Geographic regional differences in rocuronium bromide dose-response relation and time course of action: an overlooked factor in determining recommended dosage

BACKGROUND: Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. METHODS: Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. RESULTS: Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/- 59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148 +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8 min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively). CONCLUSIONS: The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.     

Dose-Response of Rocuronium Bromide in Children Anesthetized with Propofol: A Comparison with Succinylcholine

Background: The aim of this study was to determine the potency of rocuronium during propofol/fentanyl/N2 O anesthesia in children and to compare the time course of action of rocuronium at doses of two and three times the ED95 with that of succinylcholine.

Methods: Rocuronium (120, 160, 200, or 240 micro gram/kg) was administered to 48 children aged 2-10 yr. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor digiti minimi to supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s every 10 s. Potency was determined by log-probit transformation and least-squares linear regression analysis of dose and response. In a second group of 30 children, the onset and recovery profile of rocuronium at doses of two and three times the ED95 was compared with that of succinylcholine (2 mg/kg).

Results: Values for ED50 and ED95 were 210 +/- 24 and 404 +/- 135 micro gram/kg, respectively. The time to 90% neuromuscular block after 1.2 mg/kg rocuronium (three times the ED95), 33 +/- 5 s (mean +/- SD), did not differ significantly from that after succinylcholine, at 30 +/- 7 s; however, both were significantly less than that after 0.8 mg/kg rocuronium, 46 +/- 8 s (P < 0.05). The time to 25% recovery from 1.2 micro gram/kg rocuronium, 41 +/- 13 min, was approximately 50% greater than that after 0.8 mg/kg, at 27 +/- 6 min (P < 0.001), and eight times greater than that after succinylcholine, at 5.2 +/- 1.9 min (P < 0.001).     

Dose-Response Relationship and Infusion Requirement of Cisatracurium Besylate in Infants and Children during Nitrous Oxide-Narcotic Anesthesia

Background: To determine the effect of age on the dose-response relation and infusion requirement of cisatracurium besylate in pediatric patients, 32 infants (mean age, 0.7 yr; range, 0.3-1.0 yr) and 32 children (mean age, 4.9 yr; range, 3.1-9.6 yr) were studied during thiopentone-nitrous oxide-oxygen-narcotic anesthesia.

Methods: Potency was determined using a single-dose (20, 26, 33, or 40 [mu]g/kg) technique. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor pollicis to supramaximal train-of-four stimulation of the ulnar nerve at 2 Hz.

Results: Least-squares linear regression analysis of the log-probit transformation of dose and maximal response yielded median effective dose (ED50) and 95% effective dose (ED95) values for infants (29 +/- 3 [mu]g/kg and 43 +/- 9 [mu]g/kg, respectively) that were similar to those for children (29 +/- 2 [mu]g/kg and 47 +/- 7 [mu]g/kg, respectively). The mean infusion rate necessary to maintain 90-99% neuromuscular block during the first hour in infants (1.9 +/- 0.4 [mu]g [middle dot] kg-1 [middle dot] min-1; range: 1.3-2.5 [mu]g [middle dot] kg-1 [middle dot] min-1) was similar to that in children (2.0 +/- 0.5 [mu]g [middle dot] kg-1 [middle dot] min-1; range: 1.3-2.9 [mu]g [middle dot] kg-1 [middle dot] min-1).     

Comparative Clinical Pharmacology of Rocuronium, Cisatracurium, and Their Combination

Background: The comparative clinical pharmacology of cisatracurium and rocuronium and their combinations has not been reported. In this study, the authors compared the relative potency and the clinical profile and characterized the interaction of both drugs.

Methods: Two hundred twenty adults classified as American Society of Anesthesiologists physical status I and anesthetized with propofol-fentanyl-nitrous oxide were studied. In part 1, the neuromuscular-blocking effects of cisatracurium and rocuronium were assessed after administration of bolus doses of 20-50 [micro sign]g/kg and 100-300 [micro sign]g/kg, respectively. In part 2, we compared the time course of 1xED50, 1, 1.5, and 2xED95 doses of both drugs (where ED50 and ED95 are, respectively, the doses producing 50% and 95% depression of the first twitch height [T1]). In part 3, equieffective combinations of both drugs were studied to characterize their interaction.

