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.     

Clinical use in adults of 2 new muscle relaxants: atracurium and vecuronium

115 general and urologic surgery adult patients, ASA class I-II, were divided in four groups according to initial bolus and relaxant used: group A atracurium 0.6 mg X kg-1, group B 0.5 mg X kg-1, group C vecuronium 0.1 mg X kg-1 and group D pancuronium 0.1 mg X kg-1. When the single twitch recovered to 25% of control height (T25), subgroups were individualized depending on whether repeat doses of 1/3 of initial bolus were given or not, and whether reversal was spontaneous or obtained by a standard dose of neostigmine 2.5 mg and atropine 1.25 mg. By ulnar nerve stimulation at the wrist, the force of thumb adduction was recorded on a polygraph; single twitch (tw), train of four (tof) and ratio tof 4/1 (Rtof) were measured. Anaesthesia was induced with thiopentone and fentanyl without premedication and maintained with fentanyl and N2O in oxygen; the trachea was intubated once the block was at its maximum. The onset time of maximal block was 5 min for groups A, B and C, and 7.9 min for group D. T25 was 39.9 +/- 8.5 min for group A, 34.4 +/- 9.7 min for group B, 28.9 +/- 9.9 min for group C and 70.7 +/- 25.9 min for group D. A Rtof equal to 75% was achieved in less than 65 min with atracurium and vecuronium, but much later with pancuronium. Reversal at T25 was efficient, but not really required, for atracurium and vecuronium, but necessary and useful for pancuronium.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of the degree of muscle blockade: a comparative study using electromyography of the muscular relaxation induced by pancuronium, atracurium and vecuronium

To compare the muscle relaxing effect of pancuronium, atracurium and vecuronium, 99 patients operated on under neuroleptanesthesia were divided in three groups depending on whether they had received, during induction, pancuronium 0.1 mg/kg, atracurium 0.5 mg/kg, or vecuronium 0.1 mg/kg. One-fourth of the initial dose was repeated if necessary. The electromyographic study of the muscle relaxing effect was carried out with stimulation of the cubital nerve with courses of supramaximal square wave electric stimuli in 'trains of four'. The time to maximal blockade (TMB), the time of clinical effectiveness (TCE), the total duration time (TDT), the time of duration of the maintenance dose (DM 25) and the recovery index (RI) were measured. TMB was 4.3 +/- 1 min for pancuronium, 3.5 +/- 0.8 min for atracurium, and 3.3 +/- 0.98 min for vecuronium. The differences between pancuronium and the other drugs were statistically significant, but they were not so between the latter two. TCE was 67.9 +/- 13.5 min for pancuronium, significantly longer than with vecuronium and atracurium (28.2 +/- 5.7 and 31.5 +/- 4.7, respectively). TDT was 126.2 +/- 19.9 min for pancuronium, 61.2 +/- 11.5 min for atracurium and 55.5 +/- 16.7 for vecuronium. The mean duration of the repeated dose was 52.7 +/- 8.4 min for pancuronium, 19.9 +/- 5 min for vecuronium and 10.9 +/- 5 min for atracurium. RI, which was similar for atracurium and vecuronium (12.7 +/- 1.7 min and 12.8 +/- 3.3 min), was longer for pancuronium (27.7 +/- 4.3 min).     

Facilitation of rapid endotracheal intubations with divided doses of nondepolarizing neuromuscular blocking drugs

The authors sought to determine whether prior administration of a small, subparalyzing dose of nondepolarizing muscle relaxant would shorten the onset time of an intubating dose of muscle relaxant. Initially, in 60 anesthetized patients, twitch response of adductor pollicis to ulnar nerve stimulation was studied after a small dose of pancuronium 0.015 mg . kg-1, metocurine 0.03 mg . kg-1, or d-tubocurarine 0.04 mg . kg-1, followed 3 min later by pancuronium 0.08 mg . kg-1 or atracurium 0.4 mg . kg-1 administered iv. After 60 s, the minimum neuromuscular block, in all patients was 79.0 +/- 5.0%. A 95% depression or twitch tension occurred between 59.1 +/- 5.3 and 86.1 +/- 5.9 s. In another 60 patients, intubating conditions under similar regimen were studied, except the small dose of muscle relaxant was given immediately prior to induction of anesthesia. At the end of 60 s, good to excellent intubating conditions were present in 100% of the patients following the second dose of pancuronium and in 83% of the patients following atracurium. In 17% of the patients, after atracurium intubating conditions were fair. When nondepolarizing neuromuscular blocking drugs are administered in divided doses, neuromuscular blockade adequate for endotracheal intubation is achieved in less than 90 s. This facilitates rapid endotracheal intubation in a time comparable to using succinylcholine, without undesirable effects of the depolarizing neuromuscular blocking drugs.     

