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Neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium.

To compare the time course of neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium, the authors studied 98 patients anesthetized with nitrous oxide (60%) and halothane or enflurane. Neuromuscular blockade, as monitored by single stimulus-induced twitch tension (TT), was antagonized at varying degrees of spontaneous recovery (2-80% of control TT). Time to antagonism (time from injection of neostigmine or edrophonium to 90% recovery of control TT) was not different between edrophonium, 0.5 mg/kg, and neostigmine, 0.04 mg/kg, when spontaneous recovery had been allowed to occur to at least 11% of control TT prior to antagonist administration (P greater than 0.05). For profound neuromuscular blockade (TT less than or equal to 10% of control) induced by pancuronium or vecuronium, time (mean +/- SD) to antagonism with neostigmine, 0.04 mg/kg, was 7.0 +/- 2.2 min and 5.6 +/- 1.7 min, respectively, while the same for edrophonium, 0.5 mg/kg, was 20.0 +/- 8.0 min and 15.0 +/- 12.5 min, respectively (P less than 0.05). Time to antagonism of profound atracurium-induced neuromuscular blockade was 8.5 +/- 3.3 min for neostigmine, 0.04 mg/kg, and 9.8 +/- 7.0 min for edrophonium, 0.5 mg/kg, (P less than 0.05). For profound vecuronium-and pancuronium-induced neuromuscular blockade, time to antagonism by edrophonium, 1.0 mg/kg, was 4.6 +/- 3.0 min and 3.9 +/- 1.6 min respectively. The authors conclude that neostigmine, 0.04 mg/kg, antagonizes neuromuscular blockade within 12 min when TT is greater than 2% of control at time of reversal. When TT is greater than 10% of control, edrophonium, 0.5 mg/kg, produces similar time to antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Potency of pancuronium at the diaphragm and the adductor pollicis muscle in humans.

The measurement of force of contraction of the adductor pollicis muscle following supramaximal stimulation of the ulnar nerve has become a standard method to assess the effect of neuromuscular blocking drugs. However, the diaphragm is regarded as resistant to these drugs, and considerable residual respiratory power might still be present after total block of adductor pollicis function. To quantify this differential effect, train-of-four stimulation was applied to the ulnar and the phrenic nerves in patients under N2O-halothane anesthesia. The force of contraction of the adductor pollicis muscle was measured with a force-displacement transducer and compared with the diaphragmatic electromyogram (EMG). Pancuronium cumulative dose-response curves for both muscles were determined in 10 ASA Class I adults. The mean dose (+/- SEM) required to depress adductor pollicis and diaphragm responses to first twitch stimulation (ED50) was 29.5 +/- 3.5 micrograms/kg and 59.5 +/- 7.0 micrograms/kg, respectively. Corresponding values for ED90 were 45 +/- 5 micrograms/kg and 95 +/- 11 micrograms/kg, respectively, indicating that the diaphragm required approximately twice as much pancuronium as the adductor pollicis block, the diaphragm was only 24 +/- 4% blocked. It is concluded that the adductor pollicis response might underestimate the degree of diaphragmatic relaxation. On the other hand, the administration of pancuronium in a dose sufficient to produce total paralysis might result in the inability to antagonize neuromuscular block in all muscles.

Adult↗

Pancuronium and vecuronium pharmacokinetics and pharmacodynamics in younger and elderly adults.

To evaluate the effect of aging on the distribution, metabolism, and neuromuscular junction sensitivity to pancuronium and vecuronium, the authors determined the pharmacokinetics and pharmacodynamics of these drugs in 12 healthy elderly subjects (70-84 yr) and 12 young adults (30-57 yr) during halothane-nitrous oxide anesthesia. Plasma concentrations of the muscle relaxants were determined using a selective ion-monitoring mass spectrometric technique specific for the parent compound. For vecuronium, plasma clearance (3.7 +/- 1.0 and 5.2 +/- 0.8 ml X kg-1 X min-1, respectively), and volume of distribution at steady-state (179 +/- 31 and 244 +/- 38 ml X kg-1, respectively) were lower in the elderly than in young adults; values for distribution half-lives, elimination half-life, and sensitivity of the neuromuscular junction were similar for the two groups. For pancuronium, there were no statistically significant differences between groups for these pharmacokinetic or pharmacodynamic parameters. However, there was a trend toward reduced clearance (20%) and prolonged elimination half-life (16%) in the elderly as compared to the younger patients. The authors conclude that healthy elective surgical patients between the ages of 70 and 84 yr of age do not differ markedly from younger adults in their pharmacokinetic/pharmacodynamic response to vecuronium and pancuronium.

