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PubMed1984

Antagonism of pancuronium neuromuscular blockade in halothane-anesthetized ponies using neostigmine and edrophonium.

Efficacy of neostigmine (0.04 mg/kg of body weight) and edrophonium (1 mg/kg), as antagonists for pancuronium neuromuscular blockade in halothane-anesthetized ponies, was evaluated. Neostigmine and edrophonium were satisfactory antagonists, with edrophonium having a significantly (P less than 0.01) more rapid onset of action than did neostigmine. Muscarinic activity of neostigmine and edrophonium was also evaluated. Neither antagonist was administered with atropine. Gastrointestinal effects, increased salivation, and increased airway secretions were minimal with edrophonium, but were marked after neostigmine. Blood pressure increased within 1 to 2 minutes of antagonist administration. Heart rate decreased after edrophonium injection, but this occurred after blood pressure increase. Heart rate increased or did not change after neostigmine administration.

Anesthesia, General↗
PubMed1978

Plasma concentrations of pancuronium during predetermined intensities of neuromuscular blockade.

The plasma concentrations of pancuronium were monitored during i.v. infusions of the relaxant in dogs. Pancuronium was administered at rates which maintained the degree of neuromuscular blockade at three predetermined levels. The concentrations of the drug in the blood were consistent for any one animal but showed considerable overlap for the three levels of paralysis between animals. Concentrations obtained during infusion and which maintained the twitch response at 20% and 80% of control were compared, in the same dogs, with concentrations obtained during recovery from a bolus injection of pancuronium. When the infusion maintained the twitch response at 20% of the control value, the mean plasma concentration of pancuronium was 0.152 microgram ml-1. That measured after the bolus injection was 0.156 microgram ml-1. The concentrations at 80% of control were 0.094 microgram ml-1 and 0.083 microgram ml-1 respectively. The agreement between these results suggests a relationship between the plasma concentration of the relaxant and its effect during the termination of the action after a large bolus injection of the drug. As this occurs chiefly during the postdistribution equilibrium, the relatively slow decrease in plasma concentration would appear to become the rate-limiting factor in recovery from paralysis.

Animals↗
PubMed1994

[Prolonged neuromuscular blockade. Different antagonistic effects following successive exposure to vecuronium and succinylcholine in a patient with atypical plasma cholinesterase].

An 81-year-old patient had prolonged competitive neuromuscular blockade with train-of-four ratios of 0.1 and 0.5, respectively, after two successive anaesthesia procedures (enflurane-N2O/O2; vecuronium-succinylcholine-sequence) for transurethral prostate resection. Although antagonism with neostigmine was promptly successful after the first, 65-min period of anaesthesia (1.5 mg vecuronium for precurarization, 100 mg succinylcholine for intubation, 3 mg vecuronium), repetitive and chronologically staggered administration of neostigmine after the second, 30-min period of anaesthesia (1 mg vecuronium for precurarization, 100 mg succinylcholine for intubation) had hardly any effect, so that the patient had to be ventilated mechanically for a total of 4.5 h. Laboratory analysis revealed homozygous, atypical, plasma cholinesterase (790 U/l; dibucaine number 23; genotype E1aE1a). This retrospectively confirmed a succinylcholine-induced phase II block in both instances, as had already been suspected following the second anaesthetic procedure. The degree of block transformation, and thus the available time, are decisive in explaining the diverse effects of antagonism here. It must be assumed that a complete phase II block developed after the first succinylcholine exposure owing to the longer duration of anaesthesia; the purely competitive component (train-of-four ratio 0.1) was easily antagonized by neostigmine. At the time of the attempted antagonism after the second, shorter period of anaesthesia, however, block transformation was still incomplete (train-of-four ratio 0.5). The administration of neostigmine therefore rather intensified the depolarization segment of the mixed block, so that repeated attempts at antagonism then inhibited any further block transformation.

Aged↗
PubMed1991

The role of anesthetic induction agents and neuromuscular blockade in the endotracheal intubation of trauma victims.

