Rocuronium pharmacokinetic-pharmacodynamic relationship under stable propofol or isoflurane anesthesia

PURPOSE: To compare the pharmacokinetics, pharmacodynamics and the concentration-effect relationship of rocuronium in patients under stable propofol or isoflurane anesthesia. METHODS: Ten patients were randomized to receive fentanyl, propofol and nitrous oxide (60%) or fentanyl, thiopental, isoflurane (1.2% end-tidal concentration) and nitrous oxide (60%). To obtain good intubation conditions and maintain adequate muscle relaxation during surgery, patients received two bolus doses of rocuronium: 0.5 mg x kg(-1) (1.7 x ED95) at induction followed one hour later by 0.3 mg x kg(-1) (1 x ED95). Arterial blood samples were obtained over six hours after the second bolus dose. Plasma concentrations of rocuronium were measured using high pressure liquid chromatography. Muscle twitch tension was monitored by mechanomyography for the two doses. Pharmacokinetic and pharmacodynamic parameters were determined. RESULTS: No differences in rocuronium pharmacokinetic parameters were observed between both groups. After the second bolus, clinical duration was 20 +/- 6 min in the propofol group vs 39 +/- 8 min in the isoflurane group (P <0.05). The effect compartment concentration corresponding to 50% block, EC50, was higher under propofol anesthesia: 1008 vs 592 microg x L(-1) (P <0.05). CONCLUSION: Rocuronium body disposition is similar under stable propofol or isoflurane anesthesia. In contrast to isoflurane, propofol does not prolong the neuromuscular block. Therefore, the potentiating effect of isoflurane is of pharmacodynamic origin only, as explained by an increased sensitivity at the neuromuscular junction. In contrast with isoflurane anesthesia where the dose of rocuronium has to be decreased under stable conditions, no dose adjustment is required under propofol anesthesia.     

A comparison of the onset and clinical duration of high doses of cisatracurium and rocuronium.

STUDY OBJECTIVE: To determine the onset and clinical duration of cisatracurium and rocuronium in equipotent doses in balanced opioid/isoflurane anesthesia. DESIGN: Randomized, controlled study. SETTING: University hospital. PATIENTS: 40 healthy patients scheduled for elective surgery. INTERVENTIONS: Patients underwent anesthesia induction with thiopental or propofol with a cisatracurium intubating dose of either 0.15 or 0.2 mg/kg or a rocuronium dose of either 0.9 or 1.2 mg/kg. These doses correspond to three and four times the ED95 dose. MEASUREMENTS AND MAIN RESULTS: The onset time and time to 25% recovery of baseline first twitch in a train-of-four were determined using an accelerometric sensor. Rocuronium had a faster onset time that cisatracurium at equipotent doses (3 x ED95: 134 vs. 220 sec respectively, and at 4 x ED95: 95 vs. 162 sec). Recovery tended to be faster, but not statistically different for cisatracurium compared to rocuronium. CONCLUSIONS: With equipotent intubating doses of rocuronium and cisatracurium, rocuronium produces a more rapid onset of muscle relaxation. The data suggest a tendency toward more rapid clinical recovery of cisatracurium compared to equipotent doses of rocuronium, although these differences were not statistically significant.     

Duration and recovery profile of cisatracurium after succinylcholine during propofol or isoflurane anesthesia

Study Objective: To determine the duration and recovery profile of maintenance doses of cisatracurium besylate following succinylcholine, and during propofol or isoflurane anesthesia.

Design: Randomized, open-label study.

Setting: Operating suite of a university-affiliated medical center.

Patients: Forty ASA physical status I and II adult patients having elective surgery with general anesthesia lasting longer than 90 minutes.

Interventions: Following a standardized induction sequence, a baseline electromyogram (EMG) was obtained. An intubating dose of intravenous (IV) succinylcholine 1.0 mg/kg was administered. Ventilation was maintained with a face mask until the first twitch (T₁) of the evoked train-of-four (TOF) reached 10% of control when tracheal intubation was performed. Spontaneous recovery from neuromuscular blockade was allowed to occur until the first twitch returned to 25% of control. Patients then were randomized to receive cisatracurium as follows. Group 1: 0.025 mg/kg [0.5 × 95% effective dose (ED₉₅)]; Group 2: 0.05 mg/kg (ED₉₅); Group 3: 0.05 mg/kg (ED₉₅); and Group 4: 0.1 mg/kg (2×ED₉₅). Anesthesia for Groups 1 and 2 were maintained with isoflurane 1% to 2%, 66% nitrous oxide (N₂O) in oxygen (O₂), and in Groups 3 and 4, anesthesia was maintained with propofol 80 to 160 μg/kg/min, 66% N₂O in O₂. The TOF-evoked EMG was recorded at 10-second intervals. The time for the evoked EMG to spontaneously return to 25%, 50%, and 75% of the original baseline was recorded.

