Recovery of neuromuscular function and postoperative morbidity following blockade by atracurium, alcuronium and vecuronium

Recovery of neuromuscular function and postoperative morbidity were studied in 51 fit female patients who had nonemergency gynaecological laparoscopy as inpatients. They were allocated randomly to one of three groups to receive either atracurium 0.31 mg/kg, alcuronium 0.25 mg/kg, or vecuronium 0.06 mg/kg as part of an otherwise standard anaesthetic technique. There were neither differences in intubation conditions nor in the occurrence of postoperative diplopia whichever muscle relaxant was used. Deficits in grip strength and expiratory force were seen at one hour after reversal with atropine 1.2 mg and neostigmine 2.5 mg in all patients, deficits which persisted for 3 hours in those who received alcuronium. The recovery of inspiratory force was slower and less complete at up to 3 hours in those who received alcuronium and there was a high incidence of minor postoperative morbidity at up to 24 hours in each of the three groups. The only statistical difference in symptomatic morbidity was an increase in muscle weakness in those who received alcuronium compared with atracurium at 3 hours after laparoscopy. Only 25%, 20% and 31% of the patients who received atracurium, alcuronium and vecuronium respectively said that they would have liked to be day stay patients.     

Comparison of atracurium and alcuronium in day-case gynaecological surgery

Alcuronium and atracurium were used on a randomised basis as part of the anaesthetic technique for out-patient gynaecological laparoscopy. Conditions for intubation and relaxation were similar but there was a marked decrease in the incidence of minor postoperative sequelae in the atracurium group.     

Rapid onset of the action of vecuronium by administration of a precurarizing dose

The administration of vecuronium in divided doses with respect to onset of action and intubating conditions was investigated. This study was conducted in 3 parts. In part 1 the maximal precurarizing dose of 0.015 mg/kg vecuronium was found. In the second part we showed that the optimal time interval between divided doses was 3 min. In the third part we made a comparative investigation between the effect of 0.015 + 0.085 mg/kg body wt. at a 3 min interval and that of a single dose of 0.1 mg/kg body wt. vecuronium. --Neuromuscular function was assessed in semiquantitative manner, using the train of four (TOF) stimulation of ulnar nerve. Administration of vecuronium in divided doses, compared with a single dose of 0.1 mg/kg body wt., resulted in a more than 1 min earlier onset time of 1.5-2.5 min and facilitated early intubation. As soon as twitch tension had completely disappeared uniform by excellent intubating conditions were available in all cases. The administration of vecuronium in divided doses enabled better intubating conditions than the same single dose of vecuronium.     

Assessment of facial reinnervation by use of chronic electromyographic monitoring

The study of muscle reinnervation has been difficult because of lack of an accurate, reproducible method to monitor return of function. Visual assessment relies on subjective interpretation. Histology provides anatomic, not functional, information. Electromyography and anatomic tracing have been most effective in evaluating physiologic return of muscle function. It has been difficult to assess the timing of functional return electromyographically because measurements are intermittent and electrode placement varies. A method was designed to allow long-term monitoring of electromyographic (EMG) activity in the facial musculature of the rabbit. Sixteen rabbits were monitored for at least 1 month or until return of normal EMG activity was identified. Various levels of injury (nerve crush, transection without repair, and transection with immediate end-to-end anastomosis) were evaluated. EMG evidence of reinnervation was seen in all animals with nerve crush injuries as well as those with anastomoses. Physiologic continuity of the nerves was then evaluated by retrograde transport of horseradish peroxidase. All muscles showing return of EMG activity had uptake of HRP into the appropriate brain stem motor neurons. The denervated muscles showed no HRP uptake. The information gained in this study shows potential for use of this technique in comparing functional return of muscle activity between different reinnervation methods.     

Comparison between atracurium and alcuronium for muscle relaxation during laparoscopy

Atracurium 0.3 mg/kg was compared with alcuronium 0.25 mg/kg as the sole muscle relaxant for tracheal intubation and abdominal relaxation for gynaecological laparoscopy in 46 patients during nitrous oxide, oxygen and halothane anaesthesia. Speed of onset, intubation conditions, effect on blood pressure and pulse rate, and ease of reversal were compared. Alcuronium had a significantly faster onset of action than atracurium; intubation conditions were adequate and abdominal relaxation was satisfactory for both drugs. The effect of atracurium was readily reversible within 10 minutes; in contrast alcuronium was significantly more resistant and mean recovery time was 28.03 minutes. Although alcuronium provided good muscle relaxation, it is not suitable for short procedures because of difficulty in reversing its action. Atracurium allowed earlier and more complete reversal of neuromuscular block.     