Management of extensive trauma often requires immediate tracheal intubation and mechanical ventilation. The role of anesthetic induction agents and neuromuscular blockade in the airway management of the trauma victim is disputed. To better define the role of these agents in the acute management of trauma, the adult trauma registry of The Johns Hopkins Hospital was reviewed to determine the frequency of use of these agents in acute airway management and to assess the effect of these agents on the incidence of complications. Ninety-seven patients were reviewed. Thirty-one patients were intubated because of cardiopulmonary arrest. Of the remaining 66 patients, oral intubation was initially attempted in 54. When drugs were used to facilitate intubation (n = 36), the success rate was 92 per cent on the first attempt, and 100 per cent on the second attempt. When drugs were not used (n = 18), 39 per cent could not be intubated (n = 7). Subsequent drug administration resulted in successful intubation of five of seven of these patients. Nasal intubation (no drugs) was only successful in 60 per cent of the patients (50 per cent on first attempt). Four patients required a cricothyrotomy. Two other patients vomited, and one patient aspirated. None of these patients received drugs prior to the first attempt at intubation. No hemodynamic or neurologic complications, related to relaxant or induction agent use, were observed. These findings suggest that oral intubation with drugs to facilitate airway management is most likely to result in successful intubation on the first attempt and that drug use in the trauma setting is safe.

Adult↗
PubMed1987

Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium.

Three clinically used anticholinesterases--neostigmine, pyridostigmine, and edrophonium--were tested for their ability to reverse two levels (60% and 95%) of neuromuscular blockade produced by pancuronium. A controlled in vitro environment of the rat diaphragm-phrenic nerve system was used for the studies. Concentrations of anticholinesterases spanned the clinical range and were extended beyond to establish dose-response curves. Neostigmine was the most potent reversal drug (ED50 for 95% block 5.5 +/- 4 nM), followed by pyridostigmine (0.27 +/- 0.06 microM) and edrophonium (2.1 +/- 0.05 microM). The three drugs were equally effective at reversal of block and fade as measured by train-of-four stimulation. The dose-response curves for all three drugs showed a ceiling effect for reversal of tension and fade. Supraclinical concentrations of drug did not effect complete reversal, especially at 95% block. High concentrations of anticholinesterase led to randomly appearing hyperactivity manifested by spontaneous twitching and repetitive firing with severe fade on stimulation.

Animals↗
PubMed1985

Pattern of CNS recovery following reversal of neuromuscular blockade. Comparison of atropine and glycopyrrolate.

Recovery from anaesthesia was compared, in a group of patients (n = 25) receiving a mixture of glycopyrrolate and neostigmine (to reverse non-depolarizing neuromuscular blockade), with recovery in a group of patients (n = 25) receiving an atropine-neostigmine mixture. Recovery following anaesthesia was more rapid in the patients receiving the glycopyrrolate-neostigmine mixture.

Adult↗
PubMed1987

Closed-loop administration of atracurium. Steady-state neuromuscular blockade during surgery using a computer controlled closed-loop atracurium infusion.

The advent of newer muscle relaxants with predictable rates of metabolism and times of offset of neuromuscular blockade now makes it possible to use intravenous infusion safely as a mode of delivery. This has many advantages over administration by intermittent bolus. Moreover, it is feasible to use a servo system for their delivery. We have developed and evaluated such a system which is portable and requires little computer expertise to set up and use. It is a useful adjunct to routine anaesthesia, as well as a potentially powerful research tool.

Adolescent↗
PubMed1990

Can early administration of neostigmine, in single or repeated doses, alter the course of neuromuscular recovery from a vecuronium-induced neuromuscular blockade?

