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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↗

Comparison of integrated evoked EMG between the hypothenar and facial muscle groups following atracurium and vecuronium administration.

In 17 healthy patients undergoing O2.N2O.isoflurane anaesthesia, following atracurium or vecuronium administration, we compared simultaneous integrated evoked electromyograms (IEEMGs) during spontaneous recovery of the adductor digiti minimi (ADM) and orbicularis oris (OOM) muscle groups in response to train-of-four (TOF) stimulation of the ulnar and facial nerves, respectively. In all patients, the onset of neuromuscular recovery occurred first in the OOM. The time required to recover to a T4/T1 = 0.70 +/- 0.01 (SD) was earlier in the OOM compared with the ADM muscles in both the atracurium (33.4 +/- 5 vs 46.5 +/- 8, P less than 0.005) and vecuronium (46.5 +/- 12 vs 60.3 +/- 20, P less than 0.005) groups. When the OOM attained a T4/T1 = 0.70 +/- 0.01, the simultaneous T4/T1 in the ADM was 0.29 +/- 0.15 (P less than 0.05) in the atracurium group and 0.41 +/- 0.16 (P less than 0.01) in the vecuronium group. We conclude that (1) the facial muscles (OOM) recover earlier than the hypothenar muscles (ADM) and (2) an EMG T4/T1 = 0.70 in the facial muscles may not indicate adequate recovery of neuromuscular function.

Adolescent↗

Haemodynamic interactions of muscle relaxants and sufentanil in coronary artery surgery.

The haemodynamic interactions between sufentanil (S) and muscle relaxants (MR) were studied in 40 ASA physical status III or IV patients (four groups of ten) scheduled for coronary artery bypass grafting (ABG). Group I received pancuronium (P) 0.08 mg.kg-1, Group II received vecuronium (V) 0.1 mg.kg-1, Group III received atracurium (A) 0.5 mg.kg-1 and Group IV metocurine 0.1 mg.kg-1 plus pancuronium 0.02 mg.kg-1 (M-P). Sufentanil, 20 micrograms.kg-1 was administered before sternotomy, 10 micrograms.kg-1 being injected before tracheal intubation and 10 micrograms.kg-1 afterwards. Heart rate (HR), ECG leadII and V5, systolic, diastolic and mean arterial and pulmonary blood pressures, central venous pressure (CVP) and pulmonary capillary wedge pressure (W) were measured and recorded at the time of seven strategic events between the pre-induction of anaesthesia period and sternotomy. Cardiac output (CO) and systemic vascular resistances (SVR) were also measured before induction of anaesthesia and after the administration of S 10 micrograms.kg-1 plus the MR. The HR decreased from baseline values in the post-tracheal intubation period in all groups except in P group. The mean arterial pressure also decreased significantly in all groups except in the P group. The CO did not change from baseline values but SVR decreased in all groups. There was no evidence of new myocardial ischaemia according to the ECG monitoring and there was no significant difference in the HR changes between patients who had or who had not received beta-blockers in any group. We conclude that within the present study conditions and design, HR and blood pressure changed least with pancuronium.

Adrenergic beta-Antagonists↗

Relationships between block-of-twitch and train-of-four fade in the mouse phrenic nerve-diaphragm preparation.

The relationships between the block-of-twitch and train-of-four fade in the presence of nondepolarizing neuromuscular blocking drugs (d-tubocurarine, vecuronium and pancuronium) were examined in vitro by measuring the contractile tension from mouse phrenic nerve-diaphragm preparations. The slope of the block/fade relationship differed between onset of and recovery from neuromuscular block following single doses of d-tubocurarine, vecuronium or pancuronium. Decreasing the dose of d-tubocurarine or using a divided dose technique to accelerate onset (i.e., priming) increased the amount of fade for a given amount of block. In addition, the block/fade relationships for cumulative dosing and sequential dilution were the same when measurements were made at steady-state for several doses. It is concluded that the block/fade relationship in the mouse phrenic nerve-diaphragm preparation is variable, and is related to the time course of the neuromuscular block. In addition, the block/fade relationships for d-tubocurarine, vecuronium and pancuronium did not differ when determined at steady-state.