Administration of vecuronium, atracurium and pancuronium in divided doses: effect on onset and duration of action

The time to onset of neuromuscular block (as assessed by single twitch stimulation at 0.1 Hz) and the duration to 25% recovery of twitch height were measured after administration of vecuronium 0.1 mg kg-1, atracurium 0.5 mg kg-1 or pancuronium 0.1 mg kg-1, administered either as a single bolus or in divided doses, 10% being administered 4 min prior to the remaining 90%. The patients were anaesthetized with thiopentone, nitrous oxide in oxygen and i.v. fentanyl. There was no significant difference between the single- and divided-dose groups, either in the onset times (2.8 and 2.9 min for vecuronium, 2.7 and 2.4 min for atracurium and 3.3 min each for pancuronium for single- and divided-dose groups, respectively) or the duration to 25% recovery of twitch height (35 and 29 min for vecuronium, 45 and 39 min for atracurium and 87 and 93 min for pancuronium for single- and divided-dose groups, respectively).     

NEUROMUSCULAR BLOCKING EFFECTS OF ATRACURIUM, VECURONIUM AND PANCURONIUM DURING BOLUS AND INFUSION ADMINISTRATION

The potencies of atracurium, vecuronium and pancuronium werecompared using bolus injections and continuous infusions. Thesizes of the bolus injections were based on previously determinedcumulative dose-response relationships. Dose requirements for90% and 50% sustained blockade were estimated by use of continuousinfusion, and the corresponding plasma concentrations were measuredfor vecuronium and pancuronium. The effect of single bolus injectionscorrelated well with the cumulative dose-responses, confirmingrelative potencies for atracurium, vecuronium and pancuroniumof approximately 1:5:4. The maintenance doses (µg kg^-1h^-1) for 90 % blockade were: atracurium 382.8, vecuronium 101.9,and pancuronium 36.9, makingtherelativedoserequirements 10.4:2.8:1.The same dose ratio was found for atracurium and vecuroniumat 50% blockade. This required about 60 % of the doses neededfor maintenance of 90% response. The relative potency of vecuroniumand pancuronium in plasma was 1.1:1. The 25–75% recoveryindex was significantly shorter for vecuronium than for atracurium.     

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)     

Neuromuscular and cardiovascular effects of mivacurium chloride in surgical patients receiving nitrous oxide-narcotic or nitrous oxide-isoflurane anaesthesia

The neuromuscular and cardiovascular effects of mivacurium chloride were studied during nitrous oxide-oxygen narcotic (fentanyl) (n = 90) and nitrous oxide-oxygen isoflurane (ISO) anaesthesia (n = 45). In addition, a separate group (n = 9) received succinylcholine during fentanyl anaesthesia to compare its neuromuscular effects with mivacurium. Mivacurium was initially administered as a single bolus in doses from 0.03 mg.kg-1 to 0.25 mg.kg-1 to study the dose-response relationships, as well as the cardiovascular effects of mivacurium. Neuromuscular block (NMB) was measured by recording the twitch response of the adductor pollicis muscle following ulnar nerve stimulation (0.15 Hz, 0.2 ms supramaximal voltage). The ED95 values for mivacurium were estimated to be 0.073 mg.kg-1 and 0.053 mg.kg-1 in the fentanyl and ISO groups respectively. The duration of block (time from injection to 95 per cent recovery) for a dose of 0.05 mg.kg-1 mivacurium was 15.3 +/- 1.0 min and 21.5 +/- 1.3 min for fentanyl and ISO anaesthesia, respectively. The recovery index (25-75 per cent) between initial bolus dose (6.1 +/- 0.5 min), repeat bolus doses (7.6 +/- 0.6 min), mivacurium infusion (6.7 +/- 0.7 min) and succinylcholine infusion (6.8 +/- 1.8 min) were not significantly different. There was minimal change in mean arterial pressure (MAP) or heart rate (HR) following bolus doses of mivacurium up to 0.15 mg.kg-1. Bolus administration of 0.20 mg.kg-1 or 0.25 mg.kg-1 of mivacurium decreased MAP from 78.2 +/- 2.5 to 64.0 +/- 3.2 mmHg (range 12-59 per cent of control) (P less than 0.05). The same doses when administered slowly over 30 sec produced minimal change in MAP or HR.     

