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PubMed1990

Hyperbilirubinemia following exposure to pancuronium bromide in newborns.

We investigated the risk of hyperbilirubinemia in relation to the administration of pancuronium bromide among newborn infants requiring mechanical ventilation. One hundred and twenty-nine infants treated with pancuronium were compared to 129 infants who were never exposed, matched on ventilatory status, hospital, birthweight, initial total serum bilirubin, and date of hospital discharge. Overall, the adjusted summary relative risk (RR) for hyperbilirubinemia among pancuronium-exposed infants compared to nonexposed infants was 1.2 (95% confidence interval 1.1-1.4). The risk was greatest among exposed infants during the 4 days following the last dose of pancuronium (RR = 1.4; 1.0-1.8). These data suggest that the use of pancuronium in sick newborns may be associated with an increased risk of clinically important hyperbilirubinemia.

Bilirubin↗

PubMed1989

[Sufentanil: the effect on cardiocirculatory parameters and intubation conditions on administration of pancuronium or vecuronium].

A lack of uniform methodology used in the assessment of moderate doses of sufentanil in combination with non-depolarizing neuromuscular blocking drugs formed the basis of the current study which compared under randomized conditions the effects of sufentanil-pancuronium versus sufentanil-vecuronium on hemodynamics, intubating conditions and chest wall rigidity during induction of anesthesia. MATERIAL and METHODS. One hundred and twenty ASA physical status I and II patients aged between 20 and 40 years of age who were undergoing elective urological surgery were included in the study. Premedication consisted of 0.15 mg kg-1 diazepam, given orally 60 min prior to induction of anesthesia. Patients were randomly divided into eight groups of 15 each to receive 0.5 microgram kg-1 sufentanil or placebo in combination with pancuronium (groups I-IV) or vecuronium (groups V-VIII) Within each group, patients were randomly allocated to receive the relaxant either as a single bolus dose of 0.095 mg kg-1 pancuronium or 0.1 mg kg-1 vecuronium, or in divided doses (the priming principle), the smaller priming dose (0.015 mg kg-1 pancuronium or 0.015 mg kg-1 vecuronium) being administered 2 min before induction of anesthesia with 5 mg kg-1 thiopentone, followed by the second intubating dose of 0.080 mg kg-1 pancuronium or 0.085 mg kg-1 vecuronium. To maintain blind study conditions in the groups, the patients given the relaxants in one dose were given an equivalent volume of saline 2 min prior before 5 mg kg-1 thiopentone. Intubating was attempted 60 s after administration of the main dose of the relaxant, and conditions were assessed on a four-point scale: excellent, satisfactory, fair, or poor. Neuromuscular transmission was monitored with the Datex Relaxograph, a neuromuscular transmission analyzer, that utilizes the integration of the EMG response. Producing train-of-four (TOF) stimuli, with a pulse width of 100 microseconds and a frequency of 2 Hz every 20 s the following parameters were recorded by the Datex Relaxograph: The percentage of first twitch amplitude compared with the reference (T1), and the train-of-four (TOF) ratio, i.e., the ratio of last twitch height to first height. Measurements were taken after premedication in the operating room, the value which served as a baseline (t0), 1 min after sufentanil or placebo (t1), 1 min after priming or placebo (t2), 1 min after thiopentone (t3), and 1 min after intubation (t4).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1989

Autoregulation of cerebral blood flow. Effect of phenobarbital and pancuronium in the newborn piglet.

