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PubMed2002

Synthesis and structure-activity relationships of neuromuscular blocking agents.

The first use of neuromuscular blocking agents (muscle relaxants) in clinical practice (1942) revolutionised the practice of anaesthesia and started the modern era of surgery. Since 1942 introduction of tubocurarine (18) neuromuscular blocking agents have been used routinely to provide skeletal muscle relaxation during surgical procedures allowing access to body cavities without hindrance from voluntary or reflex muscle movement. After the introduction of tubocurarine and the depolarizing suxamethonium chloride (4) (1949) several nondepolarizing steroidal and nonsteroidal neuromuscular blocking agents with different onset time and duration of effect were introduced e.g. gallamine triethiodide (1) (1949), methocurine (2) (1949), alcuronium chloride (3) (1963), pancuronium bromide (9) (1968), vecuronium bromide (11) (1982), pipecuronium bromide (10) (1982), atracurium besylate (5) (1982), doxacurium chloride (6) (1991), mivacurium chloride (8) (1992), rocuronium bromide (12) (1994) cisatracurium besylate (7) (1996), and rapacuronium bromide (13) (2000). SZ 1677 (14) a steroid type nondepolarizing neuromuscular blocking agent under development (preclinical phase). This review article deals with a comprehensive survey of the progress in chemical, pharmacological and, in some respects, of clinical studies of neuromuscular blocking agents used in the clinical practice and under development, including the synthesis, structure elucidation, pharmacological actions, structure activity relationships studies of steroidal and nonsteroidal derivatives.

Androstanes↗

PubMed1998

Peribulbar anaesthesia using a mixture of local anaesthetic and vecuronium.

The aim of this double-blind, randomised study was to assess the effects of the addition of 0.5 mg of vecuronium bromide to a standard local anaesthetic mixture used for peribulbar anaesthesia. We studied 60 patients undergoing regional anaesthesia for intra-ocular surgery and were primarily interested in the quality of globe and lid akinesia. All received a mixture of 5 ml 2% lignocaine with 1:200,000 adrenaline, 5 ml 0.75% bupivacaine and 150 IU hyaluronidase with either 0.9% saline 0.25 ml (group A, n = 30) or vecuronium bromide 0.25 ml (0.5 mg) (group B, n = 30). Eye movements assessed at both 5 and 10 min were significantly reduced in the vecuronium group (group B) (p < 0.05). We conclude that the addition of vecuronium at a dose of 0.5 mg to the standard local anaesthetic mixture improves the quality of globe and lid akinesia.

Aged↗

PubMed1997

[Use of the laryngeal mask in adenoidectomy in childhood--a comparison with endotracheal intubation].

PURPOSE: Anaesthesia for adenoidectomy is possible during infancy without succinylcholine. One possibility is intubation with vecuronium bromide, whereas another possibility is the use of the laryngeal mask (LMN). The conditions for intubation as well as further details during anaesthesia are listed and compared. METHODS: 200 children are divided into 4 groups. Group A: intubation with thiopental and vecuronium bromide. Group B: LMN with thiopental, Group C and D: as A and B but the thiopental replaced by propofol. The following aspects are compared: the conditions of intubation; circulation conditions; oxygen saturation; the behaviour when coming out of anaesthesia; complications; the assessment by the surgeons. A further control of 100 routine LMN covers the complications which arose. RESULTS: Adenoidectomy can be carried out successfully with both kinds of anaesthesia. Tracheal intubation attained a better assessment by most surgeons and is easier to administer. Brief declines in the saturation of oxygen occur more frequently when using LMN. LMN has its advantages in the low irritation of the respiratory mucous membranes and results in improved behaviour on coming out of the anaesthesia, especially if used with propofol. Problems arise mainly through the use of the mouth clamp which can result in obstructions of the respiratory tract and re-intubation. These problems arise less frequently when the use of this method has become routine. CONCLUSION: LMN takes time to get used to, and places greater demands on the anaesthetist. Success of LMN depends on the cooperation and collaboration to the surgeon to lower the risk of complications. Once specific improvements in the LMN have been made, it may become the standard method for adenoidectomy in future. It is already used by us and in some outpatient departments, as well as in England and America. Our suggestions are as follows: Aims at convincing the surgeons and improving their co-operation; No routine fixation of the laryngeal mask. The laryngeal mask should be kept slightly taut before opening--preferably slowly--the mouth clamp; possible technical modifications of the mouth clamp itself, which produce a wider gap, could be adapted to the new conditions of the wider LM; reaching the necessary depth of anaesthesia through higher doses of propofol or possibly by total intravenous anaesthesia; routine wearing of the LM in the recovery room until it is no longer tolerated by the child.

