygous for the silent Es genotype,
with no detectible pseudocholinesterase enzyme activity.
These individuals may exhibit prolonged muscle paralysis for as long as 8 hours following a single dose of succinylcholine.
2018/11/11
Liu, Chih-Min

17. Plasma cholinesterase deficiency
Internationally:
Pseudocholinesterase deficiency is most common in people of European descent; it is rare in Asians
Physical:
No characteristic physical examination findings correlate with the presence of pseudocholinesterase deficiency
2018/11/11
Liu, Chih-Min

18. Plasma cholinesterase deficiency
Cause
Inherited causes
Acquired causes
2018/11/11
Liu, Chih-Min

19. Plasma cholinesterase deficiency
People, such as
neonates
elderly individuals
pregnant women
with certain physiologic conditions may have lower plasma pseudocholinesterase activity.
2018/11/11
Liu, Chih-Min

20. Plasma cholinesterase deficiency
Pathologic conditions that may lower plasma pseudocholinesterase activity include the following:
Chronic infections (tuberculosis)
Extensive burn injuries
Liver disease
Malignancy
Malnutrition
Organophosphate pesticide poisoning
Uremia
2018/11/11
Liu, Chih-Min

21. Plasma cholinesterase deficiency
Iatrogenic causes of lower plasma pseudocholinesterase activity include plasmapheresis and medications such as the following:
Anticholinesterase inhibitors
Bambuterol
Chlorpromazine
Contraceptives
Cyclophosphamide
Echothiophate eye drops
Esmolol
Glucocorticoids
Hexafluorenium
Metoclopramide
Monoamine oxidase inhibitors
Pancuronium
Phenelzine
Tetrahydroaminacrine
2018/11/11
Liu, Chih-Min

22. Plasma cholinesterase deficiency
Reduce quantity at
Liver disease
Renal failure
Pregnancy
Burns
Malnutrition
Malignancy
Hypothyroidism
Collagen vascular disease
2018/11/11
Liu, Chih-Min

23. Plasma cholinesterase deficiency
Lab test
The dibucaine (local anesthetic) number
Inhibit plasma cholinesterase activity
Normal homozygous typical genotype Plasma cholinesterase activity is 80% inhibition
Heterozygous enzyme is about 40-60% inhibition
Homozygous genotype have only 20% inhibition
2018/11/11
Liu, Chih-Min

24. Plasma cholinesterase deficiency
Medical Care
Prophylactic transfusion of fresh frozen plasma
Mechanical ventilatory support is the mainstay of treatment until respiratory muscle paralysis spontaneously resolves.
Administration of cholinesterase inhibitors, such as neostigmine, is controversial for reversing succinylcholine-related apnea in patients who are pseudocholinesterase deficient. The effects may be transient, possibly followed by intensified neuromuscular blockade.
2018/11/11
Liu, Chih-Min

25. Plasma cholinesterase deficiency
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.
2018/11/11
Liu, Chih-Min

26. Plasma cholinesterase deficiency
Medical/Legal Pitfalls:
Failure to take an adequate history of previous adverse reactions to succinylcholine, mivacurium, or cocaine in either the patient's own medical history or in the family history
Failure to monitor skeletal muscle paralysis by electrical tetanic stimulation
Failure to provide adequate respiratory function monitoring and support after the administration of succinylcholine or mivacurium
2018/11/11
Liu, Chih-Min

27. Is there more cases we didn’t know?
Induction with SCC
Maintained by non-depolarizing muscle relaxant
If the duration of operation was lasting for about 2-4 hours…
How many cases did we miss?
2018/11/11
Liu, Chih-Min

28. We describe a simple PCR method for the detection of this variant.
"Rapid identification of atypical variant of plasma butyrylcholinesterase by PCR." Ceppa, F., S. Gidenne, et al. (2002). Clin Chem Lab Med 40(8):
We describe a simple PCR method for the detection of this variant.
Thirteen out of sixteen patients tested after prolonged apnea were positive for the presence of this mutation (50.0% homozygotes and 31.3% heterozygotes), suggesting that this test contributes to the explanation of some clinical events and to their prevention in relatives of these patients.
2018/11/11
Liu, Chih-Min

29. "Mivacurium-induced prolonged neuromuscular block. " Sockalingam, I
"Mivacurium-induced prolonged neuromuscular block." Sockalingam, I. and D. W. Green (1995). Br J Anaesth 74(2): 234-6
We report a case of prolonged neuromuscular block after administration of mivacurium 0.2 mg kg-1 to a 16-yr-old patient where the duration of block was 2.5 h.
The interesting points in this case were that the patient had homozygous atypical plasma cholinesterase deficiency (both parents had a normal phenotype) following liver transplantation.
Investigations showed low plasma cholinesterase activity (343 iu litre-1; normal ) and dibucaine number was 25 (normal 76-83).
Despite possessing atypical enzyme normally associated with markedly prolonged duration of suxamethonium, on two occasions the patient received suxamethonium and responded normally.
This had not previously been reported. The patient demonstrated prolonged block with mivacurium as a result of atypical enzyme (despite normal metabolism of suxamethonium).
2018/11/11
Liu, Chih-Min