Adult↗

The potency of pancuronium at the adductor pollicis and diaphragm in infants and children.

To measure the potency of pancuronium at the diaphragm and adductor pollicis in infants and children, train-of-four stimulation was applied to the ulnar and phrenic nerves under N2O-halothane anesthesia. The force of contraction of the adductor pollicis was measured and compared with the diaphragmatic electromyogram (EMG). Cumulative dose response curves were determined for pancuronium in 18 patients divided equally into three age groups: 0-1 yr, 1-3 yr, and 3-10 yr. The potency of pancuronium at both muscles decreased with increasing age (P less than 0.05), while the adductor pollicis:diaphragm potency ratio remained constant. The mean doses (+/- SEM) required to depress adductor pollicis first twitch responses by 90% (ED90) were 42 +/- 3.3 micrograms/kg in the 0-1-yr group, 47 +/- 4.2 micrograms/kg in the 1-3-yr group, and 62 +/- 4.1 micrograms/kg in the 3-10-yr group. Corresponding figures for the diaphragm were 70 +/- 4.3 micrograms/kg, 81 +/- 5.1 micrograms/kg, and 101 +/- 4.4 micrograms/kg, respectively. The ED90 ratios (diaphragm ED90/adductor pollicis ED90) in the three age groups were 1.69 +/- .07, 1.75 +/- .14, and 1.64 +/- .09, respectively. These results are consistent with similar rates of maturation of the diaphragm and the adductor pollicis muscles in infancy and childhood. Thus, train-of-four monitoring of the adductor pollicis is likely to overestimate the degree of neuromuscular blockade of the diaphragm in pediatric patients.

Aging↗

Atracurium, vecuronium, and pancuronium do not alter the minimum alveolar concentration of halothane in humans.

The authors studied 64 unpremedicated, healthy surgical patients, aged 42 +/- 14 yr, to determine the effects of atracurium, vecuronium, and pancuronium on the minimum alveolar concentration (MAC) of halothane. Anesthesia was induced using halothane/nitrous oxide/oxygen via a mask without the administration of other drugs. Nitrous oxide was discontinued, the trachea was intubated without prior administration of neuromuscular blocking drugs, and anesthesia was maintained with halothane in oxygen. Participating patients were assigned to one of five groups: 1) no neuromuscular blocking drug (control group, n = 9); 2) atracurium 0.5 mg/kg (n = 10); 3) atracurium 1.0 mg/kg (n = 15); 4) vecuronium 0.1 mg/kg (n = 20); or, 5) pancuronium 0.1 mg/kg (n = 10). Tourniquets, inflated to 300 mmHg immediately before iv administration of neuromuscular blocking drug and 15-30 min prior to skin incision, were used to isolate extremities from circulating neuromuscular blocking drug in all patients. A positive response to stimulation was defined as movement of at least one extremity occurring distal to the tourniquet within 1 min following skin incision. The first patients in the control and atracurium groups were studied at an end-tidal halothane concentration of 0.95%. The first patient in the pancuronium group was studied at a halothane concentration of 0.75%, and the first patient in the vecuronium group at 0.70%. Subsequent patients were studied at end-tidal halothane concentrations 0.10% above or below that of the preceding patient, depending on the presence or absence of movement with skin incision. Control MAC for halothane was 0.74% +/- 0.09% (mean +/- SEM).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The neuromuscular effects of desflurane, alone and combined with pancuronium or succinylcholine in humans.

