Plasma pseudo cholinesterase deficiency leading to seven hour apnoea in a child undergoing adeno-tonsillectomy.

OBJECTIVE: We report a rare, silent, potentially fatal operative complication of seven hour apnoea in a patient undergoing adenotonsillectomy secondary to deficiency of plasma cholinesterase. Awareness of this hereditary disorder is important to otolaryngologist as; it is difficult to diagnose, can be unexpectedly alarming for parents and the surgeon. METHODS: Case report and review of world literature. RESULTS: A four-year male with obstructive sleep apnoea underwent a routine elective adenotonsillectomy; there was no spontaneous recovery of respiration following surgery. He was transferred to the intensive care unit and 7 h later was successfully weaned from the ventilator and extubated. A plasma cholinesterase level of 456 1U/L was discovered much later. CONCLUSION: To our knowledge this is the first case report of pseudo cholinesterase deficiency reported in otolaryngology literature and first in Oman. The patient should receive information about the condition, the associated risks, inheritance and need for testing other family members.

[Congenital pseudocholinesterase deficiency]. / Wrodzony niedobór cholinesterazy osoczowej.

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 UL(-1)and 2558 UL(-1), respectively (normal range 5100-11700 UL(-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.

Implications of pharmacogenomics for anesthesia providers.

The practice of anesthesia has long been considered an art and a science, with interpatient variability in drug response being the rule, rather than the exception. Pharmacogenomics, which studies the role of genetics in drug response, is emerging as a discipline that may impact anesthetic management. The purpose of this review is to provide clinicians with basic knowledge related to pharmacogenomics and its implications in anesthesia. This review focuses on pharmacogenomics related to commonly used drugs in anesthesia. Pharmacogenomics as a predictor of drug response is increasingly used in medicine and drug development. By expanding the knowledge base of anesthesia providers, pharmacogenomic considerations have the potential to improve therapeutic outcomes and individualize drug therapy, while avoiding toxic effects and treatment failure. However, because pharmacogenomics may not fully explain variability in drug response, implementation should be in conjunction with traditional anesthesia considerations.

Rationale for diagnosing deficiency of ChEs and for applying exogenous HuChEs to the treatment of diseases.

Recent evidence strongly demonstrates that acetylcholine (ACh) is not only involved in the function of the central and peripheral nervous systems, including the parasympathetic and somatic systems, but also acts as a ubiquitous cell signaling molecule or cytotransmitter, and as a hormone with paracrine, juxtacrine and autocrine properties. This active molecule exerts versatile and potent functions primarily through its specific nicotinic and muscarinic receptors (nAChRs and mAChRs, respectively). These functions modulate numerous biomechanisms, including cell growth, survival, proliferation and differentiation, cell-cell contact, cell cycle, locomotion, electrical activity, immune function, apoptosis, organization of the cytoskeleton, trophic functions, secretion, adhesion, resorption, and stress-response-regulation. By nature, the precise ACh levels and responses from receptors must be controlled and regulated by its degrading enzymes, the cholinesterases (ChEs), namely, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Once ChEs become critically deficient in quality and quantity, ACh signaling will be uncontrollably aberrant and persistent. An in-depth account of the fundamental roles of ChEs, comprising their diverse soluble and membrane-bound forms, in maintaining the functional equilibrium of ACh in the macro and microenvironment has been undertaken. This work also covers ACh receptors, signaling pathways, other interdependent and interrelated substances, functional processes, role of ChEs as first-line gatekeepers and defenses for the architecture of cells, tissues and organisms, physically, chemically, and structurally. The mechanisms of many diseases ranging from the acute cholinergic crisis to the chronic degenerative and hypergenerative disorders such as Alzheimer's disease, cancers, atopic dermatitis, may involve a deficiency of ChEs or imbalance between ACh and ChEs, initially or consequentially. It is therefore essential to ascertain a ChE deficiency, or an imbalance between ACh and ChEs, in tissues and body fluids in order for conducting clinical diagnosis, prevention and treatment. An argument is put forward on the rationale of applying exogenous human ChEs to reverse enzymatic deficiency and correct the imbalance between ACh and ChEs, to repair the affected receptors and protect against their further loss in the body, and consequently to alleviate the signs and symptoms of diseases. Evidence is adduced for the safety and efficacy of ChEs treatment.