Animals↗

Clinical experience with ORG NC45 (norcuron) as the sole muscle relaxant.

The neuromuscular effects of ORG NC45, used as the sole muscle relaxant, were compared with a succinylcholine-pancuronium sequence in patients during nitrous oxide-fentanyl anaesthesia. The subjects were divided into four groups with ten in each group. After induction of anaesthesia they received either succinylcholine, 1 mg . kg-1 or ORG NC45 in doses of 50, 70 or 90 micrograms . kg-1 and tracheal intubation was done 90 seconds later. Neuromuscular transmission was monitored using train-of-four stimulation. Succinylcholine produced 100 per cent block with uniformly excellent intubating conditions whereas the three doses of ORG NC45 were associated with blocks of 7.5, 18.7 and 30.7 per cent and acceptable conditions in only 30 per cent of subjects. Muscle relaxation was maintained in the NC45 groups with increments of 10 micrograms . kg-1 and in the succinylcholine group with pancuronium, initially as a bolus of 40 micrograms . kg-1, followed by increments of 5 mg . kg-1. All increments were given at 10 per cent recovery of twitch height. The overall requirement to maintain 90 per cent block with pancuronium was 1.1 microgram/kg-1 . min-1 compared with 1.28 microgram . kg-1 . min-1 with ORG NC45. No cumulative effects were seen with either drug during the first hour of neuromuscular blockade. At the end of the operation the neuromuscular block was antagonized with atropine 18 micrograms . kg-1, and neostigmine 36 micrograms . kg-1 and recovery was significantly more rapid with NC45 than pancuronium. We conclude that the lack of cumulation, easy reversibility and lack of cardiovascular effects suggest that NC45 has advantages over currently available non-depolarizing muscle relaxants but that its onset of action is too slow for rapid intubation.

Adult↗

Stable muscle relaxation during abdominal surgery using combined intravenous bolus and demand infusion: clinical appraisal with ORG NC45.

In order to obtain stable muscle relaxation for intra-abdominal operation, a continuous demand perfusion of ORG NC45 was administered following a loading dose of 0.07 mg . kg-1. The patients had previously been anaesthetized with methohexitone, fentanyl and nitrous oxide. The perfusion rate of ORG NC45 was regulated so that the mechanical muscular response of the adductor pollicis following a supra-maximal stimulation of the ulnar nerve was maintained at 10 per cent of its initial value. The level of relaxation thus obtained was always adequate for the surgeons. During the course of the operation the requirement for more relaxant decreased progressively, becoming stable after one half hour. Nevertheless, during stable administration, individual variations were quite marked, being 44 to 483 micrograms/M2 BSA/10 min (average 225 micrograms/M2 BSA/10 min). The duration of the infusion varied from 60 to 107 minutes (average 103 minutes). After its termination the time taken from recovery varied between 3 and 82 minutes (average 27 minutes). Having regained a single twitch height of 75 per cent patients awoke rapidly after the administration of nitrous oxide was terminated. No signs of recurarization were noticed in any of the patients. In conclusion, this method of administration of ORG NC45 assures a stable level of curarization without side-effects. However, because of the different individual levels of sensitivity which were noted, this mode of administration requires careful monitoring to avoid inappropriate dosage.

Abdomen↗

Assessment of residual curarization using low-current stimulation.

The present study employed train-of-four (TOF) stimulation at a current of 20 mA to assess the incidence and degree of residual neuromuscular blockade in 64 randomly selected Post Anesthesia Care Unit (PACU) patients. Group C (Control, n = 10) had received anaesthesia without nondepolarizing muscle relaxant; Group V (n = 25) had received vecuronium; and Group P (n = 29) had received pancuronium. At the end of surgery, each patient had been considered by his anaesthetist to have adequate neuromuscular function on the basis of clinical signs and tactile or visual evaluation of responses to TOF stimulation. However, upon testing in the PACU 15 min later, 45% (13 of 29) of Group P patients and 8% (2 of 25) of Group V patients had a TOF ration less than 0.70. This study indicates that residual curarization may be commonly encountered following long-acting relaxants despite qualitative intraoperative TOF monitoring. The present incidence, detected at a current of 20 mA, is consistent with previous reports which employed supramaximal TOF stimulation. We conclude that despite intraoperative monitoring, residual curarization following long-acting nondepolarizing agents is common and that it may be detected with TOF at a low stimulating current (20 mA).

