Ketamine potentiates nondepolarizing neuromuscular relaxants in a primate

Ketamine has many neuromuscular effects in vitro. Its neuromuscular effects in vivo have been controversial and inconsistent. To systematically examine its neuromuscular effects over a wide dose range and its interaction with all popular nondepolarizing neuromuscular relaxants, the effects of ketamine 2, 5, and 10 mg/kg IV were studied on a continuous but incomplete (50%) neuromuscular block preestablished by an IV infusion of d-tubocurarine, atracurium, vecuronium, and pancuronium. Indirectly stimulated adductor pollicis muscle response of monkeys anesthetized with 0.5-1.0% halothane in oxygen were quantified. Ketamine in the absence of a neuromuscular relaxant had no effect on the thumb twitch. In a dose-dependent manner, ketamine significantly enhanced the 50% depression of the thumb twitch preestablished by a constant IV infusion of each of the four muscle relaxants studied. Ketamine 2 mg/kg potentiated the neuromuscular relaxants in the following order of magnitude: vecuronium greater than atracurium greater than d-tubocurarine greater than pancuronium. However, with a 10 mg/kg dose of ketamine, pancuronium became as potentiated as was vecuronium, i.e., pancuronium = vecuronium greater than atracurium greater than d-tubocurarine. It is concluded that in the primate, ketamine potentiates all nondepolarizing muscle relaxants in a dose-dependent manner.     

Benzodiazepines and neuromuscular blocking drugs in patients

The interaction between four benzodiazepines (diazepam, lorazepam, lormetazepam and midazolam) and two nondepolarizing neuromuscular blocking drugs (vecuronium and atracurium) was investigated in 113 patients during general anaesthesia. Neuromuscular function was monitored by recording the mechanical twitch tension of the adductor pollicis muscle of the thumb in response to ulnar nerve stimulation with single supramaximal stimuli of 0.2 ms at 0.1 Hz. In the first group of patients a benzodiazepine (diazepam 20 mg, lorazepam 5 mg, lormetazepam 2 mg or midazolam 15 mg), was injected i.v. 15 min before a single bolus of vecuronium 45 micrograms kg-1. In the second group of patients suxamethonium 1 mg kg-1 was given for endotracheal intubation, and 30 min later the patients received atracurium 200 micrograms kg-1. Fifteen min before injection of atracurium one of the same benzodiazepines as in the first group was injected i.v. Comparisons were made with control patients receiving thiopentone. Neither benzodiazepine caused significant potentiation of neuromuscular blocking agents in comparison with control. With midazolam, however, the duration to 25% and to 75% recovery of the twitch height after vecuronium was significantly longer than with diazepam. The time to 25% recovery of the twitch height after atracurium was significantly longer in patients receiving midazolam than in those receiving diazepam. The recovery index was not influenced by the four benzodiazepines.     

Sufentanil: the effect on cardiocirculatory parameters and intubation conditions on administration of pancuronium or vecuronium