The neuromuscular effects of desflurane administered alone were studied in ten healthy human volunteers aged 20-27 yr. Also, the dose-response relationships of pancuronium and succinylcholine in surgical patients during anesthesia with desflurane (n = 13) were compared to those during isoflurane anesthesia (n = 14). In the volunteers, we measured the mechanical response of the adductor pollicis muscle to stimulation of the ulnar nerve in a train-of-four (TOF) sequence at 2 Hz and at tetanic frequencies of 50, 100, and 200 Hz, each administered for 5 s. Amplitudes of the first response (T1) in each TOF sequence and the ratios of the fourth TOF response (T4) to the first were similar at 3, 6, and 9% desflurane and decreased significantly only at 12% (P less than 0.05). Desflurane concentrations of 3-12% caused tetanic fade (greater than 10% decrement in amplitude) at 50, 100, and 200 Hz. The addition of N2O and the duration of anesthetic exposure did not alter desflurane's neuromuscular effects. The only neuromuscular variable influenced by CO2 was T1 amplitude, which decreased as arterial CO2 tension (PaCO2) increased. The doses of pancuronium that depressed T1 amplitude by 50% (ED50) were similar during anesthesia with 1.25 MAC desflurane, 10.5 +/- 2.8 micrograms/kg (mean +/- SD) and 1.25 MAC isoflurane, 12.3 +/- 5.0 micrograms/kg. The ED50 doses of succinylcholine were similar during anesthesia with desflurane 132 +/- 76 micrograms/kg and isoflurane 123 +/- 36 micrograms/kg. We conclude that desflurane significantly depresses neuromuscular function and augments the action of pancuronium and succinylcholine to a degree similar to that of isoflurane.

Adult↗

Pancuronium and the placental barrier.

Maternal and cord levels of pancuronium were estimated using a fluorimetric method in a series of ten patients. Low concentrations of pancuronium (0-04--0-1 microng/ml) were found in all the cord samples analysed, indicating placental transfer of pancuronium.

Adult↗

Nitroprusside and the duration of tubocurarine and pancuronium.

Seventy-six patients in whom sodium nitroprusside was administered in order to induce hypotension received either 0.2 mg/kg tubocurarine or 0.04 mg/kg pancuronium bromide. The duration of action of these two drugs was assessed. In contrast to previous studies in the dog, sodium nitroprusside, given concurrently with either tubocurarine or pancuronium bromide, did not result in significantly prolonged neuromuscular blockade (33.0 vs 28.6 min for tubocurarine and 39.3 vs 39.6 min for pancuronium bromide; P greater than 0.1). These findings suggest that the prolonged neuromuscular blockade which is sometimes associated with trimetaphan-induced hypotension in man, is not encountered with sodium nitroprusside.

Adolescent↗

Comparison of recovery index of rocuronium or vecuronium with simultaneously administered pancuronium in the isolated forearm.

A series of isolated forearm experiments is described in which rocuronium or vecuronium were injected into one arm, and pancuronium injected simultaneously into the contralateral arm. The time for 25%-75% twitch recovery (recovery index) was recorded in both arms. The recovery indices of rocuronium and vecuronium were similar, but that of pancuronium significantly longer. Because the recovery indices compared in any one experiment occurred in the presence of identical background plasma concentration, the differences observed in recovery index between pancuronium and either rocuronium or vecuronium are due to different rates of dissociation from the effect compartment at the neuromuscular junction.

Androstanols↗

Effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium in the cat.

To investigate the effect of different anesthetics on the pharmacokinetics and pharmacodynamics of pancuronium, 120 microgram/kg i.v., cats were anesthetized with either pentobarbital (N = 4), ketamine (N = 4), enflurane (N = 5), or halothane (N = 5). A longer onset time and duration of neuromuscular blockade occurred during enflurane and halothane anesthesia. The apparent elimination half-life was longer and the total voluem of distribution at steady state larger during halothane anesthesia. The plasma concentration of pancuronium required for neuromuscular blockades was less during enflurane than during the other three anesthetics. We conclude that inhalation anesthetics may prolong a neuromuscular blockade by altering both the pharmacokinetics and pharmacodynamics of pancuronium.

Adjuvants, Anesthesia↗

Effect of vecuronium and pancuronium on cardiac performance and transmural myocardial perfusion during ketamine anaesthesia.

