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| EDITORIAL |
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| Year : 2022 | Volume
: 1
| Issue : 2 | Page : 53-55 |
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Revisiting pseudocholinesterase deficiency: The conundrum of succinylcholine use
Bharti Wadhwa, Kirti N Saxena
Department of Anaesthesia and Intensive Care, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India
| Date of Submission | 31-Oct-2022 |
| Date of Decision | 11-Nov-2022 |
| Date of Acceptance | 12-Nov-2022 |
| Date of Web Publication | 02-Dec-2022 |
Correspondence Address:
Dr. Bharti Wadhwa
Department of Anaesthesia and Intensive Care, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi - 110 002
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/jica.jica_30_22
How to cite this article:
Wadhwa B, Saxena KN. Revisiting pseudocholinesterase deficiency: The conundrum of succinylcholine use. J Ind Coll Anesth 2022;1:53-5 |
This issue describes an interesting case of an unusual presentation of pseudocholinesterase (PChE) deficiency in a parturient undergoing emergent cesarean section by Upadaya and Garg.[1] The delayed reversal from neuromuscular blockade after administration of succinylcholine, was unlike the classic complete prolonged neuromuscular block seen in a patient with PChE deficiency. Partial, weak respiratory efforts were observed initially, but complete recovery from neuromuscular block occurred 6 h after administration of succinylcholine. The presence of PChE deficiency was confirmed by low levels on plasma assay of the enzyme.
The rapid onset and ultra-short duration of succinylcholine provide excellent intubating conditions and can theoretically facilitate an earlier reversal of NM blockade making it highly desirable in emergent situations. However, an undiagnosed PChE deficiency can convert this into a potentially life-threatening situation. Because of multiple complications related to succinylcholine, many anesthesiologists now avoid its use for emergency and elective intubation.[2],[3] The Food and Drug Administration issued a black box warning in 1993 for succinylcholine after a series of cardiac arrests occurred related to hyperkalemia in children with undiagnosed muscular dystrophy.[4]
With the decline in the use of succinylcholine and the availability of safer alternatives such as rocuronium and sugammadex, less and less is being written in textbooks about PChE deficiency.
In India, succinylcholine continues to be the primary relaxant in many centers as well as the preferred relaxant for emergent situations requiring rapid sequence induction. Most of the times, it is the junior doctors or the residents who are managing these cases. It is thus important to revisit PChE deficiency, and start a conversation on this life-threatening but relatively easy-to-manage complication following succinylcholine administration.
Cholinesterase is an enzyme that metabolizes the neurotransmitter acetylcholine into choline and acetic acid returning the neuron to its resting state.[5] There are two types of cholinesterase:
- Acetylcholinesterase (E. C. 3.1.1.7): Found mainly in conducting tissue and to a small extent in red blood cell membrane where it constitutes the Yt blood group antigen
- PChE (BuChE, EC 3.1.1.8): Also known as plasma cholinesterase, butyrylcholinesterase, or acylcholine acylhydrolase: Found primarily in the liver and is responsible for the metabolism of succinylcholine, mivacurium, and local anesthetics chloroprocaine, tetracaine, procaine, and benzocaine.
PChE or butyrylcholinesterase deficiency is a rare, acquired, or inherited condition where the PChE levels are absent or lower than normal with a reduced ability to metabolize succinylcholine and mivacurium leading to prolonged muscular paralysis from standard doses.[5]
Although PChE deficiency is a rare disorder, it is a serious condition since it is difficult to diagnose clinically preoperatively and can be potentially fatal. However, when diagnosed, it is treatable with ventilatory support till spontaneous recovery.
