Spontaneous recovery of residual neuromuscular blockade after atracurium or vecuronium during isoflurane anaesthesia

With atracurium and vecuronium, spontaneous recovery of residual neuromuscular blockade monitored electromyographically during 0.5% isoflurane anaesthesia was studied in 60 patients undergoing plastic surgery. After thiopentone, in random order, either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 was administered and isoflurane added to N2O and O2 mixture. Following spontaneous recovery of both the single twitch amplitude (T1) to 75% of the control value and the train-of-four ratio (TOF ratio) to 75%, incremental doses of the relaxant were given to maintain the T1 at less than 10%. Before the end of surgery, the blockade was again permitted to recover spontaneously. During the initial spontaneous recovery, the mean recovery time of T1 from 25% to 75% (the recovery index) with atracurium was longer (P less than 0.001) than that with vecuronium (13.2 min and 10.1 min, respectively) but, during the second recovery, the mean recovery index was shorter (P less than 0.05) with atracurium than with vecuronium (16.1 min and 19.8 min, respectively). The recovery time from T1 75% to TOF ratio 75%, indicating the recovery rate of residual neuromuscular blockade, with atracurium was about 15 min after both the initial and the second recoveries. With vecuronium, the respective recovery times were significantly (P less than 0.001) longer (25.6 min and 38.5 min, respectively). It is concluded that with vecuronium there is slower spontaneous recovery of residual neuromuscular blockade than with atracurium.     

Priming doses of atracurium and vecuronium depress swallowing in humans.

The administration of low doses of muscle relaxant may cause peripheral muscular weakness including difficulty in swallowing. In the present study, the effect of priming doses of atracurium and vecuronium on swallowing was studied. Sixty patients undergoing elective surgery under general anesthesia were divided randomly into four groups of 15 patients and received as a priming dose either vecuronium (10 or 15 micrograms/kg) or atracurium (50 or 75 micrograms/kg). Swallowing muscle activity was measured by electromyography using submental surface electrodes. Swallowing was initiated by administration of 0.3 ml distilled water through an oral catheter. Swallowing reflex was determined by measuring the latency time (i.e., time from water administration to start of EMG activity of glossal muscles). Swallowing activity was determined by integration of the EMG of glossal muscles during swallowing. Peripheral muscle strength was determined by hand grip strength. Swallowing reflex activity and peripheral muscle strength were measured before and 3 and 6 min after administration of vecuronium or atracurium. Latency time remained unchanged after any of the priming doses. Integrated EMG decreased significantly (P < .001) 3 and 6 min after all priming doses tested (42-75% of baseline value). Only after atracurium 75 micrograms/kg was the hand grip strength significantly decreased (P < .01). These results suggest that owing to its effect on swallowing, the priming dose should be used with caution.     

Recovery from neuromuscular blockade: residual curarisation following atracurium or vecuronium by bolus dosing or infusions

We conducted a survey of the incidence of Postoperative Residual Curarisation (PORC) in two groups of patients following the use of atracurium or vecuronium. In the first group (B) the neuromuscular blocking drugs were administered by bolus dosing, and in the second group (I) by continuous infusion. On arrival in the recovery room, neuromuscular function was assessed both by compound evoked electromyogram (EMG) in a train of four pattern and also clinically, by the ability to sustain a headlift for >5 seconds, and to cough. Results were obtained from 150 patients (100 in group B and 50 in group I). The incidence of PORC, as defined by a train of four ratio of <0.7, on arrival in the recovery room was 12% in group B, and 24% in group I. Clinical criteria of adequate neuromuscular reversal revealed different results, with the majority of patients being unable to perform either clinical test on arrival in recovery. Those patients in whom a peripheral nerve stimulator was used intra-operatively did not have a reduced incidence of PORC. We have demonstrated that PORC is still a common occurrence even with intermediate duration of action neuromuscular blocking drugs.     