Adenoidectomy↗

PubMed1994

Comparative use of various mydriatic drugs in kestrels (Falco tinnunculus).

The mydriatic effect of 3 curare-like neuromuscular blocking agents was tested in European kestrels (Falco tinnunculus) after topical application. Alcuronium chloride (5 mg/ml) was found to be effective at a dose of 1 drop (20 drops = 1 ml) administered twice at a 15-minute interval. Mydriasis was achieved at t = 26 +/- 11 minutes, maximal effect was reached at t = 60 +/- 39 minutes, and sufficient mydriasis ended at t = 364 +/- 134 minutes. Nevertheless, side effects, including temporary full paralysis in 1 bird, indicated that this drug should not be used. Pancuronium bromide (2 mg/ml) had an inconsistent effect on each bird at a dose of 2 drops administered twice at 15-minute intervals, and total mydriasis was not reached in 5 of 8 birds. Mydriasis was achieved at t = 34 +/- 11 minutes, maximal effect was reduced and reached at t = 43 +/- 13 minutes, and sufficient mydriasis ended at t = 90 +/- 39 minutes. Vecuronium bromide (4 mg/ml) was administered at a dose of 2 drops, 3 times, at 15-minute intervals. Mydriasis was achieved at t = 23 +/- 8 minutes, maximal effect was reached at t = 65 +/- 12 minutes, and sufficient mydriasis ended at t = 253 +/- 65 minutes. Side effects were not detected. Vecuronium bromide should be used in raptorial birds whenever retinal examination requires fundoscopy.

Alcuronium↗

PubMed1993

[Anesthesia in a patient with carnitine deficiency syndrome].

A patient with carnitine deficiency syndrome for tracheostomy and resection of tracheal granuloma was anesthetized with nitrous oxide and sevoflurane and vecuronium bromide. Potentiation of effect of vecuronium was minimal, and anesthetic course was uneventful. Carnitine is essential for transportation of long chain fatty acids into mitchondrial matrix. Its deficiency causes metabolic failure in skeletal muscle and accumulation of acyl-CoA in central nervous system. Carnitine deficiency syndrome is associated with a number of metabolic disorders of fatty acid. Signs and symptoms of the syndrome include skeletal muscle weakness, cardiomyopathy, liver disfunction, central nervous system disorders, hypoketotic hypoglycemia and so forth. Since fasting, infection, or shivering have been shown to deteriorate carnitine deficiency syndrome, there is a risk of triggering the acute episode perioperatively. Moreover, there is a possibility of prolonged effect of muscle relaxants and delay in emergence from anesthesia due to preexisting brain damage. These problems should be considered in perioperative period.

Adolescent↗

PubMed2006

[Anesthetic management for a patient with postural hypoxemia].

Postural hypoxemia is rare in patients with no organic cardio-pulmonary diseases. This is caused by closure of the airway in the dorsal area at functional residual capacity in patients on supine position, and may cause difficulty or inability in management of induction and maintenance of general anesthesia. A 69-year-old patient (BMI 28.6) was scheduled for subtotal gastrectomy. After epidural catheter insertion at T 10-11, general anesthesia was induced by thiamylal sodium followed by paralyzing dose of vecuronium bromide, and the trachea was intubated. Anesthesia was maintained with continuous epidural administration of bupivacaine, inhalation of sevoflurane and nitrous oxide in oxygen and intravenous vecuronium bromide. Patients were mechanically ventilated with pressure limit of 19-20 cmH2O, a respiratory rate of 8 breaths per minutes, and a fresh gas flow rate of 2.5 l x min(-1). Respiratory mechanics were measured with a Capnomac Ultima anesthetic gas analyzer and a side-stream spirometry device (Datex instrumentarium Corp., Helsinki, Finland). We found that expiratory tidal volume and thorax-lung compliance decreased with increased PETCO2 on supine position and transabdominal cephalad retraction of the liver. We tried to maintain the alveolar recruitments by PEEP and higher thorax-lung compliance by the Fowler position. These procedures exerted favourable effects on respiratory mechanics of this patient.

Anesthesia, General↗

PubMedDate not supplied

The effect of propofol and alfentanil on the increase in intraocular pressure due to succinylcholine and intubation.