Neuromuscular blockade following high-dose vecuronium administration

To determine the onset time, duration of action and recovery time of high-dose vecuronium, 70 patients were assigned to receive either 100, 150, 200 or 300 micrograms.kg-1 of vecuronium for muscle relaxation during elective surgery. Neuromuscular blockade was continuously quantitated by recording the EMG response to stimulation of the ulnar nerve. The onset time from the time of vecuronium administration to maximum blockade decreased from 4.6 +/- 1.1 to 2.4 +/- 0.5 min when the vecuronium doses increased from 100 to 300 micrograms.kg-1. Significant differences were observed in the onset time between the 100 micrograms.kg-1 dose and the other dose groups. Endotracheal intubating conditions were excellent in all patients except 3 in the 100 micrograms.kg-1 dose group. The duration of action from the time of injection to 25% recovery increased from 32 +/- 9 to 138 +/- 48 min in a dose dependent manner. The duration of action after increment doses of 40 or 50 micrograms.kg-1 up to 25% recovery of T1 did not vary significantly within the same dose group. With an initial dose of 150 micrograms.kg-1 and subsequent increment doses of 50 micrograms.kg-1 or less, the duration of action remained constant. The recovery time from 25 to 75% recovery was within 11 minutes when antagonists were administered. High-dose vecuronium may, therefore, be a useful alternative to SCC, when a rapid onset is required and to pancuronium, when a rapid recovery from neuromuscular blockade is requested.     

Onset of the effect and intubation conditions following atracurium, verocuronium and suxamethonium

1. The onset of neuromuscular blockade following i.v. injection of atracurium 0.3, 0.4, or 0.5 mg/kg; vecuronium 0.08 or 0.1 mg/kg; and succinylcholine 1.0 mg/kg was studied in 205 adult patients during induction of anesthesia by means of the compound action potential (EMG) of the hypothenar muscle, which was indirectly stimulated via the ulnar nerve above the wrist, using the Datex Relaxograph. At the same time, the intubation conditions at 0.5, 1, 2, or 3 min after injection were assessed using a scoring system (Crul 1983) related to ease of laryngoscopy, movement of vocal cords and coughing, and reflex movements of the extremities. 2. Neuromuscular blockade and intubation conditions 2 min after administration of atracurium 0.3 mg/kg were 60 +/- 10% and 8.7 +/- 0.3; after 0.4 mg/kg 74 +/- 4% and 10.3 +/- 0.3; and after 0.5 mg/kg 86 +/- 5% and 11.8 +/- 0.2. After 0.08 mg/kg vecuronium 76 +/- 3% and 7.4 +/- 0.5 were recorded and after 0.1 mg/kg 85 +/- 6% and 10.5 +/- 0.4. Motor blockade 1 min after succinylcholine was 98 +/- 2% and intubation conditions scored 11.3 +/- 0.3. Relating intubation conditions to neuromuscular blockade yielded a close correlation and surprisingly good or very good intubation conditions (score more than 10) at a motor blockade of 80% (resp. 20% transmission). 3. Although succinylcholine is still the muscle relaxant with the most rapid onset of action, the new drug atracurium seems to satisfactorily facilitate tracheal intubation within an acceptably short time interval of 2 min after injection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pharmacodynamics of high-dose vecuronium in children during balanced anesthesia.

