mivacurium and Paralysis

The Danish Cholinesterase Research Unit (DCRU) is a nationwide unit for patients carrying mutations in the butyrylcholinesterase enzyme (BChE). BChE hydrolyzes the neuromuscular blocking drugs succinylcholine and mivacurium. Patients with mutations in the butyrylcholinesterase gene are at risk of experiencing a prolonged effect of the drugs, such as weakness or paralysis for hours. In order to diagnose the referred patients correctly, DCRU combines results such as BChE activity, genotyping, pedigree and clinical reactions to succinylcholine or mivacurium.

Topics: Butyrylcholinesterase; Denmark; Humans; Isoquinolines; Mivacurium; Mutation; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Paralysis; Succinylcholine; Time Factors

The Danish Cholinesterase Research Unit (DCRU) is a nationwide unit for patients carrying mutations in the butyrylcholinesterase enzyme (BChE). BChE hydrolyzes the neuromuscular blocking drugs succinylcholine and mivacurium. Patients with mutations in the butyrylcholinesterase gene are at risk of experiencing a prolonged effect of the drugs, such as weakness or paralysis for hours. In order to diagnose the referred patients correctly, DCRU combines results such as BChE activity, genotyping, pedigree and clinical reactions to succinylcholine or mivacurium.

Topics: Butyrylcholinesterase; Denmark; Humans; Isoquinolines; Mivacurium; Mutation; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Paralysis; Succinylcholine; Time Factors

After myorelaxants, myalgia and residual curarization may complicate recovery. Local anaesthesia and minimally invasive airway management make myorelaxants disputable in many outpatient procedures; nevertheless, neuromuscular blockade may be necessary to facilitate intubation or maintain muscle relaxation. Agent selection criteria are discussed.. Reduced hospital time is not associated with central neuraxial or peripheral nerve block. To reduce the risk for residual block, neuromuscular monitoring is mandatory. Use of reversal agents should not be restricted, although studies have shown higher incidence of postoperative nausea and vomiting following their use. Higher succinylcholine dosage is followed by lower incidence of myalgia. The relationship between fasciculation and myalgia is unclear. Sodium channel blockers or nonsteroidal antiinflammatory drugs may prevent myalgia. Sugammadex functions as a chelating agent.. Ear-nose-throat, open eye surgery and laparoscopy may demand myoresolution. Regional and minimally invasive anaesthesia are alternative solutions. Central and peripheral nerve blocks are associated with increased induction time, reduced pain scores, and decreased need for analgesics. Central neuraxial block, however, is associated with prolonged outpatient unit stay. Bad intubating conditions may cause pharyngo-laryngeal complications: the decision to avoid myorelaxants for tracheal intubation appears illogical. Incidence of postoperative residual curarization remains very high. Sugammadex offers new perspectives.

Topics: Ambulatory Surgical Procedures; Anesthesia, Conduction; Anesthesia, General; Benzylisoquinolines; Cholinesterase Inhibitors; gamma-Cyclodextrins; Humans; Intubation, Intratracheal; Isoquinolines; Mivacurium; Muscle Relaxants, Central; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Pain, Postoperative; Paralysis; Postoperative Nausea and Vomiting; Practice Guidelines as Topic; Risk Assessment; Steroids; Succinylcholine; Sugammadex

Topics: Adult; Butyrylcholinesterase; Female; Heterozygote; Humans; Isoquinolines; Mivacurium; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Paralysis

After receiving mivacurium, a short-acting neuromuscular blocking agent used for intubation before surgery, a patient experienced prolonged paralysis and prolonged apnea that required ventilator support. Although this complication is rare, all critical care nurses should be aware of it so they can be competent in managing and providing holistic and comprehensive nursing care to the patient and the patient's family. Although this complication has been documented in the anesthesia literature, it has received little mention in critical care nursing journals.

Topics: Amputation, Surgical; Apnea; Butyrylcholinesterase; Female; Humans; Isoquinolines; Middle Aged; Mivacurium; Neuromuscular Blocking Agents; Paralysis

Topics: Abnormalities, Multiple; Congenital Hypothyroidism; Female; Humans; Infant; Isoquinolines; Mivacurium; Neuromuscular Nondepolarizing Agents; Paralysis; Syndrome

Pseudocholinesterase deficiency is usually identified when an anesthetized patient has prolonged paralysis after receiving neuromuscular blocking agents dependent on pseudocholinesterase enzymes for hydrolysis. This rare complication, most frequently associated with succinylcholine, can occur with the use of mivacurium, one of the newer nondepolarizing muscle relaxants also hydrolyzed by pseudocholinesterase. Prolonged paralysis has occurred 3 times in the past 2 years at this pediatric hospital after administration of mivacurium. The following case study describes causality and interventions for a patient with prolonged paralysis after receiving mivacurium.

