rapacuronium and cisatracurium

Rapacuronium bromide (rapacuronium; ORG-9487) is a nondepolarising muscle relaxant (NMBA) with a low potency [90% effective dose (ED90) 1 mg/kg], which to some extent is responsible for its rapid onset of action. Because of the high plasma clearance (5.3 to 11.1 mg/kg/min) of rapacuronium, its clinical duration of action following single bolus doses up to 2 mg/kg in adults is short (i.e. <20 minutes). Rapacuronium forms a pharmacologically active 3-desacetyl metabolite, ORG-9488, which may contribute to a delay in spontaneous recovery after repeat bolus doses or infusions. After rapacuronium 1.5 mg/kg clinically acceptable intubating conditions are achieved within 60 to 90 seconds in the majority of adult and elderly patients undergoing elective anaesthesia. However, in a rapid-sequence setting. intubating conditions are less favourable after rapacuronium 1.5 to 2.5 mg/kg than after succinylcholine. 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. Therefore, it seems worthwhile to consider only doses of rapacuronium < or = 1.5 mg/kg to facilitate rapid tracheal intubation, and to use succinylcholine or rocuronium rather than rapacuronium in a rapid-sequence setting. Rapacuronium, however, is a suitable alternative to mivacurium chloride (mivacurium) and succinylcholine for short procedures (e.g. ambulatory anaesthesia). Rocuronium bromide (rocuronium) is a relatively low-potent, intermediateacting NMBA. Its main advantage is the rapid onset of neuromuscular block whereby good or excellent intubating conditions are achieved within 60 to 90 seconds after rocuronium 0.6 mg/kg (2 x ED95), and within 60 to 180 seconds after smaller doses (1 to 1.5 x ED95). Larger doses of rocuronium (> or = 1 mg/kg) seem to be suitable for rapid-sequence induction under relatively light anaesthesia. However, it is still a matter of controversy whether, in the case of an unanticipated difficult intubation, the long duration of rocuronium administered in such large doses outweighs the many adverse effects of succinylcholine. Rocuronium has mild vagolytic effects and does not release histamine, even when administered in large doses. Rocuronium is primarily eliminated via the liver and its pharmacokinetic profile is similar to that of vecuronium bromide (vecuronium). Unlike vecuronium, roc

Topics: Adult; Aged; Androstanols; Animals; Atracurium; Child; Dose-Response Relationship, Drug; Half-Life; Hemodynamics; Humans; Infant; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Vecuronium Bromide

Topics: Androstanols; Atracurium; Child; Dose-Response Relationship, Drug; Humans; Infant; Isoquinolines; Mivacurium; Muscles; Neuromuscular Blocking Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Vecuronium Bromide

The pharmacokinetics of 6 new neuromuscular blocking drugs are described. These are the aminosteroids pipecuronium bromide, rocuronium bromide and rapacuronium bromide (ORG-9487) and the benzylisoquinolinium diesters doxacurium chloride, mivacurium chloride and cisatracurium besilate. In healthy individuals, these drugs all have similar volumes of distribution. Their pharmacokinetics are influenced little by age or anaesthetic technique, but renal and hepatic disease may significantly alter their distribution and elimination. Pipecuronium resembles pancuronium in its pharmacokinetic and neuromuscular blocking profile, but is devoid of cardiovascular effects. It has a low clearance (0.16 L/h/kg) and long elimination half-life (120 minutes). It is largely eliminated through the kidney. Rocuronium has a similar pharmacokinetic profile to vecuronium but its onset of action is more rapid and duration of action slightly shorter. Its clearance (0.27 L/h/kg) is intermediate between those of pipecuronium and rapacuronium, but its elimination half-life is long (83 minutes). The pharmacokinetics of rocuronium are altered by renal and hepatic disease; the latter probably has the more significant effect. Rapacuronium has a rapid onset, and a bolus dose has a short duration of action. It has a high clearance (0.59 L/h/kg) but a long elimination half-life (112 minutes). Doxacurium has a pharmacokinetic and pharmacodynamic profile similar to pipecuronium. It has a high potency and is devoid of cardiovascular effects. In adults, it has a low clearance (0.15 L/h/kg) and long elimination half-life (87 minutes). Mivacurium is a mixture of 3 stereoisomers. It has a short to intermediate duration of action. It is hydrolysed by plasma cholinesterase. Inherited or acquired alterations in plasma cholinesterase activity are associated with changes in the pharmacokinetics and time course of action of mivacurium. The 2 active isomers (cis-trans and trans-trans) have a high clearance (4.74 L/h/kg) and very short elimination half-lives (approximately 2 minutes). Cisatracurium is the 1R-cis 1'R-cis isomer of atracurium. It has similar pharmacokinetics and pharmacodynamics to atracurium. It is mainly broken down by Hofmann (non-enzymatic) degradation. Cisatracurium has an intermediate clearance (0.3 L/h/kg) and short elimination half-life (26 minutes). Hepatic and renal disease have little effect on its pharmacokinetics.

