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A comparison of the muscarinic antagonist actions of pancuronium and alcuronium.

1 In the pithed rat, muscarine (2.5-10 microgram/kg i.v.) normally produced bradycardias, but tachycardias were seen in the presence of pancuronium (0.1-1.0 mg/kg i.v.) and alcuronium (0.1-5.0 mg/kg i.v.). 2 The tachycardia was probably a result of muscarinic receptor stimulation, because it was antagonized by atropine (10 microgram/kg i.v.) and pirenzepine (10-30 microgram/kg i.v.). The location of these muscarinic receptors is probably within the sympathetic ganglia since the tachycardias were inhibited by pretreatment with propranolol (1 mg/kg i.v.) or reserpine (5 mg/kg i.p. 24 h prior to study). 3 In the rat isolated atria preparation, pancuronium was 86 times more potent as an antagonist of the effects of muscarine than in the rat isolated superior cervical ganglion. The mechanism of action in both tissues may be non-competitive. 4 Pancuronium selectivity antagonized atrial inhibitory muscarinic responses compared to excitatory muscarinic responses in sympathetic ganglia in the rat.

Alcuronium↗

Reversal by suramin of neuromuscular block produced by pancuronium in the anaesthetized rat.

1. Rats were anaesthetized with sodium pentobarbitone and maximal twitches of a tibialis anterior muscle were evoked by stimulation of the motor nerve. 2. Suramin, injected intravenously in a series of cumulative bolus doses, each 15 mg kg-1, completely reversed a 90% depression of twitches maintained by a continuous intravenous infusion of pancuronium. The cumulated dose necessary to restore twitches to 50% of their control amplitude was 35 mg kg-1. Suramin did not modify a similar degree of block produced by suxamethonium, nor did it affect the amplitude of control maximal twitches, even in cumulative doses up to 150 mg kg-1. 3. The effects of bolus doses of suramin (85 mg kg-1), neostigmine (0.03 mg kg-1) and 4-aminopyridine (1.2 mg kg-1), calculated to restore pancuronium-blocked twitches to 95% of control amplitude, were compared. Suramin produced the most rapid reversal (1.1 +/- 0.5 min), but its duration of action was the shortest (9.4 +/- 1.6 min). Suramin was without effect on heart rate or blood pressure in the doses used. 4. The results showed that suramin reversed neuromuscular block produced by nondepolarizing blocking drug, pancuronium, but was without effect on a block produced by the depolarizing blocking drug, suxamethonium. Its short duration of action suggests that suramin would probably not be of value clinically as a reversal agent. However, it is possible that it might serve as a starter compound for the synthesis and development of a new class of reversal agents for use in anaesthetic practice.

4-Aminopyridine↗

Investigation of the effects of paralysis by pancuronium on heart rate variability, blood pressure and fluid balance.

The effects of pancuronium bromide on the cardiovascular system and fluid balance in preterm ventilated neonates was investigated. Infants were selectively paralysed if actively expiring. Their results were compared to a control group of similar gestational age, ventilated during the same study period, but who received no paralysing agent. There was no significant difference in the blood pressure of the two groups. Treatment with pancuronium was not associated with differences in blood pressure variability. All paralysed infants showed a significant reduction in heart rate variability which persisted during treatment. This was not present in the control infants. Paralysed infants, despite fluid restriction, had evidence of fluid retention, being significantly heavier than the control babies from day 3 onwards and above their birthweight by day 7. No paralysed or control infant developed a pneumothorax or renal failure. We conclude that selective treatment with pancuronium is without adverse effects on blood pressure but strict attention to fluid balance is essential.

Blood Pressure↗

Intravascular pancuronium bromide infusion for prenatal diagnosis of twin-twin transfusion syndrome.