PURPOSE: The aim of this study was to evaluate the effects of propofol and alfentanil on the increase in intraocular pressure (IOP) due to succinylcholine and intubation, in comparison with thiopental sodium and vecuronium bromide. METHODS: Forty patients aged 20-50 years, scheduled for elective surgery requiring endotracheal intubation, were assigned to four groups of ten. General anesthesia was induced with 2.5 mg/kg propofol in Group I, 2.5 mg/kg propofol and 10 microg/kg alfentanil in Group II and 5 mg/kg thiopental in Groups III and IV; muscle relaxation was obtained with either 1.5 mg/kg succinylcholine (Group I, II and III) or 0.1 mg/kg vecuronium bromide (Group IV). In all patients mean arterial pressure, heart rate, oxygen saturation and IOP were recorded before (baseline) and after induction, after the muscle relaxant and after endotracheal intubation. RESULTS: Compared with their baseline values in Group I IOP decreased significantly after propofol (p<0.01) and increased significantly after intubation (p<0.01). In Group II IOP decreased significantly after propofol and alfentanyl (p<0.001), remained low after succinylcholine (p<0.01) and did not change after intubation. In Group III IOP decreased significantly after thiopental (p<0.001) and increased significantly after intubation (p<0.001). In Group IV it decreased significantly after thiopental (p<0.001), remained low after vecuronium (p<0.001) and increased significantly after intubation (p<0.05). CONCLUSIONS: In all Groups, IOP did not increase significantly after succinylcholine, but only anesthesia induced with propofol and alfentanil prevented the increase in IOP due to intubation.

Adult↗

PubMed1999

Effect of pharmaceutical services on adherence to criteria-for-use guidelines in the operating room.

Guidelines for the use of neuromuscular blocking agents (NMBAs) and sedatives during two- to four-hour surgical procedures were developed, and the effect of pharmacy presence on adherence to the guidelines was determined. Differences in cost per dose of the NMBAs pancuronium bromide, cisatracurium besylate, and vecuronium bromide were determined. Pancuronium was designated as the first-line agent in the NMBA guidelines, cisatracurium as the second-line agent, and vecuronium as the third-line agent. In the sedative guidelines, lorazepam was the first-line agent, midazolam was the second-line agent, and propofol was the third-line agent. Pharmacy presence in the operating room was provided during January 1997. The pharmacist made a preliminary decision about the most appropriate agent and encouraged guideline adherence. Cost and adherence data were compared with data for November 1996 and March 1997. During January, the NMBA guidelines were followed 75% of the time and the sedative guidelines were followed 15% of the time; the corresponding rates for March were 40% and 12%. Compared with November 1996, a saving of $5.61 per case was observed in January in the NMBA category and a saving of $2.77 was observed in March; between January and March, there was an increase of $2.84 per case. Pharmacy presence in the OR was associated with better adherence to criteria-for-use guidelines for NMBAs and sedatives; NMBA cost savings associated with implementation of the guidelines were higher when a pharmacist was present.

Humans↗

PubMed1992

[Vecuronium in pediatric anesthesia. Repeated bolus vs continuous infusion].

Vecuronium bromide was employed in 26 pediatric patients; 18 received vecuronium infusion and 11 intermittent bolus administration. The aim of the study was to evaluate the pharmacodynamics of the drug, the lack of cumulative properties, the best infusion rate, the possible advantage of the infusion technique. Neuromuscular blockade monitoring was performed in all patients. In the results, vecuronium shows lack of cumulative properties. The best infusion rate was 0.13 +/- 0.02 mg/kg/h. The continuous infusion allows the employment of lesser doses of the drug than the intermittent administration.

Adolescent↗

PubMed1992

[Clinicopharmacology of Arduan].

The paper presents clinicopharmacological investigations of Arduan carried out in Hungary and in other countries. The aim of the research work is to find an ideal muscle relaxant without side-effects, which are mainly cardiovascular. Pipecuronium bromide (Arduan) is a compound with steroid structure; it has a long duration of action and, most importantly, it does not affect circulation. The properties of pipecuronium bromide will be discussed and compared to those of pancuronium and vecuronium bromide.

Androstane-3,17-diol↗

PubMed1992

Antagonism of vecuronium by one of its metabolites in vitro.

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.

Animals↗

PubMed1999

Laryngeal chemodenervation: effects of injection site, dose, and volume.

A canine model was used to measure changes in laryngeal adductory pressure (LAP) following injections of vecuronium bromide, a short-acting neuromuscular blocking agent. At a constant volume, LAP was inversely related to the dose (and concentration) of vecuronium injected. At a constant dose (0.05 mg), LAP did not vary significantly over a wide range of injection volumes, from 0.05 to 0.50 mL. At a constant dose and volume, the site of injection was varied among the anterior, middle, and posterior vocal fold, the interarytenoid region, and the anterior contralateral vocal fold. Reduction in LAP was greatest (p<.05) for the posterior vocal fold injection site (78% reduction); less reduction was seen for the middle (54%) and anterior (52%) vocal fold and interarytenoid (43%) injection sites. These results have implications for laryngeal botulinum toxin injections, which are discussed.