A lack of uniform methodology used in the assessment of moderate doses of sufentanil in combination with non-depolarizing neuromuscular blocking drugs formed the basis of the current study which compared under randomized conditions the effects of sufentanil-pancuronium versus sufentanil-vecuronium on hemodynamics, intubating conditions and chest wall rigidity during induction of anesthesia. MATERIAL and METHODS. One hundred and twenty ASA physical status I and II patients aged between 20 and 40 years of age who were undergoing elective urological surgery were included in the study. Premedication consisted of 0.15 mg kg-1 diazepam, given orally 60 min prior to induction of anesthesia. Patients were randomly divided into eight groups of 15 each to receive 0.5 microgram kg-1 sufentanil or placebo in combination with pancuronium (groups I-IV) or vecuronium (groups V-VIII) Within each group, patients were randomly allocated to receive the relaxant either as a single bolus dose of 0.095 mg kg-1 pancuronium or 0.1 mg kg-1 vecuronium, or in divided doses (the priming principle), the smaller priming dose (0.015 mg kg-1 pancuronium or 0.015 mg kg-1 vecuronium) being administered 2 min before induction of anesthesia with 5 mg kg-1 thiopentone, followed by the second intubating dose of 0.080 mg kg-1 pancuronium or 0.085 mg kg-1 vecuronium. To maintain blind study conditions in the groups, the patients given the relaxants in one dose were given an equivalent volume of saline 2 min prior before 5 mg kg-1 thiopentone. Intubating was attempted 60 s after administration of the main dose of the relaxant, and conditions were assessed on a four-point scale: excellent, satisfactory, fair, or poor. Neuromuscular transmission was monitored with the Datex Relaxograph, a neuromuscular transmission analyzer, that utilizes the integration of the EMG response. Producing train-of-four (TOF) stimuli, with a pulse width of 100 microseconds and a frequency of 2 Hz every 20 s the following parameters were recorded by the Datex Relaxograph: The percentage of first twitch amplitude compared with the reference (T1), and the train-of-four (TOF) ratio, i.e., the ratio of last twitch height to first height. Measurements were taken after premedication in the operating room, the value which served as a baseline (t0), 1 min after sufentanil or placebo (t1), 1 min after priming or placebo (t2), 1 min after thiopentone (t3), and 1 min after intubation (t4).(ABSTRACT TRUNCATED AT 400 WORDS)     

Experimental pharmacology of atracurium dibesylate

Atracurium dibesylate is a new non depolarizing muscle relaxant, metabolized by a non enzymic pathway, the Hofmann elimination. The potency of atracurium in animals was similar to d-tubocurarine and six times less than that of pancuronium. In the cat, the ED50 was 130 micrograms . kg-1; an intravenous dose of 250 micrograms . kg-1 atracurium was sufficient to cause complete neuromuscular block; its duration was 29 min. Single twitch block was readily antagonized by neostigmine 50-100 micrograms . kg-1 or edrophonium 200 micrograms . kg-1. Halothane potentiated the block given by atracurium. Dose ratio for 50% vagal block (ED50) and 50% neuromuscular block was 24; atracurium had weak ganglioplegic effects. 2,000 micrograms . kg-1 atracurium (eight times the neuromuscular blocking dose) reduced mean aortic pressure, heart rate, cardiac output and peripheral resistance. Such effects could be prevented by giving histamine receptor blockers prior to injecting atracurium.     

Atracurium for short surgical procedures: a comparison with succinylcholine

A comparison was made between atracurium and succinylcholine in 40 patients undergoing short gynaecological procedures of 30 minutes or less. Good intubating conditions were produced in 76.7 +/- 39.3 seconds (mean +/- S.D.) with succinylcholine 1 mg . kg-1 and 198 +/- 84 seconds with atracurium 400 micrograms . kg-1. Muscle relaxation was maintained with the initial dose of atracurium or with repeated boluses of succinylcholine. The mean time of surgery was 17.65 +/- 5.3 minutes in the atracurium group and 15.2 +/- 4.6 minutes in the succinylcholine group. Residual neuromuscular block with atracurium was reversed with neostigmine 0.036 mg . kg-1 and atropine 0.018 mg . kg-1. Recovery of neuromuscular function following reversal, assessed by return of all responses to train-of-four stimulation occurred in 5.05 +/- 4.6 minutes in the atracurium group but half the above doses of neostigmine and atropine were repeated in three patients. We conclude that a single dose of atracurium 400 micrograms . kg-1 is suitable for intubation and maintainance of muscle relaxation for short surgical procedures. However, the onset of action is slow, compared to succinylcholine. Residual neuromuscular block can be antagonised with standard doses of neostigmine, less than 20 minutes after the initial dose of relaxant. Atracurium appears to be a suitable alternative for short procedures where succinylcholine is unsuitable or contraindicated.     

