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Comparison of pancuronium and vecuronium for fetal neuromuscular blockade during invasive procedures.

Neuromuscular blocking agents, used to arrest fetal motion for invasive intrauterine procedures, may cause temporary fetal heart rate changes. After 21 invasive procedures using either pancuronium bromide or vecuronium bromide, post-procedure fetal heart rate tracings were retrospectively compared. Pancuronium was associated with an increased fetal heart rate and decreased beat-to-beat variability for 2.5 hours after its use, whereas vecuronium caused no fetal heart rate changes. Vecuronium bromide offers advantages over pancuronium, because the decreased effect on the fetal heart allows better assessment of fetal well-being immediately following invasive intrauterine procedures.

Anemia↗

Prolonged paralysis associated with long-term pancuronium use.

We cared for a 4-year-old patient who had undergone orthotopic liver transplantation and was placed on a ventilator for respiratory distress associated with Pneumocystis carinii pneumonia. The neuromuscular blocking agent pancuronium bromide 1.0-1.2 mg every hour as needed was used to facilitate artificial ventilation for 40 days. On discontinuation of pancuronium, the patient experienced severe, generalized neuromuscular dysfunction. Because no improvement was seen for 2 weeks, the acetylcholinesterase inhibitors edrophonium and pyridostigmine were instituted. Shortly thereafter the patient's condition began to improve. Gradual improvement occurred over 3-4 months and the patient has since returned to baseline neurologic function. We suggest that long-term pancuronium use was the cause of the patient's prolonged paralysis. The improvement experienced after the initiation of antidotal therapy strongly supports our proposal.

Child, Preschool↗

Interaction of the neuromuscular blocking drugs alcuronium, decamethonium, gallamine, pancuronium, ritebronium, tercuronium and d-tubocurarine with muscarinic acetylcholine receptors in the heart and ileum.

Neuromuscular blocking drugs have a high affinity for muscarinic acetylcholine receptors in the heart atria and ileal smooth muscle. In experiments on homogenates, alcuronium, gallamine, pancuronium, tercuronium and ritebronium inhibited the binding of the muscarinic antagonist (3H)quinuclidinyl benzilate (QNB) to rat heart atria with IC50 values of 0.15-0.53 mumol X 1(-1) and to ileal longitudinal muscles with IC50 values of 0.12-0.45 mumol X 1(-1). d-Tubocurarine and decamethonium inhibited (3H)QNB binding to these tissues with IC50 values of 6.2-8.5 mumol X 1(-1). For each neuromuscular blocking drug, the IC50 values were virtually identical for (3H)QNB displacement in the homogenates of the atria and of the ileal muscle. Alcuronium and gallamine differed from the other blocking agents in that they produced less steep (3H)QNB displacement curves both in the atria and the ileal muscle; Hill coefficients for the binding of alcuronium and gallamine to atrial and ileal homogenates were lower than unity. On isolated atria, gallamine, pancuronium, ritebronium and tercuronium antagonized the inhibition of tension development caused by the muscarinic agonist, methylfurmethide, with Kd values which were of the same order of magnitude as the IC50 values for the displacement of (3H)QNB binding to homogenates; the Kd of alcuronium was 12.5 times higher. d-Tubocurarine and decamethonium did not antagonize the effects of methylfurmethide at concentrations up to 100 mumol X 1(-1). On isolated ileal longitudinal muscle, gallamine and pancuronium antagonized the effects of methylfurmethide with Kd values that were 53 times and 100 times higher than their respective Kd values in the atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcuronium↗

Clinical pharmacokinetics of pancuronium bromide.

Plasma concentrations of pancuronium bromide have been studied in seven surgical patients following a 6 mg intravenous bolus injection of the drug for neuromuscular blockade. Concurrently, evoked muscle twitch response was monitored for each patient as a measure of the pharmacodynamic effect of the drug. The plasma decay curve for pancuronium was found to be biphasic and after rigorous statistical analysis the data were interpreted according to a 2-compartment open model. The half-life of the beta-phase varied between 89.5 and 161.5 min. The apparent volume of distribution of the central compartment ranged from 62.9 to145.5 ml/kg and the plasma clearance from 57.6 to 187.3 ml/min. At the first sign of recovery from neuro-muscular blockade the mean pancuronium plasma level was found to be 0.218 mcg/ml. The mean duration of action as measured from time of onset of paralysis to 20% recovery was 83.4 min with the plasma level at 20% being 0.169 mcg/ml corresponding to 45.4% of dose remaining to be eliminated from the body.

Adult↗

Pharmacokinetics of pancuronium in man: a linear system.