The diagnosis of twin-twin transfusion syndrome remains a problem. Intravascular infusion of pancuronium bromide, a nondepolarizing neuromuscular blocking agent, for the smaller of a set of twins demonstrated paralysis of both twins in one case. However, in a second case, paralysis was shown only in the smaller twin who demonstrated no transplacental vascular communications postnatally. We suggest that infusion of pancuronium bromide, 'pancuronium test', is a simple and safe method for confirming transplacental communications and aids in the diagnosis of twin-twin transfusion syndrome.

Adult↗

The cardiovascular effects of pancuronium in the dog during pentobarbitone anaesthesia.

The effect of pancuronium on the cardiovascular system of the dog was studied in 12 greyhounds who were anaesthetized with pentobarbitone 30--40 mg/kg body weight. During the study, the animals were artificially ventilated to give an end-tidal carbon dioxide in the range 4-0--4-5 per cent. Duplicate cardiac output measurements were made before and ten minutes after the intravenous administration of pancuronium (0-18 mg/kg). There was a slight (but statistically insignificant) fall in cardiac output. Heart rate, aortic and pulmonary arterial pressures remained substantially unaltered. It is suggested that pancuronium should be used in the dog when muscle relaxation is required during pentobarbitone anaesthesia. In this way cardiovascular changes related to the drugs themselves will be minimized.

Anesthesia, Intravenous↗

Pancuronium requirements during hypothermic cardiopulmonary bypass in man.

Eight patients were studied to determine the changes in pancuronium requirements during hypothermic cardiopulmonary bypass. They were anaesthetised with fentanyl as the principal agent, ventilated with oxygen and the neuromuscular junction was monitored using train-of-four stimulation. After a bolus dose of pancuronium an infusion was used to maintain the first twitch of the train-of-four at 5-15 per cent of control. Before bypass the mean pancuronium infusion rate was 0.52 (SD 0.16) micrograms/kg/min. There was a small, brief increase in requirement with the initiation of bypass to 0.62 (SD 0.38) micrograms/kg/min, which was followed by a decrease of more than 80 per cent during hypothermia to 0.08 (SD 0.03) micrograms/kg/min. Rewarming was associated with a rapid increase in requirement to 0.64 (SD 0.17) micrograms/kg/min, which decreased to 0.33 (SD 0.23) micrograms/kg/min when normothermia was re-established.

Aged↗

Muscle strength following anaesthesia with atracurium and pancuronium.

Postoperative recovery from muscle weakness was investigated by handgrip strength after general anaesthesia using short- and long-acting muscle relaxants. Handgrip strength was measured on four occasions, preoperatively, before and after premedication, and postoperatively, both as soon as the patient could sustain a five-second headlift and one hour later. Twenty patients received either atracurium 0.6 mg/kg or pancuronium 0.1 mg/kg as part of a general anaesthetic technique with neostigmine reversal. Compared with their initial preoperative hand strengths, the two relaxant groups showed only an insignificant decrease in grip strength to 92% after premedication. Postoperatively when a five-second headlift was achieved, the patients in both groups were weak. The group given atracurium had a mean of 60% of their initial grip strength and those given pancuronium had a mean of 44%. This difference in strength was statistically significant from the initial level and from each other. However, there was no difference between the groups in the time interval from administering reversal to achieving a sustained headlift. One hour later in both groups grip strength was much better, within 80% of that seen after premedication in most patients, and no significant difference in grip strength was seen between the groups. This study demonstrates that patients who receive relaxant anaesthesia have substantial muscle weakness in the recovery phase. When neostigmine reversal is used, pancuronium appears to have a similar return of voluntary muscle power to that seen with atracurium. The marked difference in elimination kinetics of these two relaxants seems to be of little importance when neostigmine reversal is used.

Adult↗

The influence of succinylcholine on the duration of pancuronium neuromuscular blockade.

Question has been raised as to whether the use of succinylcholine (SCh) to facilitate endotracheal intubation might influence the duration of subsequently used pancuronium. The authors studied the duration of pancuronium in 67 adult patients by measuring muscle response to nerve stimulation. Thirty-seven of these patients were given prior SCh while the remaining 30 were not. No significant difference in the duration of pancuronium block was found between these 2 groups.