The effect of phenobarbital and pancuronium on cerebral blood flow (CBF) and CBF autoregulation are studied in newborn piglets after chemically induced seizures with bicuculline. Given 3 or 15 min after the onset of seizures, phenobarbital significantly reduces CBF (59 +/- 11 and 56 +/- 17 vs. 84 +/- 24 ml/min/100 g - p less than 0.01). Moreover, during graded hypotension induced by graded haemorrhage, phenobarbital provides reestablishment of CBF autoregulation altered by seizures. In the same experimental model, pancuronium induces in control animals a rise of CBF (61 +/- 15 vs. 38 +/- 11 ml/min/100 g - p less than 0.001). During graded hypotension pancuronium is associated to a loss of CBF autoregulation (r = 0.76, p less than 0.001). Given as an adjunct treatment, in case of seizures, pancuronium has no significant effect on changes in cerebral haemodynamics. From these data, we conclude that pancuronium jeopardizes the haemodynamic adaptation to the induced hypovolemia and that phenobarbital may present a protective effect on cerebral haemodynamics and the subsequent risk for ischaemia or haemorrhage.

Animals↗

PubMed1988

Pancuronium-phenytoin interaction: a case of decreased duration of neuromuscular blockade.

A 33-year-old female presented for elective excision of a posterior fossa tumour following two generalized seizures six months earlier. The patient had been asymptomatic on phenytoin 300 mg/day. Two h pre-operatively, a 300-mg dose of phenytoin was administered, general anesthesia induced and pancuronium bromide given to achieve neuro-muscular paralysis. Respiration was supported and anesthesia maintained with isoflurane and nitrous oxide in oxygen. Thirty min into the operation a further 2-mg dose of pancuronium bromide was administered. One h later, the patient coughed. A peripheral nerve stimulator was applied to the right common peroneal nerve with surface electrodes. Over the next 75 min a total of 15 mg of pancuronium bromide was required. With each dose there was a complete loss of response to peripheral nerve stimulation, followed by a rapid return of full train-of-four response, accompanied by coughing and cerebral engorgement. At this point, metocurine iodide was administered with full sustained paralysis for 45 min. Blood samples collected during a second operation indicated the patient had an extremely short pancuronium elimination half-life and a small volume of distribution. Several explanations are offered including phenytoin induction of hepatic microsomal enzymes responsible for the biotransformation of pancuronium, alterations in tissue or protein binding and/or alterations in myoneuronal junctional response.

Adult↗

PubMed1982

Renal and biliary elimination of vecuronium (ORG NC 45) and pancuronium in rats.

The urinary excretion of ORG NC 45 (Vecuronium) and of pancuronium was studied in unanesthetized rats and the biliary excretion was studied in anesthetized rats. Urine and bile were analyzed for unchanged drug by a new and specific mass spectrometric assay. Pancuronium was eliminated primarily in the urine (85% +/- 6% of the dose in 12 hours), but little ORG NC 45 appeared in the urine (3.5% +/- 1.1% in 12 hours). Biliary excretion accounted for 46% +/- 4% of the ORG NC 45 dose in 7 hours, but only 7.5% +/- 5.3% of an injected dose of pancuronium appeared in the bile. Thus, it appears that ORG NC 45 (a monoquaternary ammonium compound) has a higher biliary clearance than pancuronium (a bisquaternary ammonium compound). The different biodisposition of these two compounds may be due to the greater lipophilicity and concomitant enhanced permeability into the hepatocyte of ORG NC 45. We conclude that in the rat elimination of pancuronium is primarily via the kidney whereas elimination of ORG NC 45 is dependent on nonrenal mechanisms.

Animals↗

PubMed1982

A double-blind clinical trial comparing alcuronium with pancuronium.

Alcuronium and pancuronium were compared as muscle relaxants in a randomized and double-blind trial in routine clinical circumstances during combined balanced anesthesia in 40 female patients. The course of endotracheal intubation at 2 min. was statistically significantly better (p less than 0.001) in the pancuronium group than in the alcuronium group. There were no differences between the two groups regarding relaxation, maintenance of anesthesia and postoperative recovery. In the pancuronium group the systolic blood pressure was significantly higher than in the alcuronium group at 2 minutes after induction (p less than 0.01), at 2 minutes after intubation (p less than 0.05) and before incision (p less than 0.05). Also the diastolic blood pressure was significantly higher in the pancuronium group at 2 minutes after induction (p less than 0.001), before incision (p less than 0.01) and at 2 minutes after incision (p less than 0.05) than in the alcuronium group. Thus alcuronium is preferable when hypertensive episodes are to be avoided whereas pancuronium would be more suitable when hypotension can be expected.

