Unknown Pseudocholinesterase Deficiency in a Patient Undergoing TIVA with Planned Motor Evoked Potential Monitoring: A Case Report.

Pseudocholinesterase abnormalities are a genetic cause of aberrant metabolism of the depolarizing muscle relaxant succinylcholine. This article examines a case where succinylcholine was chosen to facilitate intubation due to its ultra short duration and the request of the surgeon to monitor motor evoked potentials. Following succinylcholine administration the neurophysiologist was unable to obtain motor evoked potentials. This case study highlights the intraoperative and postoperative management of an elderly patient with an unknown pseudocholinesterase deficiency.

Use of neuromuscular monitoring to detect prolonged effect of succinylcholine or mivacurium: three case reports.

Mutations in the butyrylcholinesterase gene can lead to a prolonged effect of the neuromuscular blocking agents, succinylcholine and mivacurium. If the anaesthesiologist is not aware of this condition, it may result in insufficient respiration after tracheal extubation. However, this can be avoided with the use of objective neuromuscular monitoring if used adequately. Three case reports of prolonged effect of succinylcholine or mivacurium were presented to illustrate the importance of neuromuscular monitoring during anaesthesia. In the first case, continuous intraoperative neuromuscular monitoring allowed a prolonged neuromuscular blockade to be discovered prior to tracheal extubation of the patient. The patient was extubated after successful reversal of the neuromuscular blockade. On the contrary, neuromuscular monitoring was not used during anaesthesia in the second patient; hence, the prolonged effect of the neuromuscular blocking agent was not discovered until after extubation. In the third patient, the lack of response to nerve stimulation was interpreted as a technical failure and the prolonged effect of succinylcholine was discovered when general anaesthesia was terminated. Both patients had insufficient respiration. They were therefore re-sedated, transferred to the intensive care unit and the tracheas were extubated after full recovery from neuromuscular blockade. We recommend the use of monitoring every time these agents are used, even with short-acting drugs like succinylcholine and mivacurium.

[Residual relaxant block due to pseudocholinesterase deficiency - First manifestation in an elderly patient]. / Kasuistik: Relaxansüberhang durch Pseudocholinesterasemangel - Erstmanifestation in höherem Alter.

Pseudocholinesterase or butyrylcholinesterase (BChE) inactivates the relaxant drugs mivacurium and suxamethonium. A deficiency in plasma activity of this enzyme may result in prolonged muscular paralysis and subsequently the need for an extended duration of mechanical ventilation. We report the case of a 65-year-old patient who was diagnosed with butyrylcholinesterase deficiency for the first time during elective surgery. Neuromuscular monitoring constitutes a central diagnostic asset in ensuring patient safety.

Prolonged succinylcholine action during electroconvulsive therapy (ECT) after cytarabine, vincristine, and rituximab chemotherapy.

Succinylcholine is a depolarizing neuromuscular blocker frequently used during electroconvulsive therapy. In most patients, the duration of paralysis is brief, allowing for spontaneous respiration shortly after the therapy. We report a case of delayed return of neuromuscular function after succinylcholine administered during electroconvulsive therapy in a 72-year-old man receiving cytarabine, vincristine, and rituximab chemotherapy for chronic lymphocytic leukemia. We hypothesize that an interaction between succinylcholine and one of the chemotherapeutic agents caused the prolongation of paralysis and believe that this is the first reported case of prolonged duration of succinylcholine following this regimen of chemotherapy. Despite this unexpected prolonged neuromuscular blockade, the patient could be treated uneventfully, with attention paid to his respiratory support and with subsequent succinylcholine dose titration to effect.

Determination of suxamethonium in a pharmaceutical formulation by capillary electrophoresis with contactless conductivity detection (CE-C(4)D).

A simple method based on capillary electrophoresis with a capacitively coupled contactless conductivity detector (CE-C(4)D) was developed for the determination of suxamethonium (SUX) in a pharmaceutical formulation. A hydro-organic mixture, consisting of 100mM Tris-acetate buffer at pH 4.2 and acetonitrile (90:10, v/v), was selected as background electrolyte (BGE). The applied voltage was 30kV, and the sample injection was performed in the hydrodynamic mode. All analyses were carried out in a fused silica capillary with an internal diameter of 50 microm and a total length of 64.5cm. Under these conditions, a complete separation between SUX, sodium ions and the main degradation products (choline) was achieved in less than 4min. The presence of acetonitrile in the BGE allowed a reduction of SUX adsorption on the capillary wall. The CE-C(4)D method was validated, and trueness values between 98.8% and 101.1% were obtained with repeatability and intermediate precision values of 0.7-1.3% and 1.2-1.6%, respectively. Therefore, this method was found appropriate for controlling pharmaceutical formulations containing suxamethonium and degradation products.

