Sick Sinus Syndrome Observed in a Patient with Cholinesterase Deficiency.

A 58-year-old woman complained of general fatigue and was diagnosed with sick sinus syndrome (SSS) by ambulatory electrocardiogram, which demonstrated sinus arrest at midnight and paroxysmal atrial fibrillation (AF) at nighttime. Since her plasma cholinesterase (ChE) activity had been persistently zero, she was diagnosed with ChE deficiency. She refused permanent pacemaker implantation, and treatment with positive chronotropic drugs is ongoing. A novel association of ChE deficiency with SSS is theoretically possible rather than coincident, considering that ChE plays a key role in cholinergic influences on the sinus node leading to sinus bradyarrhythmia and on the atria, causing vagally mediated AF.

Prolonged neuromuscular block associated with cholinesterase deficiency.

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.

Organophosphate exposure with pseudocholinesterase deficiency.

A 36-year-old correctional officer was exposed to lice while at work and self-treated with chlorpyrifos, an organophosphate. The correctional officer applied chlorpyrifos to her entire body and did not wash it off for 8 to 12 hours. Eight hours after the initial application, the correctional officer developed abdominal cramps, diarrhea, sweating, excessive salivation, frequent urination, and increased bronchial secretions. After a phone consultation with the occupational health clinic, the correctional officer reported to the emergency department, was diagnosed with organophosphate toxicity, and was treated with atropine. Later testing revealed that the correctional officer had pseudocholinesterase deficiency.

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.

[Update on the current role of plasma cholinesterase]. / Papel de las colinesterasas plasmáticas. Actualización.

The antagonism of steroidal nondepolarizing neuromuscular blockers (NDMBs) moved forward recently with the introduction of sugammadex, the only drug able to immediately reverse the effects of curarization produced by NDMBs. This advance has necessitated reflection on the future role of pseudocholinesterase. In spite of the side effects of succinylcholine and published opinions on its use, this NDMB continues to be used in clinical anesthesia. Pseudocholinesterase is mainly found in the liver, plasma, and nervous system. The enzyme is synthesized in the liver in greater amounts than required although certain conditions lead to deficiency, which is usually asymptomatic. The only clinical expression is the apnea which develops after administration of succinycholine because this NDMB cannot be metabolized. In some patients, slight reductions in the antagonism of succinylcholine lead to rising neuromuscular concentrations of the drug in accordance with the degree and duration of the blockade. We review the various forms of pseudocholinesterase deficiency, including a discussion of genetic variants, clinical manifestations, and management. In addition to discussing the diagnosis of this condition and the clinical implications, we highlight the importance of practice protocols and access to a referral laboratory if one is not available within the immediate hospital.

[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.

Rocuronium antagonized by sugammadex for series of electroconvulsive therapy (ECT) in a patient with pseudocholinesterase deficiency.

We report the anesthetic management of a patient with catatonic schizophrenia and pseudocholinesterase deficiency, using the nondepolarizing neuromuscular blocking drug, rocuronium, reversed by its specific reversal agent, sugammadex, for a series of electroconvulsive therapy sessions. Rocuronium and sugammadex were used every 48 hours for 8 consecutive times and proved to be an effective and safe combination in a situation where succinylcholine was contraindicated.

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.

Síndrome colinérgico y síndrome intermedio confluyentes en una intoxicación por organofosforados / Simultaneous cholinergic and intermediate syndromes in organophosphate poisoning

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Genetic screening in the Persian Jewish community: A pilot study.

PURPOSE: Israeli investigators have identified several relatively frequent disorders due to founder point mutations in Persian (Iranian) Jews, who, for nearly three centuries up to the Islamic Revolution of 1979, were completely isolated reproductively. METHODS: Using a community-based model previously employed with Tay-Sachs disease prevention, we developed a pilot program for the Persian Jewish community of greater Los Angeles. We screened for mutations responsible for four relatively frequent autosomal recessive conditions in Persian Jews in which effective interventions are available for each: Pseudocholinesterase deficiency (butyryl cholinesterase deficiency); Congenital hypoaldosteronism (corticosterone methyl oxidase II); Autoimmune polyendocrinopathy (autoimmune regulatory element); and Hereditary Inclusion Body myopathy. RESULTS: One thousand individuals volunteered. Mutations were assessed in saliva-derived DNA and were positive for 121/1000 butyryl cholinesterase deficiency; 92/1000 Hereditary Inclusion Body myopathy; 38/1000 corticosterone methyl oxidase II; and 37/1000 autoimmune regulatory element. Ten homozygous individuals (9 butyryl cholinesterase deficiency and 1 Hereditary Inclusion Body myopathy) and 10 "at-risk" couples (seven for butyryl cholinesterase deficiency and one each for the other three disorders) were identified. These frequencies are comparable with those in Israel and indicate an extraordinary level of inbreeding, as anticipated. CONCLUSIONS: A carefully planned effort can be delivered to an "increased risk" community if detailed attention is given to planning and organization. However, availability of an effective intervention for those found to be "at-risk" or possibly affected, is essential before embarking.

[Three cases of cholinergic crisis in which serum distigmine bromide concentrations were measured].

Case 1 was a 59-year-old female who had been taking distigmine bromide 20 mg/day for 2 years. She had concurrently developed pneumonia and was admitted to the hospital. Her pupil diameter was 1.0 mm, serum ChE value was decreased at 25 IU/L. Case 2 was a 72-year-old male who had been taking distigmine bromide 15 mg/day for 8 months. He was transported to the hospital with a chief complaint of dyspnea. His pupil diameter was 2.0 mm, serum ChE value was decreased at 75 IU/L, and he had concurrent pyothorax. Case 3 was a 74-year-old male who had been taking distigmine bromide 10 mg/day for 4 years. He was transported to the hospital with a chief complaint of disturbance of consciousness. His pupil diameter was 2.0 mm, and serum ChE value was decreased at 55 IU/L. He had concurrent aspiration pneumonia. In Case 1, the distigmine bromide concentration was elevated at 13.2 ng/mL at admission. However, it decreased from the following day. The two other patients had low concentrations of distigmine bromide. In all patients, ChE levels recovered after discontinuing distigmine bromide, and respiratory conditions also improved. Distigmine bromide was no longer detected in blood before ChE levels recovered.

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.