Adult↗

Comparison of the effects of pancuronium and atracurium on the lower esophageal sphincter.

The effects of pancuronium and atracurium on the lower esophageal sphincter pressure (LESP) were studied in 24 healthy patients anesthetized with 0.5% halothane in 66% nitrous oxide in oxygen. After pancuronium (0.1 mg X kg-1) given intravenously there was a significant increase in LESP from a control value of 36 +/- 4.0 cm H2O to 50 +/- 4.6 cm H2O at 1 min. This produced an increase in barrier pressure (BRP) from 26 +/- 3.7 cm H2O to 41 +/- 4.3 cm H2O. These changes were sustained for 5 min accompanied by a significant increase in arterial pressure and heart rate. Atracurium (0.6 mg X kg-1) had no cardiovascular effects and produced little changes in either LESP or BRP. The findings of this study suggest that pancuronium may be of benefit in a rapid sequence induction.

Anesthesia↗

Pretreatment with d-tubocurarine, vecuronium, and pancuronium attenuates succinylcholine-induced increases in plasma norepinephrine concentrations in humans.

We studied in patients the effect of d-tubocurarine, which has sympathetic ganglion blocking action, on succinylcholine-induced increases in plasma levels of catecholamines, and compared it with the effects of vecuronium and pancuronium, which have little sympathetic ganglion blocking action. Thirty-two patients were divided into five groups: seven were given 3 mL saline; seven received 1 mg/kg succinylcholine; and six, seven, and five patients were given 0.08 mg/kg d-tubocurarine, 0.01 mg/kg vecuronium, and 0.01 mg/kg pancuronium, respectively, all of which were injected 5 min before 1 mg/kg succinylcholine. Succinylcholine alone significantly increased plasma norepinephrine concentrations, systolic blood pressure, and heart rate from 187 +/- 39 pg/mL (mean +/- SEM), 93 +/- 2 mm Hg, and 77 +/- 4 beats/min to 429 +/- 61 pg/mL, 120 +/- 7 mm Hg, and 102 +/- 6 beats/min, respectively, with onset of fasciculations. Pretreatment with d-tubocurarine, vecuronium, and pancuronium significantly and equally attenuated both the fasciculations and the cardiovascular responses to succinylcholine. These results suggest that the sympathetic ganglion blocking action of neuromuscular relaxants when given before succinylcholine is not an important factor in attenuation of succinylcholine-induced increases in plasma levels of catecholamines.

Adult↗

Effects of atracurium and pancuronium on the oculocardiac reflex in children.

The authors compare the effect of two muscle relaxants, atracurium and pancuronium, on the bradycardia resulting from the oculocardiac reflex during eye surgery for strabismus in children. Two groups, each composed of 15 children, received either pancuronium or atracurium during strabismus operations. Heart rate and rhythm were observed at several points during the operations, and the changes that occurred in the two groups were compared. We found that the incidence and severity of the bradycardia, the incidence of dysrhythmias, and the need for atropine administration were significantly greater in the atracurium group than in the pancuronium group.

Atracurium↗

Different F-wave recovery after neuromuscular blockade with pancuronium and mivacurium.

We performed this study to assess the recovery period after neuromuscular blockade by electromyographic F-wave analysis, a method that supplies more information about more proximal parts of the motor system than conventionally used methods, e.g., mechanomyography (MMG). In 20 neurosurgical ASA physical status I or II patients anesthesia was induced and maintained with IV fentanyl and midazolam. Patients were randomly assigned to receive either 0.25 mg/kg mivacurium (MV group, n = 10) or 0.1 mg/kg pancuronium (PC group, n = 10) intraoperatively. MMG monitoring of the adductor pollicis muscle was performed continuously. F waves were recorded at the abductor pollicis muscle of the contralateral hand at train-of-four (TOF) ratios of 0.1, 0.25, 0.5, 0.7, 0.75, 0.8, 0.85, 0.9, and 0.95. Recovery of F-wave amplitudes after neuromuscular blockade with pancuronium was significantly slower compared with mivacurium (P = 0.004) during the clinically important recovery period defined by MMG TOF ratios from 0.7 to 0.95. This electrophysiologic finding suggests a differential recovery of the motor system after administration of pancuronium and mivacurium not detected by MMG.