Measurements and Main Results: There were 10 patients in each of the four groups. The duration of action of cisatracurium 0.05 mg/kg (ED₉₅) after an intubating dose of succinylcholine is 24.5 ± 10 minutes and 21.3 ± 9 minutes during anesthesia maintained with isoflurane and propofol, respectively. Doubling the dose of cisatracurium resulted in approximately twice the duration of action (40.2 ± 7 min) during propofol anesthesia. Following a dose of cisatracurium 0.025 mg/kg (0.5×ED₉₅), the T₁ of the EMG-evoked response did not decrease below 25% in 7 of 10 patients.

Conclusion: Following succinylcholine, the duration of action of a single dose of cisatracurium 0.05 mg/kg is 20 to 25 minutes during anesthesia maintained with propofol or isoflurane. The duration and recovery profile of cisatracurium is dose dependent during propofol and isoflurane anesthetics. Cisatracurium 0.025 mg/kg is an inadequate maintenance dose following recovery from succinylcholine and it fails to provide adequate surgical relaxation.     

Neuromuscular and cardiovascular effects of mivacurium chloride (BW B109OU) during nitrous oxide-narcotic, nitrous oxide-halothane and nitrous oxide-isoflurane anesthesia in surgical patients

One hundred seventeen adult surgical patients were studied to compare neuromuscular and cardiovascular effects of mivacurium chloride during nitrous oxide-narcotic (BAL, n = 45) nitrous oxide-halothane (HAL, n = 27) and nitrous oxide-isoflurane (ISF, n = 45) anesthesia. Anesthesia was maintained with nitrous oxide (60%-70%) and oxygen (30%-40%) with end-tidal concentrations of halothane or isoflurane to yield a total MAC of approximately 1.25, or with supplemental fentanyl and thiopental as clinically indicated. Twitch response of the adductor pollicis muscle was elicited by supramaximal square wave pulses of 0.2 msec duration at a frequency of 0.15 Hz (Grass S44 stimulator) to the ulnar nerve and quantitated by a Grass FT10 transducer. Nine patients in each of the HAL and ISF groups received one of four doses of mivacurium (0.03, 0.05, 0.10 or 0.15 mg/kg). Ninety patients in the balanced anesthesia group received one of seven doses of mivacurium (0.03, 0.04, 0.05, 0.08, 0.15, 0.20, 0.25 mg/kg). The ED50, ED75 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose versus probit of maximum percentage depression of twitch height. The ED50, ED75 and ED95 for halothane and isoflurane are 0.040, 0.053 and 0.081 and 0.037, 0.043 and 0.053, respectively. The ED50, ED75, and ED95 for the balanced group are 0.039, 0.050, and 0.073 mg/kg respectively. There was no significant difference between the slopes of the HAL and BAL inhalation anesthetic dose-response curves. The slope of the ISF group was significantly than the slope of the BAL group. Intercepts of the HAL and BAL curves were not different. The isoflurane curve's intercept was significantly less than the other groups' intercepts, lying above the halothane curve, but below the BAL curve. For the 0.05 mg/kg dose, maximum block was greater in the ISF group (89.1 +/- 2.7%, n = 9) than in the HAL (70.3 +/- 7.6%, n = 9) or BAL (67.7 +/- 6.4%, n = 9) groups. At higher doses of mivacurium, isoflurane produces a greater potentiation of neuromuscular block than halothane or balanced anesthesia. There were no significant cardiovascular changes seen in any group following mivacurium doses up to 0.15 mg/kg (approximately 2xED95).     

Comparative effects of desflurane and isoflurane on vecuronium-induced neuromuscular blockade.