Adult↗

Continuous vecuronium infusion for prolonged muscle relaxation in children.

Facilitation of mechanical ventilation of the lungs using an infusion of vecuronium in 11 infants and children and four neonates in an intensive care unit is described. A loading dose of vecuronium of 0.1 mg.kg-1 was followed by an infusion at an initial rate of 0.1 mg.kg-1.hr-1. The infusion rate was adjusted to maintain a neuromuscular block of approximately 90% as assessed by the presence of one response to a train-of-four stimulation. The duration of the infusions varied from 9.5 to 179 hr. The mean dose of vecuronium administered was 0.14 mg.kg-1.hr-1 (+/- 0.05, SD) in the children and 0.11 mg.kg-1.hr-1 (+/- 0.05) in the neonates. Mean recovery times from the time of stopping the infusion until absence of apparent fade in response to tetanic stimulation were 51.7 (+/- 17.6) and 46.8 (+/- 16.5) min for the children and neonates respectively. No adverse cardiovascular or toxic effects were noted. This technique of vecuronium infusion to facilitate mechanical ventilation of the lungs is feasible and satisfactory in clinical use.

Female↗

Cumulation and reversal with prolonged infusions of atracurium and vecuronium.

A randomized, double-blind study was undertaken to compare the tendencies for cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC) when administered by continuous infusion for long surgical procedures under balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were free of neuromuscular disease. Patients in the ATR group (n = 25) received a loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at 5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg-1.min-1. During surgery, the infusions of both ATR and VEC were titrated in increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90-95%. Neuromuscular block was measured by recording the integrated evoked electromyographic response (EMG) of the first dorsal interosseous muscle in response to supramaximal TOF stimuli on the ulnar nerve. The durations of infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between 4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC, from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study period. The number of adjustments required to maintain 90-95% T1 suppression decreased between the second and fourth hours of administration, but were similar at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Anaesthetic management of a parturient with myocardial infarction related to cocaine use.

Cocaine abuse is common among parturients with an incidence of 11.8 to 20%. Myocardial infarction is a rare and lethal event during pregnancy with an incidence of 1 in 10,000 pregnancies. We present the anaesthetic management of a parturient of 36 wk gestation who suffered a myocardial infarction nine hours before delivery which was temporally related to "crack" cocaine use. The patient's cardiovascular system became unstable following cocaine use, and she required mechanical ventilatory support and pharmacologic stabilization guided by invasive haemodynamic monitoring. This patient survived a non-Q wave myocardial infarction, but the prognosis of peripartum myocardial infarction remains poor with a mortality rate of 30-40% which is increased if the infarction occurs in the third trimester or postpartum period. The optimal mode and timing of delivery after myocardial infarction is unresolved. The association between cocaine use and myocardial infarction was first described in 1982, and cocaine remains unique among local anaesthetics in its ability to compromise the cardiovascular system through both sympathomimetic effects and vasoconstrictive effects on coronary arteries. Because of the prevalence of substance abuse, cocaine use should be considered in the differential diagnosis of sudden cardiovascular compromise in parturients.

Adult↗

Continuous infusions of atracurium and vecuronium, compared with intermittent boluses of pancuronium: dose requirements and reversal.