[Interaction between mivacurium and succinylcholine from a different point of view]. / Interacción entre mivacurio y succinilcolina: vista desde otra perspectiva.

OBJECTIVES: Succinylcholine (SCH) may first be used and continue with mivacurium (MIV). MIV has been suggested as a pretreatment. Conflicting results arises from studies on SCH-MIV interaction. The following trial revisits this interaction. PATIENTS AND METHODS: The patients were intubated after randomized administration of 100 microg x Kg(-1) of mivacurium (group 1) or 1 mg x Kg(-1) of succinylcholine and, after 50% recovery, 100 microg x Kg(-1) of mivacurium (group 2). A third group received the same regimen as group 2, preceded by pretreatment with 10 microg x Kg(-1) of mivacurium. Maximum effect (MAX), onset time, the 10%-25% recovery index, and duration of effect of mivacurium were determined by electromyography. In groups 2 and 3, the corrected MAX was defined as the difference between the actual MAX effect and the residual block after administration of succinylcholine, and speed of action was defined as the ratio between MAX or corrected MAX and onset time. Data were subjected to analysis of variance and Student-Newman-Keuls and t tests for bivariate comparisons. A value of P less than 0.05 was considered significant. RESULTS: Groups 2 and 3 had significantly greater MAX effects (97% and 98%, respectively) in comparison with group 1 (93%), shorter onset times (135 and 158 seconds in groups 2 and 3 vs 279 seconds in group 1), and greater speed of action without changes in duration of effect. MAX was halved when corrected (to 47% and 49% in groups 2 and 3, respectively), and speed of action was significantly reduced (from 1.34 and 1.62 seconds/% in groups 2 and 3 respectively, to 2.69 and 3.36 seconds/%). Mivacurium pretreatment did not produce relevant clinical changes. CONCLUSIONS: When mivacurium is used before the effects of succinylcholine disappear, a residual effect is not usually taken into consideration. This study corrected MAX and calculated speed of action, demonstrating a reduction in net block and speed of action, consistent with an antagonistic action when the 2 blockers are administered sequentially.

[Infant boy with propionic acidemia: anesthetic implications]. / Implicaciones anestésicas en un niño afecto de acidemia propiónica.

A 12-month-old boy diagnosed with propionic acidemia underwent gastrostomy. The patient's general state was good and he was alert, but with reduced muscular tone (unstable when seated with support, floppy head) and with dystonic movements in all extremities. An electroencephalogram showed slightly slowed brain activity. The patient was being treated with a low protein diet, phenobarbital, L-carnitine, L-isoleucine, and biotin. Surgery was carried out in satisfactory conditions with general anesthesia without opioids combined with infiltration of the surgical wound with local anesthetic. Recovery from anesthesia was rapid and free of complications. Propionic acidemia is caused by mitochondrial propionyl coenzyme carboxylase deficiency. Most patients have episodes of severe metabolic ketoacidosis as a result of excessive protein intake, delayed development, vomiting, gastroesophageal reflux, lethargy, hypotonia, and convulsions. The anesthetic approach involves avoiding triggers of metabolic acidosis (such as fasting, dehydration, hypoxemia, and hypotension) and preventing airway complications. Agents that metabolize propionic acid (such as succinylcholine, benzylisoquinoline neuromuscular blocking agents, and propofol) are not used, as they can exacerbate acidemia. We also believe that using local or regional anesthesia in combination with general anesthesia without opiates is safe and effective for controlling pain during surgery and postoperative recovery, as that combination avoids respiratory depression in these patients, who are highly sensitive to opiates.

Pharmacokinetics and effects of succinylcholine in African elephant (Loxodonta africana) and impala (Aepyceros melampus).

