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Drugs 2001Rapacuronium 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... (Review)
Review
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, rocuronium has no metabolite. Cisatracurium besilate (cisatracurium), the IR-cis, 1'R-cis isomer of atracurium besilate (atracurium) is approximately 4 times more potent than atracurium. The onset time of cisatracurium is significantly slower than after equipotent doses of atracurium. The recommended intubating dose is 0.15 to 0.2 mg/kg (3 to 4 times ED95). Over a wide range of clinically relevant doses the recovery properties of cisatracurium are affected by neither the size of the bolus dose nor by the duration of infusion. Unlike atracurium, cisatracurium does not trigger histamine release. Like atracurium, cisatracurium undergoes Hofmann elimination. In contrast to atracurium, cisatracurium does not undergo hydrolysis by nonspecific plasma esterases. Moreover, about 77% of the drug is cleared by organ-dependent mechanisms.
Topics: Adult; Aged; Androstanols; Animals; Atracurium; Child; Dose-Response Relationship, Drug; Half-Life; Hemodynamics; Humans; Infant; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Rocuronium; Vecuronium Bromide
PubMed: 11434449
DOI: 10.2165/00003495-200161070-00003 -
Der Anaesthesist Aug 1986A prospective controlled study was conducted to compare the efficacy of vecuronium and succinylcholine for the crash-induction technique. Following precurarisation with... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
A prospective controlled study was conducted to compare the efficacy of vecuronium and succinylcholine for the crash-induction technique. Following precurarisation with 0.02 mg/kg vecuronium and 0.1 mg fentanyl (group A and B) or NaCl 0.9% and 0.1 mg fentanyl (group C) preoxygenation via face mask was maintained until the patients reported heavy eye-lids or weariness or the precurarization-time attained 120 s. The patients then received 5 mg/kg thiopentone followed by 1.5 mg/kg succinylcholine (group B) or 0.08 mg/kg vecuronium (group A) resp. 0.1 mg/kg vecuronium (group C) directly before the thiopentone. Rapid intubation and scoring of the intubation condition was performed by an anaesthetist who was unaware of the grouping. The intubation time was defined as the interval from the end of the injection of the drugs until cuff-inflation of the tracheal tube. All patients in group A and B could be intubated within 60 s, in contrast to only 15 patients in group C (p less than 0.05). The intubation conditions in the succinylcholine group and in the vecuronium group with divided doses showed no significant differences, while in group C the conditions were significantly worse. The modified crash-induction technique with vecuronium in divided doses could become beneficial in patients with contraindications of the use of succinylcholine who are at risk of aspiration.
Topics: Anesthesia; Electromyography; Humans; Intubation, Intratracheal; Succinylcholine; Vecuronium Bromide
PubMed: 2877594
DOI: No ID Found -
European Journal of Pharmacology Nov 1992The neuromuscular-blocking agent vecuronium bromide undergoes hydrolysis to three pharmacologically active metabolites (3-desacetyl, 17-desacetyl and 3,17-desacetyl...
The neuromuscular-blocking agent vecuronium bromide undergoes hydrolysis to three pharmacologically active metabolites (3-desacetyl, 17-desacetyl and 3,17-desacetyl vecuronium) which might modify the neuromuscular-blocking action of their parent compound. In order to elucidate the possible role of the interaction between vecuronium and its metabolites in the complications reported after long-term use of vecuronium in intensive care unit (ICU) patients, the relative potency of vecuronium, 3-desacetyl and 3,17-desacetyl vecuronium was determined in the rat hemidiaphragm in vitro and the mode of interaction of the above-mentioned compounds investigated. Dose-response relationships were established for each substance alone and for combinations of vecuronium with its metabolites. The relative potency at the EDmax50 levels (% maximal effect) were in the order of 1:1.2:27 for vecuronium, the 3-desacetyl derivative and the 3,17-desacetyl derivative, respectively. The mode of interaction characterized by isobolographic and algebraic (functional) analysis showed vecuronium and 3-desacetyl vecuronium to interact in an additive fashion while the combined effect of the parent compound and its 3,17-desacetyl derivative was less than additive, indicating antagonism.
