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Introduction Variants of butyrylcholinesterase are frequently associated with prolonged response to suxamethonium or mivacurium. Butyrylcholinesterase (BChE) can be characterized by phenotyping and determination of genotype. Inappropriate timing of blood sampling might interfere with phenotyping methods. However, guidelines regarding delay between exposure to anaesthesia and testing are not clearly defined. In this study, the BChE activity and phenotype in an early (T1) and late (T2) phase were compared and the phenotype/genotype correlation was assessed. Methods Patients with a prolonged paralysis after mivacurium or suxamethonium were selected after ethical committee approval and written consent. BChE activity was based on butyrylthiocholine hydrolysis rate and phenotyping on differential inhibition of BChE activity with dibucaine and fluoride. DNA sequencing allowed genotypic characterization. Results We included the results of 20 patients with prolonged neuromuscular block (NMB) induced by mivacurium or suxamethonium. In these patients, BChE activity was different at T1 and T2 (2120 [1506-2733] U L(-1)and 4055 [2810-5301] U L-1, respectively;P = 0.0014; values are mean [95% CI]). When phenotyping was possible, phenotyping at T1 and T2 yielded identical results. Phenotyping failed to identify one new variant (p.Tyr146Cys) and the K variant in 14 of 16 patients. Conclusion Anaesthesia interfered with BChE activity, but not with phenotyping. Phenotyping can be performed on blood drawn during or immediately after recovery of mivacurium or suxamethonium to screen for clinically relevant variants of BChE. However, accurate diagnosis of BChE deficiency needs further confirmation by determination of genotype.

Introduction This study sought to describe the phenotype and genotype characteristics of patients referred to our laboratory to undergo further assessment due to a suspicion of a prolonged effect of suxamethonium attributed to BChE deficiency. Methods All patients referred to our laboratory from January 2016 to December 2019 due to the suspicion of a prolonged effect of suxamethonium were included in this study. The determination of BChE activity and genotyping using complete nucleotide sequencing of the entire complementary DNA-coding region with flanking intron–exon boundaries were completed. Results During this four-year period, 58 patients were referred to our laboratory for the investigation of prolonged neuromuscular block due to BChE deficiency. Among them, 52 showed a BChE deficiency related to BCHE gene mutations. The most commonly detected genotype was compound homozygous atypical variant (p.Asp98Gly)/homozygous Kalow variant (p.Ala569Thr) (p.[Asp98Gly;Ala567Thr];[p.Asp98Gly;Ala567Thr]). Further, we recorded four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea: p.(Trp205Cys), p.(Leu222His), p.(Glu469Gln), and p.(Lys276Ter). Conclusion During a four-year period, among the 58 patients referred to our laboratory, we have found four new BCHE variants, which seem to be associated with prolonged post suxamethonium apnoea (p.(Trp205Cys), p.(Leu22His), p.(Glu469Gln), and p.(Lys276Ter)).

Succinylcholine is a short-term curare which degradation depends on its quick hydrolysis by butyrylcholinesterase (or pseudocholinesterase). Thus, a butyrycholinesterase deficiency, congenital or acquired, is a cause of a prolonged neuromuscular block. From an autosomal recessive inheritance, genetic deficiency remains the first etiology. The most frequently discussed variant is the atypical variant which caused a 2 hours prolonged curarisation after administration of succinylcholine. We report a patient who had a prolonged curarisation after succinylcholine's injection, due to a congenital butyrylcholinestérase deficiency and contributed by a lithium treatment. Extubation was only possible 7 hours after administration of curare.

Delayed awakening from anesthesia remains one of the biggest challenges that involve an anesthesiologist. With the general use of fast-acting anesthetic agents, patients usually awaken quickly in the postoperative period. The time to emerge from anesthesia is affected by patient factors, anesthetic factors, duration of surgery, and painful stimulation. The principal factors responsible for delayed awakening following anesthesia are anesthetic agents and medications used in the perioperative period. Nonpharmacological causes may have a serious sequel, hence recognizing these organic conditions is important. Certain underlying metabolic disorders such as hypoglycemia, severe hyperglycemia, and electrolyte imbalance, especially hypernatremia, hypoxia, hypercapnia, central anticholinergic syndrome, chronic hypertension, liver disease, hypoalbuminemia, uremia, and severe hypothyroidism may also be responsible for delayed recovery following anesthesia. Unexpected delayed emergence after general anesthesia may also be due to intraoperative cerebral hypoxia, hemorrhage, embolism, or thrombosis. Accurate diagnosis of the underlying cause is the key for the institution of appropriate therapy, but primary management is to maintain airway, breathing, and circulation. This comprehensive review discusses the risk factors, causes, evaluation and management of delayed recovery based on our clinical experience, and literature search on the internet, supported by the standard textbooks of anesthesiology.

