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PubMed1994

Quantifying the interaction of rocuronium (Org 9426) with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of rocuronium infusion.

The present study was designed to evaluate the interactions of rocuronium with etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane using closed-loop feedback control of infusion of rocuronium. Sixty patients were randomly assigned to one of six sequences where anesthesia was maintained with etomidate, fentanyl, midazolam, propofol, or thiopental and nitrous oxide, or with isoflurane and nitrous oxide. The possible interaction of rocuronium with the anesthetics was quantified by determining the asymptotic steady-state rate of infusion (Iss) of rocuronium necessary to produce a constant 90% neuromuscular block. This was accomplished by applying nonlinear curve fitting to data on the cumulative dose requirement during the initial 90-min period after bolus administration of rocuronium. Patient characteristics and controller performance, i.e., the ability of the controller to maintain the neuromuscular block constant at the set-point, did not differ significantly between the groups. Iss values calculated per lean body mass were 0.64 +/- 0.22, 0.60 +/- 0.15, 0.61 +/- 0.21, 0.67 +/- 0.31, 0.63 +/- 0.15, and 0.39 +/- 0.17 mg.kg-1.h-1 in the etomidate, fentanyl, midazolam, propofol, thiopental, and isoflurane groups, respectively. The isoflurane group had a lower steady-state rate of infusion of rocuronium than the other five groups (P < 0.05). Compared to intravenous anesthetics, etomidate, fentanyl, midazolam, propofol, or thiopental, isoflurane reduced the infusion requirement of rocuronium by 35%-40%.

Adult↗
PubMed1994

Quantitation of the interaction of rocuronium bromide with etomidate, fentanyl, midazolam, propofol, thiopentone, and isoflurane using closed-loop feedback control of infusion of rocuronium.

Sixty patients were randomly assigned to one of six groups (n = 10 in each case) in which anaesthesia was induced and maintained with etomidate, fentanyl, midazolam, propofol or with thiopentone and N2O, or isoflurane and N2O. After obtaining control measurements, rocuronium 0.6 mg kg-1 was given for intubation followed by an infusion, controlled by closed-loop feedback at 90% block. The steady-state rates of infusion were (in the same order) 0.64 +/- 0.22, 0.60 +/- 0.15, 0.61 +/- 0.21, 0.67 +/- 0.31, 0.63 +/- 0.15 and 0.39 +/- 0.17 mg kg-1 h-1 (Mean +/- SD). The intravenous agents did not interact with recuronium to any clinically significant degree. Isoflurane reduced the requirements by 35-40%.

Androstanols↗
PubMed1994

Neuromuscular effects of rocuronium bromide and mivacurium chloride administered alone and in combination.

