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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.

Purpose: To determine the incidence of residual neuromuscular blockade after cardiac surgery in patients receiving either rocuronium or pancuronium for muscle relaxation., Methods: In a prospective, controlled, double-blind study, 20 patients undergoing coronary artery bypass were randomized to receive either rocuronium (n = 10) or pancuronium (n = 10) during surgery. Anaesthesia was induced with sufentanil, benzodiazepine and propofol or ketamine, and maintained with air/O2/sufentanil/isoflurane. Neuromuscular blockade was induced with 0.1 ml.kg-1 from blinded syringes containing recuronium (6 mg.ml-1) (Group R) or pancuronium (1 mg.ml-1) (Group P). Relaxants were administered according to clinical criteria and reversal agents were not given. After surgery, neuromuscular transmission was assessed by train-of-four stimulation of the ulnar nerve/adductor pollicis EMG (Datex Relaxograph). Mean values from three trains of stimuli were recorded and repeated 30 min later if TOF ratio was < 0.7. Time to extubation was recorded., Results: On arrival in the ICU, nine of 10 patients in group R but only three of 10 patients in group P demonstrated four visible responses (P < 0.05). Mean TOF ratio in group P, 0.03 +/- 0.05, was less than in group R, 0.68 +/- 0.34 (P < 0.001). All patients in group P and 4 of 10 patients in group R had TOF ratio < 0.7 (P = 0.01). Time to extubation in group P (median 18, range 6-48 hr) was not statistically different from that in group R (14, 5-44 hr)., Conclusion: Residual neuromuscular block, TOF ratio < 0.7, is common after cardiac surgery but the incidence is less when pancuronium is replaced by rocuronium.

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.

Recovery after doxacurium and pancuronium neuromuscular blockade and their acceleration by neostigmine have not been compared in children. Therefore, 60 paediatric surgical patients aged 2-10 yr (ASA 1-2) were studied. They were randomized to receive doxacurium 30 micrograms.kg-1 or pancuronium 70 micrograms.kg-1 iv during propofol, fentanyl, isoflurane and nitrous oxide anaesthesia. Electromyographic (EMG) responses of the adductor pollicis to train-of-four (TOF) stimulation of the ulnar nerve were recorded every ten seconds using a Datex NMT monitor. Six patients in each relaxant group received neostigmine (0, 5, 10, 20 or 40 micrograms.kg-1) with atropine by random allocation when first twitch height (T1) had recovered to 25% of control. Spontaneous recovery after ten minutes was similar following doxacurium (mean +/- SEM values of 45.0 +/- 3.9 vs 49.5 +/- 10.0% for T1 and 25.2 +/- 3.8 vs 14.8 +/- 3.6% for TOF ratios). Dose-responses to neostigmine were calculated from the log dose vs logit of T1 or TOF ratio after ten minutes. Neostigmine-assisted recovery was not different in the two groups, with ED70 and ED90 doses for T1 of 14.3 +/- 1.8 and 25.7 +/- 2.7 micrograms.kg-1 for doxacurium and 12.5 +/- 1.7 and 25.3 +/- 2.3 micrograms.kg-1 for pancuronium. Time to recovery of TOF ratio to 70% after neostigmine 40 micrograms.kg-1 was 2.3 +/- 1.0 and 4.2 +/- 1.7 min (P = NS) following pancuronium and doxacurium, respectively. Adjusted recovery due to neostigmine alone (spontaneous recovery subtracted from the total) required two to three times higher doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