STUDY OBJECTIVE: To evaluate the neuromuscular effects of a nondepolarizing muscle relaxant (vecuronium) during anesthesia with equipotent concentrations of either desflurane or isoflurane. DESIGN: Randomized open study comparing effects of desflurane and isoflurane on vecuronium-induced neuromuscular blockade. SETTING: University-affiliated medical center. PATIENTS: Forty-five healthy adults undergoing elective surgical procedures randomly assigned to receive either desflurane, nitrous oxide (N2O), and vecuronium or isoflurane, N2O, and vecuronium for maintenance of general anesthesia. INTERVENTIONS: Following a standardized induction sequence, patients receiving either desflurane and N2O or isoflurane and N2O were administered bolus doses of vecuronium equal to 0.01, 0.02, or 0.03 mg/kg intravenously (IV) during the maintenance period. Neuromuscular transmission was measured using a Relaxograph monitor. MEASUREMENTS AND MAIN RESULTS: Vecuronium produced similar depression of neuromuscular function at equipotent (50% of the minimum alveolar concentration) end-tidal concentrations of isoflurane 0.6% and desflurane 3.0%. Following administration of vecuronium 0.01 to 0.03 mg/kg IV, onset times (3.4 +/- 0.4 minutes to 3.2 +/- 0.4 minutes and 3.2 +/- 0.5 minutes to 3.0 +/- 0.6 minutes), maximum T1 twitch depression (80% +/- 10% to 95% +/- 9% and 81% +/- 9% to 97% +/- 10%), clinical duration of blockade (12 +/- 5 minutes to 20 +/- 8 minutes and 10 +/- 5 minutes to 19 +/- 17 minutes), and T1 recovery times (10 +/- 3 minutes to 12 +/- 6 minutes and 10 +/- 3 minutes to 12 +/- 4 minutes) were similar in the isoflurane and desflurane treatment groups, respectively (means +/- SD). CONCLUSION: Vecuronium has similar neuromuscular effects when administered in the presence of desflurane 3% and isoflurane 0.6%.     

The effect of cisatracurium and rocuronium on cisatracurium precurarization and the priming principle

STUDY OBJECTIVE: To demonstrate the effect of administering a precurarizing dose of cisatracurium or rocuronium on the speed of onset of cisatracurium, and to review the possible mechanisms and value of the priming principle. DESIGN: Double-blind, randomized, controlled trial. SETTING: Inpatient anesthesia in a university teaching hospital. PATIENTS: 90 ASA physical status I and II patients undergoing elective surgery requiring endotracheal intubation. INTERVENTIONS: Three groups of 30 patients each were investigated. Following induction of anesthesia with fentanyl and propofol, Group 1 received cisatracurium 0.015 mg.k(-1), Group 2 received rocuronium 0.09 mg. kg(-1), and Group 3 (control) received normal saline. Six minutes after priming, Groups 1 and 2 received cisatracurium 0.135 mg. kg(-1) whereas Group 3 received cisatracurium 0.15 mg. kg(-1). MEASUREMENTS AND MAIN RESULTS: In each group, first twitch height and the train-of-four ratios were recorded every 10 seconds after the initial priming dose. Intubation was attempted after the first twitch height became less than 15% of baseline. The decrease in the train-of-four ratios at 6 minutes was 0.97 for cisatracurium and 0.85 for rocuronium. The onset of muscle relaxation was significantly faster after priming with cisatracurium and rocuronium (71.7 +/- 21.3 and 65 +/- 19.8 sec, respectively) compared with control (148.7 +/- 43.1 sec). Females receiving both muscle relaxants had a faster onset of paralysis than did males (65.9 +/- 20.6 vs. 79.2 +/- 20.6 and 55 +/- 14.5 vs. 71.7 +/- 20.4 sec). Intubation conditions were either excellent or satisfactory in all patients. CONCLUSIONS: Six minutes after precurarization, there is no significant difference between rocuronium and cisatracurium when used as priming drugs. An even faster onset time with both drugs was demonstrated in females. The use of priming doses of 25% to 30% of ED(95) may cause symptomatic muscle weakness. The mechanisms of the priming principle are discussed.     

