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PubMed1982

Modification by hexamethonium of the muscarinic receptors blocking activity of pancuronium and homatropine in isolated tissues of the guinea-pig.

In the guinea-pig left atrium, hexamethonium (C6) (0.1-3 mM) caused a parallel rightward shift of concentration-response curves for the negative inotropic response to carbachol (CCh) and oxotremorine (Oxo), the dose ratios obtained with the latter agonist being significantly greater than those for CCh at all concentrations of C6 investigated. In the presence of C6, the muscarinic receptor blocking activity of homatropine (20 microM) or of pancuronium (0.3-2.7 microM) appears to be reduced but if the effect of hexamethonium on concentration-response curves to the agonists is taken into consideration, the dose ratios produced by the combination of C6 with either homatropine or pancuronium were essentially as predicted for the combination of 2 competitive antagonists. The difference in the affinity of pancuronium for cardiac muscarinic receptors and ileal muscarinic receptors was also reduced in the presence of hexamethonium (0.3 mM).

Animals↗
PubMed1986

Verapamil intensifies neuromuscular blockade produced by gallamine and pancuronium at the chick neuromuscular junction.

Experiments were performed to study the effect of verapamil on neuromuscular transmission and muscle contraction at a chick skeletal muscle-nerve preparation. In addition, the effects and interactions of verapamil with some muscle relaxants were studied in the same preparation. These effects were explored by studying the effects of verapamil on: directly-and indirectly-elicited twitch contractions, and neuromuscular blockade produced by gallamine and pancuronium. The results showed that verapamil (2-200 microM) had a differential effect on the twitch responses; more reductions occurred in the indirectly-elicited twitch tension, whereas the directly-elicited twitch response was reduced only by 20-30% of maximum indirectly-elicited twitch tension. Furthermore, in low concentrations (1-20 microM), verapamil significantly increased the neuromuscular blockade produced by gallamine (28-1280 nM) and pancuronium (18-573 nM). In high concentrations (greater than 200 microM), verapamil completely blocked the indirectly-elicited twitch response and produced a marked contracture in the chick skeletal muscle (1.0 +/- 0.1 g, n = 6). It was concluded that by reducing twitch tension and inhibiting neuromuscular transmission, verapamil increases (intensifies) neuromuscular blockade produced by muscle relaxants, e.g. gallamine and pancuronium.

Animals↗
PubMed1991

Effects of pancuronium and vecuronium on creatine phosphokinase in rat isolated heart, liver, kidney and diaphragm.

1. The effects of two muscle relaxants, namely, pancuronium and vecuronium, on creatine phosphokinase (CPK) release from four different types of tissues, namely, heart, liver, kidney and diaphragm, were studied in the rat in vitro. 2. The total, neat and CPK levels (units/ml), released by muscle relaxants were measured using spectrophotometric determination at 340 nm. 3. The results showed that both muscle relaxants, in low concentrations, i.e. 0.34 or 0.32 microM, close to a clinical dose of 0.1 mg/kg, had no significant effect on CPK leakage in all four types of tissues studied. However, in concentrations 12-122 times clinical dose, the two muscle relaxants produced differential adverse effects in the tissues studied. 4. In most concentrations, pancuronium and vecuronium produced significant increases in the CPK release in the kidney and diaphragm. In contrast, pancuronium had no significant effect on CPK release in the liver and the lowest effect in the heart. Similar results were obtained with vecuronium. 5. The clinical relevance and/or implications of the present results are discussed and the results are compared to those previously reported by other workers in other preparations.

Animals↗
PubMed1992

Effect of morphine and pancuronium on the stress response in ventilated preterm infants.