Pancuronium in bolus doses of 40 to 350 microgram/kg was administered to surgical patients in order to evaluate the linearity of its pharmacokinetics. The profile of the plasma decay curve and of its urinary elimination were compared with reference to the administered dose. It was possible to superimpose the dose-normalized plasma decay-curves. The parameters of the two compartment-open model used to describe the pharmacokinetics of pancuronium were not influenced by the dose. The elimination half-life was 89 +/- 20 min and the plasma clearance was 1.84 +/- 0.38 ml/min/kg. The profiles of cumulative urinary excretion were also dose-independent. After 6 and 24 h, 57% and 69% of the administered dose, respectively, had been excreted in the urine. The results indicate that the pharmacokinetics of pancuronium is linear.

Adult↗

Pharmacokinetic and pharmacodynamic modelling with pancuronium.

The pharmacokinetics and pharmacodynamics of pancuronium were studied following intravenous infusion in eleven patients undergoing surgical anaesthesia. Measurement of the plasma concentrations (Cp) of the neuromuscular blocking agent ( NMBA ) and the concomitant intensities of paralysis allowed their simultaneous modelling. The pharmacokinetic parameters derived for pancuronium were in the range of previously reported values, except that the mean total systemic plasma clearance (0.79 +/- 0.28 ml X min-1 X kg-1) was reduced and the mean terminal phase half-life (169 min) was longer in these patients. Plasma concentration and % paralysis data were successfully fitted to a previously proposed pharmacodynamic model. This model assumes a separate effect compartment which exchanges drug directly with the central kinetic compartment (integrated effect model). The 'steady-state' Cp necessary to produce 50% paralysis ( ECpss (50] was estimated to be 0.21 +/- 0.08 micrograms X ml-1 (mechanical response) and 0.18 +/- 0.05 micrograms X ml-1 (EMG response). An analysis using the Hill equation of the Cp-response relationship, during and after the constant-rate infusion of pancuronium bromide, resulted in effective plasma concentrations for 50% paralysis ( ECp50 ) of 0.35 +/- 0.06 micrograms X ml-1 and 0.20 +/- 0.09 micrograms X ml-1, respectively, for mechanical twitch response. The corresponding values for EMG response were 0.32 +/- 0.06 micrograms X ml-1 and 0.17 +/- 0.06 micrograms X ml-1. Using this latter approach, the ECp50 estimated during onset of paralysis was significantly higher than that estimated during offset of paralysis (p less than 0.05); no such difference was apparent between this latter parameter and the ECpss (50) of the integrated effect model (p greater than 0.05). No significant differences were observed between any of the pharmacodynamic parameter estimates generated from the data obtained from the two methods of assessment of neuromuscular function (mechanical vs. EMG response) (p greater than 0.05).

Adult↗

Differential potentiation by calcium antagonists of neuromuscular blockade induced by pancuronium and succinylcholine in cats in vivo.

The effects of several calcium antagonists (verapamil, nicardipine and two diltiazem isomers, d-cis and l-cis diltiazem) alone and associated to non-depolarizing (pancuronium) and depolarizing (succinylcholine) neuromuscular blockers, were evaluated on sciatic nerve-tibialis anterior muscle preparations from cats in vivo. The calcium antagonists used (at 0.1 and 0.5 mg/kg iv) did not modify the height of muscular twitches elicited indirectly. However, these agents potentiated in a dose-dependent way the neuromuscular blockade induced by iv pancuronium (2-40 micrograms/kg) and succinylcholine (6-200 micrograms/kg). The order of potency in increasing the effects of pancuronium was nicardipine much greater than d-cis diltiazem greater than or equal to verapamil, whereas the order of potency in enhancing succinylcholine effects was d-cis diltiazem greater than or equal to verapamil much greater than nicardipine. The effects of diltiazem were stereoselective, thus the potentiation induced by d-cis diltiazem was significantly greater in all cases than that induced by l-cis diltiazem, which suggests that calcium channel blockade plays a role in these interactions. However, other mechanisms such as calcium antagonists-induced nicotinic receptor desensitization may also be involved.

Animals↗

Potentiation of pancuronium induced neuromuscular blockade by calcium channel blockers in vitro.

The calcium channel blockers verapamil, methoxyverapamil, diltiazem, and nisoldipine have been tested for interactions with the nondepolarizing muscle relaxant pancuronium bromide by using the indirectly stimulated in vitro preparation of the rat hemidiaphragm. Dose response curves of each calcium channel blocker, pancuronium bromide, and combinations of both were determined. Each of the four calcium channel blocking drugs showed agonistic interaction in potentiating pancuronium induced neuromuscular blockade.

