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PubMed1994

[Antagonism to neuromuscular effect of subcutaneous administration of pancuronium by neostigmine].

It has been reported that subcutaneous administration of pancuronium produces prolonged neuromuscular blockade. The purpose of this study was to evaluate the antagonistic effect of neostigmine on neuromuscular blockade following subcutaneous injection of pancuronium in anesthetized patients. Fourteen male patients aged 32-67 yr, weighing 50-58 kg, and scheduled for surgical operation lasting more than 6 hr were included in the study. None of the patients had paresis. Anesthesia was induced with thiamylal and SCC. Patients under N2O-oxygen-enflurane (1.0-1.5%) anesthesia, were divided into two groups (n = 7 in each group). Group A was given an intravenous bolus of pancuronium 6 mg. Group B received pancuronium 6 mg subcutaneously in the ankle. Train-of-four responses were evaluated every 12s by measuring the force of thumb adduction produced in response to supramaximal stimulation of the ulnar nerve at the wrist. When the train-of-four ratios recovered to approximately 0.2 in groups A and B, a mixture of neostigmine 1.0 mg and atropine 0.5 mg was administered. The onset of fade in train-of-four responses was significantly more rapid in group A (intravenous administration) than in group B (subcutaneous administration). Time intervals to maximum train-of-four depression from pancuronium administration in groups A and B averaged 2.6 and 125.4 min, respectively. No significant differences in the recovery times of the train-of-four ratios from 0.2 to 0.7 following neostigmine administration in groups A and B were demonstrated. None of the patients who received pancuronium subcutaneously showed recurarization following neostigmine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1996

Potentiation of atracurium by pancuronium during propofol-fentanyl-N2O anesthesia.

At the end of abdominal surgery deep neuromuscular blockade is required for peritoneal closure. Ideally injecting an intermediate acting drug like atracurium after a long acting drug such as pancuronium should deepen the neuromuscular block without the fear of an inadequate reversal at the completion of surgery. Thirty patients ASA I or II status, without known allergy to myorelaxant and without neuromuscular, hepatic or renal failure were included in this study. Anesthesia was induced and maintained with propofol, fentanyl, and N20. Normal core temperature was maintained by active warming of the upper part of the body. Blood electrolytes and the acid-base status were within the normal range. The accelerographic responses to Train-Of-Four supramaximal stimulation (TOF) of the ulnar nerve was monitored at the thumb. After obtaining a stable response with the accelerograph, the patients randomly received pancuronium (0.10 mg.kg-1, group I, n = 10 and group II, n = 10) or atracurium (0.50 mg.kg-1, group III, n = 10). An additional dose of atracurium (0.16 mg.kg-1, group I and III) or pancuronium (0.03 mg.kg-1, group II) was injected when the first response of TOF stimulation (T1) reached 25% of its initial value. Then the time to obtain a 25% twitch height of T1 (T25), the recovery index (RI 25-75), the delay to obtain 4 responses to TOF and an adequate recovery [TOF ratio of 0.70 (TOF70)] were monitored. Injection of 60% ED95 of atracurium after pancuronium resulted in a similar recovery of neuromuscular function as after 45% ED95 of pancuronium as shown by the same recovery of T25 (66.5 +/- 4.2 min versus 71.4 +/- 7.8 min, group I versus group II, p > 0.05) and TOF70 (131.6 +/- 15.7 min versus 144.0 +/- 17.5, group I versus II, p > 0.05). Nevertheless the RI 25-75 of group I was of intermediate duration between those of group II and III. Electrolytes and acid-base status were similar between groups at the beginning of surgery. Thus this study shows a synergistic effect of the combination of atracurium after pancuronium occurring in non hypothermic patients anesthetized without halogenated agents. Because the duration of action of the drug administered first governs the duration of action of the subsequent neuromuscular myorelaxant, the neuromuscular function should be closely monitored at the end of surgery if neuromuscular drugs are used in combination.

Anesthetics, Inhalation↗
PubMed1997

[Drug onset time of atracurium after pancuronium priming in elderly patients].