The phenomenon of slow onset of succinylcholine (Sch) effect in elephants was investigated by analyzing blood concentrations of Sch and its metabolite choline in elephant and impala. To assess whether the slow onset phenomenon is related to the pharmacokinetics of Sch following i.m. administration, we analyzed the time course of plasma concentrations of intact drug and its metabolite and determined its pharmacological effects. Blood samples were obtained from anaesthetized elephant (n=6) and impala (n=7) following i.m. administration of a lethal dose of Sch. Time from Sch injection to onset of apnoea and to death was significantly longer for elephant than impala (mean+/-S.D. apnoea 4.4+/-1.5 and 2.3+/-0.9 min, respectively; death 32.6+/-7.3 and 6.2+/-3.4 min, respectively). The C(max) was not different between elephants and impala (20.3+/-7.9 vs. 14.4+/-6.8 nmol ml-1, respectively) but the t(max) was significantly longer for elephants (23.0+/-7.6 vs. 3.7+/-2.2 min). Analysis of the plasma Sch and choline concentrations over time revealed that the relative amount of Sch entering the circulation within the first 30 s after i.m. injection is greater for impala than elephant. No greater rate in the plasma hydrolysis of Sch in elephant compared to impala was apparent.

Neuromuscular relaxants in the neonate.

Neuromuscular blockade frequently is employed to facilitate mechanical ventilation and other therapeutic interventions in adults and children. In recent years it has been suggested that the use of neuromuscular blockade in the management of premature infants who are ventilated for respiratory distress will reduce the incidence of barotrauma and intracranial hemorrhage. Subsequently, neuromuscular blocking agents have become some of the most commonly used medications in the intensive care nursery. A discussion of these drugs is included in this article to improve the understanding of their pharmacology, the indications and consequence of their use, and their potential side effects. Additionally, the recent introduction of new, shorter-acting agents warrants a review of current practice.

Pharmacodynamic properties of succinylcholine in greyhounds.

Succinylcholine is a depolarizing neuromuscular blocking drug, which is rapidly hydrolyzed by the enzyme pseudocholinesterase. In Greyhounds, the metabolism of certain drugs is atypical relative to other breeds, and it has been suggested that Greyhounds may be an atypical population, with lower pseudocholinesterase activity, slower hydrolysis of the drug succinylcholine, and a prolonged duration of action of the drug, compared with a mixed-breed control population. Six healthy adult Greyhounds and 6 healthy adult mixed-breed dogs were studied. Blood was drawn from each dog and analyzed for serum cholinesterase activity, and a biochemical profile was done to verify normal liver function. The dogs were anesthetized with methohexital (10 mg/kg) and isoflurane (1.25 minimal alveolar concentration) in 100% oxygen. Ventilation was controlled, fluids were administered IV (lactated Ringer solution, 10 ml/kg/h), and blood gases, blood pressure, and heart rate were monitored. The right hind limb was immobilized and a force transducer was used to monitor twitch strength of the interosseous muscle with supramaximal stimulation of the tibial nerve. Succinylcholine was administered to each dog 3 times at a dosage of 0.3 mg/kg. After drug administration, the time to 50% recovery of twitch strength (single twitch, 1/s), and 50% recovery of train-of-4 was determined. Subsequent doses were administered after complete recovery. The time to 50% recovery after succinylcholine administration in Greyhounds (38 minutes, dose 1, single twitch) was not significantly different than the time to 50% recovery in mixed-breed dogs (29 minutes, dose 1, single twitch), using either monitoring technique. Pseudocholinesterase activity was also not significantly different between the Greyhounds (1,685 mU/ml) and the mixed-breed dogs (1,588 mU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation of plasma concentration and effects of succinylcholine in dogs.

The study was undertaken to determine the pharmacokinetic values for half-life, volume of distribution, and clearance for succinylcholine (SCh) based on measurements of the drug in plasma. Three intravenous (i.v.) doses (0.5, 1.0, and 5.0 mg/kg) were compared to study the time course of paralysis and recovery and to describe the relationship of plasma concentration (Cp) and the pharmacologic effects of SCh in canines. The physiologic response to the neuromuscular blocking drug was monitored using train-of-four stimulation of the left sciatic nerve and recording the response of the corresponding gastrocnemius muscle. Time courses for paralysis and recovery were monitored, and the results were used to predict the kinetic values for the pharmacologic effects. Blood samples were taken following drug administration for direct pharmacokinetic estimations. SCh determinations were performed using ion-pair extraction, chemical demethylation, and gas chromatography with nitrogen phosphorous detection. Both kinetic analyses showed the beta half-life for SCh to be approximately 5 min for all doses. SCh has a distribution half-life of less than 1 min. There appears to be a threshold Cp below which neuromuscular function returns. Recovery following SCh induced paralysis had a rapid onset, but the duration of paralysis and the rate of recovery were especially prolonged for the 5.0-mg/kg treatment group.

