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)     

Cardiovascular effects of vecuronium, atracurium, pancuronium, metocurine and RGH-420 1 in dogs

The effect on the cardiovascular haemodynamic status of five neuromuscular blocking drugs, RGH-4201, vecuronium, atracurium, pancuronium and metocurine, was studied in five conditioned foxhounds anaesthetised with fentanyl. Changes in heart rate, mean arterial blood pressure, central venous pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, and cardiac output were recorded at 2, 5, 10, 20 and 30 min after administration of the drugs. From these, stroke volume, systemic vascular resistance and pulmonary vascular resistance were calculated. Administration of RGH-4201 was followed by a pronounced increase in heart rate, accompanied by an increase in cardiac output and a decrease in systemic and pulmonary vascular resistance. Metocurine and pancuronium resulted in a decrease of right and left filling pressures and systemic-/pulmonary vascular resistance. Changes after atracurium, vecuronium and metocurine were minimal. It is concluded that RGH-4201 causes major alterations in the cardiovascular haemodynamic status in dogs anaesthetised with fentanyl when compared to vecuronium, atracurium, metocurine and pancuronium. With respect to cardiovascular stability, atracurium and vecuronium offer advantages.     

Comparison of intubating conditions with atracurium, vecuronium and pancuronium

A blind trial, comparing time of onset of satisfactory conditions for tracheal intubation with atracurium 0.6 mg/kg, vecuronium 0.1 mg/kg and pancuronium 0.1 mg/kg is described. Intubation was attempted at 30-second intervals in 60 patients, randomly allocated to receive one of the above muscle relaxants. Patients receiving atracurium 0.6 mg/kg could be intubated from 30 to 120 seconds. Patients receiving either vecuronium 0.1 mg/kg or pancuronium 0.1 mg/kg were able to be intubated between 60 and 240 seconds. The results showed a statistically significant earlier onset of satisfactory intubating conditions with atracurium than with vecuronium or pancuronium in these doses but no difference between vecuronium and pancuronium.     

Effect of atracurium, vecuronium, pancuronium and tubocurarine on renal sympathetic nerve activity in baroreceptor denervated dogs

The mechanism of arterial hypotension induced by non-depolarizingneuromuscular blocking agents may be multifactorial and differbetween drugs. The purpose of this study was to evaluate theeffect of high-dose atracurium and equivalent doses of othernon-depolarizing neuromuscular blocking agents on haemodynamicstate and sympathetic nervous activity. In studies on 24 mongreldogs anaesthetized with alpha-chloralose, the left kidney wasexposed retroperitoneally and renal sympathetic nerve activitywas recorded continuously after bilateral sino-aortic denervationand cervical vagi section. The dogs were allocated to four groups;atracurium 1.5 mg kg^–1, tubocurarine 0.3 mg kg^–1pancuronium 0.3 mg kg^–1 or vecuronium 0.3 mg kg^–1was administered to six dogs in each group. Histamine 1 µgkg^–1 was given to two dogs in each group, 1 h before administrationof neuromuscular blocking agents. We observed that atracuriumand tubocurarine significantly decreased arterial pressure,heart rate and renal sympathetic nerve activity (P <0.05),but pancuronium and vecuronium did not. Histamine-induced arterialhypotension but did not affect heart rate or renal sympatheticnerve activity. As both arterial and cardiopulmonary baroreflexpathways were inactivated in these animals, we conclude thatatracurium decreased arterial pressure by suppressing efferentsympathetic nerve activity in a manner similar to that of tubocurarine.     

Dose-response studies of atracurium, vecuronium and pancuronium in the elderly

Dose-response curves were constructed for atracurium, vecuronium and pancuronium in elderly subjects in order to assess potency of these relaxants. The results were compared to data previously obtained for adult subjects using the same method. A single-dose method of potency determination was used in both studies. The results indicate no significant difference in the potency of these relaxants between elderly and adult subjects; the ED95S were 249 and 226 micrograms/kg for atracurium, 43.1 and 39.6 micrograms/kg for vecuronium and 65.9 and 60 micrograms/kg for pancuronium respectively in the elderly and the adults.     