Synergism occurs between some combinations of non-depolarising muscle relaxants. To test the effect of pancuronium as a priming dose of atracurium, 45 adults were anaesthetised with 25 micrograms/kg alfentanil. 75 micrograms/kg midazolam, and 0.25 mg/kg edomidate, O2/N2O and enflurane, and were randomised to one of three groups. After induction, 15 patients received 0.5 mg/kg atracurium, 15 were primed with 0.075 mg/kg atracurium and another 15 with 0.0125 mg/kg pancuronium and three minutes later 0.45 mg/kg atracurium. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG) by stimulating in a TOF pattern. Times for tI reduction of 75, 50, 25 and 0% and tI recovery to 10% were taken. There were no differences between the two groups that received only atracurium. The pancuronium priming group showed a significantly faster onset of neuromuscular blockade (tI = 0%: control group I: 76.3 +/- 15.4 sec vs. pancuronium group III: 64.3 +/- 11.3 sec) and a prolonged recovery. Pancuronium priming can shorten the onset time of atracurium while atracurium priming alone showed no shortening. This suggests a synergism for pancuronium priming in combination with atracurium.

Adult↗
PubMed1980

Pancuronium and abnormal abdominal roentgenograms.

Pancuronium bromide treatment in severely ill, mechanically ventilated infants has been shown to result in lower peak transpulmonary pressure, with an accompanying lower-than-expected incidence of pneumothorax. Infants, treated with pancuronium often demonstrate an ominous abdominal roentgenographic finding: the "gasless abdomen." Of 38 mechanically ventilated infants, 22 of 24 pancuronium-treated infants (as compared with four of 14 untreated infants) had diminished or absent bowel gas. There was no significant difference between the two groups with regard to birth weight, mortality, or incidence of respiratory distress syndrome. Pancuronium prevents swallowing of air but does not inhibit gut peristalsis, thus accounting for the evacuation of abdominal gas three hours or more after administration of the drug. Clinicians who treat infants with pancuronium should be aware of the phenomenon, to avoid needless roentgenographic studies.

Gases↗
PubMed1995

A quantitative study of the pancuronium antagonism at the motor endplate in human organophosphorus intoxication.

Nine patients with organophosphorus (OP) intoxication developing neuromuscular transmission defects were given pancuronium 1, 2, or 4 mg intravenously (IV). Thirteen patient controls with hypoxic encephalopathy received similar dosages. The responses were monitored electrophysiologically using single and repetitive nerve stimulation (20 and 50 Hz). In OP patients, pancuronium did not alter the amplitude of the single CMAP, whereas its repetitive discharges were reduced. Severe neuromuscular blocks were reversed only partially by pancuronium 4 mg. In less severe blocks, 1 and 2 mg resulted in marked improvement. In the patient controls, pancuronium 4 mg induced a severe neuromuscular block but not with 1 and 2 mg. Pancuronium dosages necessary to reverse severe OP-induced neuromuscular blockade produce a neuromuscular block when AChE activity is normal. Low dosages have little effect on normal neuromuscular transmission, but improve the block to a mild degree and may be useful as part of treatment in OP intoxications.

Acetylcholinesterase↗
PubMed1979

Pancuronium blood level monitoring in patients with tetanus.

Overdosage of muscle relaxant has been given as a possible explanation for the hypotensive episodes occurring during the management of tetanus. The aim of the present work was to study the pharmacokinetics of pancuronium during long term infusion. Pancuronium was administered to eight patients with severe tetanus for a period varying from 8 to 24 days. The concentration of pancuronium was measured daily in plasma and urine using a fluorimetric method. The plasma concentration varied from 0.27 to 0.48 microgram/ml. No tendency to accumulation was observed. The plasma concentration fell rapidly below the level associated with muscle relaxation when pancuronium was discontinued. This absence of accumulation can be explained by a rapid elimination of pancuronium through the kidney according to a process of ultrafiltration.

Adolescent↗
PubMed1977

Dual action of pancuronium on succinylcholine block.