The authors sought to determine whether neostigmine, given at a time when no response to peripheral nerve stimulation could be elicited, hastened recovery from a vecuronium-induced neuromuscular blockade (NMB). The effect of neostigmine (70 micrograms/kg) in antagonizing a profound (no-twitch) vecuronium-induced (0.1 mg/kg) NMB in 40 healthy patients was studied. Patients were randomly assigned to one of four groups specifying the sequence of neostigmine administration. Fifteen minutes after the administration of vecuronium, when there was no detectable twitch response, each patient received either neostigmine (70 micrograms/kg) with glycopyrrolate (15 micrograms/kg) or an equivalent volume of normal saline (placebo). When T1 (the first response in the train-of-four [TOF] sequence) recovered to 10% of control, patients again received either neostigmine with glycopyrrolate in the same doses as before or the placebo. The following variables were measured: times from vecuronium injection until T1 recovered to 10% (t [10]) and 90% (t [90]) of control, and time until the TOF ratio was equal to 75% (t [TOF75]). Mean values of t (90) and t (TOF75) were shorter (54.7-75.2 min and 60.4-79.5 min, respectively) for the three groups who received neostigmine as compared with patients who received two doses of placebo (104.3 and 122.6 min, respectively). There were no differences in the t (90) and t (TOF75) values among the three groups who received neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1981

Effect of diazepam on pancuronium-induced neuromuscular blockade maintained by a feedback system.

The possibility of an interaction between diazepam and pancuronium bromide was investigated in six patients undergoing general anaesthesia maintained with fentanyl, droperidol and nitrous oxide. Neuromuscular blockade was controlled using a feedback mechanism which automatically adjusted the rate of injection of pancuronium to maintain between 71.4 and 72.9% blockade. Diazepam 0.14 mg kg-1 i.v. produced blood concentrations within the therapeutic range, but did not produce consistent changes in the level of blockade, pancuronium concentration in the blood or pancuronium consumption measured over 20 min.

Adolescent↗
PubMed2006

[Neuromuscular blockades. Agents, monitoring and antagonism].

Currently, the main aims of using neuromuscular blocking agents during general anaesthesia are the improvement of surgical and intubation conditions. Neuromuscular blocking agents themselves are neither analgesic nor anaesthetic. All agents interact with the acetylcholinergic receptor at the neuromuscular junction and induce a blockade either through a continuous activation imitating the effect of acetylcholine or through a competitive antagonism against acetylcholine. Succinylcholine is the only depolarizing muscle relaxant that is in clinical use. Non-depolarizing neuromuscular blockers may be grouped by their chemical structure into benzylisoquinolines or aminosteroids, and cover the complete range from short and intermediate, to long acting agents. Possible adverse drug reactions to the single agents are also related to their mechanism of action. Moreover, pharmacokinetic properties and effects such as histamine liberation could play an important role when choosing a myorelaxant. The depth of a neuromuscular block and recovery from paralysis can be monitored using qualitative and quantitative techniques. Therefore, the monitoring of neuromuscular recovery plays an important role in the prevention of postoperative complications due to residual paralysis. In case of residual paralysis, cholinesterase inhibitors are suitable for reversal.

Anesthesia↗
PubMed1990

The effect of bambuterol (carbamylated terbutaline) on plasma cholinesterase activity and suxamethonium-induced neuromuscular blockade in genotypically normal patients.

Bambuterol (the bisdimethylcarbamate prodrug of terbutaline) is a new bronchodilator with a prolonged duration of action due to its inhibition of plasma cholinesterase during metabolism. The effect of bambuterol on suxamethonium-induced neuromuscular blockade was studied in 10 patients undergoing elective laparotomy. Thirty mg of bambuterol was given 2 h before anaesthesia, which was performed with thiopentone, fentanyl, halothane and nitrous oxide in oxygen. Neuromuscular function was monitored using supramaximal train-of-four stimulation of the ulnar nerve and a force displacement transducer. Suxamethonium 1 mg.kg-1 was given i.v. for endotracheal intubation. Plasma cholinesterase activity was measured before and after intake of bambuterol and during anaesthesia. The results from the 10 patients were compared with those of 41 patients not given bambuterol but otherwise studied during the same conditions. Following bambuterol, all patients had a significant decrease of plasma cholinesterase activity (P less than 0.001) and the suxamethonium-induced blockade was 3-4 times prolonged compared to patients not given bambuterol (P less than 0.001). Five patients with very low plasma cholinesterase activity developed a long-lasting phase II block.

Adult↗