Comparative clinical studies on vecuronium, atracurium and pancuronium in older patients

The relaxants vecuronium (Norcuron), atracurium (Tracrium), and pancuronium (Pavulon) have been investigated with respect to onset and duration of action in old patients compared with young patients. A variant of a balanced anaesthesia technique with flunitrazepam, fentanyl and N2O/O2 was used. The following equipotent doses were investigated (mg/kg body weight): vecuronium 0.07/0.10; atracurium 0.35/0.50; pancuronium 0.08/0.115. The neuromuscular function was assessed in a semiquantitative manner with the Train-of-Four (TOF). We found a trend to a delayed onset of action in old patients. This effect, however, reached a significant level with pancuronium only. The degree of relaxation after comparable doses was less after atracurium in old patients. This difference between young and old patients could not be observed after vecuronium and was hardly detectable after pancuronium. The duration of action to a 25% recovery and the early recovery phase from the appearance of the first to the fourth twitch in the TOF showed no difference between young and old patients. It is concluded that there are no considerable differences with respect to the duration of action between young and old patients. However, to obtain a similar degree of relaxation, it is recommended to use a somewhat higher dose level with atracurium.     

Effect of isoflurane and sevoflurane on the magnitude and time course of neuromuscular block produced by vecuronium, pancuronium and atracurium

We have compared the ability of equipotent concentrations of isoflurane and sevoflurane to enhance the effect of non-depolarizing neuromuscular blocking drugs. Ninety ASA I and II patients of both sexes, aged 18-50 yr, were stratified into three blocker groups (Vec, Pan and Atr), to undergo neuromuscular block with vecuronium (n = 30), pancuronium (n = 30) or atracurium (n = 30), respectively. Within each group, patients were allocated randomly to one of three anaesthetic subgroups to undergo maintenance of anaesthesia with: (1) alfentanil-nitrous oxide- oxygen (n = 10); (2) alfentanil-nitrous oxide-oxygen-isoflurane (n = 10); or (3) alfentanil-nitrous oxide-oxygen-sevoflurane (n = 10) anaesthesia. During maintenance of anaesthesia, end-tidal concentrations of isoflurane, sevoflurane and nitrous oxide were 0.95, 1.70 and 70%, respectively. Both the evoked integrated electromyogram and mechanomyogram of the adductor pollicis brevis muscle were measured simultaneously. In the Vec and Pan groups, a total dose of 40 micrograms kg-1 of vecuronium or pancuronium, respectively, was given, and in the Atr group a total dose of atracurium 100 micrograms kg-1. Each blocker was given in four equal doses and administered cumulatively. We showed that 0.95% isoflurane and 1.70% sevoflurane (corresponding to 0.8 MAC of each inhalation anaesthetic, omitting the MAC contribution of nitrous oxide) augmented and prolonged the neuromuscular block produced by vecuronium, pancuronium and atracurium to a similar degree.      

安氟醚及异氟醚对阿曲库铵临床药效的影响

目的：观察吸入１％安氟醚或等效浓度异氟醚对阿曲库铵临床药效的影响。方法：３０例择期手术病人随机分为三组，分别吸入６７％Ｎ２Ｏ（Ⅰ组），１％安氟醚（Ⅱ组）或０．６７％异氟醚（Ⅲ组）后观察阿曲库铵临床药效。结果：静注阿曲库铵０．５ｍｇ／ｋｇ后，Ⅰ、Ⅱ和Ⅲ组的起效时间分别是２．２±０．４２分、２．１±０．４２分和２．１±０．３４分（Ｐ＞０．０５），作用时间分别是４５．８５±３．７分、５５．２５±６．４７分和５５．８８±８．２５分（Ｐ＜０．０１）；维持９０％～９５％颤搐抑制所需阿曲库铵的静脉滴注速度分别为６．２７７±１．０９２μｇ·ｋｇ－１·ｍｉｎ－１、４．２７２±０．５８５μｇ·ｋｇ－１·ｍｉｎ－１和４．５０５±０．７１６μｇ·ｋｇ－１·ｍｉｎ－１（Ｐ＜０．０１）。结论：１％安氟醚及等效浓度的异氟醚均可增强阿曲库铵的临床药效，但两者之间的增强无显著差异。     

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.     