Rationale: Hereditary genetic mutations may cause congenital cholinesterase deficiency. When succinylcholine and mivacurium are applied on cholinesterase-deficient patients during general anesthesia, prolonged postoperative asphyxia occurs, which is an uncommon but very serious complication. Patient concerns: A previously healthy 30-year-old female presented prolonged spontaneous breathing recovery after general anesthesia. Diagnoses: After the patient's postoperative spontaneous breathing recovery delayed, the plasma cholinesterase was found to be 27 U/L, which was far below the normal level (4000 U/L to 13500 U/L). This patient had no disease that can cause plasma cholinesterase deficiency and was therefore diagnosed as congenital cholinesterase deficiency. Interventions and outcomes: The patient was sent to the intensive care unit (ICU) intubated for mechanical ventilator support, and on the next day the tracheal tube was removed without any complications when her spontaneous respiration resumed. Lessons: Cholinesterase is an enzyme secreted by the liver involved in many physiological processes in human body. Plasma cholinesterase commonly contains acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). When succinylcholine and mivacurium are applied on patients with cholinesterase-deficiency during general anesthesia, prolonged postoperative asphyxia occurs, which is an uncommon but very serious complication. Lately, new evidences have suggested that hereditary genetic mutations may be responsible for congenital cholinesterase deficiency.

It is known that the duration of rocuronium action can be prolonged in elderly patients and that such action shows important interindividual variability. We report a case of prolonged neuromuscular block lasting 11 h, in a woman subjected to kidney transplantation. The possible causes of such prolonged action, inherent to the drug, or related to external factors, are commented.

The pharmacodynamics and pharmacokinetics of the currently available neuromuscular blocking and reversal drugs may be altered by organ disease. Adverse effects such as prolonged neuromuscular block, postoperative residual curarisation, recurarisation, the muscarinic effects of the anticholinesterases, and the side-effects of the antimuscarinics are encountered more frequently. This review will consider these potential problems and assess the role of sugammadex in enabling the anaesthetist to avoid them. It will also present the latest knowledge regarding the safety and efficacy of sugammadex in patients with renal, hepatic, cardiovascular and pulmonary disease.

The authors report two cases of prolonged neuromuscular block after administration of mivacurium in children with previously undiagnosed plasma cholinesterase deficiency related to homozygous atypical genotype. Their anaesthetic management is described as well as determination of the phenotype of both children and their family.

Resume Le cas d'une curarisation prolongee apres chlorure de mivacurium pour cholecystectomie sous cœlioscopie est rapporte chez une patiente traitee par cyclophosphamide pour une granulomatose de Wegener. Le monitorage de la transmission neuromusculaire par train de quatre montrait une duree d'action de 75 min, apres une dose d'induction de 0,20 mg·kg −1 . Des reinjections de 1 mg, soit le quart des doses usuelles, toutes les 10 a 15 min ont suffi a l'entretien. La recuperation spontanee, sans antagonisation, a dure 40 min pour un rapport T4/T1 ≥ 70 %. L'index de recuperation du twitch 25–75 % etait de 13 min. Le dosage des butyrilcholinesterases plasmatiques montrait une activite diminuee a 50 % de la normale. Au regard de la litterature concernant la succinylcholine, la responsabilite du cyclophosphamide est vraisemblable, et discutee. Cette observation met en evidence l'interet du monitorage de la transmission neuromusculaire.

Mivacurium, a new short acting non depolarizing neuromuscular blocker, is metabolized, as suxamethonium, by plasma cholinesterase. Therefore its duration of action is increased in patients with reduced plasma cholinesterase activity. We report a case of prolonged neuromuscular block after an i.v. bolus of mivacurium (0.20 mg.kg-1) in a 69 year-old ASA II woman with an unrecognized cholinesterase deficiency undergoing a lumbar sympathectomy for arteriopathy of the lower limbs. The duration of the block was 6 h and plasma cholinesterase concentrations were very low (540 and 610 UI.L-1), as well as the dibucaine number (16%), which suggests an homozygous enzymatic deficiency. Mechanical ventilation and sedation were continued until spontaneous return of full neuromuscular function.

Mivacurium is a new neuromuscular blocking agent with a short acting time of about 30 min, due to a fast hydrolysis by pseudocholinesterases. This metabolism carries a risk for prolonged neuromuscular block in case of an acquired or congenital pseudocholinesterase deficiency. We report the case of a 75-year-old woman who experienced a neuromuscular block prolonged for 10 h after a single dose of 0.35 mg.kg-1 of mivacurium, because of a major pseudocholinesterase (1800 UI.L-1, normal value: 5400-13200 UI.L-1). The likely cause was a congenital deficiency by a homozygote genetic mutation, as usual causes of an acquired deficiency had been eliminated.

Objective: To present a case of unexpected prolonged apnoea following the administration of mivacurium, a short-acting muscle relaxant and to identify the factors for early diagnosis and management. Clinical Presentation and Intervention: A 19-year-old physically fit lady without personal or family history suggestive of anaesthetic problems had an excision of fibro-adenoma from the breast. She did not recover as quickly as was expected from the anaesthetic, which included the administration of mivacurium. She had prolonged neuromuscular blockade. She was kept ventilated and sedated. Five hours after the last dose of mivacurium, she showed signs of spontaneous respiration and at 6 h she was extubated and fully recovered. It was shown later that the patient had a pseudocholinesterase deficiency. Conclusion: Pseudocholinesterase deficiency is an uncommon occurrence but should be highly suspected in cases of prolonged paralysis following the administration of a short-acting muscle relaxant. The use of a nerve stimulator is recommended whenever muscle relaxants are used. Muscle relaxants should be used only when facilities for prolonged ventilation are available.

