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Unlabelled: We investigated the influence of the timing of neostigmine administration on recovery from rocuronium or vecuronium neuromuscular blockade. Eighty adults and 80 children were randomized to receive 0.45 mg/kg rocuronium or 0.075 mg/kg vecuronium during propofol/fentanyl/N2O anesthesia. Neuromuscular blockade was monitored by train-of-four (TOF) stimulation and adductor pollicis electromyography. Further randomization was made to control (no neostigmine) or reversal with 0.07 mg/kg neostigmine/0.01 mg/kg glycopyrrolate given 5 min after relaxant, or first twitch (T1) recovery of 1%, 10%, or 25%. Another eight adults and eight children received 1.5 mg/kg succinylcholine. At each age, spontaneous recovery of T1 and TOF was similar after rocuronium and vecuronium administration but was more rapid in children (P < 0.05). Spontaneous recovery to TOF0.7 after rocuronium and vecuronium administration in adults was 45.7 +/- 11.5 min and 52.5 +/- 15.6 min; in children, it was 28.8 +/- 7.8 min and 34.6 +/- 9.0 min. Neostigmine accelerated recovery in all reversal groups (P < 0.05) by approximately 40%, but the times from relaxant administration to TOF0.7 were similar and independent of the timing of neostigmine administration. Recovery to T1 90% after succinylcholine was similar in adults (9.4 +/- 5.0 min) and children (8.4 +/- 1.1 min) and was shorter than recovery to TOF0.7 in any reversal group after rocuronium or vecuronium administration. Recovery from rocuronium and vecuronium blockade after neostigmine administration was more rapid in children than in adults. Return of neuromuscular function after reversal was not influenced by the timing of neostigmine administration. These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated., Implications: These results suggest that reversal of intense rocuronium or vecuronium neuromuscular blockade need not be delayed until return of appreciable neuromuscular function has been demonstrated. Although spontaneous and neostigmine-assisted recovery is more rapid in children than in adults, in neither is return of function as rapid as after succinylcholine administration.

Background: Rapacuronium is a rapid-onset, short-acting neuromuscular relaxant. This multiple-center study determined neuromuscular recovery when neostigmine was given 2 or 5 min after rapacuronium., Methods: One hundred seventeen patients were randomized to receive two different doses of rapacuronium and to receive neostigmine in two different doses and at two different times. During propofol anesthesia with nitrous oxide, oxygen, and fentanyl, 1.5 or 2.5 mg/kg rapacuronium was given 1 min before tracheal intubation. Neuromuscular block was measured by train-of-four ulnar nerve stimulation every 12 s: The adductor pollicis force of contraction was recorded mechanomyographically. Two or five minutes after rapacuronium was administered, 0.05 or 0.07 mg/kg neostigmine was administered and recovery was compared with that of control patients who received no neostigmine., Results: Both doses of rapacuronium produced 100% block in all but one patient, who exhibited 97% block. Neostigmine accelerated recovery in all groups. After 1.5 mg/kg rapacuronium, the time to 25% T1 twitch recovery decreased from a mean of 16 min in control patients to mean values of 8-10 min in the treatment groups: The time to train-of-four ratio of 0.7 decreased from 38 min to 17-19 min. After 2.5 mg/kg rapacuronium, the time to 25% T1 was reduced from 23 min to 11-12 min, and the time to train-of-four ratio of 0.7 decreased from 54 min to 26-32 min. Recovery was not different among the the groups that received different doses and timing of neostigmine., Conclusions: Recovery of intense rapacuronium block was accelerated by early neostigmine administration. When given 2 min after rapacuronium, neostigmine was as effective as after 5 min, and 0.05 mg/kg neostigmine was comparable to 0.07 mg/kg neostigmine.