Topics: Animals; Diaphragm; In Vitro Techniques; Male; Muscle Contraction; Neuromuscular Depolarizing Agents; Rats; Rats, Sprague-Dawley; Respiratory Muscles; Vecuronium Bromide
PubMed: 1361438
DOI: 10.1016/0014-2999(92)90828-r -
Anesthesiology Jan 2000The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of... (Clinical Trial)
Clinical Trial Comparative Study
BACKGROUND
The authors evaluated the influence of temperature on the pharmacokinetics and pharmacodynamics of vecuronium because mild core hypothermia doubles its duration of action.
METHODS
Anesthesia was induced with alfentanil and propofol and maintained with nitrous oxide and isoflurane in 12 healthy volunteers. Train-of-four stimuli were applied to the ulnar nerve, and the mechanical response of the adductor pollicis was measured. Volunteers were actively cooled or warmed until their distal esophageal temperatures were in one of four ranges: < 35.0 degrees C, 35.0-35.9 degrees C, 36.0-36.9 degrees C, and > or = 37.0 degrees C. With temperature stabilized, vecuronium was infused at 5 microg x kg(-1) x min(-1) until the first response of each train-of-four had decreased by 70%. Arterial blood (for vecuronium analysis) was sampled at intervals until the first response recovered to at least 90% of its prevecuronium level. Vecuronium, 20 microg x kg(-1) x min(-1), was then infused for 10 min, and arterial blood was sampled at intervals for up to 7 h. Population-based nonlinear mixed-effects modeling was used to examine the effect of physical characteristics and core temperature on vecuronium pharmacokinetics and pharmacodynamics.
RESULTS
Decreasing core temperature over 38.0-34.0 degrees C decreases the plasma clearance of vecuronium (11.3% per degrees C), decreases the rate constant for drug equilibration between plasma and effect site (0.023 min(-1) per degrees C), and increases the slope of the concentration-response relationship (0.43 per degrees C).
CONCLUSIONS
Our results show that reduced clearance and rate of effect site equilibration explain the increased duration of action of vecuronium with reducing core temperature. Tissue sensitivity to vecuronium is not influenced by core temperature.
Topics: Adult; Alfentanil; Anesthesia, Inhalation; Anesthetics, Intravenous; Body Temperature; Female; Humans; Hypothermia; Male; Metabolic Clearance Rate; Models, Biological; Neuromuscular Nondepolarizing Agents; Propofol; Sex Factors; Vecuronium Bromide
PubMed: 10638903
DOI: 10.1097/00000542-200001000-00018 -
Anaesthesia Dec 2000
Topics: Adrenergic Agonists; Adult; Aged; Anaphylaxis; Epinephrine; Female; Humans; Male; Neuromuscular Nondepolarizing Agents; Resuscitation; Skin Tests; Treatment Outcome; Vecuronium Bromide
PubMed: 11121948
DOI: 10.1046/j.1365-2044.2000.01798-15.x -
Anaesthesia and Intensive Care Feb 1991
Review
Topics: Aged; Betamethasone; Brain; Female; Humans; Male; Middle Aged; Vecuronium Bromide
PubMed: 1672800
DOI: 10.1177/0310057X9101900120 -
Canadian Journal of Anaesthesia =... Dec 2000To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and... (Clinical Trial)
Clinical Trial
PURPOSE
To determine the effect of moderate and deep hypothermic cardiopulmonary bypass (CPB) on the pharmacokinetic and pharmacodynamic behaviour of vecuronium in infants and children.
METHODS
We studied 12 patients undergoing surgery for congenital heart disease under narcotic-nitrous oxide anesthesia. Neuromuscular blockade was maintained constant (TI 4-10% by Datex electromyograph) by adjusting a vecuronium infusion. Plasma vecuronium concentrations (Cpss) were analysed by HPLC to describe a pseudosteady-state during each of the pre-CPB, CPB and post-CPB phases. Paired arterial blood samples were taken 20 min apart after at least 20 min of constant infusion.
RESULTS
Nine cases were analysed, mean age 20 mo, mean weight 9 kg. Three patients had deep and six moderate hypothermia. In the pre-CPB phase Cpss fell into two groups (mean +/- SD: 330 +/- 42 ng x ml(-1); 127 +/- 27 ng x ml(-1); P < 0.001); similarly the clearances showed a bimodal distribution (mean +/- SD: 5.08 +/- 0.94; 11.51 +/- 0.2 ml x min(-1) x kg(-1) P < 0.001), although in different patients. During CPB this bimodal distribution disappeared. Vecuronium infusion rate (VIR) decreased by 84% and 92% from pre-CPB to CPB phase in deep and moderate hypothermia groups respectively (P < 0.05), paralleled by decreases in Cpss of 36% (P > 0.05) and 52% (P < 0.05).