The speed of action of several nondepolarizing muscle relaxants (gallamine, rocuronium, D-tubocurarine, atracurium, vecuronium, pancuronium and doxacurium) was tested iontophoretically at the frog cutaneous pectoris neuromuscular junction at various temperatures. If differences in rate of onset and offset are due to different molecular rates of binding (and unbinding), and of resulting conformational changes, they should be strongly temperature dependent. In contrast, if differences are due to differences in buffered diffusion, temperature dependence should be low to moderate. The onset and recovery time constants of inhibition of brief acetylcholine pulses, caused by long pulses of relaxants for all of the muscle relaxants, were inversely related to apparent dissociation constants (KD values), that ranged from 4.56 microM (gallamine) to 0.11 microM (doxacurium). The kinetics showed only modest temperature dependence (Q10 values of 1/time constant of offset were typically < 1.4). Because KD values of all muscle relaxants were even less temperature dependent (Q10 < 1.3), this suggests that the kinetics of inhibition is probably determined by the extent of buffering in the synaptic cleft, and not by binding and unbinding. Diffusion of relaxants from the synaptic cleft is expected to be strongly buffered, because the nerve terminal presents a physical barrier to diffusion, and because of extremely high density of acetylcholine receptors. The density of acetylcholine receptors can be calculated from the time constant of offset and KD values of various relaxants, assuming that buffer diffusion is determining the kinetics of action of muscle relaxants.(ABSTRACT TRUNCATED AT 250 WORDS)

The speed of action of nondepolarizing muscle relaxants is inversely related to potency. The hypothesis that this effect occurs at the end plate was tested in a frog (Rana pipiens) cutaneous pectoris muscle preparation. Brief acetylcholine pulses (10-100 ms) were applied iontophoretically from a central barrel of a triple-barrelled microelectrode located near an end plate. Long pulses (10-200 s) of muscle relaxant (gallamine, rocuronium, d-tubocurarine, atracurium, vecuronium, pancuronium, and doxacurium) were applied from one of two other barrels. The responses were a voltage change at the end plate, measured with an intracellular electrode. To evaluate potency, intracellular voltage changes following iontophoretic acetylcholine pulses were measured after application of various concentrations of muscle relaxants. The following were the equilibrium dissociation constants, which represent concentration of relaxant for 50% inhibition of response (mean plus or minus standard deviation): gallamine, 4.56 +/- 0.44 microM (n = 5); rocuronium, 0.71 +/- 0.09 microM (n = 6); d-tubocurarine, 0.59 +/- 0.07 microM (n = 4); atracurium, 0.31 +/- 0.03 microM (n = 4); vecuronium, 0.23 +/- 0.02 microM (n = 5); pancuronium, 0.18 +/- 0.03 microM (n = 3); doxacurium, 0.11 +/- 0.03 microM (n = 5). Both onset and offset of effect of muscle relaxant proceeded with an exponential time course.(ABSTRACT TRUNCATED AT 250 WORDS)

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 designed to determine the time required for potentiation of atracurium neuromuscular blockade after the introduction of enflurane. Ten ASA physical status I and II adults anesthetized with thiopental, nitrous oxide, and alfentanil were given 0.4 mg/kg atracurium besylate. The force of contraction of the adductor pollicis muscle in response to train-of-four stimulation of the ulnar nerve was recorded. When the first twitch (T1) of the train-of-four recovered to 10% of control, an atracurium infusion was started and adjusted to keep the level of blockade constant. After 15 min of stable blockade, 1.6%-1.7% end-tidal enflurane was started and maintained for up to 2 h. Venous blood samples were drawn and plasma atracurium concentrations were measured 15 min before and 0, 5, 10, 15, 30, 45, 60, 90, and 120 min after the introduction of enflurane. Atracurium plasma concentrations were 730 +/- 127 (SEM) ng/mL at time 0. During the first 30 min, no significant decrease in plasma levels occurred; but at 45 min, concentrations were only 67% +/- 8% of their initial value (P less than 0.01) and 48% +/- 2% at 120 min (P less than 0.01). This suggests that the interaction between enflurane and atracurium is time-dependent. Clinically, the interaction between atracurium and enflurane is negligible during procedures of less than 45 min.

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.