Intubating conditions after vecuronium and atracurium given in divided doses (the priming technique)

Intubating conditions have been assessed at 60 s following administration of vecuronium 0.1 mg kg-1 or atracurium 0.5 mg kg-1 given either as a single dose after induction of anaesthesia with thiopentone or in divided doses; vecuronium 0.015 mg kg-1 followed 4 or 6 min later by 0.085 mg kg-1, or atracurium 0.075 mg kg-1 followed 4 or 6 min later by 0.425 mg kg-1. In the divided dose groups the smaller initial (priming) dose was given prior to induction of anaesthesia. Onset and duration of clinical relaxation were assessed using a peripheral nerve stimulator. The intubating conditions at 60 s improved significantly, with the use of relaxants in divided doses being acceptable in 80 and 70% of patients, respectively, with vecuronium and atracurium, but the conditions are not as good as those commonly found using suxamethonium. Priming at 6 min has no advantage over priming at 4 min. The onset of complete block was accelerated with priming, but the difference was not significant. The duration of clinical relaxation of vecuronium was significantly prolonged by giving it in divided doses. Unpleasant awareness of muscle weakness was observed in 15 patients, requiring early induction of anaesthesia in five of them.     

Bradycardia in patients receiving atracurium or vecuronium in conditions of low vagal stimulation

Four groups of 20 patients each received either vecuronium or atracurium together with either glycopyrronium or saline, and underwent anaesthesia free of vagolytic drugs, and surgery devoid of vagal activity. Determinations of plasma histamine concentrations were made to examine the possible correlation between these levels and changes in heart rate and blood pressure as well as a possible relationship with skin reactions after the administration of the relaxants. Patients who received vecuronium without the anticholinergic drug, glycopyrronium, showed a greater tendency towards bradycardia (though not statistically significant) than those given atracurium. More cutaneous reactions were observed with patients who received atracurium than in those with vecuronium, but there was no correlation with plasma histamine concentrations of either relaxant group. There was no correlation either between histamine concentrations and heart rate or blood pressure associated with atracurium. The incidence of bradycardia with either relaxant is low if the anaesthetic technique and the surgery are devoid of vagal activity.     

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.     

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.     

Potency and maintenance requirement of atracurium and vecuronium given alone or together

A synergism exists between some competitive muscle relaxants. However, maintenance requirement of a combination of muscle relaxants has been evaluated only in paediatric patients. We studied 45 elective adult surgical patients (ASA I-II) during propofol-alfentanyl-N₂O-O₂-anaesthesia. The first 30 patients were randomized to receive either atracurium or vecuronium to create individual dose-response curves for these muscle relaxants. ED₉₅-values for atracurium and vecuronium were 260±9 and 59±3 μg · kg^-1, respectively (mean±s.e.mean). Requirements of atracurium and vecuronium to maintain an 85–95% neuromuscular blockade were 301 and 83 μg kg^-1 h^-1, respectively. An additional 15 patients received a combination of atracurium and vecuronium (cAV) in an equipotent dose ratio. An ED₉₅ of a cAV was 94± 7 μg · kg^-1 of atracurium together with 21±2 μg · kg^-1 of vecuronium, or 72±6% of one ED₉₅ dose of a parent agent. Potentiation was significant ( P =0.0001). A maintenance requirement of a cAV was 120 μg kg^-1 h^-1 of atracurium together with 27 μg kg^-1 h^-1 of vecuronium. Thus, a significant potentiation was maintained also during the course of anaesthesia. A cAV had an effect like one intermediate-acting agent. If a cAV is used instead of using atracurium or vecuronium alone, the maximal reduction of drug consumption would be approximately 30%.     

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)     

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).     

Residual curarization in the recovery room after vecuronium

We have investigated residual block after anaesthesia which included the use of the neuromuscular blocking agent vecuronium but no anticholinesterase, in 568 consecutive patients on admission to the recovery room. The ulnar nerve was stimulated submaximally using TOF stimulation (30 mA). Postoperative residual curarization was defined as a TOF ratio < 0.7. Of the 568 patients, 239 (42%) had a TOF < 0.7 in the recovery room. These patients had received a larger cumulative dose of vecuronium than patients who had full recovery (mean 7.7 (SD 3.6) mg vs 6.2 (2.7) mg; P < 0.05) and a shorter time had elapsed since the last vecuronium dose (117 (70) min vs 131 (80) min; P < 0.05). Of 435 patients whose trachea was extubated, 145 (33%) exhibited inadequate recovery from neuromuscular block. Six of these had one or no response to TOF stimulation and were reintubated. In the remaining 139 patients, neuromuscular block was successfully antagonized. Only 20 patients (3.5%) remembered TOF stimulation when questioned 2 h later in the recovery room, and discomfort associated with it was assessed using a visual analogue scale before discharge. We conclude that it is necessary to antagonize residual block produced by vecuronium.      