Ninety-five premature newborns who had hyaline membrane disease and were struggling against the ventilator were randomised to one of three treatment groups: morphine (group M), pancuronium (group P) or morphine with pancuronium (group M+P). The dose of morphine was 50 micrograms/kg per h but was increased to 100 micrograms/kg per h in group M infants if they continued to struggle. The dosage of pancuronium was 100 micrograms/kg given as required to inhibit spontaneous respiration. Plasma catecholamine levels were measured on entry and at 24 h. Blood pressure and ventilatory requirements were determined on entry and at 6 h. The clinical outcome of the infants was documented. Group M infants (n = 29) showed a significant reduction in noradrenaline levels (median change -2.2 nmols/l (range -47.2 to +7.2 nmols/l), although seven were withdrawn from this group because of failure to settle. Group P (n = 28) and group M+P (n = 38) showed no significant change in noradrenaline levels. Comparison between the groups showed that group M infants had a significant reduction in noradrenaline levels compared with group P. The immediate effects of treatment on blood pressure and ventilatory requirements were similar in the three groups. The clinical outcome did not differ for any of the measured parameters. When adequate sedation is achieved, morphine may reduce the stress of newborn intensive care.

Blood Pressure↗
PubMed2006

Simultaneous determination of pancuronium, vecuronium and their related compounds using LC-ESI-MS.

A simultaneous determination method of quaternary amino steroidal muscle relaxants, pancuronium (PAN), vecuronium (VEC), and 17-monodesacetyl pancuronium (17-OH-PAN), 3,17-bisdesacetyl pancuronium (3,17-OH-PAN), 3-monodesacetyl vecuronium (3-OH-VEC), 3,17-bisdesacetyl vecuronium (3,17-OH-VEC) in human serum was developed using liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS). The weak cation exchange cartridge was useful for the extraction of these compounds. Under optimized LC-ESI-MS conditions, these compounds were almost fully separated within 6.5 min. Linear responses over the concentration range 0.25-50.0 ng/mL were demonstrated for each compound. The developed method successfully detected VEC, 3-OH-VEC and 3,17-OH-VEC in serum intravenously administered with VEC. The level of 3-OH-VEC was higher than other compounds. This suggested that 3-OH-VEC was useful as a forensic probe in VEC administration.

Chromatography, Liquid↗
PubMed1988

Fetal heart rate changes after fetal intravascular treatment with pancuronium bromide.

Because of recurrent needle dislodgement secondary to fetal movement, we have altered our intravascular transfusion technique by replacing maternal premedication (meperidine and diazepam [group 1]) with fetal intravascular infusion of pancuronium bromide (Pavulon [group 2]), a nondepolarizing neuromuscular blocking agent. Baseline fetal heart rate, number of accelerations, and variability were assessed before and after transfusion in both groups. Whereas there were no changes after transfusion in the former group, those fetuses who received pancuronium bromide demonstrated a dramatic abolishment of accelerations and decrease in variability, with the heart rate pattern often appearing "sinusoidal-like." These alterations in fetal heart rate were temporary changes that reverted to normal once the fetus "awakened" from the neuromuscular blockade. We speculate that these changes in fetal heart rate are secondary to the interaction of the reported hypertensive and vagolytic effects of pancuronium bromide.

Blood Transfusion, Intrauterine↗
PubMed2002

Validation of a high-performance liquid chromatography method for the determination of pancuronium in Pavulon injections.

A new high-performance liquid chromatography (HPLC) method was developed for the quality control of pancuronium bromide and its degradation products. The HPLC method used a 5-microm Supelcogel ODP-50 (150x4 cm) column with acetonitrile-CH3OH-water-F3CCOOH (20.5:74.9:0.1, v/v) as the mobile phase (pH value 2.0 adjusted with trifluoroacetic acid) at a flow-rate 0.8 ml/min and UV detection at 210 nm. The Beer's law plots were found to be linear over the concentration range 0.4-1.2 mg/ml of pancuronium bromide and 0.04-0.08 mg/ml of desacetyl degradation products (R2=0.9995). The RSD of the peak areas was 1.09% and the recovery was 102.43%. The RSD value shows good precision, acceptable accuracy and reproducibility of the new method for the determination of pancuronium bromide in presence of its desacetyl degradation products. The method is rapid and sensitive enough to be used for Pavulon injection analysis.

Chromatography, High Pressure Liquid↗
PubMed1984

Acute cardiopulmonary effects of pancuronium bromide in mechanically ventilated newborn infants.