Topics: Adolescent; Butyrylcholinesterase; Cerebral Palsy; Female; Humans; Isoquinolines; Mivacurium; Neuromuscular Nondepolarizing Agents; Paralysis; Postanesthesia Nursing; Postoperative Complications

Topics: Cholinesterases; Fatal Outcome; Female; Humans; Isoquinolines; Mivacurium; Neuromuscular Nondepolarizing Agents; Paralysis; Postoperative Complications

Mivacurium is a benzylisoquinolone, choline-like, non-depolarizing muscle relaxant. Its onset of action is similar to that of atracurium but its duration of action is shorter (approximately 10-15 minutes). Mivacurium is metabolized by plasma cholinesterases at approximately 70% of the rate of metabolism of suxamethonium. Deficiency or abnormality of plasma cholinesterase may cause the duration of action of both suxamethonium and mivacurium to be greatly prolonged. We describe a case of prolonged mivacurium paralysis after day surgery. Laboratory investigations showed a genetic tendency toward abnormal cholinesterase levels, but markedly depressed cholinesterase activity was suggestive of additional acquired causes. This patient had a history of liver disease, malnutrition and anticholinesterase use, which we believe were the most significant factors involved.

Topics: Aged; Ambulatory Surgical Procedures; Biopsy, Needle; Endoscopy; Follow-Up Studies; Humans; Isoquinolines; Lymphoma, T-Cell; Male; Mivacurium; Paralysis; Risk Assessment; Severity of Illness Index; Time Factors; Tongue

Topics: Adult; Cholinesterases; Female; Homozygote; Humans; Isoquinolines; Mivacurium; Neuromuscular Nondepolarizing Agents; Paralysis

Topics: Adult; Alleles; Butyrylcholinesterase; Female; Heterozygote; Humans; Isoquinolines; Mivacurium; Neuromuscular Nondepolarizing Agents; Paralysis; Pedigree; Phenotype

Recovery of the train-of-four (TOF) ratio to a value > 0.70 is synonymous with adequate return of neuromuscular function, but there is little information available concerning the subjective experience that accompanies residual neuromuscular block wherein the TOF ratio is in the range of 0.70 to 0.90.. Ten American Society of Anesthesiologists' (ASA) physical status 1 volunteers were studied. Control measurements including grip strength in kilograms and ability to perform a 5-s head- and leg-lift. In addition, a standard wooden tongue depressor was placed between each subject's incisor teeth, and he or she was told not to let the investigator remove it. All subjects were easily able to retain the device despite vigorous attempts to dislodge it. Neuromuscular function was monitored with a Datex (Datex Medical Instrumentation, Inc., Tewksbury, MA) 221 electromyographic (EMG) monitor. TOF stimulation was given every 20 s, and the measured TOF fade ratio was continuously recorded. A 5 mg/kg bolus of mivacurium was then administered, and an infusion at 2 mg.kg-1.min-1 was begun. The infusion was continued until the TOF ratio decreased to < 0.70 and was adjusted to keep it in the range of 0.65 to 0.75. Signs and symptoms of weakness were recorded when the TOF ratio had been stable +/-0.03 for at least 10 min during an interval when there were no adjustments in the infusion. All tests noted previously were repeated at this time. The TOF ratio was then allowed to recover to 0.85-0.90. When stable at this level, all tests were repeated, and the infusion was discontinued. TOF measurements were continued until a ratio of 1.0 was attained and until a final set of observations was recorded.. The TOF ratio in all subjects was reduced to < 0.70. No volunteers required intervention to maintain a patient airway, and the hemoglobin oxygen saturation while breathing air was > or = 96% at all times. TOF ratios < or = 0.90 were accompanied by diplopia and difficulty in tracking moving objects in all subjects. The ability to strongly oppose the incisor teeth did not return until the TOF ratio (on average) exceeded 0.85. A sustained 5-s head-lift was not achieved until the TOF ratio averaged 0.60 (range, 0.45-0.75). At a TOF ratio of 0.70, grip strength averaged 59% of control (range, 50-75%). With certain exceptions (vision, ability to clench the teeth tightly), there was wide variation in symptomatology between patients for any given TOF ratio. It is impossible to give reliable TOF break-points at which symptoms and signs will be present or absent.. All subjects had significant signs and symptoms of residual block at a TOF ratio of 0.70; none considered themselves remotely "street ready" at this time. The authors believe that satisfactory recovery of neuromuscular function after mivacurium-induced neuromuscular block requires return of the TOF ratio to a value > 0.90 and ideally to unity.