30. One month later her levels were back within the reference range.
"Suxamethonium and mivacurium sensitivity from pregnancy-induced plasma cholinesterase deficiency.“ Davies, P. and M. Landy (1998). Anaesthesia 53(11):
A fit 36-year-old parturient received a general anaesthetic for manual removal of a retained placenta.
She underwent rapid sequence induction of anaesthesia with suxamethonium, shortly followed by 10 mg of mivacurium.
One hour later she had failed to establish adequate ventilation despite administration of drugs to reverse neuromuscular blockade.
A provisional diagnosis of suxamethonium-related apnoea was made and her lungs were ventilated overnight on the Intensive Care Unit.
Plasma cholinesterase levels at the time were reduced to one-third of normal, with normal dibucaine and fluoride numbers.
One month later her levels were back within the reference range.
2018/11/11
Liu, Chih-Min

31. "Prolonged paresis in a primigravida during and after caesarean section.“ Mekbib, T., Z. D. Djabirov, et al. (1990). Ethiop Med J 28(4):
A primigravida, who had a Caesarean section because of cervical dystocia and relative cephalo-pelvic disproportion, in Nov in Yekatit 12 Hospital, Addis Ababa, remained relaxed and without spontaneous respiration for about four hours after the completion of the operation, requiring assisted respiration.
This condition is the result of a decreased plasma cholinesterase (PCE) activity which is responsible for the breaking down of succinylcholine used in general anaesthesia as a muscle relaxant.
Although the incidence of PCE deficiency in our population is not known, it should be remembered that such a complication may be seen in hospitals where operations are carried out using succinylcholine as a muscle
2018/11/11
Liu, Chih-Min

32. "Some observations of levels of plasma cholinesterase activity within an obstetric population.“ Whittaker, M., J. S. Crawford, et al. (1988). Anaesthesia 43(1): 42-5
An account of plasma cholinesterase activity in samples of maternal and cord blood is presented.
It is confirmed that plasma exchange markedly reduces the level of activity in maternal blood, and that the level is further reduced during the first 3-4 postnatal days.
A particularly marked decrease was found in those cases in which spontaneous mid-trimester abortion occurred.
2018/11/11
Liu, Chih-Min

33. "Inhibitory effect of quinidine on plasma pseudocholinesterase activity in pregnant women.“ Kambam, J. R., J. J. Franks, et al. (1987). Am J Obstet Gynecol 157(4 Pt 1): 897-9
The effect of quinidine at therapeutic and subtherapeutic concentrations on pseudocholinesterase activity in the plasma of 16 normal pregnant women was studied.
The mean plasma pseudocholinesterase activity in the absence of quinidine (control) was / U/ml. The mean pseudocholinesterase activity in the presence of quinidine at concentrations of 0.5, 1.0, 2.0, and 5.0 micrograms/ml /- 0.09, /- 0.09, /- 0.10, and / U/ml, respectively.
At therapeutic concentrations needed to treat cardiac arrhythmias (2 to 5 micrograms/ml), quinidine inhibited pseudocholinesterase activity by 60% to 70%.
All the plasma samples had a normal dibucaine number (78 to 85).
We recommend caution when succinylcholine and/or ester-type local anesthetics are used in pregnant women receiving quinidine.
2018/11/11
Liu, Chih-Min

34. "Plasma cholinesterase in pregnancy--effect of enzyme activity on the duration of action of succinylcholine.“ Gyasi, H. K., O. Mohy, et al. (1986). Middle East J Anesthesiol 8(5):
The duration of action of succinylcholine, 1 mg/kg and plasma cholinesterase activity were compared in 25 pregnant women undergoing cesarean section and 25 non-pregnant women undergoing elective surgery.
Neuromuscular activity was assessed by observation of thumb adduction, following stimulation of the ulnar nerve at the wrist.
The duration of action of succinylcholine was significantly longer and enzyme levels significantly lower in the pregnant women.
Monitoring of neuromuscular function is recommended when succinylcholine is used in pregnant women.
2018/11/11
Liu, Chih-Min

35. Prolonged neuromuscular blockade as a result of malnutrition-induced pseudocholinesterase deficiency Ahtsham Niazi, MB Journal of Clinical Anesthesia Volume 16 • Number 1 • February 2004
Mivacurium is a short-acting neuromuscular blocking drug, ideal for short surgical procedures. The brief duration of action depends on rapid hydrolysis by plasma cholinesterase.
An inherited or acquired deficiency of plasma cholinesterase can prolong the effect of mivacurium.
We present an unusual case of unanticipated postoperative apnea following mivacurium administration, as a result of acquired plasma cholinesterase deficiency, in a patient with previous uneventful exposure to both mivacurium and suxamethonium (succinylcholine).
2018/11/11
Liu, Chih-Min

36. What can we do in the future?
Ask!
Was the patient or any family member ever felt weak after a previous anesthetic or needed a breathing machine after a routine surgical problem?
Be suspicious!
Pray?
2018/11/11
Liu, Chih-Min

37. Thanks for your attention
Good luck!
2018/11/11
Liu, Chih-Min