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PubMed1983

Interactions between tubocurarine, pancuronium and alcuronium demonstrated in the rat phrenic nerve-hemidiaphragm preparation.

The interactions between tubocurarine, pancuronium and alcuronium on neuromuscular transmission have been studied in an isolated neuromuscular preparation (the rat phrenic nerve-hemidiaphragm). Mixtures of tubocurarine and pancuronium, and tubocurarine and alcuronium were found to have a more potent effect than the additive effects of the individual agents when given alone, that is, mixtures were synergistic. Mixtures of alcuronium and pancuronium did not exhibit this phenomenon. Possible mechanisms for these findings are discussed.

Alcuronium↗
PubMed1983

Comparative investigations on the cardiovascular effects of Org NC45 and pancuronium in dogs.

Cardiovascular effects of Org NC 45 and pancuronium were examined in seven anaesthetized dogs. Systemic circulatory effects were measured after increasing doses administered as a single i.v. bolus. Cardiac effects were measured after intracoronary (i.c.) injection of the equivalent dose of the respective neuromuscular blocking agent, which produced 90% neuromuscular blockade. Org NC 45 i.v. did not cause any significant cardiovascular changes, whereas pancuronium i.v. produced significant and dose-related increases in heart rate, left ventricular (LV) dP/dtmax and cardiac output (CO). After i.c. injection of equipotent doses, neither drug induced any significant change in haemodynamic measurements. This implies that neither drug exerted a direct influence on cardiac contractility, the increases in LV dP/dt max and CO following pancuronium being dependent on heart rate.

Animals↗
PubMed1983

Neuromuscular and vagal blocking actions of pancuronium bromide, its metabolites, and vecuronium bromide (Org NC45) and its potential metabolites in the anaesthetized cat.

The neuromuscular and cardiac vagus blocking actions of pancuronium, vecuronium (Org NC45) and their respective potential hydroxy metabolites have been studied in the chloralose-anaesthetized cat. Pancuronium was three times more potent as a neuromuscular blocker than its 3-hydroxy derivative, 20 times more potent than the 17-hydroxy derivative and 45 times more potent than the 3,17-dihydroxy derivative. The vagal:neuromuscular block ratios measured at 50% inhibition for these compounds were pancuronium 3.0, 3-hydroxy derivative 6.4, 17-hydroxy derivative 1.1 and 3,17-dihydroxy derivative 0.36 (a value greater than unity indicated greater potency at the neuromuscular junction). Vecuronium was 1.4 times more potent than its 3-hydroxy derivative, 24 times more potent than the 17-hydroxy derivative and 72 times more potent than the 3,17-dihydroxy derivative as a neuromuscular blocker. The vagal:neuromuscular block ratios were vecuronium 79.8, 3-hydroxy derivative 40.4, 17-hydroxy derivative 0.85 and 3,17-dihydroxy derivative 0.15. The 3-hydroxy derivative of vecuronium, the most likely first metabolite of vecuronium, thus possessed only slightly less neuromuscular blocking potency than vecuronium, coupled with a high safety margin between neuromuscular and vagal blocking doses. In addition, the time-course of its action was not different from that of vecuronium. Thus, it is concluded that this potential metabolite is unlikely to give rise to tachycardia in man. It is unlikely that the 17-hydroxy and 3,17-dihydroxy derivatives of vecuronium would be produced in sufficiently great quantities by metabolism from vecuronium to result in either tachycardia or residual neuromuscular blockade.

Animals↗
PubMed1984

In vitro interaction of diazepam and oxazepam with pancuronium and suxamethonium.

In vitro studies using the rat phrenic nerve-hemidiaphragm preparation were performed to investigate the effects of diazepam and three of its metabolites on indirectly evoked twitch tension. Diazepam, desmethyldiazepam and temazepam alone caused an increase in twitch tension in lower concentrations, followed by complete depression in higher concentrations. Oxazepam did not cause an initial increase in twitch tension, but showed an immediate and dose-dependent depression. Cumulative concentration-response curves for pancuronium and suxamethonium in the presence of different concentrations of diazepam or oxazepam showed that small concentrations of diazepam, which did not change twitch tension alone, caused antagonism of the action of pancuronium, but not of suxamethonium. With oxazepam no such antagonism was observed. In liminal and supraliminal concentrations, both diazepam and oxazepam potentiated the action of pancuronium and suxamethonium. Possible implications for in vivo interactions are discussed.

