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

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

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

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

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

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

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

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

Discussion 2018/11/11 Liu, Chih-Min

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

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

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

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

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

Plasma cholinesterase deficiency Heterozygous atypical Plasma cholinesterase EuEa 1/50 to 1/480 Lengthened by about 50-100% 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

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

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

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

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

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

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

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

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

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

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

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

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

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): 799-801 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

"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 600-1400) 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

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): 1109-11. 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

"Prolonged paresis in a primigravida during and after caesarean section.“ Mekbib, T., Z. D. Djabirov, et al. (1990). Ethiop Med J 28(4): 197-200. A primigravida, who had a Caesarean section because of cervical dystocia and relative cephalo-pelvic disproportion, in Nov. 1988 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

"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

"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 0.67 +/- 0.11 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 0.48 +/- 0.09, 0.38 +/- 0.09, 0.29 +/- 0.10, and 0.19 +/- 0.09 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

"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): 379-85. 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

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

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

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