Background: Rapacuronium is a new nondepolarizing muscle relaxant with rapid onset and offset. As part of a study to determine its neuromuscular effects, the authors sampled plasma sparsely to determine the influence of age, gender, and other covariates on its pharmacokinetic characteristics., Methods: Of 181 patients receiving a single bolus dose of 0.5-2.5 mg/kg rapacuronium, 43 (aged 24-83 yr) had plasma sampled 3 or 4 times to determine plasma concentrations of rapacuronium and its metabolite, ORG9488. Pharmacokinetic analysis was performed using a population approach (mixed-effects modeling) to determine the influence of demographic characteristics and preoperative laboratory values on the pharmacokinetic parameters., Results: Rapacuronium's weight-normalized plasma clearance was 7.03 x (1 - 0.0507 x (HgB - 13)) ml x kg(-1) x min(-1), where HgB is the patient's preoperative value for hemoglobin (g/100 ml); however, rapacuronium's blood clearance (11.4+/-1.4 ml x kg(-1) x min(-1), mean +/- SD) did not vary with hemoglobin. Rapacuronium's weight-normalized pharmacokinetic parameters were not influenced by age, gender, or other covariates examined. Plasma concentrations of ORG9488 were typically less than 14% those of rapacuronium during the initial 30 min after rapacuronium administration., Conclusions: In this patient population, neither age nor gender influence elimination of rapacuronium. This finding contrasts to an age-related decrease in plasma clearance observed in a study of 10 healthy volunteers and in a pooled analysis of the pharmacokinetic data from 206 adults in multiple clinical studies. Even if ORG9488 has a potency similar to that of rapacuronium, its plasma concentrations after a single bolus dose of rapacuronium are sufficiently small to contribute minimally to neuromuscular blockade.

The purpose of this multicenter, randomized, assessorblind placebo-controlled study was to determine which of five doses of the new, rapid-onset neuromuscular relaxant, ORG 9487, provided both good to excellent tracheal intubating conditions 60 s after administration and a clinical duration of action < 20 min in 120 younger (aged 18-64 yr) and 61 elderly (aged 65-85 yr) adult patients. Anesthesia was induced with fentanyl (2-5 micrograms/kg) and thiopental (3-6 mg/kg) and maintained with N2O/O2 and a propofol infusion (50-300 micrograms.kg-1.min-1). Neuromuscular train-of-four (TOF) monitoring by electromyography (Datex Relaxograph) commenced immediately after anesthetic induction and was followed, within 30 s, by one of five doses of ORG 9487 (0.5, 1.0, 1.5, 2.0, 2.5 mg/kg) or a placebo. Tracheal intubation was attempted at 60 s and again, in the case of failure, at 90 s. Conditions were assessed with a 4-point scale. Maximum block, clinical duration (time to 25% T1 recovery), and recovery (TOF > or = 0.7) were measured. Dose-dependent changes were observed in tracheal intubating conditions and neuromuscular block. Good to excellent intubating conditions at 60 s were present in most younger adult (52 of 60) and elderly (26 of 31) patients administered doses > or = 1.5 mg/kg. Mean clinical durations < 20 min were observed in adult patients at doses up to 2.0 mg/kg and in geriatric patients up to 1.5 mg/kg. Thus, doses of 1.5-2.0 mg/kg ORG 9487 enabled both rapid tracheal intubation and a short clinical duration of action in adult and elderly patients.