Animals↗
PubMed1984

Prejunctional and postjunctional effects of tubocurarine and pancuronium in man.

The effects of small doses of tubocurarine and pancuronium on peak tetanic tension and tetanic maintenance were compared. Forty patients undergoing elective orthopaedic procedures under general anaesthesia were studied. Changes in neuromuscular transmission were measured by recording the isometric contraction of the adductor pollicis muscle evoked by supramaximal stimulation of the ulnar nerve at the wrist. Small doses of pancuronium affected predominantly the peak tetanic tension, while small doses of tubocurarine affected mainly tetanic maintenance. Thus, different degrees of depression of peak tetanic tension and tetanic maintenance were observed with tubocurarine and pancuronium. This clinical study supports Bowman's hypothesis, based upon laboratory findings in the cat, that prejunctional and postjunctional effects of neuromuscular blocking agents depend on their affinity for cholinoceptors at different sites.

Adult↗
PubMed1985

Interaction between pancuronium bromide and vecuronium bromide.

The interaction between two non-depolarizing neuromuscular blocking agents, pancuronium bromide and vecuronium bromide, has been studied at standardized levels of neuromuscular blockade and alternating the sequence of their administration, in 40 surgical patients. The drug administered first appeared invariably to play a dominant role in influencing both the dose requirements and the duration of action of the subsequent neuromuscular blocker. This resulted in reduced dose requirements and significant prolongation of action of vecuronium administered after pancuronium and increased dose requirements and shortening of neuromuscular blocking action of pancuronium given during vecuronium-induced partial neuromuscular blockade. Possible mechanisms of such interaction are discussed.

Adult↗
PubMed1987

Haemodynamic effects of vecuronium, pancuronium and atracurium in patients with coronary artery disease.

Thirty patients with ischaemic heart disease scheduled for coronary artery bypass grafting were randomly allocated to three equal groups. Following morphine, hyoscine and pentobarbitone premedication, anaesthesia was induced with diazepam 0.3 mg kg-1. Five minutes later neuromuscular blockade was induced with pancuronium 0.1 mg kg-1, vecuronium 0.1 mg-1 or atracurium 0.5 mg kg-1, followed after 6 min by fentanyl 25 micrograms kg-1. Pancuronium and atracurium caused significant increases in heart rate, while vecuronium induced little change. Systemic vascular resistance decreased significantly from 1515 dyn s cm-5 to 1200 dyn s cm-5 following atracurium. Cardiac index was increased transiently in the atracurium group, but a more sustained increase was observed following pancuronium. Nine patients in the atracurium group showed skin flushing and one developed skin weals.

Atracurium↗
PubMed1988

Effects of atracurium, vecuronium or pancuronium pretreatment on lignocaine seizure thresholds in cats.

Among the non-depolarizing neuromuscular blocking drugs, atracurium appears to be unique in its ability to produce cerebral stimulation in lightly anaesthetized animals. This effect is attributed to the atracurium metabolite, laudanosine. The following studies were performed to determine if pretreatments with the non-depolarizing neuromuscular blockers pancuronium, atracurium or vecuronium would differ in their effects on the seizure threshold of lignocaine. Adult mongrel cats were anaesthetized with 1.0 MAC halothane in oxygen and nitrogen. Ventilation, blood-gas tensions, acid-base balance and temperature were controlled. Cats received pancuronium 0.2 mg kg 1 i.v. (n = 7), atracurium 1.0 mg kg-1 i.v. (n = 7) or vecuronium 0.2 mg kg-1 i.v. (n = 7). Ten minutes after the administration of the myoneural blocker, all cats received lignocaine 4 mg kg-1 min-1 i.v. until the onset of EEG evidence of generalized seizure activity. At seizure onset, there were no statistically significant differences among the cumulative lignocaine doses or the serum lignocaine concentrations in cats pretreated with pancuronium, atracurium or vecuronium.

Anesthesia, Inhalation↗
PubMed1988

Differential effects of calcium channel blocking agents on pancuronium- and suxamethonium-induced neuromuscular blockade.