Variability of duration of action of neuromuscular-blocking drugs in elderly patients

BACKGROUND: Steroid-based, non-depolarizing neuromuscular-blocking (NMB) drugs (e.g. rocuronium, vecuronium) are characterized by organ-dependent elimination and significantly longer durations of action in elderly compared to young patients. Cisatracurium is a benzylisoquinolinium NMB drug with a duration of action not altered by ageing. The objective of the study was to determine if elderly patients had less variability in duration of action with 2 x ED95 of cisatracurium compared to equipotent doses of rocuronium or vecuronium. METHODS: Informed consent was obtained from 66 elderly patients with normal renal and liver function. Preoperative midazolam (1 mg) was given IV. The anaesthestic induction was with 5 mg kg(-1) thiopental and 2 microg kg(-1) fentanyl. The patients received 0.6 mg kg(-1) rocuronium, 0.1 mg kg(-1) vecuronium or 0.1 mg kg(-1) cisatracurium. Anaesthetic maintenance was with sevoflurane in oxygen/nitrous oxide. Neuromuscular-blocking duration of action was defined as the return of T1 twitch height to 25% of control. Variability was determined by subtracting the actual duration of action from the mean duration of action for each drug. RESULTS: The durations of action (range, min) were: cisatracurium, 37-81; vecuronium, 35-137; and rocuronium, 33-119. The median of the variability of duration was significantly less with cisatracurium (7 min) compared to vecuronium (18 min) and rocuronium (18 min) (P < 0.05). CONCLUSION: When used with sevoflurane/N(2)O, there was a two-fold greater variability of duration of neuromuscular blockade in elderly patients receiving rocuronium or vecuronium compared with cisatracurium.     

The relationship of posttetanic count and train-of-four responses during recovery from intense cisatracurium-induced neuromuscular blockade

Posttetanic count (PTC) has been used to quantify intense degrees of nondepolarizing neuromuscular blockade. Our objective in the present investigation was to discern whether PTC correlates with recovery from intense cisatracurium-induced neuromuscular blockade under both inhaled and IV anesthesia. In 60 patients, anesthesia was induced with propofol 2 mg/kg and fentanyl 1.5 micro g/kg IV. Recovery from intense neuromuscular blockade induced by cisatracurium (0.15 mg/kg) was studied in 2 groups. Group 1 (n = 30) had anesthesia maintained with propofol 100-200 micro g x kg(-1) x min(-1) and 60% N(2)O in O(2), whereas Group 2 (n = 30) had anesthesia maintained with isoflurane (end-tidal concentration 0.8%) and 60% N(2)O in O(2). Neuromuscular functions were monitored using acceleromyography. Cycles of posttetanic stimulation were repeated every 6 min with train-of-four (TOF) stimulation in between. Measurement included times to posttetanic responses and to the first response to TOF stimulation (T(1)), as well as the correlation between PTC and T(1). In Group 1, the mean times to PTC(1) and T(1) were 35.6 +/- 7.5 and 46.9 +/- 6.5 min, respectively. Corresponding times in Group 2 were 39.5 +/- 6.8 and 56.7 +/- 5.4 min, respectively. There was a good time correlation, r = 0.919 for propofol (Group 1) and r = 0.779 for isoflurane (Group 2), between PTC and T(1) recovery in both groups. The PTC when T(1) appeared ranged between 8 and 9 in Group 1 and 8 and 14 in Group 2. Conforming to original observations with other neuromuscular blocking drugs, there is a correlation between PTC and TOF recovery from intense cisatracurium-induced neuromuscular blockade allowing better monitoring of this intense degree of blockade during both IV (propofol) and isoflurane anesthesia. IMPLICATIONS: Monitoring posttetanic count during intense neuromuscular blockade allows the clinician to estimate the intensity of the blockade and estimate recovery time. The relationship between posttetanic count and train-of-four recovery from intense cisatracurium-induced neuromuscular blockade was documented under both IV and inhaled anesthesia.     

Dose-response relation and time course of action of pipecuronium bromide in humans anesthetized with nitrous oxide and isoflurane, halothane, or droperidol and fentanyl

The dose-response of pipecuronium bromide, the time course of its neuromuscular blocking effects, and the reversibility of the residual block by neostigmine and edrophonium have been investigated in patients undergoing various types of anesthesia. The estimated doses of pipecuronium required for 95% depression of the twitch height were 44.6, 46.9, and 48.7 micrograms.kg-1 during anesthesia with nitrous oxide (65%) and isoflurane (group 1), halothane (group 2), or droperidol/fentanyl (group 3), respectively. The potentiating effects of the volatile anesthetics were reflected by the significant prolongation of the duration of both initial (50.0 +/- 4.3, 36.0 +/- 3.3, and 29.0 +/- 2.0 minutes) and maintenance doses (56.0 +/- 2.5, 49.5 +/- 3.3, and 41.2 +/- 1.6 minutes) of pipecuronium during anesthesia with nitrous oxide and isoflurane, halothane, or droperidol/fentanyl, respectively. Both edrophonium chloride (0.5 mg.kg-1) and neostigmine methylsulphate (40 micrograms.kg-1) promptly reversed the residual block induced by pipecuronium. No side effects attributable to pipecuronium were seen in this study.     