Adult↗

PubMed1980

Cardiovascular and neuromuscular effects of Org NC 45, pancuronium, metocurine, and d-tubocurarine in dogs.

We compared the cardiovascular and neuromuscular effects of Org NC 45 with those of pancuronium, metocurine, and d-tubocurarine in six dogs anesthetized with halothane. The ED90 (dose of drug which produced a 90% depression of twitch tension) of Org NC 45, pancuronium, metocurine, and d-tubocurarine was 14 +/- 3, 22 +/- 3, 63 +/- 19, and 130 +/- 19 micrograms/kg, respectively. All subsequent neuromuscular and cardiovascular effects were determined from a dose equal to 3 times the ED90 of muscle relaxant. Org NC 45, pancuronium, metocurine, and d-tubocurarine produced a neuromuscular blockade with a during (time from relaxant administration until recovery 50% of the original twitch tension) of 42 +/- 2, 108 +/- 10, 109 +/- 21, and 100 +/- 19 minutes, respectively. Org NC 45 caused no significant cardiovascular changes. Pancuronium increased heart rate, mean arterial blood pressure, cardiac output, and pulmonary wedge pressure, and it decreased systemic vascular resistance (p less than 0.05). Although metocurine also increased heart rate and cardiac output (p less than 0.05), mean arterial blood pressure and pulmonary wedge pressure did not change. d-Tubocurarine decreased all cardiovascular parameters except heart rate which increased significantly (p less than 0.05). We conclude that Org NC 45 produces a neuromuscular blockade of shorter duration with fewer cardiovascular changes than that of pancuronium, metocurine, or d-tubocurarine.

Animals↗

PubMed1981

Use of pancuronium in children with congenital heart disease.

Dosage of pancuronium required to produce 90% neuromuscular blockade, time of onset of action of pancuronium and changes in heart rate and arterial pressure were evaluated in 30 children with congenital cardiovascular disease during intravenous anesthesia. Neuromuscular blockade was measured using train-of-four stimulation (2 Hz for 2 seconds) and twitch count. The 90% blockade was defined as being one twitch felt on the stretched abducted thumb. In 10 children given 0.03- to 0.01-mg/kg increments of pancuronium at 2-minute intervals the mean (+/-SD) dose required to produce 90% neuromuscular blockade was 0.10 +/- 0.02 mg/kg with a range from 0.08 to 0.14 mg/kg. In 20 children given 0.1 mg/kg of pancuronium, 90% neuromuscular blockade was achieved in 4.45 +/- 1.58 minutes. Children less than 2 years of age did not differ from the older children nor did cyanotic children differ from the acyanotic children. There were no significant changes in heart rate or arterial pressure. In one case bigeminy during intubation was seen. No children had tachycardia after pancuronium.

Blood Pressure↗

PubMed1977

[On the inhibition of cholinesterases by pancuronium (author's transl)].

1. The inhibition by pancuronium of acetylcholinesterase (AChE) and of plasma cholinesterase (ChE) was investigated in vitro regarding a) the sensitivity of both enzymes; b) the mechanism and constants of inhibition; and c) the relationship between the neuromuscular blocking and the anticholinesterase activity of pancuronium. 2. Pancuronium is a reversible inhibitor of both AChE and ChE. The inhibitory potency regarding ChE ([I]50=2.7 X 10(-7) M; Ki=4.2 X 10(-8) M) is highly selective and about 1000-fold higher than compared to AChE ([I]50=2.4 X 10(-4) M; Ki=3.5 X 10(-5) M). 3. The kinetic analysis by means of an Lineweaver-Burk plot and an Arunlakshana-Schild plot displayed a pure competitive mechanism of inhibition. 4. The inhibition of AChE and ChE is thought to be induced by a reversible binding of pancuronium to the anionic subsite of the active center, thus decreasing the formation of the primary enzyme-substrate complex. 5. The clinical administration of pancuronium for muscular relaxation during anaesthesia (0.01-0.08 mg/kg) will result in a concentration of approximately 10(-7)=10(-6) M in the extracellular fluid. Thus, an inhibition of plasma ChE can be expected to occur under clinical conditions, however, probably without practical significance.