Potentiation of atracurium by pancuronium and d-tubocurarine

In 60 adult patients undergoing general surgical procedures, the effect of pancuronium or d-tubocurarine "pretreatment" on the injection of a 0.1 mg X kg-1 bolus of atracurium was measured in two separate studies. In study 1, the patients received either 0.5 mg (approximately 0.007 mg X kg-1) or 1.0 mg (approximately 0.015 mg X kg-1) pancuronium, or placebo (saline) three minutes before the injection of atracurium 0.1 mg X kg-1. In study 2, the patients received 0.05 mg X kg-1 or 0.1 mg X kg-1 d-tubocurarine, or a placebo. The degree of neuromuscular blockade was assessed by evoked mechanogram (adductor pollicis muscle) using supramaximal train-of-four stimulation. Patients receiving pancuronium or d-tubocurarine pretreatment (equal to an ED5-ED15 dose) showed significantly greater inhibition of twitch (ED70-ED80) and train-of-four ratio compared with the placebo groups (ED35-ED40). Pretreatment with the larger dose of d-tubocurarine (0.1 mg X kg-1) was associated with significant neuromuscular blockade. It is concluded that pancuronium and d-tubocurarine pretreatments potentiate the clinical action of 0.1 mg X kg-1 atracurium in man by 35-100 per cent.     

Train-of-four fade of non depolarizing muscle relaxants: an insight into the mechanism of precurarization

This study was carried out to assess the prejunctional effect of non depolarizing muscle relaxants during the onset of neuromuscular blockade using the train-of-four ratio (TR). The prejunctional effect was compared with previous results concerning the ability of the relaxants to prevent suxamethonium-induced fasciculations. Fifty-three adult patients were relaxed with small incremental doses of either alcuronium (0.03 mg.kg-1), atracurium (0.04 mg.kg-1), pancuronium (0.01 mg.kg-1), d-tubocurarine (0.05 mg.kg-1) or vecuronium (0.01 mg.kg-1) during anaesthesia with thiopentone, fentanyl and nitrous oxide in oxygen. The muscle relaxant was given after recovery from an initial suxamethonium blockade needed for tracheal intubation. The evoked integrated EMG response to supramaximal train-of-four (2 Hz) stimulation was recorded every 20 s. TR % was calculated at different first twitch (T1) levels during the onset of neuromuscular blockade. Significant changes occurred at the 100% and 90% T1 levels, alcuronium having the lowest mean TR values. Atracurium, pancuronium and vecuronium gave similar TR values. Results with d-tubocurarine placed it between alcuronium and the others. These train-of-four ratio results were compared with the ability of non depolarizing muscle relaxants to prevent fasciculations. In conclusion, the stronger the train-of-four fade, the greater was the ability of the relaxant to prevent suxamethonium-induced fasciculations. This supports the theory that the blockade of prejunctional cholinergic receptors is the mechanism of action of precurarization.     

Rapid tracheal intubation with atracurium--a comparison of priming intervals

To determine the optimal interval between the administration of the priming dose and the intubating dose, atracurium was given to 44 patients either in a single dose of 0.5 mg X kg-1 or in an initial dose of 0.06 mg X kg-1 followed two, three or five minutes later with 0.44 mg X kg-1. When atracurium was given as a single bolus of 0.5 mg X kg-1 the time to 100 per cent twitch suppression (onset time) was 90.9 +/- 36 (mean +/- SD) seconds. When the priming interval was two minutes, the onset time of the intubating dose was 76.6 +/- 42.2 seconds (p = NS). But when the priming interval was three or five minutes, the onset times were 42.2 +/- 16.5 (p less than 0.01) and 52.6 +/- 28.8 (p less than 0.05) seconds respectively. Waiting for five minutes after the administration of the priming dose did not improve the intubating conditions. It is concluded that three minutes appears to be the optimal time interval for the administration of atracurium in divided doses. When a priming dose of atracurium is given three minutes before the intubating dose, it can provide an alternative to succinylcholine for rapid endotracheal intubation.     