Summary An 11-day-old neonate with renal failure caused by dysplastic kidneys was anaesthetised with thiopentone, vecuronium, nitrous oxide and oxygen, for insertion of a long-term peritoneal dialysis catheter. Complete neuromuscular block of 210 minutes’duration ensued after the initial dose of vecuronium (97 μg/kg). Partial block persisted for a further 30 minutes. The prolonged neuromuscular block in this case may have been because of proportionately greater dependence on renal clearance of vecuronium in neonates.

Neuromuscular blocking drugs in intensive care units (ICU) may cause complications, including prolonged neuromuscular block as a result of overdosage and post-ventilation muscle weakness. These may be increased by using inappropriately high infusion rates for infants, in whom published studies are scarce, and by failure to monitor neuromuscular block. There is little ICU experience of acceleromyography, which may permit more reliable monitoring. To determine appropriate vecuronium infusion rates, 12 neonates/infants (median age 4 (interquartile range (IQR) 2-5) months) and 18 children (median age 3.07 (2-10 yr) were studied. The vecuronium infusion rate was adjusted to maintain train-of-four (TOF) at 1 response using the TOF guard accelerometer. Recovery time was measured from cessation of infusion until spontaneous TOF ratio recovery of 0.7. Neonates and infants required 45% less vecuronium (mean infusion rate 54.7 (SEM 4.23) micrograms kg-1 h-1) than older children (98.7 (7.07) micrograms kg-1 h-1) and had faster recovery to 70% T4/T1 (45 (IQR 20-51) min vs 65 (55-103) min), with no evidence of prolonged weakness. Routine monitoring of neuromuscular block in ICU is essential; acceleromyography is convenient and reliable.

Summary Mivacurium is a relatively new short-acting nondepolarizing neuromuscular blocker. A recommended dose of 0.15-0.2 mg kg"1 provides tracheal intubating conditions within 2.5 min and duration of action of 15-30 min, making it a possible alternative to suxamethonium for short procedures requiring tracheal intubation. However, in common with suxamethonium its metabolism depends primarily on plasma cholinesterase and its duration of action is prolonged in patients with reduced plasma cholinesterase activity. We present a case of unexpected prolonged neuromuscular block in a child with previously undiagnosed plasma cholinesterase deficiency. (Br. J. Anaesth. 1995; 74: 237-238)

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).

Vecuronium was used to provide muscle relaxation in a patient who subsequently developed prolonged neuromuscular blockade (8 h) after anaesthesia. The aetiology of this condition, and the possible role of vecuronium, are discussed.

SUMMARY This report describes the potentiation of a suxamethonium-induced (0.1 mg\kg) neuromuscular block in two children with atypical serum cholinesterase activity, and compares it with a control response demonstrated in a homozygote brother. In the atypical homozygote patients, suxamethonium produced a markedly prolonged neuromuscular block associated with partial desensitization as evidenced by tetanic fade and post-tetanic facilitation. The use of neostigmine 0.05 mg\kg for reversal was followed by a paradoxical potentiation of the block and a marked delay in recovery. It is suggested that in atypical homozygotes, the development of desensitization after suxamethonium does not necessarily imply that the block will be reversed with neostigmine.

A case is described of prolonged neuromuscular block in a patient who was given the muscle relaxant vecuronium followed by bolus injections of the antibiotics gentamycin and clindamycin.

The possibility of "recurarization" after antagonism of the competitive neuromuscular block with anticholinesterases was studied. Observations were made on the time-course of the block in five patients at risk from recurarization because of multiple organ failure and who demonstrated unusually prolonged blockade. In none of these patients did the block recur. We conclude that, provided spontaneous recovery of neuromuscular transmission has made progress before the antagonism, and that the patient does not deteriorate or become exhausted afterwards, recurarization is unlikely.

Dose-duration relationships for vecuronium were determined and the duration of action produced by vecuronium 0.3 mg kg−1 shown to equal that of pancuronium 0.1 mg kg−1. Using these doses, the neuromuscular blocking properties and cardiovascular effects of the two drugs were compared. With large dose administration of vecuronium (0.3 mg kg−1), both the onset time (mean 81 s) and the 25–75% recovery index (mean 13.9 min) were about one-half those associated with pancuronium (means 168.5 s and 29.3 min, respectively). The duration of action until 25% recovery was similar with both drugs. There was no evidence of cardiovascular instability with the large dose of vecuronium. Heart rate, however, was significantly slower (range 89.7–94.2% of control) 2–20 min after the injection of vecuronium. Vecuronium 0.3 mg kg−1 may have more favourable neuromuscular blocking effects than pancuronium 0.1 mg kg−1 and may be preferable to pancuronium when prolonged neuromuscular blockade is required.