The short-term effects of muscle relaxation with pancuronium bromide on arterial blood gas values, heart rate, and arterial blood pressure were studied in 49 neonates receiving mechanical ventilation. After pancuronium administration, mean PaO2 increased from 61.9 +/- 30.0 to 80.9 +/- 52.8 mm Hg (P = 0.006), mean PaCO2 decreased from 40.1 +/- 13.0 to 37.5 +/- 13.3 mm Hg (P = 0.03), and mean heart rate rose from 146.2 +/- 24.9 to 161.0 +/- 20.5 beats/min (P less than 0.001). Arterial blood pressure did not change significantly. When results were analyzed by diagnosis (meconium aspiration syndrome, hyaline membrane disease, pneumonia), only infants with meconium aspiration syndrome had a significant improvement in oxygenation (P = 0.008). Six of 18 patients with hyaline membrane disease responded to muscle relaxation, with a decrease in PaO2 of 10 mm Hg or more. No significant correlation was found between change in PaO2 and birth weight, gestational age, postnatal age, or change in heart rate. A weak correlation (r = -0.37, P less than 0.006) was observed between change in PaO2 and change in PaCO2. Although the reasons for the divergence in response in different groups of patients are not entirely clear, the risk of deterioration with pancuronium therapy should be kept in mind, particularly if treatment in an infant with hyaline membrane disease is being considered.

Blood Gas Analysis↗
PubMed1994

Effects of morphine and pancuronium on lung volume and oxygenation in premature infants with hyaline membrane disease.

To determine the effect of analgesia and paralysis on lung volume and oxygenation in premature infants supported by mechanical ventilation because of hyaline membrane disease, functional residual capacity (FRC), and arterial/alveolar oxygen tension ratio were measured in nine premature infants with hyaline membrane disease before and after the administration of morphine sulfate and pancuronium bromide. Without a change of positive end-expiratory pressure, ventilator rate and peak inspiratory pressure were increased before the first set of measurements to minimize the contribution of the infants' own respiratory effort to total ventilation. These ventilator settings were then held constant (except fraction of inspired oxygen) before and after the administration of the drugs. The FRC was measured with a multiple-breath N2 washout technique by means of whole-body plethysmography to measure airway flow. The FRC and the ratio of arterial to alveolar oxygen tension decreased in seven of nine patients after treatment with morphine and pancuronium. The decrease in FRC for all patients was significant (2.4 +/- 2.9 ml/kg; p < 0.05), and a significant correlation was demonstrated between the change in the arterial/alveolar oxygen tension ratio and the change in FRC (r = 0.82; p < 0.01). Gestational age, birth weight, postnatal age, severity of lung disease, and time after the administration of morphine and pancuronium were not significantly correlated with the change in FRC. We believe that a decrease in oxygenation caused by alveolar derecruitment occurred even though the ventilator settings had been increased before the first set of measurements. The decrease in FRC in these infants, who are thought to have alveolar instability because of surfactant deficiency, may have resulted from the loss of expiratory braking mechanisms. We conclude that analgesia and paralysis should be used with caution under these circumstances.

Functional Residual Capacity↗
PubMed1982

[Comparison of the hemodynamic effects of fazadinium, pancuronium and alcuronium in coronary insufficiency (30 cases)].

Cardiovascular effects of neuromuscular blocking agents mainly guide the choice of these relaxants in patients with cardiovascular disease. The purpose of this study was to compare the hemodynamic effects of fazadinium (1 mg . kg-1), pancuronium (0,08 mg . kg-1) and alcuronium (0,2 mg . kg-1) in 30 coronary patients without beta-blocking therapy. No hemodynamic changes were observed after pancuronium. Fazadinium induced at the fifth minute a mean five p. 100 decrease in mean arterial pressure, cardiac index, stroke volume and systemic vascular resistance. At the fifth minute with alcuronium, mean arterial pressure decreased (22 p. 100) (p less than 0.01) with a decrease in cardiac index (12 p. 100), stroke volume (8 p. 100) and systemic vascular resistance (10 p. 100). This study shows that pancuronium and fazadinium are well tolerated. Alcuronium induces at the fifth minute a significant decrease in arterial pressure. This effect does not seem to be deleterious in normovolemic patient with coronary artery disease without beta-blocking therapy.