Adult↗

Effects of priming with pancuronium or rocuronium on intubation with rocuronium in children.

Rocuronium is a non-depolarizing neuromuscular blocking agent which has a rapid onset and intermediate duration of action. The goal of this study was to compare the neuromuscular blocking actions of rocuronium with and without a priming dose of pancuronium or rocuronium in children. Thirty patients were randomly allocated into 3 groups. Ten patients received a single dose of 0.6 mg/kg rocuronium (Group I). The others received either 0.015 mg/kg pancuronium (Group II) or 0.06 mg/kg rocuronium (Group III) 3 minutes before an intubating dose of 0.54 mg/kg rocuronium was given. Neuromuscular blockade was measured via accelerographic response to single stimulations (1 Hz) of the ulnar nerve until maximal twitch depression was reached followed by train-of-four (TOF) stimuli (2 Hz) at 15 second intervals for the remainder of recovery. Groups were compared with regard to onset time, duration and recovery indices. The onset time and duration of block did not differ significantly between groups. However, the time to recovery in group II (24.5 +/- 9.9 min) was significantly prolonged compared to that in group I (12.7 +/- 3.1 min) or group III (12.7 +/- 3.9 min). We concluded that the use of rocuronium with a preceding dose of either pancuronium or rocuronium provided no advantage for intubation in children.

Androstanols↗

The kinetics of inhibition of nicotinic acetylcholine receptors by (+)-tubocurarine and pancuronium.

Equilibrium conditions of neurotransmitter concentration and receptor binding are never achieved during synaptic transmission at the neuromuscular junction. Thus, it is important to determine the binding kinetics of drugs that act this synapse. Previous determinations of the dissociation rate of (+)-tubocurarine have produced inconsistent results ranging from 0.1 to 4000/s. Here, we used a direct approach to measure association (l(on)) and dissociation (l(on)) rates for two competitive antagonists (clinically used as nondepolarizing muscle relaxants), pancuronium and (+)-tubocurarine, at nicotinic acetylcholine receptors (nAChR). We made macroscopic current recordings from outside-out patches of BC3H-1 cells expressing embryonic mouse muscle nAChR. We used a three-tube rapid perfusion system to make timed applications of antagonists and acetylcholine to the patch. We made independent measurements of the equilibrium inhibition (IC(50)) and the kinetics of onset and recovery of antagonist inhibition at 20 to 23 degrees C. Rate constants were calculated from the predictions of a single (high-affinity) site model of competitive inhibition. For pancuronium: IC(50) = 5.5 +/- 0.5 nM (mean +/- S.D.), l(on) = 2.7 +/- 0.9 x 10(8) M(-1) s(-1), l(off) = 2.1 +/- 0.7/s [corrected] x 10(8)/s. For (+)-tubocurarine: IC(50) = 41 +/- 2 nM, l(on) = 1.2 +/- 0.2 x 10(8) M(-1) s(-1), l(off) = 5.9 +/- 1.3/s. The kinetic results are consistent with the equilibrium results in that l(off)/l(on) is in good agreement with the IC(50) values. All differences between the antagonists are significant at the p < 0.001 level. The higher affinity of pancuronium is caused by a faster association rate (2.2-fold) coupled with a slower dissociation rate (2.8-fold). The association rates of both antagonists are comparable with or greater than the association rate for acetylcholine binding to nAChR.

Animals↗

Comparative evaluation of neuromuscular blockade and reversibility of AH 8165 and pancuronium bromide in man.

