Congenital pseudocholinesterase deficiency
*Remigiusz Gelo1, Anna Jurek-Gelo2, Ryszard Wardaszko2, Andrzej Kański1
12nd Department of Anaesthesiolgy and Intensive Therapy, Medical University of Warsaw
2Institute of Physiology and Pathology of Hearing in Warsaw
Background. Congenital pseudocholinesterase (pChe) deficiency is a rare genetic abnormality which may lead to prolonged duration of action of muscle relaxants that are hydrolysed by pChe. We describe two cases in which mivacurium resulted in neuromuscular block lasting several hours.
Case reports. Two non-related male patients, aged 26 and 7 years, scheduled for elective ENT surgery, received propofol, desflurane, remifentanil and mivacurium. At the end of the surgery it was not possible to reverse the neuromuscular blockade, and there were no responses to TOF or post-tetanic stimulation. Neuromuscular transmission returned spontaneously after 7, and 4 h, respectively. Postoperative assay revealed severe pChe deficiency in both patients, with values of 3393 U L-1 and 2558 U L-1, respectively (normal range 5100-11700 U L-1). Family screening confirmed the presence of pChe deficiency in both cases.
Conclusion. In any case of unexpected prolonged muscle relaxation after mivacurium, pChe deficiency should be considered and its activity measured. When confirmed, careful family screening is mandatory.
Inherited cholinesterase deficiency is a rare genetic defect. Atypical genes – single (heterozygote) or double (homozygote) – alter the sequence of amino acids in the enzyme structure, which impairs its activity. As a result, the action of skeletal muscle relaxants broken down by cholinesterase, such as suxamethonium and mivacurium, prolongs markedly, ever to several hours [1, 2, 3].
The objective of the report was to present two cases of prolonged neuromuscular block in patients with plasma cholinesterase deficiency undergoing general anaesthesia with mivacurium.
Case 1. A 26-year-old male office worker, previously healthy, was admitted to hospital for nasal septum repair. Physical examination did not disclose any significant abnormalities except for overweight 105 kg (height 178 cm). Moreover, laboratory results were within normal limits. The patient was qualified for surgery under general anaesthesia. Since the procedure was anticipated to be short, anaesthesia was induced with propofol 200 mg, mivacurium 20 mg and maintained with desflurane 0.7-0.8 MAC and remifentanil administered at a rate of 0.1 µg kg-1 min-1. During the 30-minute procedure, the patient was stable.
On completion of surgery, desflurane and remifentanil were discontinued. Shortly after, the vivid reaction of pupils to light developed, heart rate accelerated and arterial pressure increased yet the patient did not resume spontaneous respiration. The examination of neuromuscular conduction performed using a stimulator revealed the lack of response to train-of-four (TOF) stimulation; moreover, the posttetanic count (PTC) was zero. Prolonged action of the relaxant was suspected. Sedation was administered with a continuous infusion of propofol and artificial lung ventilation initiated.
The neuromuscular conduction test carried out 5 h later demonstrated PTC – 2, TOF – 2. The neuromuscular block subsided completely 7 h after administration of mivacurium. Ventilation was discontinued and the endotracheal tube removed. Two days later the patient was discharged home in satisfactory general status; consultations at the outpatient clinic of neuromuscular diseases were recommended. The electromyogram performed in the outpatient setting excluded myasthenia gravis yet disclosed decreased plasma cholinesterase activity – 3393 U L-1 (normal range 5100-11700 U L-1). Moreover, screening of the family members demonstrated decreased cholinesterase activity in the patient`s brother.
Case 2. A 7-year-old healthy boy, without history of surgery and anaesthesia, was admitted for surgical removal of the pharyngeal tonsil and drainage of the tympanic cavity. No major health problems were found. Laboratory tests were normal. The patient was qualified for surgery under general anaesthesia. Anaesthesia was induced with inhalation sevoflurane; skeletal muscles were relaxed with intravenous mivacurium 4 mg (0.17 mg kg-1 b.w.). After endotracheal intubation anaesthesia was maintained with a continuous infusion of remifentanil at a rate of 0.1 µg kg-1 min-1. Anaesthesia for the 20-minute procedure was uneventful. After completion of surgery and discontinuation of sevoflurane and remifentanil, attempts were made to restore spontaneous breathing for 20 min, yet failed. The test of neuromuscular conduction revealed the reason: total lack of response to TOF and PTC stimulations. Prolonged action of the muscle relaxant was diagnosed; artificial lung ventilation was initiated following the sedation with p
The first symptoms of the return of muscle strength were observed two hours after administration of mivacurium. Weaning from the ventilator and extubation were possible at 4 h after muscle relaxant administration. The patient was observed for 2 days and discharged from hospital in satisfactory general condition.