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.     

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.     

Recovery times following edrophonium and neostigmine reversal of pancuronium, atracurium, and vecuronium steady-state infusions

The ability of edrophonium and neostigmine to antagonize nondepolarizing neuromuscular blockade produced by steady-state infusions of atracurium, pancuronium, and vecuronium was studied in 71 adult patients anesthetized with nitrous oxide and halothane. Infusion rates of blocking drugs were adjusted so that single twitch depression as measured by the evoked integrated EMG of the hypothenar muscles was kept at 10% of control. Two minutes after the termination of the infusion either edrophonium (0.75 mg/kg) or neostigmine (0.05 mg/kg) was administered. Single twitch depression and train-of-four (T4/T1) fade was recorded during the recovery period. T4/T1 fade ratios observed at 20 min postreversal were 0.80 (atracurium-edrophonium); 0.76 (vecuronium-edrophonium); 0.44 (pancuronium-edrophonium); 0.95 (atracurium-neostigmine); 0.89 (vecuronium-neostigmine); and 0.68 (pancuronium-neostigmine). Under conditions of this study neostigmine produced more rapid and complete recovery than did edrophonium. Although edrophonium produced adequate antagonism of atracurium if 20-30 min were allowed to elapse, edrophonium reversal of pancuronium was rarely acceptable even at 30 min. Increasing the dose of edrophonium to 1.0 mg/kg produced single twitch values of 0.90 at 5 min postreversal but did not increase the rate of recovery of the train-of-four fade ratio. Neostigmine reversal of pancuronium, on the other hand, generally produced T4/T1 ratios of greater than 0.70 in 20-30 min. Although the pattern of recovery seen after reversal of vecuronium was in general quite similar to that seen after atracurium, two patients in the vecuronium-edrophonium group showed delayed recovery and also failed to respond significantly to subsequent doses of neostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of enflurane and isoflurane on resistance to reabsorption of cerebrospinal fluid in dogs

Using the technique of ventriculocisternal perfusion, resistance to reabsorption of cerebrospinal fluid (Ra) was calculated from determinations of the rate of reabsorption of cerebrospinal fluid (Va) at differing cerebrospinal fluid pressures in dogs. Ra was examined during prolonged anesthesia (5.0-6.0 h) with enflurane (2.2%, end expired) or isoflurane (1.4%, end expired). Compared with previously reported normal values for Ra in dogs (220-224 cmH2O . ml-1 . min), enflurane increased Ra to 274 +/- 4 cmH2O . ml-1 . min (mean +/- SEM), and isoflurane decreased Ra to 104 +/- 1 cmH2O . ml-1 . min. The alterations of cerebrospinal fluid (CSF) dynamics caused by enflurane, namely increase of both Ra and the rate of production of cerebrospinal fluid (Vf), may contribute to the sustained increase of intracranial pressure observed during prolonged anesthesia with enflurane. In contrast, the different alterations of CSF dynamics caused by isoflurane, namely decrease of Ra with no change in Vf, may explain, in part, why minimal increase of intracranial pressure is observed during prolonged anesthesia with isoflurane. Because decreased Ra improves spatial compensation by cerebrospinal fluid volume for increased intracranial pressure, isoflurane may offer an advantage over enflurane in patients at risk because of increased intracranial pressure.     

Hemodynamic effects of atracurium, vecuronium and pancuronium during sufentanil anesthesia for coronary artery bypass

A study was undertaken to evaluate the cardiovascular effects of sufentanil, in combination with three different muscle relaxants, used as sole anesthetic with 100% O2 in 30 patients undergoing elective coronary artery vein graft surgery. Patients were randomly allocated to receive pancuronium (P), vecuronium (V) or atracurium (A) for muscle relaxation. All patients received 15 micrograms/kg sufentanil at induction followed by 5-10 micrograms/kg sufentanil prior to sternotomy. At the 95% level of significance no statistical difference was found for any of the measured and derived cardiovascular parameters between groups P, V and A, except for a decreased systolic blood pressure in the atracurium group after induction. Sufentanil in combination with pancuronium or vecuronium provided stable hemodynamic conditions throughout anesthesia. Atracurium was less satisfactory. We conclude that there is no advantage to be gained, in the presence of beta blockade, from the use of the new generation muscle relaxants as compared to pancuronium during high-dose sufentanil anesthesia for coronary artery vein grafting.     