This study was designed to determine the effect of prolonged infusion on the ease of reversal of atracurium and vecuronium, and whether factors which potentiate the block delayed reversal. In phase one, 40 patients were randomized (double blind) to determine the steady state conditions for atracurium and vecuronium. Fourteen atracurium patients and 17 vecuronium patients were evaluable. The unblinded second phase involved the steady state conditions using halothane or isoflurane and atracurium infusions. The infusion required for 95% twitch depression (TD95) for atracurium was 7.6 +/- 1.1 micrograms.kg-1 x min-1. The requirement for vecuronium changes with time: TD95 at 30 min was 1.01 +/- 0.16, at 60 min 0.89 +/- 0.12 and after 90 min 0.85 +/- 0.17 micrograms.kg-1 x min-1 (P < 0.05). The mean TD95 was 0.94 +/- 0.23 micrograms.kg-1 x min-1. Multivariate regression analysis of the infusion data revealed a vecuronium model predicting TD95 by the duration of infusion (P < 0.05) and weight (P = 0.05). Atracurium TD95 was predicted by age (P = 0.05). The addition of an inhalation agent to atracurium reduced the infusion rate by 2.01 +/- 0.28 micrograms.kg-1 x min-1 (P = 0.0001) for each increase in MAC. The mean reversal times for atracurium with three different anaesthetics and for vecuronium were not different. Reversal of pancuronium blockade, from less profound twitch depression (86.4 vs 95%) took twice as long as for atracurium and vecuronium for which the following predictors were identified: age, weight, duration of infusion, level of blockade, and type of anaesthetic, using a stepwise regression model.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Fading responses in the evoked EMG after rocuronium in cats.

This study was performed to evaluate the inhibitory effect on motor nerve terminals by rocuronium using recovery curves of muscle compound action potentials (CAPs) and train-of-four ratios (TOFRs) in anaesthetized cats, and to compare the results with other relaxants reported previously. Recovery curves were derived from the amplitude of the CAP induced in the gastrocnemius muscle by the second of a paired stimulus (test response) to the sciatic nerve and compared with results evoked by the first component (conditioning response). The interval between the paired stimuli was increased stepwise from 7 to 1,000 msec, and the differences in amplitude of the test and conditioning responses were plotted on a graph by relating the changes in paired intervals. The recovery curve after rocuronium was less inhibited than after pancuronium, (100.4 +/- 5.9%, 82.3 +/- 6.7% and 68.5 +/- 6.7% at 60, 100 and 500 msec intervals, compared with 70.3 +/- 3.3%, 59.0 +/- 4.7% and 46.7 +/- 4.3% after pancuronium (P < 0.05). The recovery curves with d-tubocurarine were more depressed than with pancuronium; however, the RC with vecuronium was similar to that of rocuronium. The degree of fade in TOF by rocuronium was also less than those seen with d-tubocurarine and pancuronium. The results obtained suggest that rocuronium has less inhibitory effect on motor nerve terminals than do d-tubocurarine and pancuronium, and has a similar effect to that of vecuronium.

Androstanols↗

Vecuronium is more potent in Montreal than in Paris.

This study was undertaken to compare the potency of vecuronium in patients anaesthetized in Montreal or Paris. Anaesthesia was induced with thiopentone and maintained with N2O, and intermittent boluses of thiopentone and fentanyl in 18 patients in Paris and 19 in Montreal. Neuromuscular blockade was measured using train-of-four stimulation of the ulnar nerve. The force of contraction of the adductor pollicis muscle was measured. Single doses of vecuronium, 20, 30, or 40 micrograms.kg-1 were given by random allocation. Dose response curves were constructed by obtaining the linear regression of the logit of the first response (T1) neuromuscular blockade versus log dose. The patients in Paris required 27% more vecuronium (95% confidence limits 5-53%; P = 0.01) for the same intensity of blockade. In Montreal, the ED50 and ED90 (+/- SEE for the mean) values were 26.0 +/- 1.4 and 44.2 +/- 2.5 micrograms.kg-1 compared with 33.0 +/- 3.3 and 71.9 +/- 7.2 micrograms.kg-1 in Paris respectively. The patients were comparable with respect to age, sex, height and weight. These results confirm, for vecuronium, the transatlantic difference in potency of neuromuscular blocking drugs which was previously observed with d-tubocurarine between London and New York.