Clinical evaluation of atracurium besylate in patients at risk: major burns

Atracurium besylate 0.5 mg/kg-1, an intermediate-duration non-depolarizing neuromuscular relaxant, was administered slowly (over 75 sec) in anesthesia induction of 61 patients with major thermal injury undergoing surgical excision and immediate skin-grafting procedures. Patients' mean +/- SD age was 40 +/- 9, body weight 64 +/- 2, burn size ranging from 20% to 90% of body surface area (BSA), postburn day of surgery 5th and more. Induction of anesthesia was carried out with sodium thiopental 2-5 mg/kg-1 plus fentanyl 2.8 micrograms/kg-1 e.v. and after few minutes atracurium 0.5 mg/kg-1 e.v. Anesthesia was maintained with N2O/O2 (70%/30%), isoflurane and small amounts of fentanyl. The mean arterial pressure and heart rate were recorded at I, II, III, IV, V min post atracurium administration. The endotracheal intubation conditions were assessed by a "IOT score". Results are expressed as mean value +/- standard deviation. The significance of the difference in mean values was analysed by t-test. Little haemodynamic changes occurred; intubating conditions showed a relative hyposensitivity of burn patients to atracurium, more severely burned patients (greater than 50-60%) exhibiting greater resistance.     

A pharmacodynamic analysis of the onset of neuromuscular blockade by nondepolarizing muscle relaxants--the pharmacodynamics of a large dose of vecuronium

From Sheiner's equation on pharmacokinetics and pharmacodynamics, we derived a new equation which described the pharmacodynamics of nondepolarizing muscle relaxants during the onset phase. This equation showed that log (l0/l-1) had a linear relation to log (t) where "t" is the time after the administration of nondepolarizing muscle relaxant and "l" and "l0" are the twitch height at t = t and t = 0 respectively. It also implies that the administration dose (D) is inversely proportional to the onset time (OT), i.e., D.OT = const. We proved that these two relations held well for the actual 7 cases of vecuronium use in man. In conclusion, when vecuronium dose level was within 0.15-0.30 mg.kg-1 i.v., the dose was inversely proportional to the onset time which was defined as the time interval from the end of the administration of vecuronium until the single twitch was depressed under 5% of control value, i.e., Dose (mg.kg-1) x onset-time (sec) not equal to 24. During anesthesia with enflurane as well as during neuroleptanesthesia, a dose of vecuronium 0.3 mg.kg-1 (n = 7) was found to produce a duration of neuromuscular blocking action equal to the mean duration produced by pancuronium 0.1 mg.kg-1.     

Comparative clinical studies of vecuronium, atracurium and pancuronium

The new relaxants vecuronium (Norcuron) and atracurium (Tracrium) have been compared with pancuronium (Pavulon) with respect to onset and duration of action and intubating conditions under clinical situations. A variant of the balanced anaesthesia technique with flunitrazepam, fentanyl and N2O/O2 was used. The following doses were considered equipotent (mg/kg body weight): vecuronium 0.07/0.10; atracurium 0.35/0.50; pancuronium 0.08/0.115. The degree of neuromuscular block was assessed in a semiquantitative manner, using the train of four. No difference between the three relaxants in onset of action was found. After the high doses, however, full paralysis developed 60 s earlier. The same is true of intubating conditions. Good or very good intubating conditions were obtained in the majority of cases 3 minutes after injection of the drug. Following the higher dose, good intubating conditions are achieved approximatively 1/2-1 min sooner. Both new relaxants allow for relatively rapid intubation without the inconvenience of a long duration of action. After a low initial dose the following time for recovery to 25% was noted (means +/- S.D., min): vecuronium 20.3 +/- 7.0; atracurium 28.0 +/- 3.1; pancuronium 53.3 +/- 14.8. The early recovery phase (from 5% to 25% recovery) was 6.1 +/- 2.4 after vecuronium, 8.3 +/- 1.7 after atracurium, 17.2 +/- 10.8 after pancuronium. There is a good correlation between our semiquantitative results, using the train of four, and quantitative recordings of muscle contractions reported in the literature. Both drugs show no cumulative effect after five repeated administrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variability of onset times within and among relaxant regimens.

