Topics:
bronchial spasm

RAPACURONIUM (16-N-allyl, 17-β-propionate analog of vecuronium) is a new rapid-onset, short-acting, nondepolarizing steroidal neuromuscular blocking drug. Concern has been raised with respect to possible respiratory effects of rapacuronium. The following case report describes a patient in whom severe bronchospasm developed after rapacuronium administration.

A 34-yr-old woman, American Society of Anesthesiologists class I, who weighed 90 kg and was 173.5 cm tall was scheduled to undergo laparoscopic tubal ligation. Her medical history was not significant, except for hepatitis B at the age of 13 yr and a history of depressive disorder. The patient was not taking medication. She was a smoker (10 cigarettes per day). Examination was unremarkable. Routine monitoring was used. The patient was preoxygenated, achieving an oxygen saturation measured by pulse oximetry (Spo2) of 100%. Anesthesia was induced with 1 mg midazolam, 150 μg fentanyl, and 200 mg propofol, followed immediately by 1.4 mg/kg rapacuronium. Anesthesia was maintained immediately with 4% inspired desflurane in oxygen. One minute after administration of rapacuronium, intubation was achieved easily. Severe bronchospasm (wheezing, increased airway pressure during positive pressure ventilation [peak inspiratory pressure of 45 cm H2O], and prolonged expiratory phase) occurred just after tracheal intubation. Positive pressure ventilation became exceedingly difficult. Inhalational bronchodilator (albuterol) therapy was administered via  an AeroVent®Collapsible Holding Chamber (Monaghan Medical Corp., Plattsbrug, NY) attached to the inspiratory limb of the anesthetic circuit. Spo2decreased to 85% despite the administration of 100% oxygen, and PETco2was 47 mmHg. This lasted for 7 min. The clinical picture gradually improved afterward, and Spo2increased slowly to 92%. Approximately 15 min after rapacuronium administration, the wheezing resolved, the peak inspiratory pressure decreased to 28 cm H2O, and Spo2increased to 96%. The content of one albuterol nebulizer was administered during this event. Each actuation administers 90 μg albuterol. After this event, anesthesia was maintained with 60% nitrous oxide and desflurane (end-tidal concentration, 2.6–3.0%) in oxygen. Neuromuscular block was maintained with 0.2 mg/kg rocuronium. At the end of surgery, 0.03 mg/kg neostigmine and 0.006 mg/kg glycopyrrolate were administered to the patient for antagonism of residual neuromuscular block. The patient had an uneventful recovery. No further bronchospasm was noted during her postoperative course.

Although the overall reported incidence of bronchospasm (in controlled trials) after rapacuronium and succinylcholine were 3.2 and 2.1%, respectively (data from Organon Inc., West Orange, NJ), others 1noted 18 incidents of such events (10.7%) after rapacuronium compared with 7 cases (4.1%) after succinylcholine. In the latter study, only one patient in the rapacuronium group, who had a history of obstructive airway disease, had severe bronchospasm after intubation. 1Our patient had severe bronchospasm after rapacuronium despite the facts that she was not asthmatic and that she received propofol for induction. Kahwaji et al.  2reported two serious adverse effects (tachycardia and bronchospasm) that occurred in a 29-yr-old, 100-kg man with American Society of Anesthesiologists physical status I within 30 s of administration of 2.0 mg/kg rapacuronium.

Rapacuronium may release histamine and produce slight changes in blood pressure and heart rate after administration. 3However, it seems that the bronchospasm noted with rapacuronium is mediated via  mechanisms that do not seem to be related to histamine release. 3The affinity of neuromuscular blockers for the muscarinic receptor seems to have some influence on neural control of airway caliber. Pancuronium and atracurium (but not vecuronium) were found to enhance the increases in pulmonary resistance induced by vagus nerve stimulation, probably by blocking prejunctional muscarinic receptors (M2) that physiologically inhibit vagally mediated increases in pulmonary resistance. 4,5Blockage of M3 muscarinic receptors on airway smooth muscle inhibits vagally induced bronchoconstriction. 5Pancuronium and gallamine had affinities for the M2 muscarinic receptor within the clinical dose range. 6The affinity of rapacuronium for muscarinic receptors has not been studied. Therefore, there is insufficient evidence to make a definite statement on how rapacuronium induces bronchospasm. It seems prudent, therefore, to avoid using rapacuronium in patients with asthma or airway hyperreactivity.

1.
Sparr HJ, Mellinghoff H, Blobner M, Nolge-Schoniburg G: Comparison of intubating conditions after rapacuronium (Org 9487) and succinylcholine following rapid sequence induction in adult patients. Br J Anaesth 1999; 82: 537–41
2.
Kahwaji R, Bevan DR, Bikhazi G, Shanks CA, Fragen RJ, Dyck JB, Angst MS, Matteo R: Dose-ranging study in younger adult and elderly patients of ORG 9487, a new rapid-onset, short-duration muscle relaxant. Anesth Analg 1997; 84: 1011–8
3.
Levy JH, Pitts M, Thanopoulos A, Szlam F, Bastian R, Kim J: The effects of rapacuronium on histamine release and hemodynamics in adult patients undergoing general anesthesia. Anesth Analg 1999; 89: 290–5
4.
Vettermann J, Beck KC, Lindahl SG, Brichant JF, Rehder K: Actions of enflurane, isoflurane, vecuronium, atracurium, and pancuronium on pulmonary resistance in dogs. A nesthesiology 1988; 69: 688–95
5.
Okanlami OA, Fryer AD, Hirshman C: Interaction of nondepolarizing muscle relaxants with M2and M3muscarinic receptors in guinea pig lung and heart. A nesthesiology 1996; 84: 155–61
6.
Hou VY, Hirshman CA, Emala CW: Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors. A nesthesiology 1998; 88: 744–50