The neuromuscular properties of AH 8165 were compared to those of pancuronium bromide in 66 patients during analgesic anesthesia procedures. Administration of 0.5 mg/kg AH 8165 and 0.04 mg/kg pancuronium bromide produced very similar degrees of non-depolarizing block. AH 8165 acted quicker and therefore gave better conditions for intubation. Spontaneous recovery of muscle twitch tension was slightly shorter for AH 8165 than for pancuronium bromide, whether small or larger amounts of drugs were used. Administration of neostigmine caused rapid and complete return of muscle twitch tension, well-maintained tetanus and insignificant posttetanic potentiation within 20 minutes, with a similar efficiency of competitive neuromuscular block reversal for both drugs.

Adult↗

Alfentanil combined with vecuronium or pancuronium for use in eye surgery.

The usefulness of alfentanil for eye surgery, when combined with either vecuronium or pancuronium, was evaluated in 44 fit anticholinergized patients. Following thiopentone, four min after the administration of the relaxant (0.1 mg/kg), and two min after the administration of alfentanil (15 micrograms/kg), a sixth of the patients bucked on introducing the endotracheal tube. The anesthesia for cataract extraction was maintained using alfentanil-relaxant-N2O in 18 patients. In 16 of them, a low dose alfentanil regimen, occasionally supplemented with thiopentone, was satisfactory, and the recovery of alertness was rapid. In 26 patients, alfentanil, 25 micrograms/kg, supplemented with isoflurane, efficiently obtunded the hemodynamic response after traction of extrinsic eye muscles at the commencement of major surgery. The patients receiving vecuronium presented with lower heart rates, than did those receiving pancuronium (P < 0.05). During major operations, nodal rhythm was more frequent in the vecuronium group, than in the pancuronium group (P < 0.0001).

Aged↗

[Chronopharmacology of pancuronium in rats anesthetized by CT 1341 (Alfatésine)].

A circadian variation in the curarizing ability of pancuronium bromide (Pavulon) has been documented in an homogenous group of 100 Wistar AF-SPF adult male rats anaesthetized by the steroid anaesthetic althesin (Alfatésine, CT 1341). Animals were maintained at 24 +/- 2 degrees C and synchronized with natural light 06.00 to 18.00 and darkness (october 1977). We observed significant circadian rhythms for both of these agents: first the induction of anaesthesia by althesin was markedly pronounced at 15.30 and varied with season. Secondly the maximum effect of pancuronium was recorded at 08.00. When rats were anaesthetized by sodium pentobarbital under similar experimental conditions but during a different season (january to may) we observed a similar circadian rhythm for pancuronium. These data indicate that: a) the type of anaesthesia used in the protocol may not be of importance in demonstration of a curarizing rhythm in the rat but, b) the possibility of a seasonal component being present and effecting this rhythm needs to be investigated.

Alfaxalone Alfadolone Mixture↗

Does pancuronium or cisatracurium delay the rate of arousal following remifentanil-based anesthesia?

STUDY OBJECTIVE: The present report investigates the rate of arousal following remifentanil-based anesthesia associated with the coadministration of pancuronium, which inhibits butyrylcholinesterase, or cisatracurium, which is partially metabolized by nonspecific esterases, versus vecuronium that is eliminated independently of ester hydrolysis. DESIGN, SETTING AND PATIENTS: Sixty patients, ASA I-II, scheduled for elective abdominal surgeries were enrolled in a double-blinded prospective study. In fact, patients were equally divided into three Groups with each Group receiving remifentanil and either one of the following three muscle relaxants: pancuronium, vecuronium or cisatracurium. MEASUREMENTS: The rate of arousal following discontinuation of anesthesia was assessed by Modified Aldrete Score. Time to eye opening on verbal command, tracheal extubation, Modified Aldrete Score >9, and time to discharge from the recovery room were recorded. MAIN RESULTS: Time to eye opening on verbal command, tracheal extubation, Modified Aldrete Score >9, and time to discharge from the recovery room were not significantly different between the three groups. CONCLUSION: The results suggest that recovery following remifentanil-based anesthesia is not delayed by the coadministration of pancuronium, cisatracurium versus vecuronium; and by the use of neostigmine for reversal of neuromuscular blockade.

Abdomen↗