Neuromuscular blocking drugs: onset and intubation.

For more than 40 years, succinylcholine has been the traditional choice of muscle relaxant to facilitate tracheal intubation, particularly for anesthesia in the emergency patient with a full stomach. This presentation reviews factors that determine the onset of neuromuscular blockade, particularly with regard to tracheal intubation. Measurement of neuromuscular block, both clinical and via nerve stimulators, is described and compared, and correlations with intubating conditions are attempted. The onset of action of different muscle groups in humans is examined in an attempt to explain timing differences leading to the more rapid onset of block seen in the laryngeal and ventilatory muscles than in the muscles of the hand, which are the usual site of neuromuscular monitoring. The onset of different relaxants is compared, and attempts are made to relate the differences to neuromuscular pharmacology so as to understand the reasons for the rapid onset of succinylcholine (rapid metabolism) and rocuronium (poor potency). None of the currently available drugs, or those undergoing clinical investigation, possesses the rapid onset and prompt recovery of succinylcholine. Despite the formidable side effect profile of succinylcholine, it has not been replaced by a nondepolarizing agent for use in emergency conditions. However, the alternatives, particularly rocuronium and mivacurium, are drugs with a greater safety profile that, in many circumstances, can substitute for succinylcholine.

Muscle relaxants and reversal agents.

This article has discussed the anatomy and physiology of the neuromuscular junction and excitation-contraction coupling. The pharmacokinetics and pharmacodynamics of various depolarizing and nondepolarizing neuromuscular blocking agents were presented. Techniques of reversal and the need for concomitant administration of anticholinergics were discussed. Assessment of the postoperative patient, including types of neuromuscular blockade, criteria for successful extubation, and drugs and physiologic states that could prolong neuromuscular blockade were outlined. Because the recovery room nurse is relied on for continuous assessment of the postoperative patient, it is imperative that the nurse have a comprehensive knowledge of intraoperative factors that relate to the patient's recovery. The recovery room nurse should be an expert in the assessment of postoperative patients.

Pharmacokinetic properties of succinylmonocholine in surgical patients.

Intoxications with succinylcholine (SUX) lead to a potentially lethal respiratory paralysis, and forensic cases involving accidental or deliberate SUX-application have been reported. Detection of SUX as well as its metabolite succinylmonocholine (SMC) is difficult: both substances are analytically challenging, and the extremely short plasma half-life of SUX additionally hampers detection of the parent compound. Pharmacokinetic data are scarce on SUX and non-existent on SMC. To enhance forensic knowledge concerning SUX intoxications, plasma pharmacokinetics of SMC were investigated in anesthetized patients. Fifteen subjects scheduled for a surgical procedure were included in this study. Muscle-relaxation was initialized with a bolus injection of 80-100 mg SUX. Blood sampling was performed within 6 h after SUX application using paraoxonized tubes. Collected plasma was processed according to a validated isotope dilution high-performance liquid chromatography-tandem mass spectrometry method using ion-pair solid-phase extraction. Pharmacokinetic parameters were derived from a user-defined as well as a three-compartment model. For SMC, peak plasma concentrations were reached after 0.03-2.0 min. In contrast to SUX, SMC was more slowly and more extensively distributed, featuring triphasic plasma concentration time profiles. Pharmacokinetic key parameters were subject to interindividual variation of potential forensic importance, with terminal half-lives of 1-3 h indicating a detection interval of 8-24 h for SMC in plasma. SMC was proven to be the only realistic SUX marker in a forensic context. The present work defines meaningful detection windows for plasmatic SMC after SUX application and offers guideline values for forensic toxicological casework.

¿Estimulador de nervio periférico para succinilcolina?, tranquilidad para pacientes y anestesiólogos / A peripheral nerve stimulator for succinylcholine? Peace of mind for patients and anaesthesiologists

No disponible