Animals↗

Urine catecholamine excretion after large doses of fentanyl, fentanyl and diazepam and fentanyl, diazepam and pancuronium.

The effects of fentanyl (0.5 mg/kg iv), fentanyl with diazepam (1 mg/kg iv) and fentanyl, diazepam and pancuronium (0.1 mg/kg iv) on heart rate (HR), mean arterial blood pressure (BP), cardiac output (QT), urine flow rate and urine epinephrine and norepinephrine excretion were determined in nine dogs. Fentanyl did not significantly change QT or BP but did reduce HR and urine flow rate (P less than 0.05). Urine epinephrine and norepinephrine excretion rates were signicantly increased by fentanyl (P less than 0.05). Diazepam caused no significant further changes in QT, BP or HR 30 minutes after administration, but urine epinephrine and norepinephrine excretion rates were reduced to control (pre-fentanyl) levels. Addition of pancuronium after fentanyl and diazepam increased urine flow rate to pre-fentanyl levels and elevated QT, BP and HR above controls but produced no significant change in urine epinephrine or norepinephrine excretion. These data suggest that fentanyl increases catecholamine blood levels and imply that the latter may be one mechanism by which cardiovascular dynamics are maintained stable during fentanyl anaesthesia. Our findings also demonstrate that cardiovascular stimulation after pancuronium is not associated with increased urinary catecholamine excretion.

Animals↗

Effect of pancuronium on intraocular pressure changes induced by succinylcholine.

The study was undertaken to evaluate the influence of pretreatment with a small dose of pancuronium on intraocular pressure changes associated with administration of succinylcholine and tracheal intubation. Thirty patients divided into control and study groups were anaesthetized with sodium thiopentone (3-5 mg mg.kg-1) and intubation with the aid of succinylcholine (1 mg.kg-1). The control group received saline pretreatment while the study group received pancuronium 1 mg three minutes before succinylcholine. Anaesthesia was maintained with nitrous oxide and oxygen (70:30). A Schiotz tonometer was used to measure intraocular pressure before induction of anaesthesia, one minute after succinylcholine and immediately after intubation. Patients in the control group demonstrated significant elevation of intraocular pressure at one minute after succinylcholine and immediately after intubation, while the study group showed no significant change at the same observation periods. These findings indicate that pretreatment with pancuronium 1 mg three minutes before succinylcholine may be beneficial in patients with high intraocular pressure and penetrating injuries of the eye.

Adolescent↗

Pancuronium, vecuronium, and d-tubocurarine inhibit and succinylcholine stimulates choline acetyltransferase activity.

The effects of the nondepolarizing muscle relaxants (NDMR), pancuronium, vecuronium, and d-tubocurarine and a depolarizing muscle relaxant, succinylcholine, were studied on choline acetyltransferase (ChAT) activity. A radiochemical assay was used in the determination of ChAT activity using purified placental enzyme. Pancuronium at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 3, 10, 15, 40 and 85 per cent, respectively; vecuronium at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 5, 10, 26 and 57 per cent, respectively; d-tubocurarine at concentrations of 10(-6) M, 10(-5) M, 10(-4) M, and 10(-3) M inhibited ChAT activity by 0, 4, 12.5 and 29 per cent, respectively; whereas succinylcholine at concentrations of 10(-7) M, 10(-6) M, 10(-5) M, and 10(-4) M activated ChAT activity by 8, 10, 1, and 2 per cent, respectively. Even though our present data demonstrated a significant dose-dependent inhibitory effect on ChAT activity by pancuronium, vecuronium and d-tubocurarine, it is unlikely that this inhibitory effect will contribute to the mechanism of action of NDMR. Our data, however, may suggest an additional mechanism for the phenomena of tetanic and train-of-four fades that are seen following the administration of nondepolarizing muscle relaxants.

Carbon Radioisotopes↗

Neostigmine reversal of D-tubocurarine and pancuronium bromide combinations in man.

This study measured the neostigmine reversal of a non-depolarizing block in 17 patients, each given d-tubocurarine and pancuronium bromide in an alternating sequence. Reversal times were similar to those previously reported for pancuronium bromide alone. It is concluded that the anaesthetist may alternate between d-tubocurarine and pancuronium bromide without fear of difficulty with neostigmine reversal.

Adult↗

The effect of metocurine and metocurine-pancuronium combination on intraocular pressure.