Sixty ASA physical status I and II adults received 0.3 mg/kg succinylcholine to determine the effect of prolonged administration of thiopental and that of nitrous oxide on succinylcholine neuromuscular blockade. Succinylcholine was administered either 1 min (group 1) or 6 min (groups 2 and 3) after induction of anesthesia with thiopental. In group 2, anesthesia was maintained with thiopental and the patients' lungs were ventilated with oxygen. In group 3, anesthesia was maintained with only 70% nitrous oxide in oxygen. Train-of-four stimulation of the ulnar nerve was started 30 s before the administration of succinylcholine and repeated every 12 s. The force of contraction of the adductor pollicis muscle was measured. Maximum blockade (mean +/- SEM) did not vary significantly between group 1, where thiopental had been administered for 1 min, and group 2, where it had been administered for 6 min (group 1: 61% +/- 6%; group 2: 54% +/- 8%). However, the addition of nitrous oxide increased neuromuscular blockade (group 3: 80% +/- 6%; P less than 0.05 compared with group 2). The degree of twitch augmentation, i.e., greater than maximal response, and times to twitch augmentation and to maximum blockade did not vary significantly among the groups. It is concluded that nitrous oxide increases succinylcholine neuromuscular blockade and that this is manifest within 6 min. This effect is not due to the duration of the anesthetic because thiopental, administered over a similar time period, did not potentiate succinylcholine.

Double-burst stimulation (DBS), a new technique to evaluate neuromuscular function, consists of two 50-Hz trains of 60-ms duration and 750 ms apart. DBS was compared with train-of-four (TOF) stimulation in 21 children aged 3-10 yr, during halothane anesthesia. On one arm the ulnar nerve was stimulated supramaximally with TOF stimulation every 12 s and the force of the evoked contraction of the adductor pollicis measured with an FTO3 force transducer and recorded on paper. Atracurium (0.4-0.5 mg.kg-1) was administered. During recovery from neuromuscular blockade, TOF stimulation was interrupted periodically and DBS substituted. The same stimulation patterns were applied to the ulnar nerve of the other arm simultaneously, and the clinical anesthesiologist was asked to estimate the degree of fade with both. There was good correlation between the measured TOF ratio (ratio of fourth to first response) and DBS ratio (ratio of second to first response). The TOF and DBS ratios above which fade could no longer be appreciated manually were (mean +/- SEM) 0.44 +/- 0.03 and 0.67 +/- 0.04 (P = 0.0002). Corresponding ranges were 0.3-0.8 for TOF and 0.4-0.9 for DBS, but DBS fade was always apparent if TOF fade could be detected. Therefore, in children, DBS is more sensitive than is TOF stimulation for the clinical assessment of recovery from neuromuscular blockade.

Double-burst stimulation was compared with train-of-four stimulation in 23 adult patients receiving atracurium. Train-of-four was interrupted in 11 subjects every 2 minutes by one double-burst stimulation, and re-applied 6-30 seconds later; the height of the first double-burst response, compared with its control, was depressed slightly more than T1. The relationship between double-burst stimulation ratio and train-of-four ratio was indistinguishable from the line of identity. The train-of-four response, if repeated more than 12 seconds after double-burst stimulation, was not depressed compared with pre double-burst stimulation values. Fifteen anaesthetists were asked to detect fade manually in the second part of the study, while train-of-four was recorded on the opposite arm. One hundred and fourteen determinations were made in 12 patients. Fade was detected manually more often with double-burst stimulation than with TOF.

Subparalyzing doses of d-tubocurarine (dTC) given before succinylcholine decrease the duration of neuromuscular blockade. In animal preparations, they also abolish succinylcholine-induced twitch augmentation, defined as a greater-than-maximal contraction in response to a single stimulus. To determine quantitatively the effect of dTC on succinylcholine potency and on twitch augmentation in humans, 60 adult patients, ASA physical status I or II, were assigned randomly to receive either 0.05 mg/kg of dTC or saline 2 min before induction of anesthesia with fentanyl and thiopental. Train-of-four stimulation was applied every 12 s to the ulnar nerve and the force of contraction of the adductor pollicis muscle was measured. One minute after induction of anesthesia, 0.15, 0.20, 0.25, 0.35, or 0.50 mg/kg of succinylcholine was given. The height of the first twitch (T1) reached 121% +/- 6% (mean +/- SEM) of control without dTC, and was virtually abolished by dTC pretreatment (105% +/- 1%, P less than 0.01). Twitch augmentation was more noticeable with lower doses of succinylcholine, and was not observed in the response to the fourth stimulus of the train of four (T4). The potency of succinylcholine was decreased by approximately one-half in the dTC-pretreated groups. The ED50 was 0.27 +/- 0.04 mg/kg without dTC and 0.50 +/- 0.06 mg/kg with dTC (P less than 0.002). The corresponding values for ED90 were 0.51 +/- 0.07 and 1.02 +/- 0.12 mg/kg, respectively (P less than 0.02). The ED95 values were 0.63 +/- 0.09 and 1.28 +/- 0.15 mg/kg, respectively (P less than 0.02). The slopes of the regression lines did not deviate significantly from parallelism.(ABSTRACT TRUNCATED AT 250 WORDS)