性别因素对七氟醚增强顺阿曲库铵或罗库溴铵肌松效应的影响

目的 探讨性别因素对七氟醚增强顺阿曲库铵或罗库溴铵肌松效应的影响.方法 择期全麻手术患者240例,年龄20～60岁,ASA分级Ⅰ或Ⅱ级,BMI 20～30 kg/m2,随机分为2组(n=120):顺阿曲库铵组和罗库溴铵组,各组按性别和麻醉药再分4个亚组(n=30):女性异丙酚组、男性异丙酚组、女性七氟醚组和男性七氟醚组.各异丙酚组靶控输注异丙酚,血浆靶浓度2～6 μg/ml,各七氟醚组吸入七氟醚,于靶控输注或待呼气末七氟醚浓度稳定于1.71%5 min后,静脉注射顺阿曲库铵0.15 mg/kg或罗库溴铵0.6 mg/kg.记录肌松起效时间、肌松作用峰值时间、T1 25%恢复时间和TOFR25%恢复时间.结果 与异丙酚麻醉比较,女性患者七氟醚麻醉时,罗库溴铵TOFR 25%恢复时间延长,顺阿曲库铵肌松作用峰值时间、T1 25%恢复时间和TOFR 25%恢复时间延长,男性患者七氟醚麻醉时,罗库溴铵起效时间缩短,肌松作用峰值时间、T1 25%恢复时间和TOFR 25%恢复时间延长,顺阿曲库铵肌松作用峰值时间、T1 25%恢复时间和TOFR 25%恢复时间延长(P＜0.05或0.01);七氟醚麻醉时与男性患者比较,女性患者罗库溴铵T1 25%恢复时间和TOFR 25%恢复时间缩短,顺阿曲库铵起效时间缩短(P＜0.05或0.01).结论 七氟醚对罗库溴铵肌松的增强作用存在性别差异,男性强于女性;对顺阿曲库铵肌松的增强作用无明显性别差异.     

Double-blind comparison of the variability in spontaneous recovery of cisatracurium- and vecuronium-induced neuromuscular block in adult and elderly patients

BACKGROUND: This study was designed to compare variability in the offset of two neuromuscular blocking agents with different elimination pathways. METHODS: The spontaneous recovery profiles of cisatracurium and vecuronium were compared in adult (18-64 years) and elderly (> or =65 years) patients receiving N2O/O2/fentanyl/propofol anaesthesia. Patients were randomised to receive an initial bolus dose and maintenance doses of 3xED95, respectively, 0.6xED95 for cisatracurium (0.15 and 0.03 mg.kg-1) or 2xED95, respectively, and 0.4xED95 for vecuronium (0.1 and 0.02 mg.kg(-1)), as recommended in their prescribing information. Administration of the study drugs was double-blinded, and neuromuscular transmission was monitored using mechanomyography of the evoked response of the adductor pollicis, following ulnar nerve stimulation. RESULTS: The clinically effective duration (minutes) of the initial bolus dose, defined as the mean time to 25% T1 recovery (+/-SD), for the adult and elderly patients was 53.5+/-9.8 and 57.3+/-11.5 for cisatracurium, respectively, and 34.1+/-9.0 and 47.5+/-14.4 for vecuronium, respectively. The duration of spontaneous sufficient recovery (SSR), defined as the mean (+/-SD) time interval in minutes from 25% T1 recovery to a T4:T1 ratio > or =0.8 after the last bolus dose, for the adult, respectively, elderly patients was 28.3+/-8.0 and 31.7+/-10.0 for cisatracurium and 38.5+/-13.2 and 60.3+/-26.1 for vecuronium. CONCLUSION: Whereas both the clinically effective duration and the duration of SSR are comparable between the adult and the elderly patients receiving cisatracurium, they differ substantially between these two age groups for vecuronium. Furthermore, the variability in offset is significantly lower in patients receiving cisatracurium, especially in the elderly, which may be of particular clinical interest.     