The effects were studied of several calcium channel blocking agents on muscle twitch, and possible interactions between these drugs and pancuronium and suxamethonium, using a rat phrenic-hemidiaphragm preparation. Nicardipine, verapamil and diltiazem each caused a concentration-related depression of muscle response. Nicardipine had the most, and diltiazem the least, potent effect. Verapamil and diltiazem 5 and 10 mumol litre-1 caused a concentration-dependent enhancement of suxamethonium-induced neuromuscular blockade, but increased the effect of pancuronium only at 10 mumol litre-1. Nicardipine 10 mumol litre-1 significantly enhanced pancuronium-induced neuromuscular blockade, but not that produced by suxamethonium.

Animals↗
PubMed1989

Pancuronium allergy: a case report.

A case of anaphylactic shock to pancuronium bromide is described in which a type I immunological reaction occurred. A 33-yr-old male anaesthetist, with no family or personal history of allergy, collapsed soon after induction of anaesthesia. The drugs used included fentanyl, droperidol, thiopentone and pancuronium. Diffuse erythema occurred, with probable cardiac arrest. The patient was treated with cardiac massage, sympathomimetics and cortisone, and made a complete recovery. Examination (skin tests, passive transfer according to Prausnitz and Küstner, in vitro lymphocyte transformation test, total IgE assay) revealed that the allergic reaction was to pancuronium bromide.

Adult↗
PubMed1995

Antagonism of pancuronium- and pipecuronium-induced neuromuscular block.

We have compared the antagonism of neuromuscular block produced by pipecuronium with pancuronium in 80 anaesthetized surgical patients using mechanomyography and electromyography. Pancuronium 0.1 mg kg-1 or pipecuronium 0.07 mg kg-1 was given after induction of anaesthesia and neuromuscular block was adjusted to 75% twitch depression at the time of antagonism. The following regimens were used: edrophonium 0.5 and 1.0 mg kg-1, neostigmine 0.04 mg kg-1, pyridostigmine 0.3 mg kg-1 and edrophonium 0.25 mg kg-1 with pyridostigmine 0.15 mg kg-1. Antagonism was evaluated also by the head lift test. There was no difference between the reversibility of neuromuscular block produced by pancuronium or pipecuronium. Edrophonium produced a significantly faster antagonism than neostigmine or pyridostigmine but onset of action was not significantly faster than that of edrophonium with pyridostigmine. All regimens produced 100% (or near 100%) antagonism of twitch response within 15 min. However, TOF fade antagonism was more complete with pyridostigmine, neostigmine and edrophonium 1.0 mg kg-1 than with edrophonium 0.5 mg kg-1. The head lift test indicated somewhat less antagonism with edrophonium 0.5 and 1.0 mg kg-1. Using five monitoring methods, the rank order of reversal potency was: pyridostigmine approximately neostigmine > edrophonium 1.0 mg kg-1 > edrophonium+pyridostigmine > edrophonium 0.5 mg kg-1.

Adult↗
PubMed1996

Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium.

We have compared the ability of equipotent concentrations of isoflurane and sevoflurane to enhance the effect of non-depolarizing neuromuscular blocking drugs. Ninety ASA I and II patients of both sexes, aged 18-50 yr, were stratified into three blocker groups (Vec, Pan and Atr), to undergo neuromuscular block with vecuronium (n = 30), pancuronium (n = 30) or atracurium (n = 30), respectively. Within each group, patients were allocated randomly to one of three anaesthetic subgroups to undergo maintenance of anaesthesia with: (1) alfentanil-nitrous oxide-oxygen (n = 10); (2) alfentanil-nitrous oxide-oxygen-isoflurane (n = 10); or (3) alfentanil-nitrous oxide-oxygen-sevoflurane (n = 10) anaesthesia. During maintenance of anaesthesia, end-tidal concentrations of isoflurane, sevoflurane and nitrous oxide were 0.95, 1.70 and 70%, respectively. Both the evoked integrated electromyogram and mechanomyogram of the adductor pollicis brevis muscle were measured simultaneously. In the Vec and Pan groups, a total dose of 40 micrograms kg-1 of vecuronium or pancuronium, respectively, was given, and in the Atr group a total dose of atracurium 100 micrograms kg-1. Each blocker was given in four equal doses and administered cumulatively. We showed that 0.95% isoflurane and 1.70% sevoflurane (corresponding to 0.8 MAC of each inhalation anaesthetic, omitting the MAC contribution of nitrous oxide) augmented and prolonged the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree.

Adolescent↗
PubMed1997

The use of 0.25% lidocaine with fentanyl and pancuronium for intravenous regional anesthesia.

