rapacuronium and Bronchial-Spasm

The administration of rapacuronium increases the risk of severe bronchospasm. There have been no studies of pulmonary function directly demonstrating airway constriction with rapacuronium in children. In this study, 10 ASA physical status I or II patients (aged 2-6 yr) were randomly divided into 2 equal groups, receiving either rapacuronium or mivacurium. Anesthesia was induced with sevoflurane and maintained with remifentanil (0.2-0.3 microg. kg(-1). min(-1)) and propofol (200-250 microg. kg(-1). min(-1)) infusions. We performed three sets of pulmonary function tests: baseline, after the administration of muscle relaxant, and after the administration of a beta(2) agonist. In both groups, there were no changes in static respiratory compliance. The increase in total respiratory system resistance after the administration of rapacuronium did not reach statistical significance (214.4% +/- 122.65% of baseline, P approximately 0.1), whereas maximal expiratory flow at 10% of forced vital capacity (MEF)(10) and MEF(functional residual capacity) on partial flow-volume curves by the forced deflation technique decreased markedly (53.4% +/- 18.49%, P < 0.01 and 41.3% +/- 27.42%, P < 0.001, respectively). With the administration of mivacurium, no changes were observed in respiratory system resistance (109.5% +/- 30.28%). MEF(10) decreased slightly (77.0% +/- 9.03%, P < 0.005) whereas MEF(FRC) did not (81.2% +/- 29.85%, not significant). After the administration of a beta(2) agonist, all measurements returned to baseline. Thus, the administration of rapacuronium consistently results in lower airway obstruction with minimal changes in static respiratory compliance when compared with mivacurium.. Pulmonary function tests in the present study showed that rapacuronium consistently causes severe bronchoconstriction, confirming clinical case reports of bronchospasm. The bronchoconstriction is reversible with albuterol. Mivacurium also causes very mild subclinical bronchoconstriction.

Topics: Airway Obstruction; Anesthesia; Anesthesia, Inhalation; Bronchial Spasm; Child; Child, Preschool; Female; Humans; Isoquinolines; Lung Compliance; Male; Mivacurium; Monitoring, Intraoperative; Neuromuscular Nondepolarizing Agents; Respiratory Function Tests; Respiratory Mechanics; Vecuronium Bromide

Topics: Bronchial Spasm; Humans; Neuromuscular Nondepolarizing Agents; United States; United States Food and Drug Administration; Vecuronium Bromide

A safe and effective ultra-short-acting nondepolarizing neuromuscular blocking agent is required to block nicotinic receptors to facilitate intubation. Rapacuronium, which sought to fulfill these criteria, was withdrawn from clinical use due to a high incidence of bronchospasm resulting in death. Understanding the mechanism by which rapacuronium induces fatal bronchospasm is imperative so that newly synthesized neuromuscular blocking agents that share this mechanism will not be introduced clinically. Selective inhibition of M2 muscarinic receptors by muscle relaxants during periods of parasympathetic nerve stimulation (e.g., intubation) can result in the massive release of acetylcholine to act on unopposed M3 muscarinic receptors in airway smooth muscle, thereby facilitating bronchoconstriction.. Competitive radioligand binding determined the binding affinities of rapacuronium, vecuronium, cisatracurium, methoctramine (selective M2 antagonist), and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; selective M3 antagonist) for M2 and M3 muscarinic receptors.. Rapacuronium competitively displaced 3H-QNB from the M2 muscarinic receptors but not from the M3 muscarinic receptors within clinically relevant concentrations. Fifty percent inhibitory concentrations (mean +/- SE) for rapacuronium were as follows: M2 muscarinic receptor, 5.10 +/- 1.5 microm (n = 6); M3 muscarinic receptor, 77.9 +/- 11 microm (n = 8). Cisatracurium and vecuronium competitively displaced 3H-QNB from both M2 and M3 muscarinic receptors but had affinities at greater than clinically achieved concentrations for these relaxants.. Rapacuronium in clinically significant doses has a higher affinity for M2 muscarinic receptors as compared with M3 muscarinic receptors. A potential mechanism by which rapacuronium may potentiate bronchoconstriction is by blockade of M2 muscarinic receptors on prejunctional parasympathetic nerves, leading to increased release of acetylcholine and thereby resulting in M3 muscarinic receptor-mediated airway smooth muscle constriction.