Aged↗
PubMed1998

[Histamine plasma concentration and cardiovascular effects of non-depolarizing muscle relaxants: comparison of atracurium, vecuronium, pancuronium and pipecuronium in coronary surgical patients at risk].

OBJECTIVE: Cardiovascular effects of four commonly used non-depolarising muscle relaxants and their ability to increase histamine plasma concentrations were studied in patients scheduled for coronary artery bypass grafting. METHODS: 40 patients were included in the study after informed consent. After premedication with Flunitrazepam (2 mg p.o.) on the evening before and 1 hour prior to surgery anaesthesia was induced with Flunitrazepam (4-6 micrograms kg-1). Fentanyl (3 micrograms kg-1) und Etomidate (150 micrograms kg-1) and the patients were ventilated via face mask with 50% N2O in oxygen. Patients were randomly allocated to one of four groups, and, 15 min after induction of anaesthesia, received equipotent doses of either Pancuronium (0.09 mg kg-1, n = 10). Pipecuronium (0.08 mg kg-1, n = 10), Atracurium (0.6 mg kg-1, n = 10), or Vecuronium (0.1 mg kg-1, n = 10) injected over 20 seconds via a central venous catheter. Cardiovascular variables were determined in the awake patient, 15 min after induction of anaesthesia and following administration of the respective muscle relaxant. In addition, plasma histamine concentrations were assessed before and after relaxation. Evoked muscular response to TOF simulation of the ulnar nerve (plethysmo-mechanogram) was continuously recorded to determine the onset of neuromuscular blockade. RESULTS: Heart rate, mean arterial pressure and cardiac index significantly decreased in all patients following induction of anaesthesia while systemic vascular resistance remained unchanged. Only Pancuronium caused a significant increase in heart rate (53 +/- 11 to 61 +/- 15 min-1) whereas cardiac index and mean arterial pressure did not change significantly. No other neuromuscular blocking agent caused any changes in the cardiovascular variables measured and histamine plasma concentrations remained within the reference range in all of the four groups with no differences detectable between groups. CONCLUSIONS: All investigated neuromuscular blocking agents exhibited marked cardiovascular stability which permits their use, being based exclusively on pharmacodynamic and pharmakokinetic considerations even in patients with coronary heart disease. If an increase in heart rate appears beneficial Pancuronium may be advantageous.

Anesthesia↗
PubMed1975

Althesin and pancuronium in chronic liver disease.

In 32 patients with chronic liver disease, undergoing major abdominal surgery, anaesthesia was induced with either Althesin (alphaxalone and alphadolone acetate) or thiopentone, and maintained with nitrous oxide, oxygen and increments of either pethidine or fentanyl. The patients were ventilated artificially to maintain PaCO, values in the normal range. Pancuronium bromide was used as the muscle relaxant. Liver function tests at 24 hr and 5 day after surgery showed only minor changes compared with findings before operation. There was no significant difference between the Althesin and thiopentone groups. In two patients with severe obstructive jaundice there was difficulty in reversing the effects of pancuronium, but "pancuronium resistance" was observed in all patients. It is concluded that the anaesthetic sequence described, with either Althesin or thiopentone induction, is satisfactory with respect to changes in liver function in patients with chronic liver disease undergoing major surgery.

Adolescent↗
PubMed1975

A clinical comparison of AH8165 and pancuronium as muscle relaxants in patients undergoing cardiac surgery.

The non-depolarizing muscle relaxant AH8165 has been compared at two doses (0.5 and 1.0 mg/kg) with pancuronium (0.1 mg/kg) during induction of anaesthesia for patients having major cardiac surgery. After barbiturate-opiate premedication and thiopentone induction, administration of pancuronium was followed by no significant alteration in heart rate or arterial pressure. Both doses of AH8165 werr followed by significant tachycardia, and the higher dose by arterial hypotension. The lower dose of AH8165 was unsatisfactory for tracheal intubation, but the AH8165 1 mg/kg gave intubating conditions similar to those with pancuronium 0.1 mg/kg.

Adult↗
PubMed1977

Conditions for tracheal intubation following fazadinium and pancuronium.