STUDY OBJECTIVE: To evaluate the consistency of times to 95% twitch height depression (T95%) in groups of patients receiving identical induction and relaxant regimens. DESIGN: Prospective, noncontrolled, blinded study. SETTING: Ambulatory surgical unit at a university medical center. PATIENTS: Seventy-five ASA physical status I and II patients undergoing general endotracheal anesthesia. INTERVENTIONS: Patients received succinylcholine 1.5 mg/kg or a nondepolarizing regimen with doses ranging from approximately 1.5 to 6 times the ED95, with or without a priming dose. MEASUREMENTS AND MAIN RESULTS: For each of the eight relaxant regimens used in five or more patients, the intraregimen variability of T95% (at the adductor pollicis muscle upon ulnar stimulation at 0.1 Hz) was expressed as SD and range, and the individual data points were displayed. There was wide intraregimen variability. For each regimen, the slowest T95% was at least 73% longer than the fastest T95%. For the 16 patients receiving a priming dose plus an intubating dose 5 or more times the ED95, the median T95% was 95 seconds; however, T95% was beyond 120 seconds in 5 of the 16 cases. CONCLUSIONS: The wide variability in onset times among subjects receiving the same regimen indicates that monitoring of neuromuscular response, preferably to a relatively slow rate of neurostimulation, is essential if one elects to use moderate to high doses of atracurium and/or vecuronium for rapid-sequence induction in a patient in whom movement or coughing is unacceptable. Since onset times were not symmetrical about the mean, the magnitude and frequency of unacceptable onset times would not be fully appreciated unless the individual data points were displayed. Such information may be critical when reporting the suitability of a neuromuscular blocking drug for rapid intubation.     

Accelerated onset of non-depolarizing neuromuscular blocking drugs: pancuronium, atracurium and vecuronium. A comparison with succinylcholine

The time of onset and degree of neuromuscular blockade (NMB) in 80 anaesthetized patients, following either a single bolus injection of pancuronium 0.95 mg kg-1, atracurium 0.53 mg kg-1 or vecuronium 0.07 mg kg-1, or divided doses of pancuronium 0.15 mg kg-1, atracurium 0.07 mg kg-1 or vecuronium 0.01 mg kg-1 administered 3 min or 5 min before the second dose of pancuronium 0.08 mg kg-1, atracurium 0.46 mg kg-1 or vecuronium 0.06 mg kg-1, were determined and compared to the same parameters measured following succinylcholine administration (1 mg kg-1). The time to maximum NMB (100%) following the administration of succinylcholine was 58.1 +/- 5.3 s, whereas the time to maximum NMB (100%) following a single bolus injection of either pancuronium, atracurium or vecuronium was 130.6 +/- 22.2, 93.0 +/- 6.4, 127.5 +/- 13.0 s, respectively. These values for time to maximum NMB are significantly longer than the time required for succinylcholine to achieve maximal blockade. The time to attain maximum NMB following divided doses of pancuronium, atracurium or vecuronium separated by 3 min decreased significantly to 77.9 +/- 4.3, 77.5 +/- 7.6, 89.0 +/- 8.6 s, respectively. However, when the two doses of drug were separated by 5 min, only small, non-significant further decreases occurred in the time required to achieve maximum blockade. Although the time to maximum NMB following divided doses of pancuronium, atracurium or vecuronium is significantly longer than that for succinylcholine, divided dosing significantly decreases the time required to reach maximal NMB.     

