Succinylcholine and Plasma cholinesterase deficiency Is there more

Succinylcholine and Plasma cholinesterase deficiency Is there more we didn’t see? 1 9/9/2020 Liu, Chih-Min

Case l l l 2 2004/5/6 馬X珮 Female 39/1 3927666 05 A -11 -01 Uterine myoma No any special medical history 9/9/2020 Liu, Chih-Min

Case l Induction agent – l Maintain – l Cisatracurium, volatile agent Reverse – 3 Atropine, fentanyl, propofol, SCC Atropine, Enlon 9/9/2020 Liu, Chih-Min

Case l Total operation time – l Recovery time – 4 About 90 minutes 9/9/2020 Liu, Chih-Min

Case l At the beginning of recovery – – – 5 Suction with reflex Reverse with atropine and Enlon Peripheral muscle weakness No respiration movement No eye opening 9/9/2020 Liu, Chih-Min

Case l l l Keep ventilator support for 30 minutes Eye opening Muscle weakness – – l Recovery of respiratory muscle with small tidal volume – 6 Can not head elevation Hand elevation for 2 seconds 50 ml- 100 ml 9/9/2020 Liu, Chih-Min

Case l l l 7 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 9/9/2020 Liu, Chih-Min

Case l Patient recall – – 8 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 9/9/2020 Liu, Chih-Min

Discussion 9 9/9/2020 Liu, Chih-Min

What happened to her? 10 9/9/2020 Liu, Chih-Min

Myasthenia Gravis or Plasma cholinesterase deficiency 11 9/9/2020 Liu, Chih-Min

Is Myasthenia Gravis possible? l No history of MG – l Clinical course not likely – – – l 12 The incidence is about 1: 10, 000 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 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency? l What is plasma cholinesterase? – – – 13 a glycoprotein enzyme Produced by liver Metabolize SCC, ester local anesthetics and mivacurium (NMB) 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l l 14 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. 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Heterozygous atypical Plasma cholinesterase – Eu. Ea – 1/50 to 1/480 Lengthened by about 50 -100% – Longer than 5 minutes but shorter than 1 hour Homozygous atypical. Plasma cholinesterase – Ea. Ea – l 15 – 1/3000 to 1/3200 – Prolonged to 4 -8 hours 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l The most severe form – – l 16 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. 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Internationally: – l Physical: – 17 Pseudocholinesterase deficiency is most common in people of European descent; it is rare in Asians No characteristic physical examination findings correlate with the presence of pseudocholinesterase deficiency 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Cause – – 18 Inherited causes Acquired causes 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l People, such as – – 19 neonates elderly individuals pregnant women with certain physiologic conditions may have lower plasma pseudocholinesterase activity. 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Pathologic conditions that may lower plasma pseudocholinesterase activity include the following: – – – – 20 Chronic infections (tuberculosis) Extensive burn injuries Liver disease Malignancy Malnutrition Organophosphate pesticide poisoning Uremia 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Iatrogenic causes of lower plasma pseudocholinesterase activity include plasmapheresis and medications such as the following: – – – – 21 Anticholinesterase inhibitors Bambuterol Chlorpromazine Contraceptives Cyclophosphamide Echothiophate eye drops Esmolol Glucocorticoids Hexafluorenium Metoclopramide Monoamine oxidase inhibitors Pancuronium Phenelzine Tetrahydroaminacrine 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Reduce quantity at – – – – 22 Liver disease Renal failure Pregnancy Burns Malnutrition Malignancy Hypothyroidism Collagen vascular disease 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Lab test – – – 23 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 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Medical Care – – – 24 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 succinylcholinerelated apnea in patients who are pseudocholinesterase deficient. The effects may be transient, possibly followed by intensified neuromuscular blockade. 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Patient Education: – – 25 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. 9/9/2020 Liu, Chih-Min

Plasma cholinesterase deficiency l Medical/Legal Pitfalls: – – – 26 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 9/9/2020 Liu, Chih-Min

Is there more cases we didn’t know? l l 27 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? 9/9/2020 Liu, Chih-Min

"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 l l 28 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. 9/9/2020 Liu, Chih-Min

"Mivacurium-induced prolonged neuromuscular block. " Sockalingam, I. and D. W. Green (1995). Br J Anaesth 74(2): 234 -6 – – – 29 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). 9/9/2020 Liu, Chih-Min

"Suxamethonium and mivacurium sensitivity from pregnancy -induced plasma cholinesterase deficiency. “ Davies, P. and M. Landy (1998). Anaesthesia 53(11): 1109 -11. – – – 30 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 onethird of normal, with normal dibucaine and fluoride numbers. One month later her levels were back within the reference range. 9/9/2020 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. l l l 31 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 9/9/2020 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 – – – 32 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. 9/9/2020 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 l l l 33 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. 9/9/2020 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. – – 34 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. 9/9/2020 Liu, Chih-Min

Prolonged neuromuscular blockade as a result of malnutritioninduced pseudocholinesterase deficiency Ahtsham Niazi, MB Journal of Clinical Anesthesia Volume 16 • Number 1 • February 2004 l l l 35 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). 9/9/2020 Liu, Chih-Min

What can we do in the future? l Ask! – l l 36 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? 9/9/2020 Liu, Chih-Min

Thanks for your attention Good luck! 37 9/9/2020 Liu, Chih-Min