The effects of pretreatment with both sub-paralyzing and paralyzing doses of pancuronium and d-tubocurarine, on the onset and duration of succinylcholine-induced neuromuscular blockade were evaluated and compared in 225 patients. D-tubocurarine antagonized both onset and duration of succinylcholine block, while pancuronium produced a dual effect, antagonizing the onset and potentiating the duration of succinylcholine block. Pretreatment with d-tubocurarine (0.07 mg/kg, 0.3 mg/kg and 0.6 mg/kg) increased the time to onset of succinylcholine paralysis from 28 to 118%, and decreased the duration from 16 to 37%. Pancuronium (0.02 mg/kg, 0.04 mg/kg and 0.08 mg/kg) also antagonized the onset of succinylcholine paralysis with increases of 32 to 114%, but potentiated its duration from 30 to 103% compared with succinylcholine alone in the same patients. Although pancuronium markedly inhibited serum cholinesterase in vitro (I50=5 X 10(-7) mol) there was only a 10% inhibition of cholinesterase in vivo after pancuronium 0.08 mg/kg.

Adult↗
PubMed1982

Resistance to pancuronium in an asthmatic patient treated with aminophylline and steroids.

A 17 year old male with a history of bronchial asthma was admitted to the intensive care unit in severe respiratory distress. During a two week period of intensive respiratory care he received large doses of aminophylline and corticosteroids. In addition, pancuronium was given to facilitate ventilation and to reduce airway pressure. Large doses of pancuronium, as much as 5 mg/hr, were required to stop spontaneous respiratory efforts and restlessness. The total pancuronium dose given during the two week period was 800 mg. One hour after pancuronium was discontinued the patient could open his eyes and move his lips. Peripheral nerve stimulation indicated partial paralysis which improved promptly following a test dose of edrophonium. The authors speculate the aminophylline, which is a known inhibitor of the enzyme phosphodiesterase, raised the level of c-AMP and, in turn, the level of acetylcholine at the neuromuscular junction and thus antagonized the blocking effect of pancuronium. In addition, the large doses of corticosteroids that the patient had received may have enhanced the release of acetylcholine and further facilitated neuromuscular transmission.

Adolescent↗
PubMed1995

Left ventricular regional wall motion and haemodynamic changes following bolus administration of pipecuronium or pancuronium to adult patients undergoing coronary artery bypass grafting.

The objective of this study was to compare the haemodynamic and myocardial effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting (CABG) during benzodiazepine/sufentanil anaesthesia. Twenty-seven ASA III-IV patients received lorazepam (1-3 mg) po and midazolam ( < 0.1 mg.kg-1) i.v. before induction of anaesthesia with sufentanil (3-8 micrograms.kg-1) was administered to facilitate tracheal intubation. According to random allocation, each patient received either pipecuronium (150 micrograms.kg-1) or pancuronium (120 micrograms.kg-1) after sternotomy but before heparinization. Mean arterial pressure, central venous pressure (CVP), pulmonary artery pressure (PAP), ST segment position and ECG (leads III, V5, AVF) were monitored continuously throughout the procedure. Thermodilution determinations of CO in triplicate were made immediately before, and at two and five minutes after muscle relaxant administration. Multiplane transoesophageal echocardiography (TEE, midpapillary short axis views of the left ventricle) images were continuously recorded from ten minutes before until ten minutes after muscle relaxant administration and graded by two experienced echocardiographic readers. Heart rate, MAP and CO increased after administration of pancuronium (by 13.6 beats.min-1, 10.8 mmHg and 1.0 L.min-1 respectively) but not after pipecuronium (P < 0.05). Evidence of myocardial ischaemia was not detected in any patients using ECG ST segment analysis or TEE assessment of left ventricular wall motion. We conclude that pancuronium caused increases in HR, MAP and CO but that neither pancuronium nor pipecuronium caused myocardial ischaemia.

Adult↗
PubMed1983

Neostigmine antagonism of succinylcholine phase II block: a comparison with pancuronium.