Results: The calculated ED50 values and their 95% confidence intervals were 111 (107-115) and 215 (207-226) [micro sign]g/kg for rocuronium and cisatracurium, respectively. Compared with equipotent doses of cisatracurium, rocuronium had a faster onset, and a faster spontaneous T1 and train-of-four recovery times that were significant except at maximum recovery with the 2xED95 dose. The interaction between rocuronium and cisatracurium was synergistic, and the time profile of the combination group was different from that of the single-dose groups.     

Equi-lasting doses of rocuronium, compared to mivacurium, result in improved neuromuscular blockade in patients undergoing gynecological laparoscopy

PURPOSE: To compare equi-lasting doses of a short-acting (mivacurium) to an intermediate-acting (rocuronium) neuromuscular relaxant, with regard to intubating conditions, efficacy, number of maintenance doses, hemodynamic alterations, adverse events and costs, in patients undergoing laparoscopic gynecological surgery. METHODS: Sixty patients were randomly allocated to receive either 0.2 mg*kg(-1) (3 x ED(95)) mivacurium or 0.5 mg*kg(-1) (1.7 x ED(95)) rocuronium, under propofol/fentanyl anesthesia. T1, first twitch of the train-of-four (TOF) and TOF ratio (T4:T1) were used to evaluate neuromuscular block using the Relaxometer(R) mechanomyograph. The trachea was intubated when T1 was maximally suppressed. Neuromuscular block was maintained at 25% T1 with equi-lasting doses of 0.075 mg*kg(-1) mivacurium or 0.15 mg*kg(-1) rocuronium. RESULTS: Mean (min) +/- SD mivacurium onset time (1.9 +/- 0.4) was longer than that of rocuronium (1.3 +/- 0.3). This did not yield a statistical difference in intubating conditions between the two groups. Interval 25-75% T1 recovery and time to 0.8 TOF recovery were prolonged following rocuronium (11.9 +/- 3.9, 52.6 +/- 15.5 respectively) compared to mivacurium (6.7 +/- 2.3, 39.2 +/- 8.1 respectively). More patients, 22/30, required mivacurium maintenance doses compared to 14/30 patients in the rocuronium group. Arterial blood pressure declined and 13/30 patients manifested erythema following mivacurium administration. The acquisition costs of rocuronium (6.93 Euro/patient) were 23% lower compared to mivacurium (8.96 Euro/patient). CONCLUSION: Equi-lasting doses of rocuronium resulted in favourable intubating conditions more rapidly, improved hemodynamic stability, required less frequent administration of maintenance doses and were not associated with erythema, compared to mivacurium.     

Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery.

The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a "blinded" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate.     

Reversal of Profound Rocuronium Neuromuscular Blockade by Sugammadex in Anesthetized Rhesus Monkeys

Background: Reversal of neuromuscular blockade can be accomplished by chemical encapsulation of rocuronium by sugammadex, a synthetic [gamma]-cyclodextrin derivative. The current study determined the feasibility of reversal of rocuronium-induced profound neuromuscular blockade with sugammadex in the anesthetized rhesus monkey using train-of-four stimulation.

Methods: Four female rhesus monkeys each underwent three experiments. In each experiment, first, a 100-[mu]g/kg dose of rocuronium was injected and spontaneous recovery was monitored. After full recovery, a 500-[mu]g/kg dose of rocuronium was injected. Up to this point, all three experiments in a single monkey were identical. One minute after this rocuronium injection, either one of the two tested dosages of sugammadex (1.0 or 2.5 mg/kg) was injected or saline was injected.