Topics: Adult; Female; Humans; Isoquinolines; Male; Masseter Muscle; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Paralysis; Vision, Ocular

Based on a train-of-four (TOF) ratio greater than 0.70 as the standard of acceptable clinical recovery, undetected postoperative residual paralysis occurs frequently in postanesthesia care units. In most published studies, detailed information regarding anesthetic management is not provided. The authors reexamined the incidence of postoperative weakness after the administration of long- and short-acting neuromuscular blockers because few, if any, such comparative studies are available.. Ninety-one adult patients were studied. In group 1 (mivacurium, n = 35), anesthesia was induced with propofol/ fentanyl and maintained with nitrous oxide, desflurane, and opioid supplementation. The response of the adductor pollicis to ulnar nerve stimulation was estimated by palpating the thumb. Mivacurium (0.20 mg/kg) was administered for tracheal intubation, and an infusion was adjusted to maintain the TOF count at 1. When surgery was completed, the infusion was discontinued. When a second twitch could be detected, 7.0 micrograms/kg atropine and then 0.5 mg/kg edrophonium were administered. At 5 and 10 min, the mechanical TOF response was measured. Additional measurements were recorded if possible. Patients were tracheally extubated and discharged from the operating room when they could respond to verbal commands and no TOF fade was palpable. In group 2 (pancuronium-desflurane anesthesia, n = 29), the protocol was identical to that of group 1, except that 0.07 mg/kg pancuronium was administered for tracheal intubation. Additional increments (0.5 to 1 mg) were given as needed. Antagonism was accomplished with 0.05 mg/kg neostigmine and 0.01 mg/kg glycopyrrolate. In group 3 (pancuronium propofol-opioid, n = 27), the protocol was identical to that of group 2, except that anesthesia was maintained with nitrous oxide and a propofol-alfentanil infusion. In all groups, patients were assessed until a TOF ratio of 0.90 or more was achieved.. All of the patients in group 1 had TOF ratios greater than 0.80 on arrival in the postanesthesia care unit. Twenty of 35 patients had TOF ratios 0.90 or more while they were still in the operating room. Thirty-three of 35 patients had TOF ratios 0.90 or more within 30 min of reversal, and this value was reached in all patients by 45 min. Recovery parameters in groups 2 and 3 did not differ from each other. Hence data from these groups were pooled. Fifty-four of 56 patients who received pancuronium had TOF values of 0.70 or more, the remaining two patients had values of 0.6 to 0.7. In contrast to the mivacurium group, however, only four patients achieved a TOF ratio of 0.90 or greater while still in the operating room. Finally, eight of these patients did not achieve this degree of recovery within 90 min of reversal.. These results suggest that if nondepolarizing neuromuscular blockers are administered using tactile evaluation of the TOF count as a guide, critical episodes of postoperative weakness in the postanesthesia care unit should occur infrequently even with long-acting relaxants. Nevertheless, if full recovery is defined as return to a TOF ratio of 0.90 or more, then short-acting agents would appear to offer a wider margin of safety.

Topics: Adult; Aged; Anesthesia Recovery Period; Anesthesia, Inhalation; Anesthetics, Intravenous; Desflurane; Female; Humans; Isoflurane; Isoquinolines; Male; Middle Aged; Mivacurium; Neuromuscular Nondepolarizing Agents; Pancuronium; Paralysis; Postoperative Complications; Propofol

Mivacurium, a nondepolarizing muscle relaxant, is metabolized by plasma cholinesterase. Although edrophonium does not alter plasma cholinesterase activity, we have observed that doses of edrophonium that antagonize paralysis from other nondepolarizing muscle relaxants are less effective with mivacurium. We speculated that edrophonium might after metabolism of mivacurium, thereby hindering antagonism of paralysis. Accordingly, we determined the effect of edrophonium on neuromuscular function and plasma mivacurium concentrations during constant mivacurium infusion.. We infused mivacurium to maintain 90% depression of adductor pollicis twitch tension and then gave edrophonium in doses ranging from 125-2,000 micrograms/kg without altering the mivacurium infusion. Peak twitch tension after edrophonium was determined to estimate the dose of edrophonium antagonizing 50% of twitch depression for antagonism of mivacurium; plasma cholinesterase activity and mivacurium concentrations before and after edrophonium were measured. Additional subjects were given 500 micrograms/kg edrophonium to antagonize continuous infusions of d-tubocurarine and vecuronium.. With mivacurium, edrophonium increased twitch tension in a dose-dependent manner: the dose of edrophonium antagonizing 50% of twitch depression was 2,810 micrograms/kg. The largest dose of edrophonium (2,000 micrograms/kg) produced only 45 +/- 7% antagonism. Edrophonium, 500 micrograms/kg, antagonized mivacurium markedly less than it antagonized d-tubocurarine and vecuronium. Edrophonium increased plasma concentrations of the two potent stereoisomers of mivacurium 48% and 79%, these peaking at 1-2 min; plasma cholinesterase activity was unchanged.. Edrophonium doses that antagonize d-tubocurarine and vecuronium are less effective in antagonizing the neuromuscular effects of mivacurium during constant infusion. Edrophonium increases plasma mivacurium concentrations, partly or completely explaining its limited efficacy; the mechanism by which edrophonium increases mivacurium concentrations remains unexplained. Our results demonstrate that antagonism of mivacurium by edrophonium is impaired, and therefore we question whether edrophonium should be used to antagonize mivacurium.

Topics: Adolescent; Adult; Cholinesterases; Dose-Response Relationship, Drug; Drug Interactions; Edrophonium; Humans; Infusions, Intravenous; Isoquinolines; Middle Aged; Mivacurium; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Paralysis