To assess the efficacy of neostigmine antagonism of succinylcholine phase II block, succinylcholine infusions were given to 17 patients for durations varying from 44 to 192 minutes. A control group (17 patients) received a pancuronium infusion for similar times. Ninety per cent neuromuscular block was maintained in these two groups by adjustment of the infusion rates and, in a third group, with intermittent doses of pancuronium. Neuromuscular transmission was monitored with train-of-four stimulation every 12 seconds and anaesthesia was maintained with N2O-O2-enflurane. Ten minutes after the infusion was stopped, atropine and neostigmine were given to all patients who received pancuronium and to 11 patients in the succinylcholine group whose train-of-four ratio (T4/T1) was less than 0.7. During the subsequent 15 minutes, recovery was more rapid in the succinylcholine group than in either the pancuronium-infusion or pancuronium-bolus groups. It is concluded that succinylcholine-induced phase II block can be safely and rapidly antagonized with neostigmine.

Adult↗
PubMed1987

Severe cardiovascular changes associated with pancuronium after cardiopulmonary resuscitation and after brain injury.

Severe hypertension, tachycardia or ECG changes have been reported following i.v. administration of pancuronium to patients with pheochromocytoma or bronchial asthma. These cardiovascular changes were explained by an interaction between autonomic effects of pancuronium and elevated serum catecholamines or aminophylline. We noted similar cardiovascular changes associated with i.v. administration of pancuronium in two patients after successful cardiopulmonary resuscitation and in two with midbrain hemorrhage and epidural hematoma. In these patients, pancuronium produced no abnormal cardiovascular changes when given during elective surgery or before the occurrence of midbrain hemorrhage. Thus, ischemic brain damage may play a role in producing the severe cardiovascular changes associated with pancuronium.

Aged↗
PubMed2004

Instability of pancuronium in postmortem blood and liver taken after a fatal intramuscular Pavulon injection.

The present study was designed to determine the stability of pancuronium in postmortem blood and liver during storage. Results were obtained using the method by Kerskes et al. [C.H.M. Kerskes, K.J. Lusthof, P.G.M. Zweipfenning, J.P. Franke, The detection and identification of quaternary nitrogen muscle relaxants in biological fluids and tissues by ion-trap LC-ESI-MS, J. Anal. Toxicol. 26 (2002) 29-34.], modified and validated in our laboratory. Target analytes were isolated after enzymatic hydrolysis followed by solid phase extraction (BondElut C18 column). Internal standardisation was carried out using laudanosine and the target ions were monitored by LC-ESI-MS (monitoring ions m/z 358 for IS and 286 for pancuronium). Materials were taken from a 46-year-old woman, who had been found dead. A syringe (2 ml) and an empty ampoule of Pavulon (4 mg/2 mL) were found in her hand. The residual volume of fluid in the syringe was 0.7 ml. An autopsy was performed six days after death. It revealed a needle mark on the left thigh. Postmortem materials (muscle from the injection site, blood and liver) and the syringe with fluid were stored for four months in a freezer at -20 degrees C. The initial pancuronium concentrations were 81 ng/mL in blood and 532 ng/g in liver. The analyte was stable when stored at -20 degrees C in blood even up to seven months. In liver samples its concentrations were variable. Pancuronium in blood stored at 20 degrees C underwent degradation very rapidly. After three months of storage these blood samples had concentrations not greater about 10% of the initial value. The degradation patterns of pancuronium depended on temperature and the biological matrix.

Drug Stability↗
PubMed1992

Rapid-sequence intubation of head trauma patients: prevention of fasciculations with pancuronium versus minidose succinylcholine.

INTRODUCTION: Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration. Standard rapid-sequence intubation requires a nondepolarizing blocking agent before succinylcholine administration. HYPOTHESIS: Prevention of fasciculations during rapid-sequence intubation of head trauma patients can be accomplished as safely and effectively with minidose succinylcholine as with a defasciculating dose of pancuronium. DESIGN: A prospective, randomized, double-blind study. SETTING: An inner-city county trauma center with 70,000 patient visits per year. PARTICIPANTS: Sequential adult head trauma patients requiring rapid-sequence intubation who had no contraindications to succinylcholine or pancuronium. INTERVENTIONS: Each head trauma patient requiring rapid-sequence intubation who met the inclusion criteria received standard rapid-sequence intubation maneuvers and lidocaine (1 mg/kg) IV. Patients were randomized to receive either minidose succinylcholine (0.1 mg/kg) or pancuronium (0.03 mg/kg) IV one minute prior to the full paralytic dose of succinylcholine (1.5 mg/kg) IV. Fasciculations were recorded using a graded visual scale. RESULTS: Of 46 patients, eight of 19 (42%) in the pancuronium group and six of 27 (22%) in the succinylcholine group experienced fasciculations. No statistically significant difference in fasciculations was detected between the two groups using chi 2 analysis. Complete relaxation of the cords was present in all but two patients, one in each group. No patient in either group experienced emesis or significant dysrhythmias. CONCLUSION: Pretreatment with minidose succinylcholine causes no greater incidence of fasciculations than pancuronium in rapid-sequence intubation of head trauma patients in an ED setting. Thus succinylcholine may be used as the sole paralytic agent in rapid-sequence intubation of head trauma patients.