Results: Injection of 100 [mu]g/kg rocuronium resulted in a mean neuromuscular blockade of 93.0% (SD = 4%), and profound blockade was achieved by injection of 500 [mu]g/kg. In all experiments, a 100% neuromuscular blockade was achieved at this dose. After injection of the high rocuronium dose, the 90% recovery of the train-of-four ratio took 28 min (SD = 7 min) after saline, 26 min (SD = 9.5 min) after 1 mg/kg sugammadex, and 8 min (SD = 3.6 min) after 2.5 mg/kg sugammadex. Signs of residual blockade or recurarization were not observed. Injection of sugammadex had no significant effects on blood pressure or heart rate.     

Probability of acceptable intubation conditions with low dose rocuronium during light sevoflurane anaesthesia in children

BACKGROUND: To define the rocuronium doses which would provide 50%, 90%, and 95% probability of 'acceptable' intubation conditions during light sevoflurane anaesthesia, we studied 60 children aged 2-7 years in a prospective, randomised, assessor blinded study. METHODS: After mask ventilation with 1 MAC sevoflurane/N2O for 17+/-1 (x+/-SD) min we administered rocuronium (either 0.15, 0.22, 0.3, 0.5, or 1.0 mg. kg(-1)) or placebo, and quantified the evoked force of the adductor pollicis muscle. Intubation conditions were assessed before and 2 min after injection of the test drug. RESULTS: Intubation conditions were improved significantly with rocuronium and scored 'acceptable' in 70%, 90%, and 100% of the children after injection of rocuronium 0.15, 0.22, and 0.3 mg x kg(-1), respectively. In parallel, twitch tension decreased to 53% (6-100), 26% (11-100), and 11% (0-19) of baseline (median (range)). Recovery of train-of-four ratio to 0.8 was achieved 13 (7-19), 16 (8-28), and 27 (23-44) min after injection of the respective rocuronium doses. Higher rocuronium doses did not further improve intubation conditions but only prolonged time of neuromuscular recovery. Logistic regression analysis revealed that rocuronium 0.11 (CI 0.05-0.16), 0.21 (0.14-0.28), and 0.25 (0.15-0.34) mg x kg(-1) provides a 50%, 90%, and 95% probability of 'acceptable' intubation conditions in children during 1 MAC sevoflurane/N2O anaesthesia, respectively. Furthermore, we calculated that force depression of adductor pollicis muscle to 81% (CI 72-90), 58% (42-74), and 50% (29-71) of baseline is associated with 50%, 90%, and 95% probability of 'acceptable' intubation conditions. CONCLUSIONS: Submaximal depression of muscle force with low dose rocuronium improves intubation conditions in children during light sevoflurane anaesthesia while allowing rapid recovery of neuromuscular function. However, when using low dose rocuronium neuromuscular monitoring may be helpful to detect children with inadequate response to the relaxant so as to avoid an unsuccessful intubation attempt.     

The prolonged duration of rocuronium in Chinese patients

We compared the potency and duration of action of rocuronium in Chinese and Caucasian patients during general anesthesia. Thirty-six women (18 Caucasian and 18 Chinese) and 36 children (18 Caucasian and 18 Chinese) were evaluated during the administration of propofol/fentanyl anesthesia. Patients in each age group were randomized into three subgroups to receive single doses of 0.06, 0. 12, or 0.18 mg/kg rocuronium (adults) or 0.12, 0.18, or 0.24 mg/kg rocuronium (children). Neuromuscular blockade was assessed by electromyography of the adductor pollicis after train-of-four (TOF) stimulation of the ulnar nerve. Dose response curves were constructed when maximum neuromuscular depression of the first twitch of the train (T(1)) was obtained. A second bolus dose of rocuronium was then administered to a total dose of 0.6 mg/kg. The times of spontaneous recovery to T(1) 10%, 25%, and 90% of control and to TOF 0.25, 0.50, and 0.70 were recorded. For both adults and children, recovery occurred later in Chinese than in Caucasian patients (P<0.05 for T(1) of 10%, 25%, 75%, and 90% and TOF to 0.7). The 50% effective dose was smaller in Chinese adults (125+/-63 vs. 159+/-66 microg/kg) and Chinese children (171+/-43 vs. 191+/-46 microg/kg) than in Caucasian adults and children, but the difference was not statistically significant. In adults, time to 25% T(1) recovery was 43+/-13 min in Chinese patients and 33+/-10 min in Caucasian patients (P<0.05). The corresponding values were more rapid for children: 30+/-10 and 24+/-6 min (P<0.05). We conclude that the recovery from rocuronium neuromuscular blockade was longer in Chinese compared with Caucasian patients and in adults compared with children.     