Purpose: To determine whether detection of residual blockade is improved by using the accelerograph. A secondary objective was to compare acceleromyographic measurements with those obtained by electromyography., Methods: In a prospective, randomized, double-blind investigation, 22 anaesthetized children were studied during recovery from neuromuscular blockade following 0.1 mg.kg-1 vecuronium i.v.. Assessments of depth of block began 10 min after injection and were repeated at one minute intervals using electromyography (Datex, Relaxograph) in one hand, and acceleromyography (Biometer, Tofguard) in the other, to measure response of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve. Monitoring was stopped when no fade was visible and TOF ratio > or = 0.7. The electromyographic (EMG) and acceleromyographic (AMG) data were compared with corresponding observations of the number of twitches and TOF fade in the visible responses of the thumb, made by the attending anaesthetist. The method of Bland and Altman was used to compare differences between AMG and EMG data., Results: During recovery from neuromuscular blockade, fade was no longer visible clinically 38.6 +/- 10.4 min (mean +/- SD) after the administration of vecuronium. This corresponded to TOF ratios of 0.04 +/- 0.23 by AMG and 0.34 +/- 0.21 by EMG. Usually, two twitches were visible before AMG detected the first twitch. The time to TOF ratio > or = 0.7 by AMG and EMG was similar at 49.1 +/- 10.5 and 50.9 +/- 9.0 min, respectively. The bias between AMG and EMG was one minute, with limits of agreement from -10 to nine min., Conclusion: AMG is superior to visual assessment in detecting residual neuromuscular block and provides similar estimates of recovering block as the more cumbersome EMG.

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)

Background: Increasing age appears to be associated with a slower onset of neuromuscular blockade, but such an effect has not been studied with the same doses of the same drugs across pediatric and adult age groups., Methods: The authors measured the evoked compound action potential of the adductor pollicis muscle in response to 0.1-Hz stimulation of the ulnar nerve, during fentanyl-thiopental-oxygen anesthesia, in 160 patients aged 1-3 yr, 3-10 yr, 20-40 yr, or 60-80 yr. Subparalyzing doses of vecuronium (0.03 mg/kg) or succinylcholine (0.3 mg/kg), or paralyzing doses of vecuronium (0.1 mg/kg) or succinylcholine (1.0 mg/kg), were administered to ten patients in each age group., Results: Onset time, defined as the time from injection to maximum depression of response with a subparalyzing dose or the time from injection to ablation of visible response with a paralyzing dose, varied with age in all groups (P < 0.001). For 0.3 mg/kg succinylcholine, it increased from 49 +/- 6 s in 1-3-yr-old patients, to 104 +/- 9 s in 60-80-yr-old patients (P < 0.00001). For 0.03 mg/kg vecuronium, onset time was 3.6-5.9 times longer than for succinylcholine, increasing from 219 +/- 15 s in 3-10-yr-old patients to 473 +/- 30 s in 60-80-yr-old patients (P < 0.00001 by linear regression). For paralyzing doses, succinylcholine 1.0 mg/kg had an onset time of 58 +/- 7 s and 95 +/- 7 s, in 1-3-yr-old and 60-80-yr-old patients, respectively (P < 0.001). For 0.1 mg/kg vecuronium, onset time varied between 125 +/- 19 s in 1-3-yr-old patients to 295 +/- 31 s in 60-80-yr-old patients (P < 0.00001), and was 2.1-3.3 times longer than 1 mg/kg succinylcholine., Conclusions: Increasing age is associated with slower onset for both succinylcholine and vecuronium. When equipotent, subparalyzing doses of succinylcholine and vecuronium are compared, onset time is 4.5 times as long with vecuronium.

The effect of early blood sampling on the description of the vecuronium pharmacokinetic-pharmacodynamic relationship was studied following a bolus injection. Sample collection every 10 sec during the first 2 min showed a high concentration peak at 30 to 40 sec, accounting for an important proportion of the total area under the plasma concentration-time curve (AUC). Neglecting it, using only blood samples drawn at 1 and 2 min (limited sampling), led to a significant overestimation of noncompartmentally derived values of mean residence time, clearance, volume of distribution at steady-state and rate of transfer of vecuronium into the effect compartment. Compartmental pharmacokinetics could not be applied to concentration-time curves constructed with early samples, but limited sampling data were fitted to a 2-compartment model. Derived compartmental pharmacokinetic and pharmacokinetic-pharmacodynamic parameters were similar to those obtained noncompartmentally with complete sampling every 10 sec, because back-extrapolation to time zero contributed to the increase in the AUC. However, compartmental analysis does not provide an accurate description of concentration changes following injection.