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.     

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.     

The effect of anticonvulsant therapy on two doses of rocuronium-induced neuromuscular blockade

Larger and more frequent doses of steroidal neuromuscular blocking agents are required to paralyze patients taking anticonvulsants (carbamazepine and phenytoin). We compared the effects of rocuronium on onset, duration, and speed of recovery from neuromuscular blockade (NMB) in anticonvulsant-treated (Tx) and untreated (C or control) patients. Thirty-eight neurosurgical patients were enrolled: 11 Tx and 8 C patients received 0.6 mg/kg rocuronium; 9 Tx and 10 C patients received 1.2 mg/kg rocuronium. Anesthesia was induced with midazolam, fentanyl, and thiopental, and maintained with N2O and isoflurane in O2. The evoked compound electromyograph (EMG) of the hypothenar eminence was recorded (train-of-four supramaximal stimulus at 2 Hz every 20 seconds). Rocuronium was administered after baseline EMG was recorded. Data = mean +/- SD. Rocuronium 1.2 mg/kg significantly shortened onset time [depression of baseline height of first twitch (T1) to 10% of baseline] of NMB versus rocuronium 0.6 mg/kg in both Tx (2.5+/-2 versus 3.3+/-2 minutes) and C (1.3+/-1 versus 2.8+/-1 minute) patients. Duration (recovery to 25% of T1) of NMB was significantly shorter in the Tx patients than in the C patients who received rocuronium 0.6 mg/kg (21+/-9 versus 45+/-20 minutes), but similar in Tx and C patients who received 1.2 mg/kg rocuronium (56+/-24 versus 69+/-21 minutes). The speed of recovery (time from 10 to 25% recovery of T1) was significantly slower in Tx patients who received 1.2 mg/kg rocuronium (9+/-5 minutes) than in those who received 0.6 mg/kg (5+/-3 minutes) and not different from controls who received 0.6 (9+/-4 minutes) or 1.2 mg/kg (12+/-7 minutes) rocuronium. We recommend the use of rocuronium 1.2 mg/kg and very frequent monitoring of NMB in anticonvulsant-treated patients to avoid premature and extremely rapid recovery after the standard 0.6 mg/kg rocuronium.     

Mivacurium chloride (BW B1090U)-induced neuromuscular blockade during nitrous oxide-isoflurane and nitrous oxide-narcotic anesthesia in adult surgical patients

The neuromuscular and cardiovascular effects of mivacurium were studied in 90 adult patients during nitrous oxide-oxygen-isoflurane (n = 45, ISO group) and nitrous oxide-oxygen-narcotic (n = 45, BAL group) anesthesia. Neuromuscular blockade was measured using electromyographic activity of the adductor pollicis muscle after supramaximal stimulation of the ulnar nerve at 2 Hz for 2 seconds at 10-second intervals. To estimate dose-response relations, three subgroups of nine patients in the ISO group received mivacurium doses of 0.025, 0.03, and 0.04 mg/kg, respectively. Similarly, three subgroups of nine patients in the BAL group received mivacurium doses of 0.03, 0.04, and 0.05 mg/kg, respectively. The ED50 and ED95 of mivacurium in each group were estimated from linear regression plots of log dose vs probit of maximum percentage depression of neuromuscular function. The estimated ED50 values for the ISO and BAL groups were 0.029 and 0.041 mg/kg, respectively. The estimated ED95 values for the ISO and BAL groups were 0.045 and 0.058 mg/kg, respectively. Recovery indexes were measured in 26 patients who received ED95 or greater doses of mivacurium in either the ISO or BAL groups. The recovery index was shorter in the BAL group (5.5 +/- 1.6 minutes [n = 10]), than in the ISO group (7.4 +/- 3.0 minutes [n = 16]). The addition of isoflurane (0.5-0.75% end-tidal concentration) to nitrous oxide-narcotic anesthesia augments the degree of neuromuscular blockade from a given dose of mivacurium and also prolongs the recovery index.     