Maintenance of a normal to low intraocular pressure during ocular surgery is of critical importance. The prime considerations for anaesthetic management include adequate depth of anaesthesia, normal carbon dioxide and arterial oxygen tensions, stable cardiovascular status and avoidance of stimuli likely to raise central venous pressure. Non-depolarizing muscle relaxants are associated with a reduction in intraocular pressure. Metocurine, a non-depolarizing relaxant, formerly known as dimethyltubocurarine, has been recently reintroduced into clinical practice. Metocurine has been reported to be 1.8 times more potent than d-tubocurarine and has the clinically advantageous cardiovascular effects of stable heart rate and mean blood pressure with minimal associated histamine release. When combined with pancuronium, metocurine potentiates the neuromuscular blocking properties, so that small doses of both drugs in combination produce effective neuromuscular block. This study was designed to assess the suitability of metocurine 0.3 mg.kg-1 and metocurine 0.08 mg.kg-1 plus pancuronium 0.02 mg.kg-1 as muscle relaxants for ocular surgery. The results demonstrated that metocurine and metocurine-pancuronium combination in the above doses combined with sodium thiopentone 5 mg.kg-1 produced ideal conditions for intubation of the trachea in 4.45 (+/- 0.19 SE) minutes and 4.35 (+/- 0.16 SE) minutes respectively. In both treatment groups intraocular pressure was reduced below control values and a pattern of intraocular pressure stability ideal for ocular surgery was obtained during the 10 minutes observation period. The delayed onset of sufficient paralysis for tracheal intubation - 4.45 (+/- 0.19 SE) minutes for metocurine and 4.35 (+/- 0.16 SE) minutes for the combination - makes these techniques unsuitable for emergency ocular surgery because of the long interval when the airway is unprotected.

Adolescent↗

Comparison of meperidine and pancuronium for the treatment of shivering after cardiac surgery.

Shivering after cardiac surgery can produce adverse haemodynamic and metabolic sequelae. In this study, the metabolic effects of shivering and the efficacy of treatment with meperidine or pancuronium were studied, using a metabolic cart, in 61 patients who had undergone cardiac surgery. The patients received premedication with morphine, perphenazine and diazepam or lorazepam, and were anaesthetised with fentanyl or sufentanil and diazepam. Muscle relaxation was achieved with pancuronium. Patients were monitored with a radial arterial line, pulmonary artery catheter and oesophageal and urinary bladder temperature probes. Rewarming to an oesophageal temperature of 38 degrees C was achieved before the termination of CPB and was maintained for a minimum of 15 min reperfusion time. Every 15 min after surgery, the patients' temperature at three sites (pulmonary artery, oesophagus, bladder) and shivering scores were monitored. Hourly measurements were made of haemodynamic variables (MAP, PAOP, CVP, SVR, PVR, CI), carbon dioxide production, oxygen consumption and respiratory quotient. If the patient shivered, the measurements were recorded prior to drug treatment and repeated 30 min later following randomization to either: meperidine 0.25 mg.kg-1 (Group 1), meperidine 0.5 mg.kg-1 (Group 2) or pancuronium 0.06 mg.kg-1 intravenously (Group 3). Thirty-two patients shivered and mean VO2 and VCO2 values were greater in the shivering group than in the nonshivering patients (VO2 334.8 +/- 17.6 vs. 240.5 +/- 8.8 ml.min-1; VCO2 238.8 +/- 17.2 vs 199.2 +/- 8.4 ml.min-1, P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Accelerated onset and delayed recovery of d-tubocurarine blockade with pancuronium in infants and children.

The effect of age on the onset and duration of action of a d-tubocurarine (DTC) neuromuscular blockade with and without pancuronium priming in children was examined. Sixty ASA physical status I or II patients in three age ranges (0-1 yr, 1-3 yr and 3-10 yr) were anaesthetized with thiopentone, halothane and nitrous oxide. Each patient received either a single paralyzing dose of DTC 0.4 mg.kg-1, or DTC 0.36 mg.kg-1 preceded three minutes earlier by pancuronium 0.007 mg.kg-1. Evoked force of contraction of the adductor pollicis was measured using train-of-four stimulation applied every 12 sec. Time to 90 per cent first twitch depression after a single dose of DTC increased with increasing age (r = 0.65, p less than 0.01), and was 1.6 min (SEM +/- 0.3) in the 0-1 yr group, 1.9 +/- 0.3 min (1-3 yr), and 5.2 +/- 1.2 min (3-10 yr). Time to ten per cent spontaneous recovery after single dose DTC was shorter in older individuals (r = 0.40, p less than 0.05), being 36.4 +/- 5.1 min in infants 0-1 yr, 30.6 +/- 4.6 min (1-3 yr), and 24.0 +/- 2.7 min (3-10 yr). Priming with pancuronium accelerated the onset significantly in all age groups with 90 per cent T1 depression occurring at 0.7 +/- 0.1 min (0-1 yr), 0.9 +/- 0.1 min (1-3 yr), and 2.1 +/- 0.6 min (3-10 yr). However, priming delayed recovery, especially in infants.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

Cyclosporine-pancuronium interaction in a patient with a renal allograft.