Atracurium and pancuronium in renal insufficiency

The duration and possible accumulation of atracurium and pancuronium were studied in 59 patients (29 anephric and 30 normal) anaesthetized with 0.5% halothane in O2/N2O and supplemented by fentanyl. Equipotent doses of atracurium (0.5 mg.kg-1) and pancuronium (0.1 mg.kg-1) were given for intubation. Atracurium had a lower potency in anephric patients. The duration (first twitch response (TI) return to 20% of control) for atracurium was 28 min in anephric and 36 in normal patients. The corresponding mean times for pancuronium were 171 and 123 min, but with a very wide variation range 20-380 min and 45-360 min, respectively). The duration of up to 8 incremental doses of atracurium (0.1 mg kg-1) was 27-29 min in normal patients and of up to 13 increments was 25-34 min in anephric patients. Pancuronium (0.015 mg kg-1) was given in a maximum of 4 increments. In normal patients the mean durations were 40-56 min, and in anephric patients 65-100 min. The duration of pancuronium, but not of atracurium, was prolonged with repeated injections (up to 2.7 times) in anephric patients. After pancuronium the spontaneous recovery was significantly slower in anephric patients, while the induced recovery was rapid and reliable in all groups. We conclude that atracurium is a safe and reliable muscle relaxant in normal and anephric patients, while pancuronium in both groups has a disturbing variation in duration and, in addition, signs of significant accumulation in anephric patients. The use of a nerve stimulator is mandatory.     

Neuromuscular blockade for rapid tracheal intubation in children: comparison of succinylcholine and pancuronium

To compare the effectiveness of succinylcholine and pancuronium for rapid intubation in children, 49 healthy children ages two to eight years were studied. After induction of anaesthesia with thiopentone and atropine, and administration of droperidol, fentanyl, nitrous oxide, and oxygen, each child received one of the following muscle relaxants: succinylcholine 1.5 mg X kg-1 (n = 12), succinylcholine 1.0 mg X kg-1 (n = 13), pancuronium 0.15 mg X kg-1 (n = 11), or pancuronium 0.10 mg X kg-1 (n = 13). The force of thumb adduction was measured by stimulating the ulnar nerve with repetitive supramaximal single twitches (0.15 Hz). The time to 95 per cent twitch depression (mean +/- S.D.) was most rapid with succinylcholine 1.5 mg X kg-1 (40.8 +/- 3.0 seconds) and succinylcholine 1.0 mg X kg-1 (51.8 +/- 14.0 seconds), slowest with pancuronium 0.10 mg X kg-1 (150.9 +/- 38.0 seconds), and intermediate with pancuronium 0.15 mg X kg-1 (80.3 +/- 21.8 seconds) (p less than 0.005). The intubating conditions were excellent in 100% of the children who received succinylcholine 1.5 and 1.0 mg X kg-1, and pancuronium 0.15 mg X kg-1, but were excellent in only 69 per cent of those who received pancuronium 0.10 mg X kg-1. We conclude that succinylcholine 1.5 mg X kg-1 produces the most rapid onset of excellent intubating conditions in children. In children in whom succinylcholine is contra-indicated, pancuronium 0.15 mg X kg-1 provides excellent intubating conditions within 80 seconds.     

Duration of action of vecuronium after an intubating dose of rapacuronium, vecuronium, or succinylcholine