Reduced duration of muscle relaxation with rocuronium in a normocalcemic hyperparathyroid patient

PURPOSE: To report a case of reduced duration of action of rocuronium in a patient with normocalcemic hyperparathyroidism (HPT). CLINICAL FEATURES: A 56-yr-old patient with primary HPT, who had had surgical resection of three and a half parathyroid glands nine months previously, was referred to our institution for further investigation of a persistent increase in parathyroid hormone. Preoperatively, the patient had a normal serum ionized and total calcium. The patient was diagnosed with a persistent parathyroid adenoma and was scheduled for an elective parathyroidectomy. General anesthesia was induced with iv propofol, fentanyl and succinylcholine. Intraoperatively, anesthesia was maintained with nitrous oxide in oxygen, and isoflurane. Neuromuscular blockade was attained using incremental doses of rocuronium. The average duration of 0.15 mg x kg(-1) incremental doses of rocuronium was 5.9 min (expected: 13-18 min), and that of 0.2 mg x kg(-1) was ten minutes (expected: 19-23 min). CONCLUSION: Primary HPT even in the absence of hypercalcemia may result in resistance to competitive blockade by rocuronium. It suggests that primary HPT may cause acetylcholine receptor up-regulation resulting in hyposensitivity to non-depolarizing muscle relaxants.     

Neuromuscular pharmacodynamics of rocuronium in patients with major burns

Rocuronium, which has a short onset time and is free of hyperkalemic effects, could be considered for rapid-sequence induction of anesthesia in patients with burns. In this study, we assessed the neuromuscular pharmacodynamics of rocuronium in patients with major burns. Adults aged 18-59 yr who had a major burn injury (n = 56) and a control group of 44 nonburned patients were included. Rocuronium was used at 3 times (0.9 mg/kg) or 4 times (1.2 mg/kg) the 95% effective dose. Anesthesia consisted of propofol and fentanyl with nitrous oxide and oxygen. Neuromuscular block was monitored with an acceleromyograph by using train-of-four stimulation. The onset time to 95% neuromuscular block was prolonged in burned compared with nonburned patients (115 +/- 58 s versus 68 +/- 16 s for 0.9 mg/kg; 86 +/- 20 s versus 57 +/- 11 s for 1.2 mg/kg). Dose escalation shortened the onset time, prolonged the duration of action, and improved intubating conditions in burned patients. All recovery profiles were significantly shorter in burned versus nonburned groups with both doses. Resistance to the neuromuscular effects of rocuronium was partially overcome by increasing the dose. A dose up to 1.2 mg/kg provides good tracheal intubating conditions after major burns.     

Reversal of rocuronium with edrophonium during propofol versus sevoflurane anesthesia

BACKGROUND: The use of volatile anesthetics for maintenance of anesthesia can enhance the action of non-depolarizing muscle relaxants and interfere with the reversal of neuromuscular blockade. In this study, we studied the antagonism of rocuronium with edrophonium-atropine during propofol- versus sevoflurane-based anesthesia. METHODS: Following induction of anesthesia with propofol (2-2.5 mg kg(-1), i.v.) and fentanyl (1-2 microg kg(-1) i.v.), rocuronium 0.6 mg kg(-1) i.v. was administered to facilitate tracheal intubation. Patients were then randomized to receive either a propofol infusion (100 microg kg(-1) min(-1)) or sevoflurane (1.0%, end-tidal) in combination with nitrous oxide 66% for maintenance of anesthesia. Neuromuscular blockade was monitored using electromyography at the wrist, and reversed with edrophonium 1.0 mg kg(-1) and atropine 0.015 mg kg(-1) when the first twitch hight (T1) of the train-of-four (TOF) stimulation recovered to 25% of the baseline value. Anesthetic maintenance with propofol or sevoflurane was continued following reversal until a TOF ratio of 0.7 was attained. RESULTS: The clinical duration of action (i.e., time to 25% T1 recovery) was similar during both propofol- (39.3+/-14.6 min) and sevoflurane-based (48.1+/-19.7 min) anesthesia. However, the reversal time from 25% T1 to TOF ratio of 0.7 was significantly longer with sevoflurane [Median 2.8 (range 0.5-18.8) min] compared with propofol [1.5 (0.75-3) min] (P<0.05). CONCLUSIONS: We conclude that the clinical duration of action after a single dose of rocuronium, 0.6 mg kg(-1) i.v., was similar during both propofol- and sevoflurane-based anesthesia. However, the reversal of rocuronium-induced residual blockade was slower and more variable in the presence of sevoflurane.     