Adult↗
PubMed1995

[Tetraparesis in an infant after prolonged administration of pancuronium].

Long-term administration of pancuronium for ventilatory support of adults with ARDS may result in severe tetraparesis, with areflexia and atrophy of distal muscles. This adverse effect occurs rarely in paediatric intensive care units. We describe a case of tetraparesis after prolonged pancuronium infusion in a 9-month-old girl who experienced a severe bronchopneumonia caused by para-influenza virus, requiring endotracheal intubation and mechanical ventilation. To decrease chest wall rigidity, pancuronium was administered over 11 days, with a total dose of approximately 120 mg of pancuronium bromide. The day after discontinuation of the muscle relaxant she had a severe tetraplegia with areflexia, but normal head movements. Electromyography showed a normal neuromuscular transmission. She recovered from tetraplegia three months later. Other causes of peripheral neuropathy were eliminated. Electroencephalograms and head CT-scans were normal. The recovery pattern observed in our patient corresponded to the process of regeneration seen after axonal degeneration. It is suggested that these neuromuscular complications were caused by prolonged high-dosage pancuronium treatment, associated with corticosteroid and aminoglycoside administration.

Bronchopneumonia↗
PubMed1983

[Comparative study of ORG NC 45 and pancuronium during anesthesia].

The muscle relaxant effects of ORG NC 45 and pancuronium were compared in anesthetized patients with normal liver and renal functions. In all patients, the muscle relaxant effect was monitored by measuring the strength of the adductor pollicis muscle elicited by supramaximal stimulation of the ulnar nerve at the wrist. Different modes of administration of the muscle relaxants were used. In order to facilitate tracheal intubation, a dose of 100 mu X kg-1 of ORG NC 45 or pancuronium was administered. This dose was followed or not according to the type of surgery by repeated doses of 25 micrograms X kg-1. The results of this study indicate that ORG NC 45 is much shorter acting than pancuronium, and non cumulative. The dose of 100 micrograms X kg-1 produced adequate conditions for tracheal intubation 3 to 4 min after the administration of the muscle relaxant. The recovery of the muscle strength to 75% of control value was achieved 46 min and 100 min after a single dose of 100 micrograms X kg-1 of ORG NC 45 and pancuronium respectively. The interval of time between repeat injections averaged 20 min for ORG NC 45 and 40 min for pancuronium.

Adolescent↗
PubMed2003

Pancuronium bromide, a non-depolarizing muscle relaxant which promotes apoptosis of blood lymphocytes in vitro.

BACKGROUND: Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function. METHODS: Following isolation, lymphocytes were incubated with pancuronium bromide at a clinically relevant concentration (0.136 micro mol l-1) for 3 h at 37 C in a 5% carbon-dioxide-humidified atmosphere and the frequency of apoptotic lymphocytes was then measured. We also investigated crucial steps in the apoptotic process, including Fas/Fas ligand (FasL) phenotype, intracellular expression of the interleukin-1beta-converting enzyme (ICE) p20, mitochondrial membrane potential (DeltaPsim), generation of mitochondrial reactive oxygen species, and glutathione (GSH) levels. Control experiments were performed incubating cells in the complete culture medium added with the dilution medium of the drug without addition of the drug. RESULTS: Expression of Fas, FasL and ICEp20 was six-fold, four-fold, and five-fold increased, respectively, among pancuronium-treated lymphocytes with respect to control cultures (P = 0.0001). The percentage of cells exhibiting either dissipation of mitochondrial membrane potential or increased production of reactive oxygen species was seven-fold increased following exposure to pancuronium compared with untreated lymphocytes (P = 0.0001). These findings were associated with a decrease in GSH level. In addition, the frequency of apoptotic cells was 10-fold greater among lymphocytes cultured in the presence of the drug with respect to control cultures. (P = 0.0001). CONCLUSION: Our data suggest an apoptogenic effect of pancuronium in vitro at clinically relevant concentration on peripheral blood lymphocytes. This could be implicated in the transient immune suppression following a surgical operation.