Rapacuronium (RAP) is a new, rapid-onset, short-duration, nondepolarizing neuromuscular blocker. If RAP is used to facilitate endotracheal intubation, what will the duration of a subsequent maintenance dose of vecuronium (VEC) be? We investigated the duration of action of a maintenance dose of VEC after intubation with RAP, VEC, or succinylcholine (SUC). Adult surgical patients under general anesthesia were randomly allocated to receive a tracheal intubating dose of RAP 1.5 mg/kg, VEC 0.1 mg/kg, or SUC 1 mg/kg. The anesthetic was induced with propofol and maintained with propofol, nitrous oxide, and oxygen. Neuromuscular function was monitored with electromyography. Recovery of the intubating dose of neuromuscular blocker was allowed to occur spontaneously until the first twitch of the train-of-four (T1) reached 50% of baseline, and then VEC 0.025 mg/kg (0.5 x 95% effective dose [ED(95)]) was administered. The onset, duration, and recovery to T1 = 25% and 50% were recorded. The durations of action (recovery of T1 25%) after intubating doses of RAP, VEC, and SUC were 13.7 +/- 5.3, 43.2 +/- 13.2, and 9.2 +/- 3.7 min (mean +/- SD), respectively (P < 0.0001). The times to maximum depression of T1 after a maintenance dose of VEC (0.5 x ED(95)) were 5.4 +/- 2.9, 5.1 +/- 2.5, and 5.3 +/- 2.8 min (mean +/- SD) for the RAP, VEC, and SUC groups, respectively. Recoveries to T1 25% after VEC for the RAP, VEC, and SUC groups were 18.9 +/- 11.5, 21.5 +/- 8.03, and 12.8 +/- 8.4 min, and at T1 50% they were 21.5 +/- 9.1, 30.8 +/- 9.5, and 15.5 +/- 9.7 min (mean +/- SD), respectively (P < 0.001, RAP and VEC versus SUC). The duration of action of a maintenance dose of VEC was similar after an intubating dose of RAP or VEC but was shortened when preceded by an intubating dose of SUC. IMPLICATIONS: The duration of action of a maintenance dose of vecuronium was longer after an endotracheal intubating dose of rapacuronium compared with succinylcholine.     

A comparative evaluation of intubating doses of atracurium,d-tubocurarine,pancuronium and vecuronium in children

To determine the onset and recovery times and haemodynamic effects of intubating doses of atracurium (0.4 mg.kg-1), d-tubocurarine (0.8 mg.kg-1), pancuronium (0.12 mg.kg-1), and vecuronium (0.07 mg.kg-1), sixty-seven children aged one to eight years were studied under halothane and nitrous oxide anaesthesia. The time to maximum twitch depression and the time to recovery to T1/Tc 25 per cent were recorded with an integrated evoked EMG recorder. The heart rate and systolic blood pressure were recorded for five minutes after drug administration and prior to intubation. There was no difference in onset times between drugs. The recovery time to T1/Tc 25 per cent following vecuronium (25.5 +/- 6.3 min) was shorter than following atracurium (37.5 +/- 7.0 min). Recovery times for d-tubocurarine and pancuronium were greater than sixty minutes. Elevation of heart rate occurred after administration of pancuronium (+29.8 per cent to +38.6 per cent) and d-tubocurarine (+31 per cent to +34.9 per cent), but no change was observed after atracurium or vecuronium. Elevation of blood pressure was greatest following pancuronium (+10.8 to +14.8 per cent). No significant change was observed following atracurium or vecuronium. A transient lowering of blood pressure (-9.3 per cent) occurred following d-tubocurarine.     

Maintenance of surgical muscle relaxation by repeat doses of vecuronium and atracurium at three different dose levels.

The time-course of the neuromuscular effects of vecuronium (n = 25) and atracurium (n = 25) has been compared at three different levels of maintenance dose in anaesthetized patients. Following intubation with vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1, surgical muscle relaxation was maintained by using increments of equipotent maintenance doses equivalent to 0.5, 1.0 and 1.5 x ED95 for each drug. Repeat doses were administered each time the twitch height, depressed by the previous dose, returned to 25% of its control value. The apparent increase in the duration of action, i.e. the difference between the duration of the last and the first maintenance dose, did not reach statistical significance and approximated 3 +/- 2, 6 +/- 4, 11 +/- 5 and 3 +/- 2, 8 +/- 13, 5 +/- 7 min following the low, medium and high maintenance doses of vecuronium and atracurium, respectively.     

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.