Rapid Tracheal Intubation with Rocuronium: A probability Approach to Determining Dose

Background: Rapid tracheal intubation with rocuronium has not been studied using a probability-based approach. The authors aimed to predict doses of rocuronium giving 90% and 95% probability of intubation within 60 s and to estimate their durations of action.

Methods: After premedication with midazolam, 2 mg, anesthesia was induced in 80 subjects with fentanyl, 2 [micro sign]g/kg, followed 3 min later by propofol, 2 mg/kg. Patients received randomly rocuronium, 0.0, 0.4, 0.8, or 1.2 mg/kg (n = 20/dose). Laryngoscopy began 40 s later, aiming for intubation at 60 s, and conditions were graded perfect, acceptable, or unacceptable, with the first two conditions being successful intubation. Anesthesia was maintained with isoflurane 0.5-1.0% (end-tidal) and fentanyl. Duration of action was time until reappearance of the first tactile train-of-four response. The dose versus fraction of patients with successful intubation was analyzed by logistic regression. Doses giving 90% and 95% (D (90) and D95) probability of successful intubation were calculated.

Results: Intubation was successful in 7, 11, 18, and 19 patients in the 0.0, 0.4, 0.8, and 1.2 mg/kg groups, respectively. The D90 and D95 doses (95% confidence limits in parentheses) were 0.83 (0.59-1.03) and 1.04 (0.76-1.36) mg/kg, respectively. Estimated time until first tactile train-of-four response after D90 and D95 doses was 32 and 46 min, respectively.     

不同年龄患儿罗库溴铵药效学的比较

目的 比较新生儿、婴儿、幼儿和儿童罗库溴铵的药效学.方法 择期全麻手术患儿160例,ASAⅠ或Ⅱ级,根据年龄分为4组(n=40):新生儿组、婴儿组、幼儿组及儿童组.各组随机选取患儿20例,采用4次累积给药法静脉注射罗库溴铵,初始剂量:新生儿组40 μg/kg,婴儿组80 μg/kg,幼儿组及儿童组均为120 μg/kg,后3次均追加罗库溴铵40μg/kg.每次给药后.观察TOF反应.当T1连续3次稳定不变时,给予下一次剂量.采用概率单位法计算T1抑制50%、90%、95%的用药量(ED50、ED90、ED95).各组随机选取20例患儿,静脉注射2倍ED95剂量的罗库溴铵,记录肌松起效时间、高峰时间、临床肌松时间、体内作用时间和恢复指数.结果 与新生儿组比较,幼儿组和儿童组罗库溴铵ED50、ED90和ED95均升高(P<0.01),婴儿组上述指标差异无统计学意义(P>0.05).婴儿组、幼儿组和儿童组罗库溴铵起效时间、临床肌松时间和体内作用时间缩短,恢复指数降低(P<0.01);与幼儿组比较.儿童组罗库溴铵ED50、ED90和ED95升高(P<0.01).结论 不同年龄患儿对罗库溴铵的量效关系和时效关系存在明显的差别,新生儿对罗库溴铵的敏感性最强.     

Lack of interaction between propofol and vecuronium.