Recovery from neuromuscular blockade after either bolus and prolonged infusions of cisatracurium or rocuronium using either isoflurane or propofol-based anesthetics

We examined the recovery characteristics of cisatracurium or rocuronium after bolus or prolonged infusion under either isoflurane or propofol anesthesia. Sixty patients undergoing neurosurgical procedures of at least 5 h were randomized to receive either isoflurane with fentanyl (Groups 1 and 2) or propofol and fentanyl (Groups 3 and 4) as their anesthetic. Groups 1 and 3 received cisatracurium 0.2 mg/kg IV bolus, spontaneously recovered, after which time an infusion was begun. Groups 2 and 4 received rocuronium 0.6 mg/kg IV, spontaneously recovered, and an infusion was begun. Before the end of surgery, the infusion was stopped and recovery of first twitch (T(1)), recovery index, clinical duration, and train-of-four (TOF) recovery was recorded and compared among groups by using appropriate statistical methods. Clinical duration was shorter for rocuronium compared with cisatracurium using either anesthetic. Cisatracurium T(1) 75% recovery after the infusion was shorter with propofol compared with isoflurane. Cisatracurium TOF 75% recovery was similar after either bolus or infusion, but rocuronium TOF 75% recovery after the infusion was delayed. Infusion rates decreased for cisatracurium but remained relatively constant for rocuronium regardless of the anesthetic used. Isoflurane enhances the effect of both muscle relaxants but prolonged cisatracurium recovery more than rocuronium. Of the two muscle relaxants studied, rocuronium's recovery was most affected by length of the infusion. Cisatracurium may be a more desired muscle relaxant for prolonged procedures because recovery was least affected by prolonged infusion. Implications: This study describes the effect of different anesthetic techniques on the recovery of two different muscle relaxants, cisatracurium and rocuronium, when administered as either a single bolus or prolonged infusion during neurosurgery. This study demonstrates the feasibility of using these relaxants for these prolonged procedures.     

Effect of maintenance bolus on the recovery profile of a short-acting nondepolarizing muscle relaxant

STUDY OBJECTIVE: To evaluate the effect of different maintenance boluses of a short-acting nondepolarizing neuromuscular blocking drug on its spontaneous recovery profile during anesthesia. DESIGN: Prospective, randomized, double-blind, dose-ranging study. SETTING: University-based medical center. PATIENTS: 69 ASA physical status I and II consenting adult outpatients undergoing general anesthesia with an anticipated duration of at least 2 hours. INTERVENTIONS: Patients were randomized to one of three study groups. Following induction of anesthesia with propofol and fentanyl, rapacuronium 1.5 mg x kg(-1) intravenously (i.v.), was administered to facilitate tracheal intubation. Anesthesia was maintained with desflurane 4% end-tidal in combination with nitrous oxide 67% in oxygen. When the first twitch (T(1)) in the train-of-four (TOF) returned to 25% of its baseline value, a maintenance dose of rapacuronium 0.25 mg x kg(-1) i.v. (Group 1), 0.5 mg. kg(-1) i.v. (Group 2), or 0.75 mg. kg(-1) i.v. (Group 3) was administered. The time course of neuromuscular block was monitored at the wrist using standard electromyography. MEASUREMENTS AND MAIN RESULTS: The times for recovery of the T(1) to 25% of the baseline value following different maintenance doses of rapacuronium were only 6.3 +/- 2.2, 7.5 +/- 2.3, and 9.6 +/- 2.5 minutes, in Groups 1, 2 and 3, respectively. However, the times for the TOF ratio to return to 0.7 were 44 +/- 15, 53 +/- 20, and 66 +/- 30 minutes in Groups 1, 2, and 3, respectively. Although recovery times were significantly longer after rapacuronium 0.75 mg x kg(-1) i.v. (Group 3), there were no significant differences in any of the recovery variables between Groups 1 and 2. CONCLUSIONS: Spontaneous recovery of the T(1) to 25% of the baseline value occurred 6 to 10 minutes after a maintenance bolus dose of rapacuronium 0.25 to 0.75 mg x kg(-1) i.v. However, recovery to a TOF>0.7 required 44 to 66 minutes during desflurane anesthesia.