Adult↗
PubMed1996

[Profile of the effect of succinylcholine after pre-curarization with atracurium, vecuronium or pancuronium].

OBJECTIVE: The depolarizing muscle relaxant succinylcholine (SCh) may cause several side effects including muscle fasciculations and postoperative myalgia. These can be attenuated or even prevented by prior administration of a non-depolarizing muscle relaxant. A study was conducted to detect any difference between clinically established approaches concerning the successful prevention of muscular side effects and the influence on the time profile of SCh action. METHODS: The study included 64 patients (ASA status I or II) who underwent elective surgery under general anesthesia. The patients were divided into four groups; the demographic data did not differ significantly between the groups (see table 1). Before the injection of SCh (1 mg/kg) for intubation, the control group received saline (K), the other groups 5 mg Atracurium (A), 1 mg Vecuronium (V), or 1 mg Pancuronium (P), respectively. Neuromuscular block was quantified after train-of-four (TOF) stimulation of the tibial nerve by accelerometry at the toe. The first response was used to determine the onset time, duration of effect, and recovery index. It was noted whether SCh led to muscular activity. Postoperatively, patients were asked whether they experienced any muscular sequelae. Statistical significance was assessed at the 5% probability level by the Mann-Whitney-U test and the CHi2 test (Fisher's exact test, if appropriate). RESULTS: SCh caused a complete neuromuscular block in all patients. Most patients in the control group exhibited muscular contractions than in the other groups (see table 2), but only two patients reported light myalgia. There was no statistically significant difference between the four groups in the onset time and the recovery index of SCh. The duration of the effect was significantly reduced by atracurium (7.5 min) or vecuronium (8.2 min) as compared to the placebo (11.8 min) and pancuronium (13.5 min) (see figure). CONCLUSION: The prolonged duration of the SCh effect after pancuronium is probably due to the known inhibition of cholinesterase by pancuronium. The short duration of action after Atracurium and Vecuronium can be explained by the competitive antagonism at the receptor causing an increased amount of unbound SCh. The duration of the SCh effect may be influenced according to clinical needs by the choice of the non-depolarizing muscle relaxant. The significantly reduced duration of complete neuromuscular block after Atracurium or Vecuronium as precurarizing agents may be advantageous in cases where a fast recovery of spontaneous breathing is essential. If a reduction of the SCh blockade has to be avoided, Pancuronium should be selected for prior administration.

Adult↗
PubMed1977

Disposition kinetics of pancuronium bromide in patients with total biliary obstruction.

Plasma concentrations of pancuronium were measured in nine patients undergoing surgery because of total biliary obstruction. When compared with the averaged model-independent pharmacokinetic parameters obtained for normal patients, the terminal half-life of 270 min was more than twice normal (132 min, P less than 0.001); the plasma clearance of 59 ml min-1 was less than half the normal rate for pancuronium (123 ml min-1, P less than 0.003). These significant alterations to the pharmacokinetics of pancuronium were associated with prolongation of neuromuscular blockade. Following a bolus injection of pancuronium 6 mg, there was a mean time of 114 min (normals 70 min, P less than 0.05) before the evoked twitch response had returned to 5% of the control value. The pattern of urinary excretion of the drug and its metabolites did not differ from that of normal patients. To avoid excessive dosage during prolonged surgery for total biliary obstruction, it is recommended that supramaximal nerve stimulation be used to indicate the need for the administration of further doses of pancuronium.

Aged↗