The haemodynamic effects of vecuronium and pancuronium were studied in 20 healthy patients during diazepam/ketamine anaesthesia. Anaesthesia was induced with glycopyrrolate 3 micrograms/kg, diazepam 0.3 mg/kg and ketamine 1.0 mg/kg as a bolus and 1.0 mg/kg over 10 min. After induction, anaesthesia was maintained with ketamine infusion 1.0 mg/kg/h. The lungs were ventilated with 50% nitrous oxide in oxygen. Equipotent doses of vecuronium (74 micrograms/kg) or pancuronium (99 micrograms/kg) were administered for intubation. The thoracic impedance, ECG and phonocardiogram were recorded during the induction of anaesthesia. The results suggest that vecuronium has no cardiovascular effects during ketamine anaesthesia, whereas pancuronium due to its chronotropic effect, causes a deterioration in left ventricular performance.

Anesthesia, General↗

Vecuronium and atracurium in the elderly: a clinical comparison with pancuronium.

The intubating conditions, time to complete block and duration of clinical relaxation were observed in a group of 101 elderly patients (aged over 65 years) following pancuronium 0.1 mg kg-1, vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1. The intubating conditions in the three groups were similar when assessed at 2 min following relaxant administration. The time to complete block was shortest with vecuronium (4.3 min) in comparison to atracurium (5.0 min) and pancuronium (6.0 min), but the differences were not statistically significant. The duration of clinical relaxation, however, was significantly shorter with vecuronium (37 min) and atracurium (35 min) in comparison to pancuronium (99 min).

Aged↗

Hemodynamic effects of atracurium, vecuronium and pancuronium during sufentanil anesthesia for coronary artery bypass.

A study was undertaken to evaluate the cardiovascular effects of sufentanil, in combination with three different muscle relaxants, used as sole anesthetic with 100% O2 in 30 patients undergoing elective coronary artery vein graft surgery. Patients were randomly allocated to receive pancuronium (P), vecuronium (V) or atracurium (A) for muscle relaxation. All patients received 15 micrograms/kg sufentanil at induction followed by 5-10 micrograms/kg sufentanil prior to sternotomy. At the 95% level of significance no statistical difference was found for any of the measured and derived cardiovascular parameters between groups P, V and A, except for a decreased systolic blood pressure in the atracurium group after induction. Sufentanil in combination with pancuronium or vecuronium provided stable hemodynamic conditions throughout anesthesia. Atracurium was less satisfactory. We conclude that there is no advantage to be gained, in the presence of beta blockade, from the use of the new generation muscle relaxants as compared to pancuronium during high-dose sufentanil anesthesia for coronary artery vein grafting.

Adult↗

Thiopentone reduces the haemodynamic response to induction of high-dose fentanyl-pancuronium anaesthesia in coronary artery surgical patients.

Thirty-three coronary artery bypass graft patients anaesthetized with high-dose fentanyl (50 micrograms/kg)-pancuronium-oxygen were divided into one control group receiving additional saline and two groups receiving additional 1 mg/kg or 2.5 mg/kg of thiopentone before laryngoscopy and intubation. During laryngoscopy and intubation, systemic arterial pressures, heart rate and rate-pressure-product remained at considerably elevated levels caused by pancuronium in the control group. Both doses of thiopentone reduced these haemodynamic values close to their initial levels. Cardiac index and left ventricular stroke work index were significantly decreased, especially by the higher thiopentone dose, as compared with the control group. However, there were no statistical differences between the haemodynamic changes produced by the two doses of thiopentone. Sedative or hypnotic supplementation of high-dose fentanyl anaesthesia seems to be necessary if pancuronium is used as a muscle relaxant. A small increment of thiopentone, 1 mg/kg, was enough to return haemodynamic parameters almost to their initial levels, whereas the effect of 2.5 mg/kg of thiopentone was unnecessarily strong.

Aged↗

Cardiovascular effects of vecuronium, atracurium, pancuronium, metocurine and RGH-4201 in dogs.

