罗库溴铵和阿曲库铵联合应用的肌松效应分析

目的探讨罗库溴铵和阿曲库铵联合应用时的肌松效应。方法择期全麻手术女性成年患者147例,丙泊酚和舒芬太尼静脉诱导,输注丙泊酚维持麻醉。面罩辅助或控制呼吸,用加速度仪以连续4次刺激(TOF)方式透皮刺激腕部尺神经,获取肌松药作用起效时间和T1最大抑制程度(Tmax)。按观测项目将患者均分成四组。结果阿曲溴铵ED95为(220.8±3.6)μg/kg,罗库溴铵ED95为(286.3±3.1)μg/kg。0.5×ED95的罗库溴铵与阿曲库铵联合使用,肌松效应达到T1抑制93%~97%时,阿曲库铵的剂量为63.6μg/kg。罗库溴铵0.5×ED95与阿曲库铵63.6μg/kg联合使用,Tmax为(95.3±0.9)%,变异系数1.0%。Ⅳ组中三个亚组的Tmax基本相同,合用组作用起效时间比阿曲库铵组快(P<0.01)。给予肌松药前和注药后5min内,MAP和HR的波动幅度均小于5%。结论罗库溴铵与阿曲库铵合用呈协同作用。当罗库溴铵剂量为0.5×ED95时,为获得T1抑制95%的肌松效应,阿曲库铵的合理用量为63.6μg/kg,比阿曲库铵的ED95减少71.2%。     

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.     

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)     

Histaminoid responses to atracurium, vecuronium and tubocurarine

Sixty patients scheduled for elective surgery underwent intradermal testing with 0.1 ml of the following solutions diluted in 0.9% saline: vecuronium and tubocurarine (1 in 1,000), atracurium (1 in 1,000 and 1 in 10,000), thiopentone (1 in 100) and also a 0.9% saline control. Thirty minutes later, an area of erythema of greater than 1.5 cm, or a wheal exceeding 1.0 cm in diameter, was recorded as a positive reaction. The patients then randomly received equipotent doses of atracurium, vecuronium or tubocurarine during a standardized anaesthetic induction. Any cutaneous reaction and the percentage fall in systolic pressure three minutes after administration of the relaxant were recorded. In 51 patients plasma IgE levels were measured. The incidence of positive cutaneous reactions to intradermal and intravenous relaxants was significantly different with each agent (p less than 0.01). The percentage fall in systolic pressure after tubocurarine was significantly different relative to the other two agents (p less than 0.01). This was regarded as reflecting potency in releasing histamine and placed the relaxants in the same order: tubocurarine, atracurium and vecuronium. The response to intradermal administration was no guide to the subsequent response after intravenous administration of the three relaxants. IgE levels below 15 IU X ml-1 occurred significantly more often in females and were associated with a significantly higher incidence of cutaneous reactions after intradermal atracurium (1 in 1,000 and 1 in 10,000) (p less than 0.05 and 0.001 respectively) and tubocurarine (1 in 1,000). With these two agents, generalized flushing after intravenous administration was also more common in this group, relative to the normal/high IgE group.     

A new infusion design for atracurium and vecuronium

An infusion technique, designed to reduce the duration of period of no response to nerve stimulation following atracurium (Group I) and vecuronium (Group 2), was studied in 30 patients during neurolept anaesthesia. For intubation a combination of a small bolus injection of the relaxant (ED50) and a continuous infusion were administered. The tactile response to nerve stimulation was used to quantify the degree of relaxation and to adjust the speed of infusion. On the other arm the mechanical twitch was recorded blindly for control. Good to excellent intubation conditions were obtained in 4.3 min with atracurium and in 4.0 min with vecuronium. The total dose given for intubation was 0.36 mg kg-1 atracurium (0.24-0.49 mg kg-1) and 0.064 mg kg-1 vecuronium (0.046-0.084 mg kg-1). The period of no response was zero in seven patients in Group I and in four patients in Group 2. In the remaining patients in Group I the period of no response ranged from 5.0-25.0 min, median 10.9 min, and in Group 2 from 2.5-15.6 min, median 9.5 min. At the time of extubation the train-of-four ratio was 0.71 and 0.72 in Group I and 2, respectively. It is concluded that it is possible to achieve a stable, adjustable, and easily reversible block with this technique, even during surgery of short duration.     