We estimated the potency of vecuronium and measured the onset and duration of its action during total intravenous anesthesia with propofol to examine the possibility of any interaction between these two drugs. Propofol infusion was administered according to a three-step dosage scheme, and neuromuscular block was monitored by measuring the force of contraction of the adductor pollicis muscle after single-twitch stimulation of the ulnar nerve at 0.1 Hz. A control group of patients were similarly studied during anesthesia with thiopental, nitrous oxide, oxygen, and fentanyl. The ED50 and ED95 (dose required to produce a 50% and 95% depression of twitch tension, respectively) of vecuronium in patients given total intravenous anesthesia (n = 24) were 24 (22-27, 95% confidence limits) and 41 (37-48, 95% confidence limits) micrograms/kg, respectively, and in the control group (n = 24), 20 (17-24) and 39 (34-37) micrograms/kg, respectively. The onset of action of an 80-micrograms/kg dose (2 x ED95) of vecuronium was 3.6 +/- 1.2 and 4.1 +/- 1.7 min (mean +/- SD), in the propofol (n = 10) and control (n = 10) groups, respectively. The respective times to recovery of the twitch height to 25% of control and the recovery indices (25%-75% recovery of twitch height) in the propofol versus control groups were 28.3 +/- 6.6 and 28.0 +/- 1.7 min and 13.3 +/- 6.8 and 15.4 +/- 11.9 min, respectively. There were no significant differences in any of the measured variables between the propofol and control groups, indicating the lack of any interaction between propofol and vecuronium.     

术前急性高容量血液稀释对罗库溴铵量-效关系的影响

Objective To study the influence of preoperative acute hypervolaemic haemodilution (AHHD) on the dose-response relationship of rocuronium.Methods Forty patients were randomly allocated to AHHD group or control group (n=20).Anesthesia was maintained with propofol and remifentsnyl using TCI,and rocuronium was randomly given with one of six doses(60 μg/kg).AHHD was conducted with preoperative infusion of 15 ml/kg 6% hydroxyethyl starch at a rate of 30 ml/min.Neuromuscular function was assessed using an accelograph with train-of-four stimulation at wrist.The dose-response relationship of rocuronium was determined with cumulative dose-response technique.Results Hb,Hct,TPP and ALB decreased markedly (P＜0.05) after AHHD.AHHD did not result in a significant shift in rocuronium dose-response curve.There was no significant difference in ED50,ED90,and ED95 between the AHHD group[(192.1±24.9) μg/kg,(309.9±42.7) μg/kg,(322.0±44.4) μg/kg,respectively]and the control group [(178.5±34.7) μg/kg,(209.1± 47.8)μg/kg,(304.1±49.5) μg/kg,respectively].Conclusion These results demonstrate that the potency of rocuronium is not affected by AHHD,and rocuronium may become an ideal choice of relaxant in occasion of applying AHHD.     

Dose-response relationship of rocuronium: a comparison of electromyographic vs. acceleromyographic-derived values

BACKGROUND: Acceleromyography (AMG) is being employed with increasing frequency as a research tool. However, there is almost no information available regarding the accuracy of values for drug potency obtained using AMG. This study was an attempt to determine if AMG-derived ED(50/95) values are interchangeable with those measured with a more traditional neuromuscular monitor. METHODS: Thirty adult patients were studied. Anesthesia was induced and maintained with N20, propofol, and supplementation opioid. Tracheal intubation was accomplished without muscle relaxants. Simultaneous ipsilateral AMG and EMG responses to 0.10 Hz stimulation was recorded. Following instrument calibrations, a single dose of rocuronium was administered. The first patient received a bolus of 0.17 mg kg(-1) of rocuronium. Using the Hill equation with a postulated slope of 4.50, the ED(50) was calculated. The second subject received a dose which approximated the calculated ED(50) for patient no. 1. Successive subjects were given a dose based on the running average of the estimated ED(50). RESULTS: The AMG-derived ED50/95 values for rocuronium (0.163 +/- 0.055 and 0.314 +/- 0.105 mg mg(-1)) were virtually identical to those established using EMG (0.159 +/- 0.043 and 0.306 +/- 0.084 mg kg(-1)). While mean peak twitch depression (Delta T1) was the same in both groups for individual subjects Delta T1 differed by +/- 20% (95% confidence interval). DISCUSSION: Acceleromyography-derived twitch heights for individual patients are not necessarily interchangeable with information obtained using electromyography. Nevertheless, acceleromyography appears to be a valid methodology for determining the drug potency when a population rather than an individual subject is being studied.     