维库溴铵对全麻患者脑电熵指数和脑电双频谱指数监测镇静深度的影响

目的观察全身麻醉过程中,维库溴铵对脑电熵指数——状态熵（AE）和反应熵（RE）以及脑电双频谱指数（BIS）的影响。方法ASAⅠ级或Ⅱ级择期手术患者60例,随机分为4组（n=15）：Ⅰ组为对照组,静脉注射生理盐水;Ⅱ组、Ⅲ组、Ⅳ组为试验组,分别静脉注射维库溴铵0．03、0．06、0．12 mg/kg。麻醉诱导采用异丙酚靶控输注（TCI）,当效应室浓度（CE）达到3．5μg/ml时,按组别静脉注射维库溴铵或等容积生理盐水,5 min后静脉注射芬太尼3μg/kg,行气管插管,观察5 min后将Ⅰ组、Ⅱ组、Ⅲ组维库溴铵剂量补足到0．12 mg/kg。记录诱导前即刻、CE达到3．5μg/ml、注射维库溴铵或生理盐水后1、2、3、4、5 min、气管插管前即刻、插管后即刻及插管后1、3、5 min的RE、AE、BIS、HR和MAP。结果与维库溴铵静脉注射前即刻比较,4组静脉注射后各时点RE、SE、BIS、HR、MAP差异无统计学意义（P＞0．05）;4组间静脉注射前后RE、SE、BIS、HR、MAP比较差异无统计学意义（P＞0．05）。与插管前即刻比较,4组插管后即刻及插管后1min时RE、SE、BIS、HR和MAP均升高（P＜0．05或0．01）;与Ⅰ组比较,Ⅱ组、Ⅲ组、Ⅳ组插管后即刻和插管后1 min RE、SE和BIS降低（P＜0．05）,但3组间比较差异无统计学意义（P＞0．05）。结论在深度镇静且无伤害性刺激时,维库溴铵对脑电熵指数和BIS无影响;存在伤害性刺激时（如气管插管）,即使小剂量（0．03 mg/kg）的维库溴铵也可降低脑电熵指数和BIS的升高幅度。     

Time course of action of combinations of vecuronium and pancuronium

Vecuronium 0.1 mg/kg, pancuronium 0.1 mg/kg, vecuronium 0.075 mg/kg + pancuronium 0.025 mg/kg, vecuronium + pancuronium 0.05 mg/kg each and vecuronium 0.025 mg/kg + pancuronium 0.075 mg/kg were compared with respect to time taken to onset of effect, duration of clinical relaxation and intubation conditions in five groups of 20 patients each. The time to onset and intubating conditions were similar in all the groups, indicating that the combinations have no advantage over the individual drugs. The duration of clinical relaxation was 25 minutes with vecuronium, and increased as the proportion of pancuronium in the mixture increased, being 56 minutes with pancuronium 0.1 mg/kg.     

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.     

Comparison of vecuronium with ORG 9487 and their interaction

Purpose

To compare the pharmacodynamic behaviour of vecuronium with that of ORG 9487. we measured the time-course of action of equipotent doses of ORG 9487 and vecuronium and investigated their mutual interaction when given in succession.

Methods

Sixty ASA I–II patients were anaesthetized with thiopentone, fentanyl halothane and nitrous oxide and assigned randomly to four groups. Each patient received an initial dose (ID) of either vecuronium (V) or ORG 9487 (O) followed by maintenance doses (MD_n) of either V or O (ID/MD: O/O, V/O, O/V, and V/V). The time course of action was measured mechanomyographically, determining the duration until 25% recovery of the single twitch (DUR₂₅).

Results

The onset time of an ID of ORG 9487 was shorter than that of an ID of vecuronium (96vs 203 sec. P < 0.001). The DUR₂₅ of the ID of ORG 9487 was less than half that of vecuronium (10.7 ± 2.8 vs 28.8 ± 6.1 min, P< 0.001). The DUR₂₅ of MD₁ and MD₂ of ORG 9487 were shorter than those of vecuronium (O/O: 7.3 ± 2.8 and 8.5 ± 2.4 mm. V/O: 12.7 ± 3.3 and 11.5 ± 3.5 min,vs O/V. 16.4 ± 4.5 and 20.6 ± 4.7 min: V/V: 18.8 ± 3.0 and 20.1 ± 3.8 min, respectively, P < 0.05). An ID of vecuronium prolonged the DUR₂₅ of MD₁ and MD₂ of ORG 9487 (P < 0.05)

Conclusion

ORG 9487 is a muscle relaxant with a shorter duration of action than vecuronium. Maintenance doses of ORG 9487 are also shorter acting than roughly equipotent maintenance doses of vecuronium, irrespective of which relaxant is given initially.     