To compare the speed of onset, intubating conditions, duration of action, and recovery from neuromuscular blockade with vecuronium to those with succinylcholine, 40 ASA physical status 1 or 2 children (ages 2-9 yr) were studied during N2O-O2-opioid anesthesia. Each child was randomly assigned to receive a bolus dose of one of the following muscle relaxants: succinylcholine 2.0 mg/kg (n = 10), vecuronium 0.1 mg/kg (n = 10), vecuronium 0.2 mg/kg (n = 10), or vecuronium 0.4 mg/kg (n = 10). The evoked electromyogram of the abductor digiti minimi to train-of-four stimulation was monitored. We found that with succinylcholine, the time to 95% twitch depression (speed of onset, mean +/- SD), 24 +/- 7 s, was significantly less than that with each dose of vecuronium: 0.1 mg/kg, 83 +/- 21 s; 0.2 mg/kg, 58 +/- 17 s; and 0.4 mg/kg, 39 +/- 11 s, respectively (P less than 0.05). The time to laryngoscopy and intubation did not differ significantly between succinylcholine (48 +/- 10 s) and vecuronium 0.4 mg/kg (57 +/- 13 s); however, both were significantly less than than with vecuronium 0.1 and 0.2 mg/kg (P less than 0.005). The intubating conditions were excellent in 100% of patients. The duration of action was least with succinylcholine (5.7 +/- 1.5 min) and increased with increasing doses of vecuronium: 0.1 mg/kg, 23.9 +/- 5.1 min; 0.2 mg/kg, 55.2 +/- 11.6 min; and 0.4 mg/kg, 74.6 +/- 9.9 min, respectively (P less than 0.001). The recovery index was most rapid with succinylcholine (1.6 +/- 0.4 min) and was slowest with vecuronium 0.4 mg/kg (22.6 +/- 2.1 min) (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Intubationsbedingungen nach Gabe von Atracurium und Vecuronium Bolusmethode vs. Primingtechnik

Prompted by the ongoing discussion of the pros and cons of using succinylcholine, this study was conducted to compare the responses to bolus injections of atracurium or vecuronium with those after sequential injection of these drugs (priming principle). We evaluated the earliest possible intubation times, intubating conditions, and the onset times (i.e. times from the end of injection to the maximum blockade) under conditions approaching real use as closely as possible. Methods. The randomized and double-blind study was carried out with 80 ASA risk class 1 and 2 patients. Approval of the institutional ethics committee was obtained, and each patient gave informed consent. Patients were randomly allocated to four study groups of 20 patients each. Isotonic saline was administered to those patients assigned to the atracurium or vecuronium bolus groups, whereas the patients assigned to the other two groups received a priming injection of either atracurium (0.05 mg/kg) or vecuronium (0.01 mg/kg). We observed the patients for signs of incipient muscular weakness before the induction of anaesthesia. Anaesthesia was induced with thiopental 3.5 min after the first injection (5 mg/kg and 50–100?mg before intubation). After a further 1 min during which adequate mask ventilatin with oxygen was assured, corresponding to a priming interval of 4.5?min, 0.5 mg/kg of atracurium or 0.1 mg/kg of vecuronium was administered to the patients in the bolus groups and 0.45 mg/kg of atracurium or 0.09 mg/kg of vecuronium as intubating doses to those in the priming groups. Intubation was attempted at 90, 120, 150 and 180?s thereafter. Intubating conditions were evaluated on the basis of laryngoscopy, vocal cord movement and coughing or bucking of the patients. Neuromuscular function was monitored via accelerometry at the adductor pollicis muscle (TOF stimulation of the ulnar nerve every 15?s). Results. The priming doses did not diminish the elicited twitches of the adductor pollicis muscle, but led to heavy eyelids and double vision in 35% of the atracurium patients and 47% of the vecuronium patients; these symptoms were well tolerated by the patients. At the time of intubation the adductor pollicis muscle was relaxed to approximately the same degree in all groups (mean±SD for the TOF ratios in the bolus groups was 0.46±0.37 for atracurium, 0.45±0.4 for vecuronium; in the priming groups 0.52±0.39 for atracurium, 0.53±0.36 for vecuronium). The administration of the relaxants in divided doses significantly shortened the intubating time after atracurium (100 vs 124?s) and improved the intubating conditions of vecuronium (good vs tolerable), but had no effect on the time course of the neuromuscular blockade (onset times in the bolus groups 224±84?s for atracurium and 209±64 s for vecuronium; in the priming groups 249±112?s for atracurium and 205±52 s for vecuronium). Conclusions. The priming technique presented here is clinically superior to the bolus method and therefore should be preferred in all elective cases and in those patients in whom succinylcholine is contraindicated.     