Intubating conditions were studied in two groups of patients who received either fazadinium 1 mg/kg or pancuronium 0.1 mg/kg (group 1), or either fazadinium 0.5 mg/kg or pancuronium 0.08 mg/kg (group 2). In group 1 intubating conditions were studied at 30, 45, 60 and 75 s after injection of the relaxant drug, and in group 2 at 60 s after injection. Fazadinium provided better intubating conditions than pancuronium during the first 60 s after administration in group 1 (P less than 0.01). In group 2 there was no significant difference between the conditions provided by the two drugs.

Humans↗
PubMed1980

Constrictive effect of pancuronium on capacitance vessels.

The effects of pancuronium 0.08 mg kg-1, metocurine 0.4 mg kg-1 and tubocurarine 0.4 mg kg-1 on vascular tone were studied in 26 patients undergoing open heart surgery during total cardiopulmonary bypass. With a fixed rate of perfusion, arterial pressure is related directly to total peripheral resistance, while the volume of blood remaining in the extracorporeal reservoir is related inversely to vascular capacity, which depends primarily on venous tone. Pancuronium increased the reservoir volume (average of 780 +/- SEM 250 ml (P less than 0.01). We conclude that under certain circumstances pancuronium constricts capacitance vessels in man.

Adult↗
PubMed1980

Comparison of haemodynamic effects of metocurine and pancuronium in patients with coronary artery disease.

The haemodynamic effects of large bolus doses of metocurine 0.45 mg kg-1 and pancuronium 0.1 mg kg-1 were compared in patients with coronary artery disease anaesthetized with diazepam, anileridine and nitrous oxide. Hypotension occurred more frequently after metocurine and was a result of a decrease in systemic vascular resistance. After pancuronium there was no increase in arterial pressure or heart rate, but a small increase in cardiac index. The decrease in heart rate after metocurine was the principal cause of the statistically significant difference in cardiac index between the two groups. Contrary to previous findings, metocurine did not attenuate circulatory responses to tracheal intubation. During surgical stimulation, two of the 10 patients of the pancuronium group developed significant ST segment depression and three patients had a rate-pressure product greater than 12 000 mm Hg beat min-1. However, the difference in rate-pressure product between the groups was not statistically significant.

Anesthesia, General↗
PubMed1982

Impaired neostigmine antagonism of pancuronium during enflurane anaesthesia in man.

We have compared the rates of recovery of pancuronium-induced neuromuscular blockade after administration of neostigmine during anaesthesia maintained with nitrous oxide and intermittent narcotics, halothane or enflurane. Thirty patients were studied in whom anaesthesia was maintained with 70% nitrous oxide in oxygen with: fentanyl or thiopentone, halothane (0.55-0.65% end-tidal), or enflurane (1.3-1.4% end-tidal). Muscle twitch response was measured using train-of-four stimulation. Pancuronium 3 mg/70 kg was antagonized with neostigmine 2.5 mg/70 kg at 10% spontaneous recovery of the first twitch of the train compared with control. There were no significant differences between the times to 10% spontaneous recovery of the first twitch or the rates of train-of-four recovery after neostigmine when the narcotic and halothane groups were compared. However, enflurane anaesthesia, in comparison with fentanyl, was associated with a significant increase in the time to 10% recovery (57.9 +/- 6.0 min v. 35.4 +/- 7.0 min) and with decreases in the train-of-four recoveries at 4, 5, 10, 20 and 30 min after neostigmine. We conclude that, under the conditions of this study, the antagonism of pancuronium-induced neuromuscular blockade with neostigmine was impaired during enflurane but not halothane anaesthesia.

Adult↗
PubMed1982

Dose-response relation for atracurium, ORG NC 45 and pancuronium.

The potencies of atracurium, Org NC 45 and pancuronium were determined using cumulative dose-response curves. The effective doses producing 95% twitch depression were 279 microgram kg-1, 56 microgram kg-1 and 64 microgram kg-1 respectively, the relative potency being 1:5.0:4.3. The calculated log-probit dose-response curves showed the steepest slope for pancuronium, although the slopes did not deviate significantly from the parallel. The three drugs provided equal and generally good intubating conditions at approximately 95% twitch depression. Greater arterial pressure and heart rate were seen with pancuronium than with atracurium and Org NC 45.

Adult↗