围术期TOF监测与残余肌松潘库溴铵与维库溴铵的比较

目的研究潘库溴铵与维库溴铵术后残余肌松发生率,探讨围术期应用TOF监测降低术后残余肌松发生率的可行性.方法81例ASAⅠ～Ⅱ级成年择期手术病人,随机分为维库溴铵监测(V+M)组;维库溴铵未监测(V)组;潘库溴铵监测(P+M)组及潘库溴铵未监测(P)组4组.麻醉方法为静脉注射2.0～2.5mg/kg异丙酚,潘库溴铵或维库溴铵0.08～0.12mg/kg,3min后气管插管,麻醉维持应用50%N2O、异氟醚,间断给予芬太尼.使用TOF-GUARD监测仪监测肌松.P+M组和V+M组在TOF计数出现1～2个颤搐反应时给新斯的明0.04mg@kg-1、阿托品0.02mg@kg-1.拮抗;P组和V组根据临床反应判断是否给予拮抗及剂量.观察各组病人到ICU后残余肌松发生率(T4/T1＜0.70)及持续时间.结果4组病人到ICU后残余肌松发生率分别为V+M组23.80%、V组39.13%、P+M组42.11%、P组83.33%,P组残余肌松发生率显著高于V组(P＜0.01),而且监测组残余肌松发生率显著低于未监测组(P＜0.05).4组残余肌松持续时间分别为V+M组(11.11±5.48)min、V组(30.00±15.12)min、P+M组(21.15±11.62)min、P组(44.87±31.39)min,未监测组明显长于监测组(P＜0.05).未监测组潘库溴铵及维库溴铵总的用药量分别大于监测组(P＜0.05).结论1.围术期TOF监测可明显降低残余肌松发生率;2.潘库溴铵残余肌松发生率及持续时间均显著高于维库溴铵,在无神经肌肉功能监测的情况下,应用潘库溴铵应严加注意;3.应用非去极化肌松药阻滞后进行术后肌松拮抗是必要的.     

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.     

Comparison of thumb acceleration and thenar EMG in a pharmacodynamic study of alcuronium

We compared thumb acceleration (Acc) and thenar electromyography (EMG) techniques by evaluating the neuromuscular blocking properties of alcuronium in 14 ASA physical status I patients. The dose-response curves determined by the two techniques were parallel but the EMG-curve was shifted 25% to the right (P less than 0.001). Acc reflected 8-11% greater neuromuscular block than simultaneous EMG in every patients (P less than 0.05). Concurrently, the duration of greater than 90% neuromuscular block maintained by alcuronium 280 micrograms/kg was significantly longer when measured by the Acc transducer (30 vs. 19 min, P less than 0.001). Although the TOF ratios were in good correlation (r2 = 0.82), clinically significant differences existed between the two simultaneous techniques. The results underline the importance of the method of assessment of neuromuscular transmission when evaluating the action of neuromuscular blocking drugs.     

Protracted action of vecuronium in a patient with chronic renal insufficiency treated by dialysis

Although the pharmacokinetics of vecuronium are altered by the loss of kidney function, they do not differ significantly between patients with normal renal function and patients with renal failure. Therefore, the drug has become a preferred neuromuscular blocking agent in anuric patients. The author observed complete relaxation--verified by nerve stimulation--for more than 3 h following a single dose of 0.09 mg/kg vecuronium in a patient with chronic renal failure. Liver function was normal, and no drugs known to interact with vecuronium were used. The authors conclude that the altered pharmacokinetics of vecuronium in anuric patients might cause clinically significant effects in some patients.     

Onset and duration of action of vecuronium in the elderly: comparison with adults

The onset and duration of action of vecuronium were studied in young adult (n = 30; mean age 34 +/- 11.1 (s.d.) yr), middle-aged (n = 20; mean age 60 +/- 5.8 yr) and elderly patients (n = 30; mean age 80 +/- 4.6 yr) anaesthetised with thiopentone, nitrous oxide in oxygen and halothane. Neuromuscular block was monitored by applying the train-of-four (TOF) stimulation at 2 Hz to the ulnar nerve every 12 s. Half the patients in each group received 0.08 and the other half 0.12 mg kg-1 of the relaxant. The time to return of T1 (first response in the TOF sequence) to 25% of control was 28 +/- 5.2 (s.d.), 34 +/- 7.1 and 39 +/- 10.2 min following 0.08 mg kg-1 dose (P less than 0.05 between the elderly and young adults) and 45 +/- 9.2, 48 +/- 6.2 and 69 +/- 19.2 min following 0.12 mg kg-1 dose, respectively, in the three age groups (P less than 0.05 between the elderly and the other two groups). The recovery indices (time for 25-75% recovery of T1) after the 0.08 mg kg-1 was 9.6 +/- 3.4, 13.6 +/- 5.1 and 17.4 +/- 6.1 min, respectively (P less than 0.05 between the elderly and young adults). There was no significant difference in any of the parameters between the young adults and the middle-aged. The onset of block at each dose was not significantly different between the three age groups; however, the time to maximum effect was significantly shorter with the higher dose in the young and the middle-aged, but not in the elderly. Regression analysis of the data between age and the duration of action and recovery index suggested a significant prolongation (P less than 0.05) of these parameters in the elderly.     