The present study was designed to assess the efficacy of fentanyl and pancuronium combined with dilute lidocaine solution for intravenous regional anesthesia of the arm. Forty adult patients undergoing upper limb surgery were randomly allocated to receive either 0.6 mL/kg of 0.5% lidocaine (3 mg/kg) or 0.6 mL/kg of 0.25% lidocaine (1.5 mg/kg) with 1 microg/kg of fentanyl and 0.5 mg of pancuronium. The onset of sensory and motor blocks was significantly shorter in the 0.5% lidocaine group (P < 0.05). However, no differences in analgesia or motor blockade were found between the two groups at 20 min tourniquet time. Regional anesthesia was considered successful in more than 85% of patients. One patient in the 0.25% lidocaine group experienced a transient diplopia after tourniquet release. Postoperative analgesia time was similar in the two groups. We conclude that the addition of fentanyl plus pancuronium to the lidocaine solution reduces the dose of the local anesthetic and possibly systemic toxicity.

Adult↗
PubMed1980

Neostigmine, pyridostigmine, and edrophonium as antagonists of pancuronium.

This study was performed to compare the effects of three anticholinesterases on rates of recovery from pancuronium-induced neuromuscular blockade. Pancuronium (3 mg/70 kg) was antagonized during nitrous oxide-oxygen-halothane anesthesia, in man, with neostigmine (2.5 or 5.0 mg/70 kg), pyridostigmine (10 or 20 mg/70 kg), or edrophonium (50 or 100 mg/70 kg). Reversal was attempted at 10 per cent spontaneous recovery of muscle twitch, which was measured by use of train-of-four stimulation. Following administration of the antagonists each patient had progressive recovery of neuromuscular function. Recurarization was not observed during the period of study. Recovery was most rapid with edrophonium and slowest with pyridostigmine. Five minutes after administration of the antagonists, mean T4, the height of the fourth twitch as a percentage of the first in each train, exceeded 50 per cent only with the larger dose of neostigmine and both doses of edrophonium. Thirty minutes after reversal there was no significant difference in recoveries among the drugs tested, and T4 exceeded 70 per cent for all patients. It is concluded that, under the conditions of this study, neostigmine, pyridostigmine, and edrophonium induce sustained antagonism of pancuronium-induced neuromuscular blockade. The antagonism produced by large doses of edrophonium is faster than that produced by neostigmine or pyridostigmine.

Adolescent↗
PubMed1983

A comparison of systemic and regional hemodynamic effects of d-tubocurarine, pancuronium, and vecuronium.

This study was designed to compare the effects of three neuromuscular blocking agents, in a clinically relevant dose range, on the regional distribution of blood flow measured with 15-microns radioactive microspheres in anesthetized, optimally ventilated cats. d-Tubocurarine (400, 800, and 1,600 micrograms X kg-1) caused hypotension and a decrease in ascending aortic blood flow. Pancuronium (20, 40, and 80 micrograms X kg-1) only caused a moderate tachycardia, while vecuronium (40, 80, and 160 micrograms X kg-1) was devoid of any systemic hemodynamic effect. Neither pancuronium nor vecuronium caused major changes in regional blood flows. On the other hand, d-tubocurarine increased blood flow to the stomach but decreased that to the kidneys, liver, skin, spleen, intestine, and adrenal glands. These effects of d-tubocurarine show a striking resemblance to those elicited by the infusion of histamine. Blood flow to the nerve-stimulated tibialis anterior muscle, which was about six times that of the unstimulated muscle, was decreased significantly by all three neuromuscular blockers. In conclusion, the results clearly show that, while d-tubocurarine produces major cardiovascular disturbances, pancuronium and, in particular, vecuronium do not cause serious changes in systemic and regional hemodynamics in doses that are two to four times the ED90 for neuromuscular blocking action.

Animals↗
PubMed1984

Failure of intravenous nitroglycerin to prevent intraoperative myocardial ischemia during fentanyl-pancuronium anesthesia.