A high-performance liquid chromatographic assay coupled with electrochemical detection has been developed for the determination of vecuronium and its three putative deacetylated metabolites in human plasma. A novel solid-phase extraction procedure allowed good recovery of both vecuronium and its metabolites, together with ease and speed of execution. This method was sensitive, reproducible and accurate over the therapeutic range of concentrations of vecuronium and its metabolites, and was applied successfully to a study of the pharmacokinetics of vecuronium in anaesthetized patients.

This study was designed to measure the potency of vecuronium with and without nitrous oxide. Anaesthesia was induced with thiopentone and fentanyl in 56 adult patients. The subjects were randomly assigned to receive nitrous oxide, 70%, or intermittent boluses of thiopentone and fentanyl for maintenance of anaesthesia. Train-of-four stimulation was applied to the ulnar nerve every 20 sec, and the force of contraction of the adductor pollicis muscle was measured. Vecuronium, 20, 30 or 40 micrograms.kg-1 was given by random allocation five minutes after induction of anaesthesia. Maximum depression of the first response (T1) in the train-of-four was measured, and dose-response curves were constructed. In the absence of nitrous oxide, the ED50 and ED95 were mean +/- standard error of the mean (SEM), 29.2 +/- 1.8 and 59.3 +/- 3.6 micrograms.kg-1, respectively. In the group receiving nitrous oxide, these values were 25.3 +/- 1.2 and 42.3 +/- 2.0 micrograms.kg-1 respectively. By analysis of covariance, the dose-response curves were shown to be shifted with respect to one another (P less than 0.05). Administration of nitrous oxide was associated with a 19.5% increase in potency (95% confidence limits: 1.7 to 40.4%). It is concluded that nitrous oxide has a slight potentiating effect on neuromuscular blockade, and that this effect occurs within five to ten minutes after the beginning of its administration.

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.

After anesthesia employing nondepolarizing muscle relaxants, 30%-40% of adult patients demonstrate residual paralysis with a train-of-four ratio less than 70%, but it is not known if the same is true for children. This study was designed to investigate neuromuscular transmission in 91 ASA physical status I or II day-care children (aged 0-10 yr) after halothane anesthesia in which pancuronium (n = 34), atracurium (n = 32), or vecuronium (n = 25) was administered. Peripheral nerve stimulation was used clinically to assess neuromuscular blockade during surgery. In the recovery room, the evoked response of the adductor pollicis muscle was measured by train-of-four stimulation of the ulnar nerve. This measurement was made (mean +/- SEM) at 18.0 +/- 1.5, 15.0 +/- 1.3, and 15.0 +/- 1.7 min after pharmacologic antagonism with 0.02 mg/kg atropine and 0.06 mg/kg neostigmine in the pancuronium, atracurium, and vecuronium groups, respectively. There were no differences in the ages of the patients in the three groups at 4.3 +/- 0.4, 4.0 +/- 0.4, and 5.0 +/- 0.5 yr, with 17 children less than 2 yr. Recovery from neuromuscular blockade in all three groups was almost complete. The train-of-four ratio (height of fourth twitch compared with the first) was similar in patients who had received pancuronium (96.7% +/- 0.9%), atracurium (95.5% +/- 0.9%), or vecuronium (96.3% +/- 1.3%). Therefore, postoperative muscle weakness or respiratory impairment is unlikely in pediatric day-care surgical patients more than 2 yr old when these anesthetic techniques are used.