The effect of atracurium, vecuronium and pancuronium on heart rate and arterial pressure in normal individuals

Heart rate and rhythm (from ECG) and systolic, diastolic and mean arterial pressures (using an oscillotonometer) were measured for 30 min following administration of atracurium 0.5 mg kg-1 (n = 20), vecuronium 0.1 mg kg-1 (n = 20) or pancuronium 0.1 mg kg-1 (n = 20) during steady-state anaesthesia, with nitrous oxide, oxygen and either 0.75% halothane or fentanyl 4-5 micrograms kg-1, in the absence of any surgical stimulation. Whereas atracurium and vecuronium were associated with only small and clinically unimportant changes in heart rate, pancuronium produced a marked and significant increase associated with a junctional rhythm in four patients. Atracurium produced no significant changes in arterial pressure, vecuronium produced a significant fall (20 mmHg) in diastolic pressure during halothane anaesthesia and pancuronium a significant increase in mean arterial pressure with both anaesthetic techniques. No serious bradycardias were observed with either atracurium or vecuronium. Five patients showed cutaneous signs of histamine liberation after administration of atracurium.     

Dose requirements of vecuronium, pancuronium, and atracurium during orthotopic liver transplantation.

To further elucidate the role of the liver in the clearance of vecuronium, atracurium, and pancuronium, 30 patients undergoing orthotopic liver transplantation were randomly assigned to three comparable groups to receive a continuous infusion of vecuronium, atracurium, or pancuronium. The evoked integrated compound action potential of the hypothenar eminence in response to train-of-four ulnar nerve stimulation was measured and recorded. Anesthesia was induced with 3-5 mg/kg of thiopental, 50 micrograms/kg of midazolam, and 1-5 micrograms/kg of fentanyl IV and was maintained with continuous infusions of midazolam and fentanyl while the lungs were ventilated with an air-oxygen mixture. The infusion rates of vecuronium, atracurium, and pancuronium were adjusted to achieve a T1/Tc ratio of between 0.02 and 0.10 (T1 = height of first twitch, Tc = height of control twitch). Vecuronium and pancuronium requirements, which were 0.072 +/- 0.022 and 0.042 +/- 0.015 mg.kg-1.h-1 (mean +/- standard deviation) respectively during the dissection phase, decreased significantly during the anhepatic phase to 0.036 +/- 0.021 and 0.018 +/- 0.012 mg.kg-1.h-1 and returned toward the initial values in the postreperfusion phase (0.055 +/- 0.018 and 0.032 +/- 0.012 mg.kg.-1.h-1); whereas atracurium requirements remained unchanged during the three phases (0.667 +/- 0.199, 0.567 +/- 0.142, and 0.692 +/- 0.254 mg.kg-1.h-1). These data suggest that the liver has an important role in the elimination of vecuronium and pancuronium, whereas the elimination of atracurium is unaltered during exclusion of the liver from the circulation.     

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.     

Atracurium: neuromuscular blockade in repeated administration

The neuromuscular blocking action of repeated injections of atracurium and vecuronium was studied in 74 surgical patients during balanced anaesthesia (methohexitone or etomidate, intubation after suxamethonium, fentanyl, droperidol, N2O). The initial bolus dose (ID) of atracurium was 0.25 mg/kg and of vecuronium 0.05 mg/kg followed by repeated increments (RD) of atracurium 0.1 mg/kg and vecuronium 0.0125 mg/kg when neuromuscular function (EMG) had recovered to about 30% of pre-relaxant control. Dose-response relationships revealed atracurium to be about 1/5 as potent as vecuronium; the ED50 of atracurium was 0.13 +/- 0.03 mg/kg and of vecuronium 0.023 +/- 0.007 mg/kg. The ID of both relaxants produced a neuromuscular blockade of about 90% within 4 min. The duration from the time of injection to 30% recovery was slightly longer in atracurium 26 +/- 9 min. In all patients the RD produced within 3.5 min satisfactory muscle relaxation with a neuromuscular block of about 85%. The mean duration of atracurium (18 min) was 5-10 min longer than of vecuronium (12 min). To maintain good surgical relaxation (more than 70% blockade) atracurium 0.32 mg/kg X h and vecuronium 0.056 mg/kg X h were required. No cumulation could be measured after repeated injections. The recovery time of atracurium and vecuronium at the end of anaesthesia was 10-12 min. Neither cardiovascular side-effects nor signs of histamine release were observed after both relaxants in our particular dose range. It is concluded, that atracurium is a favourable blocker for anaesthetic practice: The time of onset is approximately the same compared with vecuronium. The duration of action, however, is slightly longer but still truly intermediate long.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