Twenty patients undergoing coronary artery bypass grafting under fentanyl-pancuronium anesthesia were studied. Continuous electrocardiographic (ECG) recording by a Holter Monitor was utilized to determine the incidence of ECG changes of myocardial ischemia during the precardiopulmonary bypass period and to determine the efficacy of an intravenous nitroglycerin (iv NTG) infusion for preventing ischemic ECG changes. Patients in Group 1 (n = 9) received a 0.5 microgram . kg-1 . min-1 iv NTG infusion 20 min prior to induction of anesthesia and throughout the study. Patients in Group 2 (n = 11) received placebo. A randomized double-blind protocol was employed. Anesthesia was induced with fentanyl 3 micrograms . kg-1 . min-1. After fentanyl 25 micrograms/kg and pancuronium 0.1 microgram/kg, the trachea was intubated. After fentanyl 50 micrograms/kg surgery commenced. Prior to induction of anesthesia, iv NTG caused significant decreases in mean arterial pressure and pulmonary capillary wedge pressure, whereas placebo had no effect. However, subsequent to induction of anesthesia, hemodynamics in the two groups were identical. Fifty per cent of patients developed ECG changes of myocardial ischemia during the period from induction of anesthesia to commencement of cardiopulmonary bypass. The incidence of ischemic ECG changes was virtually identical in Group 1 (5/9) and Group 2 (5/11). Ischemic ECG changes were associated with increases in heart rate, mean arterial pressure, and rate pressure product, and decreases in the endocardial viability ratio (DPTI/SPTI). Increases in pulmonary capillary wedge pressure were not associated with myocardial ischemia. Fentanyl-pancuronium anesthesia, as administered in this study, was associated with a high incidence of myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1985

Potentiation of the combination of pancuronium and metocurine by halothane and isoflurane in humans with and without renal failure.

Dose-response relationships for a 1:4 weight ratio-mixture of pancuronium and metocurine were studied during inhalational anesthesia with halothane and isoflurane in patients with and without renal failure. The time for recovery from 10 to 20% of control thumb twitch tension also was determined. In subjects with normal renal function, relaxant doses required for 95% twitch height suppression (ED95) were 50% of those predicted by simple addition of effects when used with a balanced anesthetic technique, 37% of predicted when used with 1.3 MAC halothane, and 25% of predicted when used with 1.3 MAC isoflurane (P less than 0.05). In subjects with renal failure, ED95 values for the combination were 40% of predicted when used with 1.2 MAC halothane and 45% of predicted when used with 1.2 MAC isoflurane (NS). For relaxants used singly in renal failure, pancuronium alone was slightly enhanced by 1.2 MAC halothane (85% of predicted), while 1.1 MAC isoflurane reduced the ED95 to 57% of predicted (P less than 0.05). Similar results were obtained for metocurine alone when used in renal failure (77 and 58% of predicted when used with halothane and isoflurane, respectively) (NS). Predicted values are published results for balanced anesthesia in normals. Recovery times were prolonged twofold in renal failure (P less than 0.05). Thus, the combination of pancuronium and metocurine is synergistic to the same degree in normals and in renal failure patients, but the total blockade produced by the combination is enhanced by halothane and isoflurane only in normals.

Adult↗
PubMed1985

The cerebral effects of pancuronium and atracurium in halothane-anesthetized dogs.

Pancuronium decreases the minimal alveolar anesthetic concentration (MAC) of halothane in humans, while atracurium has a metabolite, laudanosine, which is a known cerebral stimulant. To determine if these muscle relaxants significantly alter cerebral function, their effects on cerebral metabolic rate (CMRo2), cerebral blood flow (CBF), intracranial pressure (ICP), EEG, and the cerebral energy state were studied in halothane-anesthetized dogs. Group A dogs (n = 6) were maintained at 0.86% end-expired (1.0 MAC) halothane. Thereafter, a sequence of 1) pancuronium 0.1 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; and 3) pancuronium 0.2 mg . kg-1 produced no changes in CMRo2, CBF, ICP, or EEG. Group B dogs (n = 6) also were maintained at 0.86% end-expired halothane and received the following in sequence: 1) atracurium 0.5 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; 3) atracurium 1.0 mg . kg-1; and 4) atracurium 2.5 mg . kg-1. There were no changes in CMRo2, CBF, or ICP; EEG evidence of cerebral arousal occurred in only one dog with the final dose of atracurium. Group C dogs (n = 6) received tetracaine spinal anesthesia and the minimal halothane concentration (mean +/- SE = 0.69 +/- 0.03% end-expired) that would maintain an "anesthetic" EEG pattern. Each Group C dog received the following in sequence: 1) atracurium 1.0 mg . kg-1, and 2) atracurium 2.5 mg . kg-1. EEG evidence of cerebral arousal occurred in all six Group C dogs. Arousal was not accompanied by significant increases in CBF, CMRo2, or ICP.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, Inhalation↗