The inherited form is an autosomal recessive genetic condition secondary to mutations in the butyrylcholinesterase gene, located on chromosome 3; 3q26.1-26.20.[6] Since the mutation is recessive, heterozygotes will present with an approximately 30% increase in the duration of action of succinylcholine. Whereas, homozygotes can have persistent muscular paralysis lasting >2 h and often up to 6–8 h after standard dosing.[7]
The incidence of homozygotes for abnormal PChE enzyme is approximately 1 per 2000 to 5000 people.[3] Whereas, the incidence of heterozygotes for the abnormal enzyme is approximately 1 per 500. The male-to-female incidence is 2:1 and it is more prevalent in Caucasian males of European descent, the Persian Jewish community, and Alaskan natives.[8]
In the Indian population, the Arya Vysya community belonging to Coimbatore, Tamil Nadu, state of India, is the most affected with a homozygous mutation incidence rate of 2%–4%.[9]
Acquired PChE deficiency can occur in malnutrition, pregnancy, postpartum period, liver disease, kidney disease, myocardial infarction, congestive heart failure, malignancy, chronic infections, hemodialysis, and burns. Drugs such as steroids and cytotoxic agents can significantly decrease the production of the PChE enzyme while organophosphate insecticides, monoamine oxidase inhibitors, and anticholinesterase drugs are known to inhibit the activity of the enzyme.[6]
PChE deficiency is not detected until the patient has prolonged neuromuscular blockade following exposure to succinylcholine or mivacurium.[8] Such patients usually do not have any clinical manifestations; however, sudden cardiac arrest after cocaine use has been reported in patients with PChE deficiency.[9]
The patient will either have coexisting disease states consistent with the acquired causes of PChE deficiency or may be completely asymptomatic. In the case of acquired disease, preoperative evaluation will give the anesthesiologist some insight; however, in the case of genetic inheritance, the anesthesiologist is caught off guard.
A search of literature reveals that most case reports of PChE deficiency involved unexpected prolonged paralysis after surgery. In a literature review consisting of 40 case reports, from 1956 to 2011, Hackett and Sakai found that the length of paralysis ranged from 50 min to 10 h.[10] PChE deficiency was a retrospective diagnosis in all these cases.
The patients underwent a prolonged hospital stay with a delayed extubation and unanticipated, unnecessary intensive care unit stay, thus emphasizing the need for revisiting PChE deficiency and creating awareness for timely detection and management.
Prevention is the best cure and this old adage could not be truer for a patient with PChE deficiency. A thorough preoperative evaluation can guide the anesthesiologist to the possibility of PChE deficiency. A detailed history should include medical history for acquired causes, any previous anesthesia exposure requiring extended mechanical ventilation due to neuromuscular blockade in the patient as well as any family history of relatives in susceptible populations.
Lee et al. have highlighted the importance of preoperative evaluation and were able to successfully diagnose a patient with undiscovered PChE deficiency through detailed interview and history of prolonged recovery during previous anesthesia exposure.[6]
Preoperative evaluation should include a careful history of drug intake. Recently, Zencirci has reported sertraline-associated acquired PChE deficiency and prolonged muscular paralysis following the administration of mivacurium.[11] Sertraline is a serotonin reuptake inhibitor commonly used for the treatment of depression and is considered a safe drug with minimal side effects.
Diagnosis of PChE deficiency is by exclusion. The differential diagnosis includes but is not limited to narcotic overdose, residual neuromuscular block, cholinergic crisis, myasthenic crisis, hypermagnesemia, hypokalemia, and hypophosphatemia.
Confirmation for PChE deficiency can be performed by the following techniques:
Dibucaine number is a qualitative test of PChE enzyme activity. Dibucaine is an amino amide local anesthetic that inhibits the activity of the normal variant of the PChE enzyme by 80%. Dibucaine number gives the degree of enzymatic inhibition resulting from dibucaine exposure and is 50–60 for heterozygotes and 20–30 for homozygotes.[12]
Dibucaine has minimal effect and is an unreliable predictor of atypical variant enzyme activity. Ellison et al. encountered prolonged paralysis following the administration of succinylcholine for an emergent cesarean section despite laboratory evidence of normal dibucaine number.[12] Although the enzyme was functionally normal, it was found to be low in quantity and likely had an atypical PChE enzyme variant.
A more reliable test is the plasma assays of PChE enzyme activity. The time of collection of plasma is important since succinylcholine metabolites can affect the results. The plasma samples should, therefore, be collected after muscle paralysis has completely resolved for a more correct diagnosis.
A rapid screening may be done using the Acholest Test Paper. It is a simple card test for PChE enzyme activity, wherein the time taken by the exposed Acholest Test Paper to turn from green to yellow is inversely proportional to the PChE enzyme activity in the plasma sample.
Patients diagnosed with PChE deficiency are expected to make a full recovery after administration of succinylcholine or mivacurium provided adequate mechanical ventilation and vigilant monitoring is provided to ensure the spontaneous return of motor function.