Rocuronium zur elektiven Narkoseeinleitung Verlauf der neuromuskulären Blockade und Intubationsbedingungen nach 2facher ED95 (0,6 mg/kg) und nach Dosisreduktion (0,4 mg/kg)

BACKGROUND: Rocuronium is a non-depolarising neuromuscular blocking agent structurally related to vecuronium. The compound has a rapid onset and an intermediate duration of action. The rapid onset is of importance in patients at risk for pulmonary aspiration, for elective induction of anaesthesia slower onset properties generally are accepted. In this context, we asked whether the induction dose of rocuronium may be reduced to doses smaller than 2 x ED95 in situations in which slower onset properties may be acceptable. METHODS: The time course of neuromuscular block and intubating conditions of two different doses rocuronium, 2 x ED95 (0.6 mg/kg) and 1.3 x ED95 (0.4 mg/kg), were investigated in 90 patients. We first determined the time course of neuromuscular block using electromyography (EMG), n = 15 for each group. In the second part the intubating conditions 3 min after injection of either rocuronium 0.6 mg/kg or rocuronium 0.4 mg/kg were evaluated, n = 30 for each group. RESULTS: In the present study reduction of the dose of rocuronium led to a slower onset (148 +/- 32 s vs. 220 +/- 30 s; P < 0.05) and a shorter clinical duration (21 min +/- 4 vs. 36 +/- 7 min; P < 0.05). The recovery index was modified by the dose reduction: 11 +/- 3 min after 0.6 mg/kg rocuronium and 9 +/- 2 min after 0.4 mg/kg. After both doses of rocuronium the intubating conditions were good to excellent, no difference between both rocuronium groups were found. CONCLUSION: In the present study dose reduction from 0.6 mg/kg rocuronium to 0.4 mg/kg rocuronium led to a slower onset and reduced clinical duration. However, the intubating conditions, evaluated 3 min after injection of the muscle relaxant were comparable. This offers new possibilities for muscle relaxation for surgical or diagnostic procedures of short duration and may reduce costs.     

The potency (ED50) and cardiovascular effects of rapacuronium (Org 9487) during narcotic-nitrous oxide-propofol anesthesia in neonates, infants, and children.

We studied the neuromuscular blocking effects of rapacuronium (Org 9487) (dose-response curve, onset, and 50% effective dose [ED50] value), and changes in heart rate and blood pressure, as well as evidence of histamine release in neonates, infants, and children in an open-label, randomized, two-center study. Fifteen neonates, 30 infants, and 30 children were studied. Anesthesia was induced and maintained with propofol, nitrous oxide:oxygen (60:40), and fentanyl. Mechanomyographic monitoring of neuromuscular function was performed at the thumb. The potency (ED50) for neonates, infants, and children were 0.32 (95% confidence interval [CI] 0.15-0.61), 0.28 (95% CI 0.11-0.61), and 0.39 (95% CI 0.17-0.85) mg/kg, respectively. Neonates who received 0.3, 0.6, or 0.9 mg/kg Org 9487 developed a maximum T1 twitch depression of 34 +/-28%, 98 +/- 3%, and 99 +/- 2%, respectively. Time-to-peak effect (onset time) for 0.9 mg/kg Org 9487 was 57 +/- 20 s. Maximum percent T1 twitch depression (+/-SD) in infants who received 0.3, 0.6, or 0.9 mg/kg rapacuronium was 41 +/- 34%, 96 +/- 7%, and 100 +/- 1%, respectively. Time-to-peak effect for 0.9 mg/kg Org 9487 was 62 +/- 29 s. In children 0.3, 0.6, and 0.9 mg/kg rapacuronium resulted in an average percent T1 twitch suppression of 29 +/- 23, 83 +/- 11, and 90 +/- 16, respectively. Time-to-peak effect of 0.9 mg/kg Org 9487 was 96 +/- 33 s, respectively. There was no evidence of histamine release or significant changes in heart rate or blood pressure in either group at any dose. Rapacuronium is a low-potency nondepolarizing muscle relaxant with a fast onset of relaxation and minimal cardiovascular effects. Its potency (ED50) is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg). T1 suppression (90% +/- 16) is less and time to peak effect (96 +/- 33 s) is greater (0.9 mg/kg rapacuronium) in children, compared with the combined group of infants and neonates. IMPLICATIONS: This study assesses the potency of rapacuronium (Org 9487) in pediatric patients. The potency of rapacuronium is similar in neonates (0.32 mg/kg), infants (0.28 mg/kg), and children (0.39 mg/kg).     