Topics: Animals; Atracurium; Binding, Competitive; Bronchial Spasm; Cell Membrane; CHO Cells; Cricetinae; Diamines; Indicators and Reagents; Muscarinic Antagonists; Neuromuscular Nondepolarizing Agents; Piperidines; Quinuclidinyl Benzilate; Radioligand Assay; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptors, Muscarinic; Vecuronium Bromide

Topics: Bronchial Spasm; Humans; Neuromuscular Nondepolarizing Agents; Receptor, Muscarinic M2; Receptors, Muscarinic; Vecuronium Bromide

Topics: Anesthetics, Intravenous; Bronchial Spasm; Chemistry, Pharmaceutical; Humans; Neuromuscular Nondepolarizing Agents; Propofol; Vecuronium Bromide

Topics: Bronchial Spasm; Child; Humans; Neuromuscular Nondepolarizing Agents; Vecuronium Bromide

We conducted this study to determine the risk factors for the development of bronchospasm after the administration of rapacuronium and to determine if children with bronchospasm on induction of anesthesia were more likely to have received rapacuronium compared with other muscle relaxants. In a retrospective cohort study, all anesthetic records in which rapacuronium was administered were reviewed to determine which patients developed bronchospasm during induction of anesthesia. Two-hundred-eighty-seven patients were identified, of whom 12 (4.2%; 95% confidence interval [CI], 2.2%--7.2%) developed bronchospasm during induction of anesthesia. Significant risk factors for the development of bronchospasm with administration of rapacuronium included rapid sequence induction (relative risk [RR], 17.9; 95% CI, 2.9--infinity) and prior history of reactive airways disease (RR, 4.6; 95% CI, 1.5--14.3). In a case-control study, all cases of bronchospasm during induction of anesthesia in the 5-mo time period that rapacuronium was available for clinical use were identified. Aside from the 12 cases of bronchospasm with rapacuronium, 11 additional cases of bronchospasm were associated with the use of other muscle relaxants. Four controls were randomly selected for each of the 23 cases of bronchospasm. Children with bronchospasm during induction of anesthesia were several times more likely (odds ratio, 10.1; 95% CI, 3.5--28.8) for having received rapacuronium compared with other muscle relaxants.. In a retrospective cohort study, significant risk factors for the development of bronchospasm with the administration of rapacuronium on induction of anesthesia included rapid sequence induction and prior history of reactive airways disease. In a case-control study, children with bronchospasm during induction of anesthesia were several times more likely to have received rapacuronium compared with other muscle relaxants.

Topics: Adolescent; Bronchial Spasm; Case-Control Studies; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Male; Neuromuscular Nondepolarizing Agents; Retrospective Studies; Risk Factors; Vecuronium Bromide

Topics: Ambulatory Surgical Procedures; Bronchial Spasm; Humans; Neuromuscular Nondepolarizing Agents; Succinylcholine; Vecuronium Bromide

Topics: Bronchial Spasm; Humans; Neuromuscular Nondepolarizing Agents; Vecuronium Bromide

Topics: Bronchial Spasm; Child; Female; Humans; Neuromuscular Nondepolarizing Agents; Oxygen; Vecuronium Bromide

Topics: Adult; Bronchial Spasm; Female; Histamine Release; Humans; Neuromuscular Nondepolarizing Agents; Vecuronium Bromide

Topics: Bronchial Spasm; Child; Child, Preschool; Female; Humans; Infant, Newborn; Male; Neuromuscular Nondepolarizing Agents; Vecuronium Bromide