Neuromuscular transmission was measured using train-of-four stimulation, during and after anaesthesia, in 20 patients with end-stage renal failure. Neuromuscular blockade was provided with pancuronium in single doses of either 3 or 6 mg per 70 kg, and antagonized at 10% recovery with atropine and neostigmine 2.5 mg per 70 kg. Reversal was followed by progressive recovery of muscle twitch in every patient during the 3 h of the study. Recovery was more rapid after the smaller dose of pancuronium and was inversely correlated with the duration of blockade. It is concluded that, when pancuronium is antagonized with neostigmine in patients with renal failure, neuromuscular transmission recovers without evidence of recurarization. However, when large doses of pancuronium are antagonized with neostigmine 2.5 mg, recovery may be insufficient to ensure normal ventilatory function.

The neuromuscular effect of neostigmine, 1.25 mg/70 kg, was assessed in 40 adult patients 10 min after cessation of a succinylcholine infusion. The patients had received a thiopental-nitrous oxide anesthetic supplemented by halothane or fentanyl during which they were given at least 5 mg/kg succinylcholine over more than 90 min. Train-of-four monitoring was used. Neostigmine accelerated recovery of neuromuscular function in all patients. The degree of recovery was directly related to the train-of-four ratio, and the results in patients who had received halothane were no different from those who had received fentanyl. The findings are compatible with the hypothesis that phase I block depends upon the presence of circulating succinylcholine and decreases as the latter is cleared, whereas phase II block decreases more slowly. Thus succinylcholine block can be antagonized by neostigmine if enough time is allowed for phase I block to disappear and for a pure phase II block to be present.

To determine the consequences of administering neuromuscular relaxants in divided doses, pancuronium was given either in a single dose, 0.07 mg X kg-1, or in an initial dose of 0.007 mg X kg-1 followed three minutes later with 0.063 mg X kg-1. When the drug was administered in divided dosage the onset time was reduced, the block was more intense and its duration of action was prolonged. It is suggested that such changes may be advantageous in the provision of rapid intense paralysis.

Equipotent, paralysing doses of pancuronium and tubocurarine were administered to 40 patients, aged from 1 day to 12 months, during nitrous oxide, oxygen and fentanyl anaesthesia. Neuromuscular activity was measured during onset and recovery from paralysis using train-of-four stimulation. At the same depression of the first stimulus of the train, the train-of-four ratio was decreased more during recovery than during onset with each drug and more with tubocurarine than with pancuronium. These results are qualitatively similar to those found in adults, but the decrease in train-of-four ratio was less in infants. Thus, it is concluded that prejunctional neuromuscular activity, recognized as fade in response to train-of-four stimulation, can be detected after administration of pancuronium or tubocurarine to infants, but that it is less marked than in adults.

Suxamethonium was administered to patients during recovery from non-depolarising muscle relaxation. The effect of suxamethonium varied depending upon the degree of recovery from the non-depolarising block when it was administered. Early in recovery suxamethonium produced reversal of the non-depolarising block without paralysis whereas when administered later, initial recovery of the non-depolarising block was followed by paralysis. If administered after 50% recovery the predominant effect was paralysis without initial recovery. Assessment of neuromuscular blockade with train-of-four stimulation showed that the paralysis produced by suxamethonium under these circumstances, had depolarising and non-depolarising features.