The neuromuscular blocking and cardiovascular effects of doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia

The purpose of this study was to evaluate neuromuscular and cardiovascular effects of doxacurium chloride, a new long-acting neuromuscular blocking agent, during a stable state of nitrous oxide and narcotic anesthesia. Ninety-three ASA physical status I or II patients were studied after informed written consent had been obtained. Eighty-one patients (group A) received doxacurium. The 81 patients were divided into nine subgroups according to the dose of doxacurium administered (0.01-0.06 mg.kg-1). Patients in a control group (group B) (n = 12) received pancuronium. To assess neuromuscular responses, a force displacement transducer recorded the twitch response of the adductor pollicis muscle following ulnar nerve stimulation. The ED50 and ED95 for doxacurium were estimated to be 0.013 mg.kg-1 and 0.023 mg.kg-1, respectively. The time to maximum twitch suppression following a dose of 1.0 (ED95) and 1.7 (ED95) was 10.3 +/- 1.3 min and 7.6 +/- 0.8 min, respectively. After an ED95 dose of doxacurium the time to spontaneous recovery to 95% of control twitch height was 73.7 +/- 8.7 min. With larger doses of doxacurium, 0.04 mg.kg-1 (1.7 X ED95) and 0.05 mg.kg-1 (2.2 X ED95), the time to spontaneous recovery to 95% of control twitch height was 125.8 +/- 24.8 and 204.0 +/- 21.2 minutes, respectively. When 25% twitch height recovery or more was present the reversal of doxacurium induced neuromuscular blockade was prompt.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromuscular effect of pipecuronium bromide in infants and children during nitrous oxide-alfentanil anesthesia

To determine in infants and children the neuromuscular effect of pipecuronium during alfentanil-N2O/O2 anesthesia, the authors studied 32 ASA Physical Status 1 and 2 pediatric patients undergoing minor elective surgery, divided into three groups according to their age: group 1 included 12 infants, 1.9 +/- 0.2 months old (mean +/- SE; range, 20 days to 3 months), weighing 5.2 +/- 0.3 kg; group 2, 10 infants, 6.1 +/- 0.9 months old (range, 3-11 months), 6.9 +/- 0.4 kg; and group 3, 10 children 5.6 +/- 0.9 yr old (range, 2-9 yr), 19.6 +/- 2.2 kg. Neuromuscular blockade at the ulnar nerve-adductor pollicis muscle was measured by electromyography. Incremental iv doses of pipecuronium were given (one 20 micrograms/kg first dose, followed by 10 micrograms/kg increments) to reach a 95 +/- 2% twitch depression (ED95). In children ED50 and ED95 of pipecuronium were 45.0 +/- 5.8 micrograms/kg (mean +/- SE) and 70.5 +/- 9.3 micrograms/kg, respectively. In 3- to 12-month-old infants ED50 and ED95 were 25.8 +/- 1.5 micrograms/kg and 48.7 +/- 3.5 micrograms/kg, respectively, and both significantly (P less than 0.05) less than those in children. In 0- to 3-month-old infants ED50 and ED95 were 23.7 +/- 1.7 micrograms/kg and 46.5 +/- 2.9 micrograms/kg, respectively, and also significantly (P less than 0.05) less than those measured in children. Time from maximal initial neuromuscular blockade to 75% recovery was 64.5 +/- 8.8 min in children and significantly shorter (P less than 0.05) in the two infant groups (0- to 3-month-old: 38.7 +/- 5.7 min, 3- to 12-month-old: 43.8 +/- 5.3 min, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Epidural Lidocaine Decreases Sevoflurane Requirement for Adequate Depth of Anesthesia as Measured by the Bispectral Index ® Monitor