CONCLUSION
Changes in vecuronium requirements and plasma concentrations during CPB demonstrate that vecuronium pharmacokinetics and pharmacodynamics are both affected by hypothermic CPB in infants. The finding of bimodal distributions for plasma vecuronium and vecuronium clearance highlights the need for individual monitoring of neuromuscular blockade in this age group.
Topics: Anesthesia; Cardiopulmonary Bypass; Child; Child, Preschool; Electromyography; Female; Humans; Hypothermia, Induced; Infant; Infant, Newborn; Male; Monitoring, Intraoperative; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Vecuronium Bromide
PubMed: 11132740
DOI: 10.1007/BF03019867 -
Stability of vecuronium in sterile water for injection stored in polypropylene syringes for 21 days.American Journal of Health-system... Nov 2007The stability of vecuronium bromide 1 mg/mL in preservative-free sterile water for injection for up to 21 days was studied.
PURPOSE
The stability of vecuronium bromide 1 mg/mL in preservative-free sterile water for injection for up to 21 days was studied.
METHODS
A vecuronium bromide 1-mg/mL solution was prepared by diluting 15 vials of 10-mg Vecuronium Bromide for Injection, USP, powder with preservative-free sterile water for injection and adding the solution to an evacuated i.v. bag. Identical 10-mL volumes of the solution were prepared and stored at 23-25 or 3-5 degrees C in polypropylene syringes. The stability of vecuronium was analyzed in triplicate with stability-indicating high-performance liquid chromatography immediately after preparation of solutions and at 3, 7, 14, and 21 days. The samples were also inspected for volume and color change and for visible precipitation and microbial growth.
RESULTS
The percentage of the initial vecuronium bromide concentration remaining at each time point was greater than 100% at both 23-25 and 3-5 degrees C. There were no detectable changes in volume or color and no precipitation or visible microbial growth.
CONCLUSION
Vecuronium bromide in an extemporaneously prepared solution in preservative-free sterile water for injection was stable for at least 21 days at 23-25 or 3-5 degrees C.
Topics: Chromatography, High Pressure Liquid; Drug Stability; Drug Storage; Injections; Pharmaceutical Solutions; Polypropylenes; Sterilization; Syringes; Vecuronium Bromide; Water
PubMed: 17989445
DOI: 10.2146/ajhp070224 -
Anaesthesia Apr 1987The use of an infusion of vecuronium is described in seven patients with renal and respiratory failure in an intensive therapy unit. Neuromuscular function was monitored...
The use of an infusion of vecuronium is described in seven patients with renal and respiratory failure in an intensive therapy unit. Neuromuscular function was monitored throughout using the train-of-four twitch technique. A bolus dose of vecuronium (0.1 mg/kg) was given, followed immediately by a continuous infusion (0.05 mg/kg/hour). The infusion rate was adjusted until the first twitch of the train was below 20% of control and then run at a constant rate. There was a marked variation in the dose of vecuronium administered (0.01-0.065 mg/kg/hour [corrected]). Two patients, who appeared to be most sensitive to the drug, were both receiving metronidazole. Recovery of neuromuscular function was extremely prolonged and widely variable (6-37 hours) on stopping the infusion. No adverse cardiovascular effects or evidence of histamine release were seen as a result of administration of the drug. Vecuronium is probably more suitable for administration in bolus doses rather than by infusion in patients with renal and respiratory failure.
Topics: Acute Kidney Injury; Adolescent; Aged; Critical Care; Humans; Infusions, Intravenous; Middle Aged; Muscle Contraction; Respiratory Insufficiency; Vecuronium Bromide
PubMed: 2884896
DOI: 10.1111/j.1365-2044.1987.tb03980.x -
Neonatal Network : NN Apr 1989
Comparative Study
Topics: Humans; Infant, Newborn; Pancuronium; Respiration, Artificial; Vecuronium Bromide
PubMed: 2565014
DOI: No ID Found