A case is described of a 54-year-old 55 kg patient who presented for clipping of a middle cerebral aneurysm two years after a successful renal allograft. Immunosuppression was maintained with azathioprine 100 mg daily, cyclosporine 300 mg daily and prednisone 10 mg daily. The patient had chronic hypertension controlled with nifedipine 40 mg daily and furosemide 20 mg daily. The cyclosporine level taken on the morning of surgery was 166 micrograms.L-1. Induction of anaesthesia consisted of fentanyl 350 micrograms, thiopentone 125 mg and pancuronium 5.5 mg. Anaesthesia was maintained with nitrous oxide 70 per cent in oxygen and isoflurane 0.5-1.5 per cent. No additional doses of pancuronium were given during the four hour surgical procedure. At the end of surgery, four twitches were present with train-of-four stimulation, but evidence of residual muscle paralysis was present. Residual neuromuscular blockade was reversed with atropine 1.2 mg and neostigmine 2.5 mg. Residual paralysis was present in the Recovery Room and edrophonium 10 mg was given prior to extubation. Clinical testing demonstrated adequate reversal of neuromuscular blockade. Twenty minutes following extubation, increasing respiratory distress was noted. There was clinical evidence of muscle paralysis. The patient was re-intubated. It is proposed that cyclosporine potentiated the pancuronium blockade producing prolonged neuromuscular relaxation resulting in residual paralysis following surgery. The potential interactions of cyclosporine and muscle relaxants deserve further study.

Anesthetics↗

Lack of effects of d-tubocurarine and pancuronium on the slow action potential of the guinea pig papillary muscle.

Inotropic effects of non-depolarizing muscle relaxants were examined with guinea pig ventricular papillary muscle depolarized to -47 mV in high K Ba-Tyrode solution. Field stimulation of 0.1 Hz elicited the slow action potential, a measure of the calcium current. The amplitude, the duration at 0 mV level and dV/dt of the action potential were monitored together with the contractile tension. Amelizol (3 mg X ml-1 d-tubocurarine (d-tc) and 5 mg X ml-1 chlorobutanol) depressed the four functions in a dose-dependent manner, while crystalline d-tc did not. Chlorobutanol (the antimicrobial preservative) had the same effects as Amelizol. Neither Mioblock (2 mg X ml-1 pancuronium and unpublished preservative) nor crystalline pancuronium altered the functions. These findings suggest that the negative inotropic effect of Amelizol is not due to d-tc but to chlorobutanol, which may exert its effect by depressing the calcium current. The lack of change in the slow action potential seen with pancuronium may indicate no direct effect on the calcium current, thereby further suggesting absent direct beta-adrenomimetic action of this agent.

Action Potentials↗

[Cisatracurium in coronary bypass operations--a comparison with pancuronium. Hemodynamic and neuromuscular effects in patients under chronic beta blocker treatment].

OBJECTIVE: The aim of the study was to compare haemodynamic and neuromuscular effects of cisatracurium and pancuronium in patients undergoing coronary artery bypass grafting (ASA III, good or moderately impaired LV function) who were chronically medicated with beta-adrenergic blocking agents. METHODS: 60 Patients were randomly assigned in a double-blind fashion to receive sufentanil/midazolam/etomidate and either pancuronium (2xED95, group P) or cisatracurium (2xED95, group C2 and 4xED95, group C4). Haemodynamic variables were measured using arterial and pulmonary arterial catheters, neuromuscular transmission was measured using electromyography. RESULTS: The heart rate was significantly lower in group C2 (50.2 +/- 6.8 bpm) and in group C4 (54.3 +/- 11 bpm) than in the pancuronium group (62.4 +/- 13.2 bpm) 3 min after induction of anaesthesia and until 60 min after induction. None of the other haemodynamic parameters showed any difference between groups. Onset time was 5.22 +/- 3.43 min in group P, 6.42 +/- 2.1 min in group C2 and 2.92 +/- 1.2 min in group C4. CONCLUSION: Under high-dose opioid induction, bradycardia must be considered if cisatracurium is administered to cardiac surgery patients.

Adolescent↗