BACKGROUND: Rocuronium is a new nondepolarizing neuromuscular blocking agent with a rapid onset but with intermediate duration of action. Mivacurium, on the other hand, is a new short-acting nondepolarizing neuromuscular relaxant, but of slower onset of action. The current study was undertaken to characterize the interaction between rocuronium and mivacurium. METHODS: In the first study, the dose-response relations of rocuronium, mivacurium, and their combination were studied in ASA physical status 1 or 2 patients during thiopental-fentanyl-N2O anesthesia. One hundred ten patients, randomly assigned to 1 of 11 groups of 10 patients each, received mivacurium 30, 50, or 70 micrograms.kg-1; rocuronium 100, 200, 250, or 300 micrograms.kg-1; or an equieffective combination of both drugs (1 ED50 rocuronium + 1 ED50 mivacurium; 1/2 ED50 rocuronium + 1/2 ED50 mivacurium; 1/4 ED50 rocuronium + 1/4 ED50 mivacurium; or 1/8 ED50 rocuronium + 1/8 ED50 mivacurium, where ED50 is the dose producing 50% depression of the first twitch height). In the second study, 50 patients, ASA physical status 1 or 2, anesthetized with thiopental-fentanyl-N2O, were randomly allocated to 5 groups of 10 patients each to receive one of the following neuromuscular blocking drugs or drug combination: rocuronium 600 micrograms.kg-1 (group 1), mivacurium 150 micrograms.kg-1 (group 2) rocuronium 150 micrograms.kg-1 + mivacurium 37.5 micrograms.kg-1 (group 3), rocuronium 300 micrograms.kg-1 + mivacurium 75 micrograms.kg-1 ((group 4), or rocuronium 600 micrograms.kg-1 + mivacurium 150 micrograms.kg-1 (group 5). RESULTS: The calculated ED50 values and their 95% confidence intervals were 125 (122-129) and 37 (36-38) micrograms.kg-1 for the rocuronium and mivacurium groups, respectively. The interaction between rocuronium and mivacurium was found to be synergistic. The measured ED50 of the mixture was only 62% of the predicted value assuming a purely additive interaction. In the second study, rocuronium 600 micrograms.kg-1 group and group 3 had similar onset times (99 [74-123] and 114 [100-128] s, respectively), which were significantly shorter than that observed in the mivacurium 150 micrograms.kg-1 group (178 [149-206] s). Onset times in groups 4 and 5 were significantly shorter than that in each of the other study groups (69 [63-76] and 73 [65-80] s, respectively). Clinical duration of action (recovery of T1 to 25% of baseline twitch height) was significantly greater in group 5 (55 [51-60] min) than with all other doses and agents, and briefest (P < 0.01) with mivacurium 150 micrograms.kg-1 (14.5 [12.6-16.5] min) and group 3 (14.7 [13.4-16] min). CONCLUSIONS: The interaction between rocuronium and mivacurium was found to be synergistic.

Adult↗
PubMed1996

Rocuronium priming of atracurium-induced neuromuscular blockade: the use of short priming intervals.

STUDY OBJECTIVE: To evaluate the effects of priming doses of rocuronium on the duration of priming interval and on the outcome of priming sequence using rocuronium-atracurium combination. DESIGN: Three phase, randomized, controlled study. SETTING: Inpatient anesthesia in a university hospital. PATIENTS: 144 ASA physical status I and II patients, 19 to 57 years of age, weighing 50 to 90 kg, and undergoing low-risk elective surgery. INTERVENTIONS: Phase I, two equal groups (n = 12) of adult patients anesthetized with propofol, fentanyl, and nitrous oxide (N2O), received a priming dose of rocuronium 0.1 mg/kg or vecuronium 0.015 mg/kg. Phase II included six equal groups (n = 12): Groups 1, 2, and 3 received a priming dose of rocuronium 0.1 mg/kg and atracurium 0.42 mg/kg for intubation. The priming intervals were, respectively, 1, 1.5, or 2 minutes in Groups 1, 2, and 3. Groups 4, 5, and 6 received, respectively, a bolus dose of rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg. Intubation was performed at maximum block. Phase III included four equal groups (n = 12). A priming dose of rocuronium 0.1 mg/kg (Group 1) or a placebo (Groups 2, 3, and 4) was given to awake patients. Anesthesia was induced during the one-minute priming interval. Intubating doses of atracurium 0.42 mg/kg, rocuronium 0.6 mg/kg, atracurium 0.5 mg/kg, or succinylcholine 1 mg/kg were given to Groups 1, 2, 3, and 4, respectively. Intubation was attempted 1 minute after intubating doses were administered. MEASUREMENTS AND MAIN RESULTS: Adductor pollicis response to train-of-four stimulation was recorded mechanically in Phases I and II only. The priming interval after rocuronium 0.1 mg/kg was in the range of 1 to 2 minutes. Priming doses of rocuronium resulted in significant acceleration in the onset time of intubating doses of atracurium, irrespective of the duration of the priming interval. The onset times [mean (SD)] following rocuronium-atracurium sequence in Groups 1, 2, and 3 were, respectively, 67 (17), 73 (14), and 66 (18) seconds and were comparable with the onset of bolus doses of rocuronium and succinylcholine. In Phase II, good to excellent intubating conditions were obtained in 41% to 58% of patients included in Groups 1 through 5. Excellent to good intubating conditions were obtained in all patients (100%) who received succinylcholine. In Phase III, good to excellent intubating conditions were obtained in 91% of patients who received recuronium-atracurium sequence. Symptoms of muscle weakness were not reported. CONCLUSIONS: Priming doses of recuroniums 0.1 mg/kg reduce the priming interval to 1 minute, allow early induction of anesthesia, eliminate patient discomfort, and accelerate the onset time of altracurium with intubating conditions comparable with succinylcholine and rocuronium.