Adult↗

Onset of vecuronium neuromuscular block is more rapid in patients undergoing caesarean section.

This investigation was carried out in ten patients undergoing elective Caesarean section and the results were compared with those of a control group of ten nonpregnant females of the same age group. The study investigated the onset of vecuronium neuromuscular block and the conditions of tracheal intubation when ketamine (1.5 mg.kg-1)-vecuronium 100 micrograms.kg-1) sequence was used for rapid-sequence induction of anaesthesia. The ulnar nerve was stimulated supra-maximally at the wrist with train-of-four stimuli every 20 sec, and the electromyographic response of the adductor pollicis muscle was displayed. The onset of 50% neuromuscular block as monitored by electromyography was shorter in the Caesarean group (80 +/- 30 sec) than in the control group (144 +/- 43 sec). The conditions of intubation at 50% block were adequate in both groups. Also, the onset of 90% block was shorter in the Caesarean group. The time of recovery to T1/control ratio of 25% was longer in the Caesarean group (46 +/- 10 min) than in the control patients (28 +/- 10 min). The results show that administration of vecuronium according to body weight results in a more rapid onset and delayed recovery of neuromuscular block in pregnant women undergoing Caesarean section than in the nonpregnant control patients.

Adult↗

Modification by ketamine on the neuromuscular actions of magnesium, vecuronium, pancuronium and alpha-bungarotoxin in the primate.

The neuromuscular effects of ketamine, at cumulative doses of 2.5 and 10 mg.kg-1 iv, were studied by electromyographically quantifying the thumb response evoked by ulnar nerve stimulation in 25 monkeys anaesthetized with pentobarbital-N2O-O2. Ketamine alone at these doses had no neuromuscular effects. When the EMG response was maintained at 50% of control by a continuous infusion of magnesium, vecuronium, or pancuronium, ketamine depressed the responses by an additional 13 +/- 3%, 34 +/- 7% and 32.5 +/- 3.3% (mean +/- SEM), respectively, at the highest dose, P less than 0.05. In contrast, ketamine had no effect on the neuromuscular block produced by incremental doses of alpha-bungarotoxin. These results indicate that ketamine does not act on the postjunctional acetylcholine receptor. It plays a secondary role in neuromuscular block, possibly by prejunctional or postjunctional effects independent of receptor occupation.

Animals↗

Edrophonium antagonism of vecuronium at varying degrees of fourth twitch recovery.

The purpose of this study was to determine the optimal dose of edrophonium needed for successful antagonism (train-of-four ratio, or T4/T1 > 0.7) of vecuronium-induced blockade when all four twitches were visible in response to indirect train-of-four (TOF) stimulation. Forty patients, scheduled for elective surgical procedures not exceeding 120 min, received vecuronium, 0.08 mg.kg-1, during thiopentone-N2O-isoflurane anaesthesia. Train-of-four stimulation was applied every 20 sec and the force of contraction of the adductor pollicis muscle was recorded. Increments of vecuronium, 0.015 mg.kg-1, were given as required. At the end of surgery, and provided that neuro-muscular activity had recovered to four visible twitches, edrophonium, 0.1 mg.kg-1, was given. Two minutes later, edrophonium, 0.1 mg.kg-1, was given if T4/T1 did not reach 0.7. After another two minutes, edrophonium, 0.2 mg.kg-1, was given if T4/T1 did not reach 0.7 or more. Finally, if T4/T1 was still < 0.7, a dose of 0.4 mg.kg-1 was given. Seventeen patients (42.5%) required 0.1 mg.kg-1 of edrophonium for successful reversal, sixteen patients (40%) needed a cumulative dose of 0.2 mg.kg-1 and six patients (15%) required 0.4 mg.kg-1. Only one patient received 0.8 mg.kg-1. There was a good correlation between T4/T1 two minutes after the first dose of edrophonium and pre-reversal T4/T1 (r = 0.6; P = 0.00014). All patients with pre-reversal T4/T1 > 0.23 required at most 0.2 mg.kg-1 of edrophonium for successful reversal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