Cholinesterase Inhibitors↗

PubMed1996

Effects of pipecuronium and pancuronium on cerebrospinal fluid pressure in neurosurgical patients.

Arterial hypertension and/or tachycardia may alter intracranial pressure in neurosurgical patients. We compared the effects of pancuronium 0.1 mg/kg and pipecuronium 0.1 mg/kg given as i.v. bolus on cerebrospinal fluid (CSF) pressure in 2 groups of 10 patients each scheduled for intracranial surgery in the supine position. Before surgery, no patient presented clinical symptoms of elevated intracranial pressure (ICP). Anesthesia was induced and maintained with fentanyl and midazolam. Ventilation with 50% nitrous oxide in oxygen was adjusted to maintain arterial pCO2 at 30-35 mmHg. After induction of anesthesia, CSF pressure was registered via a lumbar subarachnoid catheter before and 3, 5, 10, and 30 min after pipecuronium or pancuronium administration. Hemodynamics were monitored using radial and pulmonary artery catheters. All variables underwent analyses of variance for repeated measures with p < 0.05 considered significant. Mean CSF pressure decreased insignificantly from 15 +/- 5 mmHg (before injection) to 14 +/- 4 mmHg in patients given pipecuronium and from 13 +/- 4 mmHg to 10 +/- 3 mmHg in the pancuronium group without significant differences between the study groups. Heart rate and arterial pressure increased significantly (p < 0.001) in patients given pancuronium but remained stable after pipecuronium. Onset and duration of neuromuscular blockade were comparable between groups. Based on our results, pipecuronium is a safe alternative to pancuronium during neurosurgical procedures in patients without abnormally high intracranial pressure.

Adult↗

PubMed1991

High pancuronium sensitivity of axonal nicotinic-acetylcholine receptors in humans during organophosphate intoxication.

The effect of low-dose pancuronium on neuromuscular transmission was studied in 2 patients during the early and late stages of severe organophosphate intoxication. Single evoked compound muscle action potentials (CMAP) were followed by repetitive discharges and a decrement-increment (D-I) phenomenon with 10-, 20-, and 50-Hz supramaximal nerve stimulation. Intravenous pancuronium, 1 mg, abolished the D-I phenomenon, while the repetitive discharges of the CMAP were only partially reduced. It is postulated, that the disappearance of the D-I phenomenon with persistence of the CMAP repetitive discharges results from blockade of nicotinic-acetylcholine receptors located on the terminal axon responsible for stimulus-induced antidromic backfiring. This response to a very low dose of pancuronium indicates a high sensitivity of the axonal nicotinic-acetylcholine receptor to pancuronium in humans, as had been previously postulated from animal experiments.

Evoked Potentials↗

PubMed1987

Pancuronium and gallamine are antagonists for pre- and post-junctional muscarinic receptors in the guinea-pig lung.