Airway management using the pediatric GlideScope in a child with Goldenhar syndrome and atypical plasma cholinesterase.

We report a case of difficult intubation in a child with Goldenhar syndrome and atypical plasma cholinesterase. Intubation attempts by direct laryngoscopy and the Trachlight were unsuccessful. The airway was ultimately secured using the pediatric GlideScope in conjunction with external laryngeal manipulation.

[Accidental use of suxamethonium for general anesthesia in a patient with hereditary hypocholinesterasemia that was not recognized preoperatively].

We experienced an accidental use of suxamethonium for general anesthesia in a 26-year-old woman with hereditary hypocholinesterasemia that had not been recognized preoperatively. The patient was scheduled for total colectomy as her chronic ulcerative colitis could not be controlled with medications. Routine preoperative screening such as blood cell counts, biochemical data, chest x-ray and electrocardiogram were performed but serum cholinesterase (ChE) activity was not measured. As the preoperative patient condition was good with no abnormal history, anesthesia was induced and maintained with propofol, ketamine and fentanyl as usual. For muscle relaxation, suxamethonium was used for tracheal intubation, and vecuronium was used for the maintenance. After surgery, postanesthetic course was uneventful. One year later, as the patient was pregnant and scheduled for cesarean section, the preoperative screening was done. The biological data showed a hypocholinesterasemia without liver dysfunction. Thus, previous medical records of internal medicine were cheked. Surprisingly the record showed hypocholinesterasemia when she was 15 and 21 years of ages. However, as the physicians did not recognize hypocholinesterasemia, they did not inform the patient of it. Why did the patient have no prolonged apnea and emergence after the previous anesthesia? As the surgical time was exceeded 4 hrs, plasma suxamethonium could fortunately be less than its effective concentration at emergence. However, this case strongly suggests us that preoperative screening should be done without any omission. In addition, if serum ChE activity is not examined, use of suxamethonium should be avoided.

Anestesia em paciente obstétrica portadora de anemia falciforme e traço talassêmico após plasmaféresis: relato de caso / Anesthesia in obstetric patient with sickle cell anemia and thalassemic trait after plasmapheresis: case report

JUSTIFICATIVA E OBJETIVOS: A plasmaféresis é a técnica de tratamento de escolha para pacientes com anemia hemolítica grave. Uma de suas conseqüências é a depleção de colinesterase plasmática, o que interfere na metabolização de alguns bloqueadores neuromusculares de uso corrente na prática anestesiológica. RELATO DO CASO: Paciente com 26 anos, estado físico ASA IV, gestação de 30 semanas e 3 dias, portadora de anemia falciforme, traço talassêmico e alo-imunização para antígenos de alta freqüência. Apresentou crise de falcização, sendo transfundida com derivado sangüíneo incompatível. Evoluiu com hemólise maciça, sendo admitida com hemoglobina de 3 g/dL e hematócrito de 10 por cento, icterícia intensa, taquicardia, apatia e descoramento. Na avaliação hematológica concluiu-se ser situação de inexistência de sangue compatível para transfusão. Foi tratada com corticoterapia, imunoglobulinas e plasmaféresis. No segundo dia de internação, evoluiu com insuficiência renal aguda e edema pulmonar agudo, piora do estado geral e instabilidade hemodinâmica. Indicada a resolução da gestação em decorrência do quadro clínico da paciente e do sofrimento fetal agudo que se sobrepôs. A paciente foi admitida na sala de operações consciente, dispnéica, pálida, ictérica, SpO2 de 91 por cento em ar ambiente, freqüência cardíaca de 110 bpm e pressão arterial de 110 x 70 mmHg, em uso de dopamina (1 æg.kg-1.min-1) e dobutamina (10 æg.kg-1.min-1). Optou-se por anestesia geral balanceada, com alfentanil (2,5 mg), etomidato (14 mg) e atracúrio (35 mg) e isoflurano. Não se observou intercorrências anestésico-cirúrgicas. Ao final, a paciente foi encaminhada à UTI, sob intubação orotraqueal, e em uso de drogas vasoativas, tendo sido extubada após 3 horas. CONCLUSÕES: Este caso mostrou-se um desafio para a equipe, visto que a paciente apresentava instabilidade hemodinâmica e alteração do coagulograma, condições que contra-indicam a anestesia regional; além disto, a plasmaféresis potencialmente depleta os estoques de colinesterases plasmáticas, o que interfere na anestesia. Entretanto, o arsenal medicamentoso disponível permitiu o manuseio seguro desta situação.