Background: Epidural anesthesia potentiates sedative drug effects and decreases minimum alveolar concentration (MAC). The authors hypothesized that epidural anesthesia also decreases the general anesthetic requirements for adequate depth of anesthesia as measured by Bispectral Index (BIS).

Methods: After premedication with 0.02 mg/kg midazolam and 1 [mu]g/kg fentanyl, 30 patients aged 20-65 yr were randomized in a double-blinded fashion to receive general anesthesia with either intravenous saline placebo or intravenous lidocaine control (1-mg/kg bolus dose; 25 [mu]g [middle dot] kg-1 [middle dot] min-1). A matched group was prospectively assigned to receive epidural lidocaine (15 ml; 2%) with intravenous saline placebo. All patients received 4 mg/kg thiopental and 1 mg/kg rocuronium for tracheal intubation. After 10 min of a predetermined end-tidal sevoflurane concentration, BIS was measured. The ED50 of sevoflurane for each group was determined by up-down methodology based on BIS less than 50 (MACBIS50). Plasma lidocaine concentrations were measured.

Results: The MACBIS50 of sevoflurane (0.59% end tidal) was significantly decreased with lidocaine epidural anesthesia compared with general anesthesia alone (0.92%) or with intravenous lidocaine (1 %;P < 0.0001). Plasma lidocaine concentrations in the intravenous lidocaine group (1.9 [mu]g/ml) were similar to those in the epidural lidocaine group (2.0 [mu]g/ml).     

Pharmacokinetics of rocuronium bromide (ORG 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation.

To determine the effect of end-stage renal disease on the pharmacokinetics of reocuronium bromide (ORG 9426), a new nondepolarizing monoquaternary steroidal neuromuscular blocking drug, the authors administered 600 micrograms/kg rocuronium (2 x ED95) intravenously to ten patients undergoing cadaver renal transplantation and ten healthy patients undergoing elective minor surgery (controls). All patients were anesthetized with nitrous oxide (50-70% in oxygen) and isoflurane (end-tidal concentrations of 1.2 +/- 0.5% and 0.8 +/- 0.2%, mean +/- SD, for control and transplant groups, respectively). Plasma concentrations of rocuronium were determined by capillary gas chromatography. A population-based pharmacokinetic analysis (NONMEM) was used to determine typical values, standard errors, and interindividual variability for the pharmacokinetic parameters and to determine whether these values differed between control and renal transplant patients. Total plasma clearance (2.89 +/- 0.25 ml.kg-1.min-1, mean +/- SE) and volume of the central compartment (76.9 +/- 10.6 ml/kg) did not differ between control and renal transplant patients, whereas volume of distribution at steady state was greater in renal transplant patients (264 +/- 19 ml/kg) than in control patients (207 +/- 14 ml/kg). This resulted in a longer elimination half life in renal transplant patients (97.2 +/- 17.3 min) compared to controls (70.9 +/- 4.7 min). The authors conclude that renal failure and renal transplantation alter the distribution but not the clearance of rocuronium.