Disease relevance of

• Bronchospasm was the most common treatment-related adverse event with rapacuronium 0.3 to 3 mg/kg (3.4% of adult patients) [1].
• At least in part because of its active metabolite, rapacuronium is highly cumulative in renal failure [2].
• The most prominent adverse effects of rapacuronium (tachycardia, hypotension and bronchospasm) are dose-related, and in particular pulmonary adverse effects are observed more frequently under conditions of a rapid-sequence induction in adults [3].
• CONCLUSION: The neuromuscular blocking effect of a single bolus dose of rapacuronium in patients with cirrhosis is not different from that of patients with normal hepatic function [4].
• Five adverse experiences were related to rapacuronium administration: Bronchospasm (two instances), tachycardia (one instance), and increased salivation (two instances) [5].

High impact information on

• Pharmacokinetics and pharmacodynamics of rapacuronium bromide [2].
• Additional boluses (< or =3) of rapacuronium 0.5 or 0.55 mg/kg after an intubating bolus of 1.5 mg/kg provided continued skeletal muscle relaxation during short surgical procedures in adult patients [1].
• An additional mechanism of rapacuronium-induced bronchoconstriction is suggested by increases in baseline muscle tension [6].
• In addition, rapacuronium caused an increase in baseline tone of airway smooth muscle that was antagonized by atropine but not by previous depletion of nonadrenergic noncholinergic neurotransmitters or by inhibitors of histamine receptors, tachykinin receptors, leukotriene receptors, or calcium channels [6].
• Dynamic compliance, tidal volume, peak inspiratory flow rate, peak expiratory flow rate, and peak inflating pressure were measured after administration of either rapacuronium (1.5 mg/kg) or cis-atracurium (0.2 mg/kg) to 20 adult patients (10 received rapacuronium and 10 received cis-atracurium) anesthetized with propofol-remifentanil [7].

Chemical compound and disease context of

• The overall incidence of drug-related adverse events was similar with rapacuronium 1.5 or 2.5 mg/kg or suxamethonium chloride 1 mg/kg (8 vs. 6%) but bronchospasm, tachycardia and injection site reaction tended to occur more often with rapacuronium [1].
• METHODS: Rapacuronium (1.5 mg/kg) was administered to 10 healthy volunteers and 10 patients with renal failure who were undergoing non-transplant surgery, were 18-45 yr old, and were anesthetized with propofol [8].
• Rapacuronium administration can produce hypotension via mechanisms that do not seem to be related to histamine release [9].

Biological context of

• The patients in the 2.5 mg/kg rapacuronium group had significantly higher heart rates compared with patients in the mivacurium group [10].
• After intramuscular administration, bioavailability is 56%, and plasma rapacuronium concentrations peak within 4 or 5 min [11].
• One patient in the Rapacuronium group experienced cutaneous flushing associated with a 33% decrease in blood pressure [12].
• We have assessed the haemodynamic effects of rapacuronium (Org 9487) in adults undergoing cardiac surgery and compared these with vecuronium and placebo [13].
• The Rapacuronium group exhibited significantly larger decreases in blood pressure and systemic vascular resistance than the Vecuronium or Succinylcholine groups [12].

Anatomical context of

• Rapacuronium preferentially antagonizes the function of M2 versus M3 muscarinic receptors in guinea pig airway smooth muscle [6].
• Unlike the finding for other nondepolarizing muscle relaxants, the laryngeal muscles are not resistant to rapacuronium [14].
• METHODS: The twitch tensions of the adductor pollicis and the laryngeal adductors (via a tracheal tube cuff positioned at the vocal cords) were measured in 10 volunteers who were anesthetized with propofoL Rapacuronium, 1.5 mg/kg, was given and blood samples were collected [14].
• Haemodynamic effects of rapacuronium in adults with coronary artery or valvular disease [13].
• Rapacuronium (1.5 mg/kg) was administered at induction of anesthesia, 2 minutes after clamping the portal vein, and 5 minutes after reperfusion of the new graft [15].

Associations of with other chemical compounds

• CONCLUSIONS: Rapacuronium, 1.5 and 2.5 mg/kg, produced neuromuscular blockade as rapidly as succinylcholine and significantly faster than mivacurium [10].
• Rapacuronium augments acetylcholine-induced bronchoconstriction via positive allosteric interactions at the M3 muscarinic receptor [16].
• In all patients, neuromuscular block was antagonized using neostigmine 0.05 mg kg-1 or edrophonium 1.0 mg kg-1 (allocated randomly), 2 min after the final dose of rapacuronium [17].
• Prolonged duration of neuromuscular block with rapacuronium in the presence of sevoflurane [18].
• The pharmacodynamics and pharmacokinetics of the two most recent aminosteroid neuromuscular blocking drugs to become available, rapacuronium bromide (Org 9487) and rocuronium bromide are reviewed [19].

Gene context of

• RESULTS: Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min [20].
• When the first twitch (T1) of a train-of-four stimulus (using the TOF Guard accelerometer) returned to 5%, an infusion of rapacuronium was started at 3 mg kg-1 h-1 and adjusted to maintain T1/T0 at 10% [21].
• After three incremental doses of rapacuronium, there was a longer time to recovery of T1/T0 = 25% after neostigmine compared with edrophonium (5.1 (1.0) vs 3.3 (1.3) min; P < 0.05) but more rapid recovery to T1/T0 = 75% (10.1 (2.9) vs 16.8 (10.1) min; P < 0.05) and T4/T1 = 0.7 (19.8 (6.3) vs 35.1 (10.4) min; P < 0.05) [17].
• IMPLICATIONS: Pulmonary function tests in the present study showed that rapacuronium consistently causes severe bronchoconstriction, confirming clinical case reports of bronchospasm [22].

Analytical, diagnostic and therapeutic context of

• The onset, extent and duration of action and clinical efficacy of an intubating dose of rapacuronium appeared to be similar in the general adult population, adult patients with renal or hepatic dysfunction, patients undergoing Caesarean section, and elderly, paediatric or obese adult patients [1].
• At the recommended dose for endotracheal intubation (1.5 mg/kg), an intravenous bolus of rapacuronium has a rapid onset (approximately 1.2 to 1.8 minutes) and short duration of action (10.2 to 16.5 minutes) in adults undergoing elective surgery [1].
• Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade [23].
• Effects of rapacuronium on respiratory function during general anesthesia: a comparison with cis-atracurium [7].
• 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 [24].

References