The duration of action of mivacurium is prolonged if preceded by atracurium or vecuronium

We studied 45 patients (ASA I-II) during propofol-alfentanil-N₂O-O₂ anaesthesia to determine if recovery from neuromuscular block induced by mivacurium is influenced differently by prior injection of atracurium or vecuronium. Neuromuscular function was monitored by adductor pollicis EMG. Patients were randomized to receive two dosesof either mivacurium (150 and 70 μg kg^-1), atracurium (350 and 75 μg kg^-1) or vecuronium (70 and 15 μg kg^-1) followed by a final dose of mivacurium 70 μg kg^-1. The second and third doses of the muscle relaxants were administered at 25–30% recovery of the E₁ (first EMG response in the train-of-four series). Following the final dose of mivacurium, the EMG response recovered to 25 and 95% in 10.4±3.9 and 19.7±5.7 min (mean±SD), respectively, if mivacurium was the only muscle relaxant. Respective times were 100% longer if mivacurium had been preceded by atracurium (23.8 ± 3.3 and 39.8±6.9 mm) or vecuronium (22.6±3.5 and 44.1 ±7.9 min) ( P =0.000l). The 25–75% recovery times in the three groups were 4.9±1.0, 8.7±2.4 and 10.5±2.5 min, respectively ( P =0.0001). Our results indicate that there is no benefit in giving mivacurium at the end of surgery after peroperative use of atracurium or vecuronium.     

Histamine-release haemodynamic changes produced by rocuronium, vecuronium, mivacurium, atracurium and tubocurarine

We have examined the effects of different benzyl-isoquinolinium and steroidal neuromuscular blocking compounds on plasma concentrations of histamine, heart rate and arterial pressure in surgical patients. A single, rapid (5-s) bolus of mivacurium 0.2 mg kg-1, atracurium 0.6 mg kg-1, tubocurarine 0.5 mg kg-1, vecuronium 0.1 mg kg-1 or rocuronium 0.6 mg kg-1 was administered to 75 patients (n = 15 in each group). Anaesthesia was induced with thiopentone 6 mg kg-1 i.v. and maintained with isoflurane and 70% nitrous oxide in oxygen. Venous blood samples were obtained before induction, 1 min after thiopentone and 1, 3 and 5 min after administration of the neuromuscular blocking drug. Mivacurium, atracurium and tubocurarine caused 370%, 234% and 252% increases in plasma histamine concentrations at 1 min, respectively. Corresponding values at 3 min were 223%, 148% and 157%, respectively. These changes were significant (P < 0.01) at 1 and 3 min. In contrast, the rocuronium and vecuronium groups had no significant changes in either plasma histamine concentrations or haemodynamic variables.      

A comparison between vecuronium and atracurium in myasthenia gravis

We evaluated the effect of vecuronium bromide and atracurium besylate on the train–of–four response in the management of muscle relaxation in 20 patients with myasthenia gravis (MG) who were undergoing thymectomy. We confirmed the safe use of these two non–depolarizing muscle relaxants in MG patients. Vecuronium (0.04 mg–kg^-1) demonstrated a lesser clinical duration than did atracurium (0.2 mg–kg^-1) (38± 19 vs 50 ± 21 min, mean ± s.e.mean). The recovery time for vecuronium patients was shorter than that for atracurium patients (22 ± 18 vs 38± 18 min), but the time until onset of neuromuscular blockade was longer with vecuronium (246 ±105 vs 107 ± 103 s). During spontaneous recovery from neuromuscular relaxation, at Tl/C of 25% and 100%, the train–of–four fade with vecuronium was significantly greater than that with atracurium (0.04 ± 0.02, 0.16 ± 0.03 vs 0.17 ±0.01, 0.83 ± 0.03), suggesting that vecuronium had a greater prejunctional effect than did atracurium.     

Neuromuscular interaction between cisatracurium and mivacurium, atracurium, vecuronium or rocuronium administered in combination