The cholinesterase test performed in the outpatient setting demonstrated its decreased activity – 2558 U L-1; even lower activity was detected in his adult sister.
Genetically conditioned deficiency of plasma cholinesterase is rare in our geographical region. The clinical symptoms depend on the type of mutation and whether the affected individual is a hetero- or homozygote. To date over 60 mutations within the cholinesterase-encoding gene were recognized . The administration of mivacurium blocks neuromuscular conduction lasting in heterozygotes up to 1.5 h and in homozygotes even up to 12 h [3, 4]. Genetic deficiency of cholinesterase should be differentiated from its acquired deficiency, e.g. during pregnancy or in hepatic diseases. In the latter cases, the time of action of cholinesterase is only slightly prolonged .
Incidents of prolonged action of suxamethonium or mivacurium are always surprising for an anaesthesiologist as such complications cannot be anticipated if the patient has not been earlier anaesthetized. Although prolonged action of neuromuscular blocking agents is not life-threatening, awakening of patients who cannot breathe spontaneously and move is a very traumatic experience. Therefore, in such cases appropriate sedation should be provided and substitutive lung ventilation administered. Routine, intraoperative neuromuscular block monitoring enables early detection of the phenomenon, institution of proper management; moreover, unnecessary and potentially hazardous actions can be avoided e.g. too early extubation at residual blockage, in which case re-intubation may be required .
Each patient with prolonged neuromuscular block due to suxamethonium or mivacurium should be meticulously examined; once the cause is detected, the patient should be provided with the document containing necessary information to institute appropriate strategy during subsequent anaesthetic procedures [6, 7]. The cholinesterase activity in serum below 4000 U L-1 is sufficient and concluding evidence .
The pathologically prolonged neuromuscular block is also an indication for screening tests among family members of patients in search for those with low activity of cholinesterase who should be subjected to genetic tests to determine the type of mutation [7, 9].
Our experiences connected with attempts to diagnose the patients described above are not inspirational. Suitable biochemical and genetic tests are difficult to perform. Considering this, it was decided to create the centre for diagnosis of such cases although suxamethonium and mivacurium are not currently routinely used for anaesthetic purposes.
1. Aitkenhead A, Smith G: Anestezjologia. Urban&Partner, Wrocław 2008; 1: 89-90, 95.
2. Ostergaard D, Viby-Mogensen J: Pharmacokinetics and pharmacodynamics of mivacurium in patients phenotypically heterozygous for the usual and atypical plasma cholinesterase variants (UA). Acta Anaesthesiol Scand 2003; 47: 1219-1225.
3. Cerf Ch, Mesguish M: Screening patients with prolonged neuromuscular blockade after succinylcholine and mivacurium. Anesth Analg 2002; 94: 461-466.
4. Gatke M, Bundgaard J: Two novel mutations in the BCHE gene in patients with prolonged duration of action of mivacurium or succinylcholine during anaesthesia. Pharmacogenetics and Genomics 2007; 17: 995-999.
5. Ostergaard D, Ibsen M: Plasma cholinesterase activity and duration of action of mivacurium in phenotypically normal patients. Acta Anaesthesiol Scand 2002; 46: 679-683.
6. Barash P, Cullen B: Clinical Anesthesia – preparing for anesthesia-pharmacogenetics. Second edition, J.B.Lippincott Company, Philadelphia 1992: 603-605.
7. Viby-Mogensen J: Anesthesiology, the birth of pharmacogenetics and Werner Kalow. Can J Anesth 2004; 51: 197-200.
8. Dietz A, Rubinstein H: Colorimetric determination of serum cholinesterase and its genetic variants by the propionylothiocholine-dithiobis (nitrobenzoic acid) procedure. Sel Methods Clin Chem 1973; 19: 1309-1313.
9. Adebayo G, Williams J: Pseudocholinesterase polymorphism in an Irish population. Eur J Intern Med 2005; 16: 492-495.
II Klinika Anestezjologii i Intensywnej Terapii,
Warszawski Uniwersytet Medyczny
ul. Banacha 1 A, 02-097 Warszawa
tel.: 22 599 20 02