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

This study determined the characteristics of the neuromuscular block which followed intramuscular succinylcholine 4 mg . kg-1 in 20 infants during halothane anaesthesia. The infants were divided into two groups of ten; the first received succinylcholine in two percent solution and the second in five per cent solution. The mean maximum depression of the first twitch of the train-of-four (T1) was 89.7 +/- 5.0 per cent in 4.0 +/- 0.6 min, and the mean full recovery of T1 occurred in 15.6 +/- 0.9 min after injection. The maximum block achieved and the onset and recovery times were not affected by the concentration used. Depolarizing block, with equal depression of all twitches of the train-of-four was observed during the onset of neuromuscular blockade. During recovery, phase II block, as determined by a train-of-four ratio (T4/T1) of 0.5 or less, occurred frequently at T1 recovery of 25-50 per cent, but was not associated with prolonged paralysis. It is concluded that the onset time of 4 min for intramuscular succinylcholine 4 mg . kg-1 may be too long for emergency use in infants, and no improvement is obtained by increasing the concentration of injected succinylcholine from two to five per cent.

The study was designed to determine whether the onset of action of pancuronium in infants and children could be accelerated by its administration in divided doses. Sixty paediatric patients (0-1 yr (n = 20); 1-3 yr (n = 20); 3-10 yr (n = 20)) were studied during nitrous oxide-oxygen-halothane anaesthesia using train-of-four stimulation, and the results were compared with data obtained previously in adults. The time to onset correlated with the patient's age, and an additional, small acceleration was produced following divided doses which did not alter the duration or pattern of neuromuscular blockade. It was concluded that, in children, divided doses of pancuronium are unlikely to offer important clinical advantages.

Edrophonium was administered as a bolus of 2, 10 or 50 mg (0.03, 0.14 and 0.71 mg/kg) to antagonize neuromuscular block after pancuronium in man. Neuromuscular transmission was measured using "train-of-four" stimulation. Recovery started within 1 min, was maximum at 2 min and was then followed by a plateau of slow continued improvement. The degree of recovery increased with larger doses of edrophonium and also was related to the total amount of pancuronium administered although reversal was attempted at the same degree of spontaneous recovery. There was no evidence of recurarisation or depolarising block.

Train-of-four stimulation can shorten the apparent onset time of neuromuscular blocking drugs. This study was designed to verify whether the same occurred with neostigmine-assisted recovery, and whether this apparent acceleration could explain the previously reported effectiveness of the priming technique for reversal agents. Fourteen adults received atracurium, 0.5 mg.kg-1, during a thiopentone-nitrous oxide-enflurane anaesthetic. The ulnar nerves of both arms were stimulated with train-of-four stimulation every 12 seconds until 1 per cent recovery of first twitch, at which time stimulation in one arm was switched to single twitch. When mean first twitch height reached 10 per cent of control, neostigmine, 0.04 mg.kg-1, was administered either as a single bolus, or as a "priming" dose of 0.01 mg.kg-1, followed 3 min later by 0.03 mg.kg-1. No statistically significant differences were observed between single twitch in one arm and first twitch height of the train-of-four in the other arm for the next 10 min. With priming, first twitch height was 45 +/- (SEM) 5 per cent at 5 min and 85 +/- 6 per cent at 10 min, compared with 72 +/- 5 per cent (p less than 0.05) and 91 +/- 2 per cent (NS) respectively without priming. Train-of-four ratio was 28 +/- 3 per cent at 5 min and 65 +/- 5 per cent at 10 min with priming, versus 53 +/- 4 per cent (P less than 0.05) and 73 +/- 3 per cent (NS) respectively without priming.(ABSTRACT TRUNCATED AT 250 WORDS)

Single twitch and train-of-four stimulation were applied at 0.08 Hz to each ulnar nerve and the force of contraction of the adductor pollicis was recorded during onset of and recovery from neuromuscular blockade by suxamethonium 1 mg kg-1 or atracurium 0.4 mg kg-1. Times to 90% first twitch blockade of train-of-four were (mean +/- SEM) 0.82 +/- 0.08 and 1.98 +/- 0.18 min for suxamethonium and atracurium, respectively, compared with times to 90% single twitch blockade of 1.00 +/- 0.07 and 3.35 +/- 0.37 min, respectively (P less than 0.05 in both cases). Apparent onset time also depended on how long train-of-four stimulation had been applied before injection of atracurium. The mode of stimulation had little effect on time to 10% recovery. The results are consistent with stimulation-induced augmentation in muscle blood flow, which increased delivery of the drug to the neuromuscular junction.

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.

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.