The effect on the cardiovascular haemodynamic status of five neuromuscular blocking drugs, RGH-4201, vecuronium, atracurium, pancuronium and metocurine, was studied in five conditioned foxhounds anaesthetised with fentanyl. Changes in heart rate, mean arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were recorded at 2, 5, 10, 20 and 30 min after administration of the drugs. From these, stroke volume, systemic vascular resistance and pulmonary vascular resistance were calculated. Administration of RGH-4201 was followed by a pronounced increase in heart rate, accompanied by an increase in cardiac output and a decrease in systemic and pulmonary vascular resistance. Metocurine and pancuronium resulted in a decrease of right and left filling pressures and systemic-/pulmonary vascular resistance. Changes after atracurium, vecuronium and metocurine were minimal. It is concluded that RGH-4201 causes major alterations in the cardiovascular haemodynamic status in dogs anaesthetised with fentanyl when compared to vecuronium, atracurium, metocurine and pancuronium. With respect to cardiovascular stability, atracurium and vecuronium offer advantages.

Androstanes↗

Dose-response to pancuronium in identical twins.

The dose-response to pancuronium was determined in identical twins within an hour with the same anesthetic technique. The dose-response curves did not differ from parallelism, but one infant was more sensitive to pancuronium than the other. The recovery rates were also different. The variation in the dose response to pancuronium seems to extend to identical twins.

Anesthesia, Intravenous↗

Perioperative monitoring of neuromuscular transmission using acceleromyography prevents residual neuromuscular block following pancuronium.

The frequency of postoperative residual neuromuscular block following the use of the long-acting non-depolarizing muscle relaxants is high, and manual evaluation of the response to nerve stimulation does not eliminate the problem. In this prospective and randomized study we evaluated the hypothesis that perioperative use of acceleromyography would allow for a more rational and precise administration of the long-acting muscle relaxant pancuronium resulting in a decrease in 1) the incidence and severity of postoperative residual neuromuscular block, 2) the amount of pancuronium used, and 3) the time from end of surgery to tracheal extubation. Forty adult patients were randomized into two groups, one managed without the use of a nerve stimulator, the other monitored using train-of-four (TOF) nerve stimulation and acceleromyography. All patients were anaesthetized with diazepam, fentanyl, thiopentone, nitrous oxide, and in some patients halothane, and they all received pancuronium 0.08-0.1 mg kg-1 for tracheal intubation, and 1-2 mg for maintenance of neuromuscular block. Neostigmine 2.5 mg preceded by atropine 1 mg was administered for reversal. In the patients managed without a nerve stimulator, the trachea was extubated when the anaesthetist judged the neuromuscular function to have recovered adequately for upper airway protection and spontaneous ventilation. In patients monitored with acceleromyography, the trachea was extubated when the TOF ratio was above 0.70. In all 40 patients, TOF ratio was measured using mechanomyography immediately after tracheal extubation and the patients were evaluated for clinical signs of residual neuromuscular block.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Absence of skeletal muscle lesions after experimental restraint stress induced by pancuronium in normal and stress-susceptible pigs.

Stress-susceptible (SS) pigs develop rhabdomyolysis and increased serum levels of muscle enzymes after a 12 min experimental stress induced by the depolarizing myorelaxant succinylcholine. It is suspected that not only the stress situation but also succinylcholine itself contributes to the skeletal muscle lesions. This experiment was performed to study whether rhabdomyolysis occurs after restraint stress when succinylcholine was replaced by the non-depolarizing myorelaxant pancuronium. Four normal and four SS pigs were subjected to restraint stress by intravenous injection of pancuronium. The neuromuscular block was reversed after 12 min by neostigmine. The animals wee necropsied approximately 48 h after stress and 24 skeletal muscle groups were examined pathologically. The severity of acute myofibre lesions were graded, and the results were compared with the results from normal and SS pigs which had been subjected to restraint stress induced by succinylcholine. The serum levels of creatine kinase (CK) and aspartate aminotransferase (ASAT) stayed at the base line level after the stress. The scores for muscle lesions were significantly lower, both in normal and SS pigs, than after restraint stress induced by succinylcholine indicating no rhabdomyolysis after restraint stress induced by pancuronium. Thus succinylcholine is synergistic with stress, exacerbating its effect on skeletal muscle in SS pigs.

Animals↗