The effects of atropine, pancuronium and gallamine were tested on pre- and post-junctional muscarinic receptors in the lung. Inhibition of bronchoconstriction induced by intravenous injection of acetylcholine (ACh) was used as a measure of post-junctional receptor blockade. All three antagonists reduced ACh-induced bronchoconstriction. The effects were dose-related for atropine and pancuronium and complete inhibition was obtained with 0.01 mg/kg and 10 mg/kg respectively. Gallamine was much less potent than the other two drugs; the inhibitory effect was not dose-related and never exceeded 50% even at a dose of 10 mg/kg. In contrast, blockade of pre-junctional inhibitory muscarinic receptors in pulmonary parasympathetic nerves by these three antagonists, produced potentiation of bronchoconstriction induced by vagal-nerve stimulation. Consequently, the effect of the three antagonists on vagally-induced bronchoconstriction is dependent on the balance between their pre- and post-junctional blocking activity. Gallamine was the most effective and atropine the least effective antagonist for potentiating nerve-induced bronchoconstriction. At doses which produce 100% neuromuscular blockade, both pancuronium (0.04 mg/kg) and gallamine (4 mg/kg) potentiated vagally-induced bronchoconstriction. At these doses, pancuronium doubled and gallamine caused a four-fold increase in vagally-induced bronchoconstriction, despite partial concurrent blockade of muscarinic receptors in the smooth muscle of the airways.

Acetylcholine↗

PubMed1976

The cardiovascular effects of diazepam and of diazepam and pancuronium during fentanyl and oxygen anaesthesia.

The cardiovascular effects of diazepam 0.5 and 1.0 mg/kg and diazepam with pancuronium 0.1 mg/kg after fentanyl 0.5 mg/kg were determined in thirteen dogs premedicated with atropine. Fentanyl produced significant reductions in heart rate, cardiac ouptut and arterial blood pressure. Administration of 0.5 mg/kg of diazepam after fentanyl did not significantly alter stroke volume, arterial blood pressure or peripheral vascular resistance but did increase heart rate and cardiac output. Additional diazepam did not further change the heart rate, but did reduce stroke volume, cardiac output, arterial blood pressure and peripheral vascular resistance. Administration of pancuronium after fentanyl and diazepam produced marked elevations in heart rate, cardiac output and arterial blood pressure. There was no difference in mean heart rate and cardiac output when values prior to fentanyl and those obtained three minutes following pancuronium were compared. These data demonstrate that large doses of fentanyl decrease heart rate, cardiac these changes can be partially reversed with diazepam 0.5 mg/kg and completely antagonized with pancuronium 0.1 mg/kg.

Anesthesia, Inhalation↗

PubMed1979

Pancuronium for rapid induction technique for tracheal intubation.

Suxamethonium in a dose of 2 mg.kg-1 was compared to pancuronium in three different dosages (0.1 mg.kg-1, 0.15 mg.kg-1, 0.2 mg. kg-1) for a rapid induction (crash) technique for tracheal intubation. Pancuronium 0.1 mg.kg-1 was inferior to suxamethonium, but the larger doses of pancuronium were equally satisfactory. In those instances where suxamethonium is either contraindicated or undesirable, pancuronium in a dose of 0.15 mg.kg-1 is a suitable alternative for rapid induction for tracheal intubation.

Adult↗

PubMed1981

Cardiovascular effects of pancuronium in patients anaesthetized with enflurane and fluroxene.

The effects of pancuronium on the blood pressure and pulse rate were investigated in patients anaesthetized with either fluroxene or ethrane prior to the surgical procedure. At surgical levels of fluroxene anaesthesia, pancuronium increased the blood pressure and pulse rate significantly. In the patients anaesthetized with ethrane, the blood pressure did not change and the pulse rate rose only temporarily and to a less significant level. Analysis of the changes in pulse rate shows that the greater increase produced by fluroxene was due in part to the initial bradycardic effect of this anaesthetic. However the consistent elevation of blood pressure in this group can only be explained by sympathetic stimulation produced by fluroxene and unmasked by pancuronium. Previous administration of atropine suppresses the effect of pancuronium regardless of the anaesthetic in use.

Anesthesia↗

PubMed1987

The effect of pancuronium on the solubility of aqueous thiopentone.