We compared the dose–response relationships of cisatracurium, mivacurium, atracurium, vecuronium and rocuronium and examined the interactions of cisatracurium with mivacurium, atracurium, vecuronium and rocuronium in humans by isobolographic and fractional analyses. We studied 180 adult patients during nitrous oxide–fentanyl–propofol anaesthesia. Neuromuscular block was monitored using mechanomyography to detect the twitch response of the ulnar nerve at the wrist. The dose–response curves were determined by probit analysis. The calculated ED₅₀ values and their 95% confidence intervals were 40.9 (38.1–43.7), 49.8 (47.0–52.6), 187.2 (175.1–199.3), 36.6 (34.7–38.5) and 136.4 (129.2–143.6) μg.kg⁻¹ for cisatracurium, mivacurium, atracurium, vecuronium and rocuronium, respectively. Corresponding ED₉₅ values were 57.6 (53.5–61.7), 91.8 (88.1–95.5), 253.1 (238.9–267.3), 52.9 (49.1–56.7) and 288.7 (276.2–301.2) μg.kg⁻¹, respectively. The interaction between cisatracurium and mivacurium, vecuronium or rocuronium was found to be synergistic, but the interaction between cisatracurium and atracurium was found to be additive. Synergy between cisatracurium and vecuronium or rocuronium was greater than between cisatracurium and mivacurium.     

Intraocular pressure during rapid sequence induction: use of moderate-dose sufentanil or fentanyl and vecuronium or atracurium

We studied the effect of rapid sequence induction of anaesthesia on intraocular pressure in physically fit, ASA class I or II patients using combinations of sufentanil (1 microgram/kg), or fentanyl (5 micrograms/kg) and vecuronium (0.2 mg/kg) or atracurium (1.0 mg/kg). All patients received thiopentone (5 mg/kg), following which those in group 1 received sufentanil and vecuronium, group 2 sufentanil and atracurium, group 3 fentanyl and vecuronium, and group 4 fentanyl and atracurium. Laryngoscopy and intubation were performed 60 seconds after induction. Intraocular pressure was measured prior to induction, 30 and 60 seconds after induction, immediately after intubation, and postintubation for 5 minutes. Postinduction and postintubation intraocular pressure values in all four groups did not exceed baseline values. We conclude that in fit patients, the combination of thiopentone, moderate dose narcotics, and an appropriate dose of vecuronium or atracurium produces satisfactory conditions for intubation following rapid sequence induction without increases in intraocular pressure. This technique should not, however, be employed when multiple other injuries are present, along with an open eye.     

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)     

Electrophysiological effects of atracurium and vecuronium on normal and denervated hearts.

Atracurium and vecuronium offer some advantages with respect to other nondepolarizing muscle relaxants. However, their administration has been associated with episodes of bradycardia and asystole, the mechanism of which has not yet been clarified. In an effort to analyze the effects of these drugs on automaticity, refractoriness, and conduction, 30 dogs underwent heterotopic heart transplantation to establish a model in which a normal heart (recipient) and a denervated heart (donor) could coexist. The electrophysiological studies included the determination of cycle length (CL), sinoatrial conduction time (SACT), antegrade and retrograde atrio-ventricular (A-V) node and ventricular block points (ABP and RBP), as well as effective antegrade and retrograde A-V node (ARPAVN and RRPAVN) and ventricular refractory periods (VRPs) in both hearts. These parameters were measured in a basal state and after injection of pancuronium (0.5 mg/kg) in 10 animals, atracurium (0.5 mg/kg) in another 10 dogs, and vecuronium (0.12 mg/kg) in the remaining animals. The results showed that pancuronium produced a tachycardia, significantly facilitated A-V conduction in the donor and the recipient hearts, and lowered the A-V node refractoriness in the donor organ, while atracurium and vecuronium induced no changes from the baseline values, either in normal or denervated hearts. Based on the results of this study, the episodes of sustained bradycardia reported in association with atracurium and vecuronium are attributed to the absence of antagonism of vagal stimuli provoked by pancuronium, and/or by surgical or anesthetic manipulations.     

Spontaneous recovery of neuromuscular function after atracurium in pediatric patients

Spontaneous recovery of neuromuscular function after a bolus dose of 0.40 mg/kg atracurium was assessed in 60 newborn to adolescent patients during balanced anesthesia. Each patient was allowed to recover spontaneously until complete recovery of the single twitch (T1) response and the train-of-four ratio measured from the hypothenar muscle evoked compound EMG. The recovery times of T1 from the onset of relaxation to 10% recovery and to 100% recovery were significantly longer in patients under 10 kg of body weight than in the heavier patients (25 and 56 min vs 19 and 45 min, respectively, P less than 0.01). The rate of recovery, calculated as the recovery index (time between 25% recovery and 75% recovery of T1) was significantly longer in patients under 2 months of age than in older infants or children and adolescents. Atracurium remains, nevertheless, a relaxant of intermediate duration of action even in small infants.