Animals↗

PubMedDate not supplied

Stability and compatibility of admixtures of intravenous ciprofloxacin and selected drugs.

The stability and compatibility of ciprofloxacin with selected drugs in intravenous admixtures were studied. Ciprofloxacin 2 mg/mL in 5% dextrose was combined with each of 22 other drugs at concentrations commonly used in clinical practice. Each combination was maintained at room temperature (approximately 22 degrees C) in constant fluorescent light. Immediately after preparation and at 6 and 24 hours, each admixture was examined visually in normal fluorescent room light and the pH value was determined. For samples lacking visible precipitates or having pH changes of not more than 1 unit, ciprofloxacin concentration was assayed by using high-performance liquid chromatography. When combined with ciprofloxacin, 14 of the study drugs did not alter the concentration of ciprofloxacin, including amikacin sulfate, atracurium besylate, aztreonam, cimetidine hydrochloride, dobutamine hydrochloride, fluconazole, gentamicin sulfate, metronidazole (intravenous, ready to use), midazolam hydrochloride, norepinephrine bitartrate, pancuronium bromide, potassium chloride, tobramycin sulfate, and vecuronium bromide. There were five drugs that were determined to be incompatible with ciprofloxacin because of precipitate formation (amphotericin B, ampicillin sodium/sulbactam sodium, cefuroxime sodium, piperacillin sodium, and sodium bicarbonate). Incompatibility with ciprofloxacin based on pH changes of more than 1 unit was found with four drugs: ampicillin sodium/sulbactam sodium, ceftazidime, metronidazole hydrochloride (powder only), and ticarcillin disodium/clavulanate potassium. Intravenous ciprofloxacin 2 mg/mL admixed in 5% dextrose was stable and compatible with 14 of the 22 test drugs for up to 24 hours at room temperature. The other eight drugs should not be combined with ciprofloxacin.

Amphotericin B↗

PubMed1992

Cardiac effects of vecuronium and its interaction with autonomic nervous system in isolated perfused canine hearts.

The chronotropic and inotropic effects of vecuronium bromide and its interaction with the autonomic nervous system were investigated in the isolated, cross-circulated right atrial and left ventricular preparations of the dog. Vecuronium, injected into the external jugular vein of the support dog, induced dose-dependent decreases in heart rate and arterial blood pressure, and increased atrial contractile force with no change in sinus rate in isolated atrial preparations. Vecuronium (1-3,000 micrograms), injected into the sinus node artery of the isolated atrium, induced dose-dependent increases in atrial contractile force with small increases in sinus rate. Vecuronium also increased the ventricular contractile force in a dose-dependent manner. The positive inotropic effect was attenuated in part by propranolol, but not by either tetrodotoxin or imipramine. Vecuronium inhibited in a dose-related manner the negative chronotropic and inotropic responses to parasympathetic nerve stimulation and carbachol (CCh) and the negative followed by positive cardiac responses to nicotine, but did not attenuate the positive responses to sympathetic nerve stimulation. The ID50s for the responses to parasympathetic stimulation, CCh, and nicotine were not significantly different. Vecuronium enhanced the positive chronotropic and inotropic responses to sympathetic nerve stimulation, tyramine, norepinephrine, and isoproterenol. These results indicate that (a) vecuronium causes the positive inotropic responses mediated by nonadrenergic mechanisms and beta-adrenoceptors, (b) vecuronium blocks ganglionic and presynaptic nicotinic and postsynaptic muscarinic receptor-mediated responses similarly, and (c) vecuronium enhances beta-adrenoceptor-mediated responses in the dog heart.

Animals↗

PubMedDate not supplied

Neurologic recovery and functional improvement after vecuronium-induced quadriparesis.