The dose-response relationship and time course of the neuromuscular blockade by alcuronium

Although alcuronium has been in clinical use for almost 40 years, there is still considerable controversy in the literature regarding its neuromuscular blocking potency, the time course of the drug action and the side effects. The aim of this study was to investigate the dose-response relationship of alcuronium and to compare the time course of its neuromuscular effects with vecuronium following intubation doses of both compounds. METHODS. The study was carried out in two parts. In the first part 60 patients and in the second part 30 consenting ASA class I or II patients 20-60 years of age were included. The patients were undergoing elective gynecological or intra-abdominal operations. In the first part the patients received six different doses of alcuronium (60, 90, 120, 150, 180 or 210 micrograms/kg) in order to establish its dose-response relationship. Each dose was administered to ten patients. In the second part patients received either 300 micrograms/kg alcuronium (n = 15) or 100 micrograms/kg vecuronium (n = 15), and the time course of these two compounds (onset time, duration 25%, duration 75% and the recovery index) were compared. To test the reversibility, ten patients in each group received 30 micrograms/kg neostigmine at 25% recovery of T1. The neuromuscular effects of alcuronium and vecuronium were quantitated by EMG using the DATEX relaxograph. RESULTS. The log-logit analysis of the dose response data revealed an ED50 of 111 micrograms/kg and an ED95 of 250 micrograms/kg, which is in reasonable agreement with the measured effects following 120 micrograms/kg and 210 micrograms/kg alcuronium, resulting in 52 +/- 21% and 96 +/- 4% T1 depression, respectively. The onset time, duration 25%, duration 75% and spontaneous recovery index following 300 micrograms/kg alcuronium (5.0 +/- 3.4 min, 62 +/- 25 min, 119 +/- 38 min and 58 +/- 34 min) appeared to be significantly longer (P less than 0.05) than those observed after 100 micrograms/kg vecuronium (3.2 +/- 1.2 min, 33 +/- 7 min, 49 +/- 9 min and 18 +/- 7 min), respectively. The most striking finding of this study is the enormous individual variations observed in both neuromuscular potency and the time course of action of alcuronium. Following 150 micrograms/kg (routinely employed in daily clinical practice), the magnitude of T1 depression ranged between 19% and 100%. The same vast individual variations were observed in the time course of action following 300 micrograms/kg of alcuronium. The onset time, duration 25%, duration 75% and spontaneous recovery index ranged between 1.3 and 14 min, 22 and 110 min, 93 and 186 min and 32 and 116 min, respectively. CONCLUSIONS. The ED50 and ED95 values for alcuronium found in this study are in the same order of magnitude as 106.8 micrograms/kg and 135 micrograms/kg for ED50 and with 280 micrograms/kg for ED95, respectively, as reported by others. The long duration with slow recovery and the wide individual variation in the neuromuscular effects observed in our study have been reported earlier. Based on the above observations and because of the availability of better alternatives with fewer side effects, we conclude that alcuronium should be added to the list of obsolete neuromuscular blocking agents, together with gallamine and d-tubocurarine.     

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.     

Neuromuscular blocking action of suxamethonium after antagonism of vecuronium by edrophonium, pyridostigmine or neostigmine

The reported effects of edrophonium on a subsequent dose of suxamethonium are variable and the effects of pyridostigmine have not been evaluated extensively. We have studied this interaction in patients anaesthetized with propofol and sufentanil. After recovery from an initial bolus (1 mg kg-1) of suxamethonium, vecuronium was infused to produce 75% block. After 30 min, the infusion was discontinued and saline 5 ml, edrophonium 0.75 mg kg-1, pyridostigmine 0.24 mg kg-1 or neostigmine 0.05 mg kg-1 was given. Fifteen minutes later the mean durations of a second bolus of suxamethonium were: 10.5 (SD 3.9) min (saline), 10.9 (3.7) min (edrophonium), 18.7 (5.4) min (pyridostigmine) and 23.8 (7.4) min (neostigmine). Corresponding plasma cholinesterase activities (percentage of baseline) were: 91 (18), 87 (9), 21 (10) and 52 (26). When both treatment groups and individual patients were compared, the changes in duration of action did not correlate with changes in cholinesterase activity. These data suggest that other mechanisms in addition to cholinesterase inhibition may contribute to this drug interaction.