The ability of cumulative dose-response techniques to obtain accurate data is most likely limited by redistribution and elimination of the drug during the study period. Therefore the usefulness of these techniques would be improved by replacing the amount of drug lost. This hypothesis was assessed for the intermediate-duration neuromuscular blockers vecuronium and atracurium, and calculations were made based on a pharmacokinetic model with an effect compartment. Sixty patients received either single doses (SD) (n = 36), cumulative doses (CD) (n = 12), or CD of vecuronium or atracurium with an infusion (CDI) to replace eliminated or redistributed drug (n = 12). The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation was measured and recorded. Linear regressions were obtained between the logit transformation of neuromuscular blockade at the adductor pollicis and log dose. The potencies obtained with all three methods were within 20% of each other. For vecuronium the ED90 was (mean +/- SE) 0.034 +/- 0.002 (SD), 0.037 +/- 0.003 (CD), and 0.036 +/- 0.003 mg/kg (CDI). For atracurium the ED90 was 0.175 +/- 0.009 (SD), 0.206 +/- 0.019 (CD), and 0.179 +/- 0.015 mg/kg (CDI). Calculated values corresponded well with measured values. The calculations predicted that the agreement between single- and cumulative-dose techniques would be improved if (1) the dose increment was increased, (2) the elimination half-life was increased above 20 minutes, or (3) an infusion was added.(ABSTRACT TRUNCATED AT 250 WORDS)

Train-of-four stimulation was applied to the ulnar and phrenic nerves in 18 adult patients anaesthetized with nitrous oxide and halothane in oxygen. The response of the adductor pollicis and the diaphragm were measured. Incremental doses of atracurium and vecuronium were given, with an infusion to replace drug lost by elimination or distribution. The mean (SEM) doses of atracurium associated with 50% and 90% depression of response to the first stimulation in the train-of-four (ED50 and ED90) were 90 (9) and 133 (10) micrograms kg-1 at the adductor pollicis, and 130 (9) and 245 (17) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 and ED90 of vecuronium were 25 (2) and 38 (4) micrograms kg-1 at the adductor pollicis and 34 (3) and 58 (5) micrograms kg-1 at the diaphragm, respectively. The mean (SEM) ED50 ratios were 1.56 (0.16) for atracurium and 1.47 (0.16) for vecuronium. ED90 ratios were 1.93 (0.29) and 1.55 (0.17) for atracurium and vecuronium, respectively. It is concluded that both atracurium and vecuronium exhibit a similar degree of sparing of the diaphragm.

To determine the potencies of edrophonium and neostigmine as antagonists of nondepolarizing neuromuscular blockade produced by atracurium and vecuronium, dose-response curves were constructed for both antagonists when given at 10% spontaneous recovery of first twitch height. Ninety ASA physical status 1 and 2 adults were given either 0.4 mg/kg atracurium or 0.08 mg/kg vecuronium during thiopental-nitrous oxide-enflurane anesthesia. Train-of-four stimulation was applied to the ulnar nerve every 12 s, and the force of contraction of the adductor pollicis muscle was recorded. When spontaneous recovery of first twitch height reached 10% of its initial control value, edrophonium (0.1, 0.2, 0.4, or 1 mg/kg) or neostigmine (0.005, 0.01, 0.02, or 0.05 mg/kg) was administered by random allocation. Neuromuscular function in another ten subjects was allowed to recover spontaneously. Assisted recovery was defined as actual recovery minus mean spontaneous recovery observed in patients who were not given antagonists. First twitch recovery was initially more rapid when vecuronium was antagonized compared with atracurium, but no difference was detected after 10 min. At 10 min the neostigmine ED80 was 0.022 +/- 0.003 (SEM) mg/kg after atracurium and 0.024 +/- 0.003 mg/kg after vecuronium. The edrophonium ED80 was 0.44 +/- 0.11 mg/kg with atracurium and 0.46 +/- 0.12 mg/kg with vecuronium, giving a neostigmine:edrophonium potency ratio of 20. Atracurium train-of-four fade could be antagonized more easily with edrophonium, whereas that of vecuronium was more easily antagonized by neostigmine. It is concluded that edrophonium and neostigmine are not equally effective against atracurium and vecuronium.

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Canadian Journal of Anaesthesia / Journal Canadien d'Anesthésie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)