Vecuronium bromide (Norcuron, Organon, Inc., West Orange, NJ) is a common neuromuscular blocking agent used to facilitate mechanical ventilation. Cases have been reported in which prolonged use of vecuronium resulted in severe motor neuropathy, with or without myopathy. However, the time course of recovery, the functional prognosis, and the use of inpatient rehabilitation is not well-established. We are reporting the functional recovery of two cases with the diagnosis of severe vecuronium motor neuropathy and/or myopathy. The patients presented with pneumonia and meningococcemia, respectively, and received vecuronium during ventilatory support, which lead to quadriparesis. In one patient, vecuronium toxicity occurred while neuromuscular junction monitoring was in place. Significant improvement was noted during an average of 3 to 4 wk in a comprehensive inpatient rehabilitation program, documented by the improvement in total motor Functional Independence Measure scores for patient 1 (from 15 to 71) and for patient 2 (from 65 to 84). In addition, the distal compound motor amplitudes showed a 4-fold increase for the ulnar, a 7-fold increase for the median, an 11-fold increase for the peroneal, and a 3-fold increase for the tibial nerves on follow-up nerve conduction studies correlating with neurologic recovery. In summary, even when patients present with quadriparesis, the recovery after vecuronium toxicity appears to be favorable.

Activities of Daily Living↗

PubMed1985

Rapid tracheal intubation with vecuronium: the priming principle.

Following the administration of a single 0.1 mg/kg dose of vecuronium bromide, satisfactory conditions for tracheal intubation developed in 156 +/- 12 s (mean +/- SEM), and the clinical duration of the initial dose was 36 +/- 2 min. When the initial dose of vecuronium was administered in two increments, a 0.015 mg/kg "priming" dose, followed 6 min later by a 0.050 mg/kg "intubating" dose, intubation time decreased to 61 +/- 3 s and clinical duration to 21 +/- 1 min. The priming dose that had no unpleasant effect on premedicated, awake patients could be administered 3-4 min before, and the intubating dose 2 to 3 min after induction of anesthesia. With the described technique, comparable intubating conditions could be obtained just as rapidly with vecuronium as with succinylcholine chloride, without subjecting the patients to the side effects of and the complications occasionally encountered with succinylcholine. An added advantage of the use of a priming dose is that it will reveal undiagnosed, pathologic, or idiopathic increase of sensitivity to nondepolarizing muscle relaxants.

Adolescent↗

PubMed1986

Comparative pharmacokinetics and dynamics of vecuronium and pancuronium in anesthetized patients.

Plasma concentrations and the degree of neuromuscular blockade after a 2-min infusion of 0.1 mg/kg of vecuronium bromide or pancuronium bromide (equipotent doses) were studied in 12 gynecologic patients. The plasma concentrations of both drugs declined in a triphasic manner. The difference between the intercepts and rate constants of the two drugs was not significant. Vecuronium was removed faster from the plasma than pancuronium; this was reflected in a significantly larger plasma clearance rate for vecuronium (4 ml X min-1 X kg-1 vs 1.1 ml X min-1 X kg-1 for pancuronium). The effective plasma concentrations at 50% recovery of the twitch height were 0.11 +/- 0.02 (vecuronium) and 0.2 +/- 0.03 microgram/ml (pancuronium). The disposition kinetics were adequately described by a three-compartment model. An effect compartment was added to the model to correlate the neuromuscular effects and plasma concentrations of both drugs. The ratio between concentrations of vecuronium and pancuronium in the effect compartment at 50% twitch height was 0.83. In spite of its greater potency, vecuronium has a shorter duration of action than pancuronium.

Adult↗

PubMed1993

Halothane-diethyl ether azeotrope anesthesia under primitive conditions: guidelines for neuromuscular blockade with vecuronium.

The dose-response relationship for vecuronium during anesthesia with the azeotropic mixture of halothane and diethyl ether (HE) (66 ml of halothane mixed with 34 ml of ether in the same bottle)/oxygen was compared with halothane/nitrous oxide/oxygen anesthesia. The HE is not explosive and has preserved many of the advantageous properties of diethyl ether, making it an attractive anesthetic drug under difficult circumstances such as war or civil disaster. If muscular relaxation is needed in military anesthesia, it is essential to use a short- to medium-acting compound that can be stored without refrigeration. Vecuronium bromide fulfills these criteria. The study was conducted on 20 young (mean 24 years, range 18-31), ASA I patients. Using adductor pollicis mechanomyography and a cumulative dose technique, individual dose-response curves for vecuronium were constructed. Care was taken to keep peripheral and core temperatures normal and the times of exposure to inhalational gases equal. The results were analyzed by the log-probit method. During HE anesthesia, ED50 for vecuronium was 22 +/- 2 micrograms kg-1 (mean +/- SE) and ED90 was 49 +/- 8 micrograms kg-1. During halothane/nitrous oxide anesthesia, ED50 for vecuronium was 18 +/- 2 micrograms kg-1 (mean +/- SE) and ED90 was 39 +/- 7 micrograms kg-1. The dose-response relationships for vecuronium were similar during HE anesthesia and halothane/nitrous oxide anesthesia.

Adolescent↗