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)     

The effect of phenytoin on the magnitude and duration of neuromuscular block following atracurium or vecuronium

Patients chronically receiving anticonvulsants have been reported to be resistant to the long-acting competitive neuromuscular blockers. This study examines the effects of atracurium and vecuronium on 100 neurosurgical patients; 50 receiving chronic phenytoin therapy (group I) and 50 controls (group II). During O2/N2O/halothane anesthesia, five patients in each group were given a bolus of vecuronium 0.1 mg/kg, and a different five patients in each group were given atracurium 0.5 mg/kg, to produce neuromuscular blockade in excess of 95%. The time to maximum blockade and the recovery from atracurium was unaffected by phenytoin therapy. Recovery from vecuronium was enhanced in the phenytoin group, as demonstrated by the recovery index, defined as the time required for recovery from 25-75% of the control neuromuscular response (7.9 +/- 2.2 min compared with 17.8 +/- 5.1 min in controls, P less than 0.005). Similarly, the total duration of neuromuscular blockade, defined as recovery to 90% of control response, was significantly shorter in the phenytoin group (31.9 +/- 6.0 min compared with 69.7 +/- 12.9 min in controls, P less than 0.001). The remaining 40 patients from each group were given a preselected dose of either vecuronium (0.02-0.06 mg/kg) or atracurium (0.10-0.25 mg/kg) during anesthesia with O2/N2O/fentanyl, to generate dose-response curves for the relaxants. Using analysis of covariance, the slopes and elevations for atracurium were found to be essentially identical in the two groups; as were the calculated ED50 and ED95. Patients receiving chronic phenytoin therapy were resistant to vecuronium-induced neuromuscular blockade. With vecuronium, the dose-response curves for the two groups were parallel; the curve for phenytoin patients was shifted to the right.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of vecuronium and atracurium at low doses in minor pediatric surgery under combined anesthesia]

To compare, the time of onset and time of recovery of muscular blockade after use of half doses of vecuronium and atracurium, we studied 18 children ASA I who were proposed for short lasting pediatric surgery and combined anesthesia. Patients were divided into two groups: group V (n = 10) was treated with a single dose of 0.05 mg/kg of vecuronium and group A (n = 8) with 0.25 mg/kg of atracurium. Assessment of muscular relaxation was performed by measuring the electromyographic responses to a train of four stimuli applied to the cubital nerve at the level of the hypothenar eminence. We administered 0.02 mg/kg of atropine, 5 to 10 mg/kg of thiopental, and the muscular relaxing dose together with orotracheal intubation when the first stimulus of the train of four stimuli was blocked at 90% of its initial value (T90). Maintenance of the anesthetic level was performed with 50% of N2O-O2 without inhalational anesthetics. A caudal blockade was induced by 1 ml/kg of bupivacaine at 0.25%. We measured the following parameters of muscular relaxation: T90, T10 (time at which the 10% of the first stimulus reappears), T25 (time of clinical efficacy) and IR (index of recovery). Only 60% of patients (6 out of the 10 patients of vecuronium group and 5 out of the 8 subjects of atracurium group) achieved the T90. This occurred 2.5 +/- 0.7 min after vecuronium and 3.2 +/- 0.6 min after atracurium. T10 was 13.7 +/- 4.1 min for vecuronium and 13.3 +/- 4.1 min from atracurium. T25 occurred 18.2 +/- 6.5 min after vecuronium and 19.4 +/- 2.1 min for atracurium.(ABSTRACT TRUNCATED AT 250 WORDS)