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)     

Neuromuscular sensitivity to atracurium in humans

The relation between plasma concentration and the effects of atracurium was studied in seven patients anaesthetised with thiopentone, fentanyl and nitrous oxide-oxygen. The response to train-of-four stimulation at ten-second intervals with tetanic stimuli applied every five minutes were recorded. The first sign of transmission returning after complete blockade was usually the post-tetanic facilitated twitch, which was noted when the mean atracurium concentration was 1.15 mg 1(-1) (SD 0.77). The most sensitive parameter was the train-of-four ratio, which recovered to 0.5 when the concentration was 0.217 mg 1(-1) (SD 0.56), compared with a concentration of 0.271 (SD 0.85) at 50% recovery for twitch height, 0.221 (SD 0.029) for tetanic peak and 0.231 (SD 0.079) for tetanic fade. The value for the train-of-four ratio differed significantly (P less than 0.05) from that for the twitch height, but other differences were not significant. Once recovery commenced, these four parameters recovered at similar rates, with recovery indices (25 to 75% responses) of 14.8 (SD 1.7), 14.0 (SD 1.0), 14.3 (SD 1.8) and 13.7 (SD 2.1) minutes respectively. Post-tetanic facilitation was most marked during severe but incomplete blockade and tetanic stimulation temporarily reversed the atracurium-induced decrease in train-of-four ratio. Clinically, the use of tetanic stimulation did not improve the sensitivity of neuromuscular monitoring, but post-tetanic count may be useful where monitoring of profound relaxation is required.     

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)     

Neuromuscular and cardiovascular effects of high-dose vecuronium

The effects of bolus administration of large doses of vecuronium on the onset and duration of neuromuscular blockade and histamine release were studied during fentanyl-nitrous oxide anesthesia. Forty adults were randomly assigned to receive a bolus injection of either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. The evoked electromyogram of thumb adduction to train-of-four stimulation was monitored. The time of onset and clinical duration (mean +/- SEM) after each dose were as follows: 0.1 mg/kg, 164 +/- 27 s and 42 +/- 5 min; 0.2 mg/kg, 120 +/- 17 s and 68 +/- 8 min; 0.3 mg/kg, 88 +/- 17 s and 111 +/- 19 min; 0.4 mg/kg, 78 +/- 19 s and 115 +/- 19 min. Both time of onset and duration after doses of 0.3 or 0.4 mg/kg were significantly different from values after the lower doses. No dose-related changes in blood pressure, heart rate, or histamine release were observed. The authors conclude that large bolus doses of vecuronium can be safely used to speed the onset of blockade, but with a significantly prolonged duration of action.     

Neuromuscular effects of atracurium in man

The neuromuscular effects of atracurium were studied in 25 A.S.A. class I or II patients anesthetized by a N2O-O2 narcotic technique. In five patients incremental doses of 0.05 to 0.1 mg/kg of atracurium were given intravenously every 3 minutes until approximately 95% depression of the evoked electromyographic (EMG) response of the adductor policus muscle was produced. This required 0.25 to 0.35 mg/kg of atracurium. The duration of block (return to 95% of control) was 25 to 50 minutes. In addition, four groups of five patients each received 0.15, 0.25, 0.375, or 0.6mg/kg of atracurium. The block produced by 0.15 mg/kg was 10% to 92% and lasted 8 to 55 minutes. The block produced by 0.25, 0.375, and 0.6 mg/kg was 95% or greater with a duration of action of 30 to 68 minutes, 52 to 70 minutes, and 65 to 95 minutes, respectively. Tracheal intubation was easily carried out in all patients in whom there was a block of 90% or greater. The block could be antagonized by the common clinical combination of atropine and neostigmine. Changes in heart rate and blood pressure following atracurium were less than 5%.     

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.     

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 blockade using vecuronium in dermatomyositis

The significant features of neuromuscular blockade with vecuronium in a patient with dermatomyositis are described: vecuronium 0.08 mg/kg resulted in 90%, 0.12 mg/kg in 100% neuromuscular blockade. In contrast to claims made in some previous publications, dermatomyositis did not produce increased sensitivity to vecuronium. Onset time and duration of action were also within normal limits in our patient. Time of spontaneous recovery until antagonism with neostigmine was markedly prolonged, but the dermatomyositis was only one of various possible explanations. Although there are potential hazards in the use of neostigmine in patients with dermatomyositis, antagonism of the neuromuscular block with 2 mg neostigmine was without problems in our patient. Our data support recent suggestions to reconsider the implications of dermatomyositis for anesthesia.     

Cumulation and reversal with prolonged infusions of atracurium and vecuronium

A randomized, double-blind study was undertaken to compare the tendencies for cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC) when administered by continuous infusion for long surgical procedures under balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were free of neuromuscular disease. Patients in the ATR group (n = 25) received a loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at 5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg-1.min-1. During surgery, the infusions of both ATR and VEC were titrated in increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90-95%. Neuromuscular block was measured by recording the integrated evoked electromyographic response (EMG) of the first dorsal interosseous muscle in response to supramaximal TOF stimuli on the ulnar nerve. The durations of infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between 4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC, from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study period. The number of adjustments required to maintain 90-95% T1 suppression decreased between the second and fourth hours of administration, but were similar at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.