In this study we identified the precipitate formed when pancuronium bromide (pH 3.9) and sodium thiopentone (pH 10.6) are combined in vitro. A precipitate formed when sufficient pancuronium was added to thiopentone to decrease the pH below 9.25. The precipitate was isolated, redissolved in alkaline solution and identified as thiopentone using ultraviolet spectrophotometry. Pancuronium was soluble in water in the pH range of 2.0 to 12.0, whereas thiopentone was soluble in water only at a pH greater than 9.90. We conclude that thiopentone precipitates when combined with pancuronium because of a pH-dependent decrease in the solubility of thiopentone, rather than a chemical interaction.

Anesthesia↗

PubMed1988

A comparative evaluation of intubating doses of atracurium, d-tubocurarine, pancuronium and vecuronium in children.

To determine the onset and recovery times and haemodynamic effects of intubating doses of atracurium (0.4 mg.kg-1), d-tubocurarine (0.8 mg.kg-1), pancuronium (0.12 mg.kg-1), and vecuronium (0.07 mg.kg-1), sixty-seven children aged one to eight years were studied under halothane and nitrous oxide anaesthesia. The time to maximum twitch depression and the time to recovery to T1/Tc 25 per cent were recorded with an integrated evoked EMG recorder. The heart rate and systolic blood pressure were recorded for five minutes after drug administration and prior to intubation. There was no difference in onset times between drugs. The recovery time to T1/Tc 25 per cent following vecuronium (25.5 +/- 6.3 min) was shorter than following atracurium (37.5 +/- 7.0 min). Recovery times for d-tubocurarine and pancuronium were greater than sixty minutes. Elevation of heart rate occurred after administration of pancuronium (+29.8 per cent to +38.6 per cent) and d-tubocurarine (+31 per cent to +34.9 per cent), but no change was observed after atracurium or vecuronium. Elevation of blood pressure was greatest following pancuronium (+10.8 to +14.8 per cent). No significant change was observed following atracurium or vecuronium. A transient lowering of blood pressure (-9.3 per cent) occurred following d-tubocurarine.

Atracurium↗

PubMed1994

A comparison of pipecuronium with pancuronium on haemodynamic variables and plasma catecholamines in coronary artery bypass patients.

Pipecuronium bromide, a new neuromuscular relaxant with steroidal structure, is devoid of effects on the autonomic nervous system and may be useful in patients where haemodynamic stability is mandatory. However, tracheal intubation may alter this haemodynamic profile. Therefore, we carried out a prospective double-blind study in 30 patients undergoing coronary artery bypass surgery with the purpose (1) of determining if intubation influenced the haemodynamic stability in patients paralyzed with pipecuronium and (2) of comparing plasma catecholamine concentrations after pipecuronium with those after pancuronium. Thirty patients were randomized into two groups receiving either pipecuronium 100 micrograms.kg-1 or pancuronium 150 micrograms.kg-1 after induction of anaesthesia with midazolam and fentanyl. Haemodynamic variables and plasma catecholamines were measured before and after induction, after the muscle relaxant three times and twice after intubation. After anaesthesia induction decreases in heart rate (HR), mean arterial pressure (MAP) and cardiac index (CI) were observed in both groups. These haemodynamic variables were unchanged after pipecuronium whereas after pancuronium HR increased from 53 +/- 11 b.min-1 to 64 +/- 9 b.min-1 after induction (P < 0.05) and CI from 2.5 +/- 0.5 L.min-1 to 3.0 +/- 0.8 L.min-1 (P < 0.05). Furthermore ECG signs of myocardial ischaemia appeared in four patients after pancuronium and the decay of plasma norepinephrine concentration was slower than with pipecuronium. We conclude that pipecuronium given after induction of anaesthesia is free of sympathomimetic or vagolytic activity and does not influence haemodynamic variables for up to ten minutes after tracheal intubation.

Anesthesia, Intravenous↗