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).     

The cerebral effects of pancuronium and atracurium in halothane-anesthetized dogs

Pancuronium decreases the minimal alveolar anesthetic concentration (MAC) of halothane in humans, while atracurium has a metabolite, laudanosine, which is a known cerebral stimulant. To determine if these muscle relaxants significantly alter cerebral function, their effects on cerebral metabolic rate (CMRo2), cerebral blood flow (CBF), intracranial pressure (ICP), EEG, and the cerebral energy state were studied in halothane-anesthetized dogs. Group A dogs (n = 6) were maintained at 0.86% end-expired (1.0 MAC) halothane. Thereafter, a sequence of 1) pancuronium 0.1 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; and 3) pancuronium 0.2 mg . kg-1 produced no changes in CMRo2, CBF, ICP, or EEG. Group B dogs (n = 6) also were maintained at 0.86% end-expired halothane and received the following in sequence: 1) atracurium 0.5 mg . kg-1; 2) reversal of neuromuscular blockade with neostigmine plus glycopyrrolate; 3) atracurium 1.0 mg . kg-1; and 4) atracurium 2.5 mg . kg-1. There were no changes in CMRo2, CBF, or ICP; EEG evidence of cerebral arousal occurred in only one dog with the final dose of atracurium. Group C dogs (n = 6) received tetracaine spinal anesthesia and the minimal halothane concentration (mean +/- SE = 0.69 +/- 0.03% end-expired) that would maintain an "anesthetic" EEG pattern. Each Group C dog received the following in sequence: 1) atracurium 1.0 mg . kg-1, and 2) atracurium 2.5 mg . kg-1. EEG evidence of cerebral arousal occurred in all six Group C dogs. Arousal was not accompanied by significant increases in CBF, CMRo2, or ICP.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium

To compare the time course of neostigmine and edrophonium antagonism of varying intensity neuromuscular blockade induced by atracurium, pancuronium, or vecuronium, the authors studied 98 patients anesthetized with nitrous oxide (60%) and halothane or enflurane. Neuromuscular blockade, as monitored by single stimulus-induced twitch tension (TT), was antagonized at varying degrees of spontaneous recovery (2-80% of control TT). Time to antagonism (time from injection of neostigmine or edrophonium to 90% recovery of control TT) was not different between edrophonium, 0.5 mg/kg, and neostigmine, 0.04 mg/kg, when spontaneous recovery had been allowed to occur to at least 11% of control TT prior to antagonist administration (P greater than 0.05). For profound neuromuscular blockade (TT less than or equal to 10% of control) induced by pancuronium or vecuronium, time (mean +/- SD) to antagonism with neostigmine, 0.04 mg/kg, was 7.0 +/- 2.2 min and 5.6 +/- 1.7 min, respectively, while the same for edrophonium, 0.5 mg/kg, was 20.0 +/- 8.0 min and 15.0 +/- 12.5 min, respectively (P less than 0.05). Time to antagonism of profound atracurium-induced neuromuscular blockade was 8.5 +/- 3.3 min for neostigmine, 0.04 mg/kg, and 9.8 +/- 7.0 min for edrophonium, 0.5 mg/kg, (P less than 0.05). For profound vecuronium-and pancuronium-induced neuromuscular blockade, time to antagonism by edrophonium, 1.0 mg/kg, was 4.6 +/- 3.0 min and 3.9 +/- 1.6 min respectively. The authors conclude that neostigmine, 0.04 mg/kg, antagonizes neuromuscular blockade within 12 min when TT is greater than 2% of control at time of reversal. When TT is greater than 10% of control, edrophonium, 0.5 mg/kg, produces similar time to antagonism.(ABSTRACT TRUNCATED AT 250 WORDS)