Some authors advocate shortening the duration of the prolonged block by providing exogenous PChE through administration of fresh frozen plasma or packed red blood cells. The benefits of this need to be weighed in with the risk associated with administration of blood products vis-a-vis the extra hours of continued mechanical ventilation.[13]
Pharmacological blockade reversal with neostigmine and physostigmine is not recommended as these drugs can also inhibit the activity of PChE enzyme leading to further prolongation of the paralysis as reported by Upadaya and Garg.[1] Since the administration of neostigmine can inhibit the enzyme activity, therefore, for an accurate assessment of cholinesterase activity, a blood sample for confirmation of diagnosis should be drawn after the effect of neostigmine has dissipated.
With the significantly large number of factors for PChE deficiency, one wonders whether a better solution would be to avoid the use of succinylcholine all together?
With the availability of rocuronium and sugammadex, we have a safer and viable alternative to succinylcholine that can provide a similar condition but with fewer side effects. The concern of PChE deficiency and prolonged unexpected ventilation can become irrelevant with the routine use of these alternatives.
It is, however, important to note that in many centers, especially in the remote parts of our country, succinylcholine is the primary muscle relaxant and perhaps it may not be practically possible to say goodbye to succinylcholine as yet.
Succinylcholine is also a vital drug for breaking a refractory laryngospasm. Bui and Asher report a case where succinylcholine was emergently and successfully used to treat acute, refractory laryngospasm following extubation, but this was followed by prolonged neuromuscular blockade due to PChE deficiency.[14]
It is, therefore, prudent that a detailed preoperative evaluation for any suggestive history or acquired causes of PChE deficiency should be done. Keep a high index of suspicion in the event of delayed or inadequate recovery from neuromuscular block. Plasma enzyme assay will help confirm the diagnosis. The patient may be advised to wear a MedicAlert bracelet and the immediate family members should be encouraged to get tested keeping in mind the genetic inheritance of PChE deficiency.
| References | |  |
| 1. | Upadhyay P, Garg S. Demystifying a hassle in obstetric anaesthesia: A case report. J Indian Coll Anaesth 2022;2:74-6.  |
| 2. | Klucka J, Kosinova M, Zacharowski K, De Hert S, Kratochvil M, Toukalkova M, et al. Rapid sequence induction: An international survey. Eur J Anaesthesiol 2020;37:435-42. |
| 3. | Stäuble CG, Blobner M. The future of neuromuscular blocking agents. Curr Opin Anaesthesiol 2020;33:490-8. |
| 4. | Bhananker SM, Ramamoorthy C, Geiduschek JM, Posner KL, Domino KB, Haberkern CM, et al. Anesthesia-related cardiac arrest in children: Update from the Pediatric Perioperative Cardiac Arrest Registry. Anesth Analg 2007;105:344-50. |
| 5. | Gropper MA, Cohen NH, Eriksson LI, Fleisher LA, Leslie K, Wiener-Kronish JP, editors. Miller's Anesthesia. 9 th ed. Philadelphia: Elsevier Churchill Livingstone; 2020. |
| 6. | Lee S, Han JW, Kim ES. Butyrylcholinesterase deficiency identified by preoperative patient interview. Korean J Anesthesiol 2013;65:S1-3. |
| 7. | Thomsen JL, Nielsen CV, Palmqvist DF, Gätke MR. Premature awakening and underuse of neuromuscular monitoring in a registry of patients with butyrylcholinesterase deficiency. Br J Anaesth 2015;115 Suppl 1:i89-94. |
| 8. | Andersson ML, Møller AM, Wildgaard K. Butyrylcholinesterase deficiency and its clinical importance in anaesthesia: A systematic review. Anaesthesia 2019;74:518-28. |
| 9. | Ramaiah M, Ramakrishna P. Pseudocholinesterase deficiency in an Indian community. JPPCM 2017;3:27-30. |
| 10. | Hackett PJ, Sakai T. Pseudocholinesterase deficiency: A case report and literature review. Open J Anesthesiol 2012;2:188-94. |
| 11. | Zencirci B. Pseudocholinesterase enzyme deficiency: A case series and review of the literature. Cases J 2009;2:9148. |
| 12. | Ellison M, Grose B, Howell S, Wilson C, Lenz J, Driver R. Prolonged paralysis following emergent cesarean section with succinylcholine despite normal dibucaine number. W V Med J 2016;112:44-6. |
| 13. | Zhang C, Cao H, Wan ZG, Wang J. Prolonged neuromuscular block associated with cholinesterase deficiency. Medicine (Baltimore) 2018;97:e13714. |
| 14. | Bui DD, Asher SR. Break the spasm with succinylcholine, but risk intraoperative awareness with undiagnosed pseudocholinesterase deficiency. Case Rep Anesthesiol 2020;2020:8874617. |
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