Unexpected prolonged neuromuscular block after mivacurium: a case report.

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.

A family with hereditary serum cholinesterase deficiency.

A family with serum cholinesterase (SChE) deficiency is reported. A 64-year-old woman was admitted for the excision of colon adenoma; her laboratory data revealed a markedly decreased level of SChE. SChE genes of the patient and her family members were amplified by the polymerase chain reaction (PCR) and analyzed by direct sequencing. The patient's SChE gene had a homozygous frame shift mutation, in which an extra adenine was inserted in codon 315 (ACC-->AACC), resulting in the appearance of a new stop codon in codon 322. The family study disclosed that her brother and sister had the same frame shift mutations in homozygote and heterozygote, respectively.

Hereditary serum cholinesterase deficiency associated with severe lipid deposition in the kidney.

A 47-year-old woman who was homozygous for a silent cholinesterase gene (hereditary serum cholinesterase deficiency) presented with nephrotic syndrome and hyperlipidemia. Renal biopsy performed in 1986 demonstrated mesangial proliferative glomerulonephritis. Four years later, a second biopsy revealed progression with mesangial interpositions and severe lipid deposition in the glomeruli, tubules and interstitium. This is the first case of hereditary serum cholinesterase deficiency accompanied by renal disease. Serum cholinesterase deficiency may be related to hyperlipidemia and abnormal lipid deposition in the kidney, which promotes the progression of renal disease.

Cholinesterase deficiency and the Churg-Strauss syndrome.

We report two patients with the Churg-Strauss syndrome who were found to have decreased cholinesterase activity despite normal phenotypes. Suspicion of abnormal sensitivity to suxamethonium in the first case was raised after prolonged paralysis under anaesthesia. The findings in the second were incidental during the course of intensive care treatment. Both patients received immunosuppressive therapy. Differentiation between the effects of this and the disease process itself cannot be established.

[Cholinergic crisis in a patient with myasthenia treated by plasma exchange and anticholinesterase agents]. / Crises cholinergiques chez un myasthénique traité par échanges plasmatiques et anticholinestérasiques.

A patient with myasthenia receiving treatment with anticholinesterase agents and plasma exchanges for an acute episode, developed three successive periods of neurological deterioration during which plasma cholinesterase levels were determined. The risk of onset of a cholinergic crisis under these circumstances has been reported in the literature but not documented. The accidents in the present case were related to cumulative overdose effects of anticholinesterase agents and depletion of cholinesterase, suggesting caution in the use of anticholinesterase agents when frequent plasma exchanges are being carried out in a patient with myasthenia.

A case with silent type of pseudo-acholinesterasemia.

One case of pseudo-acholinestrasemia was experienced in our hospital. The patient was a 54-year-old female with sigmoid colon cancer. A preoperative examination showed that her cholinesterase (ChE) level was 7 IU/L (normal range: 3,700-5,400 IU/L) although no abnormalities were found in other enzymes derived from the liver, total protein and albumin level in the serum. An investigation of eight family members over two generations revealed two cases of acholinesterasemia in addition to the patient. Immunological examination by Ouchterlony's method and isoenzyme analysis by polyacrylamide gel electrophoresis showed that ChE production was absent in this case, while dibucaine or fluoride number was normal among the family members. Based on these results, it was concluded that this patient belonged to the silent type of homozygote. A case of pseudo-acholinesterasemia, which is very rare in Japan, is described.

Succinylcholine sensitivity and plasma cholinesterase deficiency.

Cholinesterase deficiency is a relatively rare condition. However, if unrecognized, this condition can be potentially fatal. The authors present a case report of cholinesterase deficiency and a review of the literature. Discussion of the preoperative evaluation and preventive measures is also included.