Topics: Aging; Androstanols; Atracurium; Female; Humans; Isoquinolines; Mivacurium; Neuromuscular Nondepolarizing Agents; Pipecuronium; Pregnancy; Rocuronium; Vecuronium Bromide

The usefulness of newer intermediate-acting muscle relaxants rocuronium and cisatracurium when used by infusion has been reviewed briefly and their main features pointed out. Comparative features of atracurium, vecuronium and mivacurium have also been described. Both new agents may have advantages for use by infusion particularly for longer procedures, due to the lack of detectable metabolites with rocuronium and production of comparatively smaller amounts of metabolites with cisatracurium.

Topics: Androstanols; Atracurium; Humans; Infusion Pumps; Infusions, Intravenous; Isoquinolines; Mivacurium; Neuromuscular Blocking Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Vecuronium Bromide

To examine the efficacy of antagonism of rapacuronium-, mivacurium-, rocuronium- and cisatracurium-induced neuromuscular block at the laryngeal adductors (LA).. One hundred four patients were randomly assigned to one of eight study groups. They either received rapacuronium 1.5 mg x kg(-1), mivacurium 0.25 mg x kg(-1), rocuronium 0.9 mg x kg(-1) or cisatracurium 0.15 mg x kg(-1). Patients in each treatment group either received edrophonium (0.5 mg x kg(-1)) at 10% recovery of the first twitch (T1) of train-of-four (TOF) at the LA or were allowed to recover spontaneously from neuromuscular block. The effect of antagonism on speed of recovery of neuromuscular function at the LA was evaluated.. The time to recovery to a TOF ratio of 0.9 at the LA, when compared to the spontaneous recovery group, was significantly shortened by the administration of edrophonium in patients receiving rapacuronium [19.2 +/- 7.8 vs 26.2 +/- 4.9 (mean +/- SD) min], rocuronium (24.7 +/- 14.3 vs 44.4 +/- 13.0 min) and cisatracurium (24.2 +/- 5.7 vs 35.1 +/- 7.6 min). Edrophonium administration did not shorten complete recovery from mivacurium-induced block (15.7 +/- 8.0 vs 17.6 +/- 6.1 min).. Recovery from rapacuronium-, rocuronium- or cisatracurium- induced neuromuscular block to a TOF ratio of 0.9 as measured at the LA was shortened by the administration of edrophonium, when compared to spontaneous recovery.

Topics: Adolescent; Adult; Androstanols; Atracurium; Cholinesterase Inhibitors; Edrophonium; Electric Stimulation; Humans; Isoquinolines; Laryngeal Muscles; Male; Middle Aged; Mivacurium; Neuromuscular Blockade; Neuromuscular Blocking Agents; Rocuronium; Time Factors; Treatment Outcome; Vecuronium Bromide

Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors, undesirable airway effects (i.e., bronchoconstriction) can result from neuromuscular blocking agents' affinity for airway muscarinic receptors. We questioned whether two new members of a bisquaternary nondepolarizing muscle relaxant family, gantacurium and CW002, demonstrated detrimental effects of airway muscarinic receptors using an in vivo model in guinea pig airways.. Urethane-anesthetized male guinea pigs were ventilated through a tracheostomy with continuous digital recordings of pulmonary inflation pressure and heart rate. The dose for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium was defined in the guinea pig. Transient and reproducible changes in pulmonary inflation pressure and heart rate were recorded after vagal nerve stimulation or intravenous injection of acetylcholine before and after pretreatment with cumulatively increasing concentrations of gantacurium, CW002, cisatracurium or a single concentration of rapacuronium.. The doses for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium were 0.064 +/- 0.006, 0.012 +/- 0.0006, 0.10 +/- 0.003, and 0.31 +/- 0.05 mg/kg, respectively. Gantacurium, CW002, and cisatracurium were without effects on baseline pulmonary inflation pressures and were devoid of significant interactions with M2 and M3 muscarinic receptors in vivo.. These findings suggest that gantacurium and CW002 are devoid of significant effects at airway muscarinic receptors particularly M3 receptors on bronchial smooth musculature at doses several fold higher than those required for functional muscle paralysis.

Topics: Acetylcholine; Anesthesia; Animals; Atracurium; Dose-Response Relationship, Drug; Drug Interactions; Guinea Pigs; Heart Rate; Isoquinolines; Lung; Male; Muscle Contraction; Muscle, Smooth; Neuromuscular Depolarizing Agents; Receptor, Muscarinic M2; Receptor, Muscarinic M3; Receptors, Muscarinic; Respiratory System; Vagus Nerve; Vecuronium Bromide

Traditionally, the clinical potency of neuromuscular blocking drugs has been measured using linear regression analysis (LRA) after log dose and probit or logit data transformation. However, probit and logit analyses are meant to handle only quantal responses with binomial error distributions, not continuous data such as per cent of maximal response. Some statisticians now consider this approach outmoded and assert that non-linear regression (NLR) is the preferred way to analyse sigmoidal dose-response relationships. We were interested in the degree to which the method of regression analysis alters calculated ED(50) and ED(95) values.. We analysed raw data for succinylcholine, rocuronium, rapacuronium, and cisatracurium from previously published studies using both LRA and NLR to determine the ED(50) and ED(95) values and the respective slopes of the dose-response relationships. We also estimated drug potency using the Hill equation (HE) using the slopes obtained from LRA and NLR.. ED(50) values calculated by NLR, LRA, or the HE were interchangeable. LRA resulted in ED(95) values that were 13-18% lower than those determined by NLR. The 95% confidence limits (CL) for the ED(50) did not exceed +/-8% of the estimated value no matter how it was calculated vs +/-20-30% for the ED(95).. The ED(50) is a very robust parameter. When comparing the potency of neuromuscular blockers, it is this value rather than the ED(95) that should be used. The CL for the ED(95), regardless of how it is calculated, are so wide that this parameter must be viewed, at best, as an approximation.

Topics: Adult; Androstanols; Atracurium; Dose-Response Relationship, Drug; Electric Stimulation; Humans; Nerve Block; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Neuromuscular Junction; Neuromuscular Nondepolarizing Agents; Regression Analysis; Rocuronium; Succinylcholine; Vecuronium Bromide

It has been estimated that more than 60% of all paediatric surgery is performed on a day case basis. The benefits of this type of surgery in children include reduced costs, avoidance of the stress of hospitalization and less disruption to family life. The growth of day surgery in children has been facilitated by the development of non-depolarizing neuromuscular blocking agents characterized by short and intermediate duration of action and fewer side-effects. The more rapid onset and shorter duration of action of non-depolarizing neuromuscular blocking agents in children should facilitate the use of these agents in place of succinylcholine for day case procedures.

Topics: Ambulatory Surgical Procedures; Androstanols; Atracurium; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Isoquinolines; Mivacurium; Neuromuscular Blocking Agents; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Rocuronium; Succinylcholine; Vecuronium Bromide