Adult↗
PubMed1996

Comparison of rocuronium and mivacurium to succinylcholine during outpatient laparoscopic surgery.

Tracheal intubating conditions and neuromuscular effects of succinylcholine, rocuronium, and mivacurium were studied in 100 healthy women undergoing outpatient laparoscopic surgery. After a standardized fentanyl-thiopental induction, tracheal intubation was facilitated with succinylcholine 1 mg/kg in Groups I (n = 23) and II (n = 25), rocuronium 0.6 mg/kg in Group III (n = 27), or mivacurium 0.2 mg/kg in Group IV (n = 25). If clinically indicated, bolus doses of rocuronium 5-10 mg (Groups I and III) or mivacurium 2-4 mg (Groups II and IV) were administered during the maintenance period. Anesthesia was maintained with desflurane and nitrous oxide 60% in oxygen. At the end of the surgery, residual neuromuscular block was reversed with edrophonium 0.5 mg/kg and atropine 10 micrograms/kg, if needed. The neuromuscular function was assessed using electromyography with a train-of-four mode of stimulation every 10 s at the wrist. Intubating conditions 90 s after succinylcholine and rocuronium were significantly better than after mivacurium. The onset time (from the end of injection until 95% suppression of the first twitch [T1]) for succinylcholine (63 +/- 21 s and 62 +/- 17 s in Groups I and II, respectively) were significantly shorter than for rocuronium (158 +/- 76 s) or mivacurium (210 +/- 93 s). Moreover, the onset times for rocuronium were significantly shorter than mivacurium. The recovery times (of T1 to 25% of the control value) were significantly shorter with succinylcholine and mivacurium than rocuronium. Significantly fewer patients needed reversal of residual neuromuscular blockade after mivacurium compared to rocuronium. One patient in Group I and six patients in Group IV displayed erythema on the upper body. Postoperative myalgia were experienced by 16% of the patients in Groups I and II compared to none in Groups III and IV. There was on difference in the incidence of postoperative nausea and vomiting among the four groups. In conclusion, rocuronium appears to be an acceptable alternative to succinylcholine for tracheal intubation. However, rocuronium's longer duration of action increases the need for reversal drugs. When rapid tracheal intubation is unnecessary, mivacurium is also an acceptable alternative to succinylcholine and is associated with a more rapid spontaneous recovery than rocuronium.

Adult↗
PubMed1993

Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients.

BACKGROUND: Succinylcholine has been the agent of choice when clinical conditions require emergency airway protection during a rapid-sequence induction of anesthesia. Rocuronium, a new nondepolarizing muscle relaxant with a brief onset of action, but devoid of the adverse reactions associated with succinylcholine, may be an alternative to succinylcholine. To test this hypothesis, the authors compared rocuronium with succinylcholine and vecuronium for rapid-sequence induction of anesthesia. METHODS: Fifty patients, ASA 1-3, were randomly designated to receive one of three intravenous doses of rocuronium (0.6, 0.9, and 1.2 mg/kg), vecuronium (0.1 mg/kg), or succinylcholine (1.0 mg/kg). Patients were premedicated with midazolam and fentanyl, and received 2-7 mg/kg thiopental for induction of anesthesia. Sixty seconds after receiving a muscle relaxant, intubation of the trachea was attempted by a clinician who was blinded to the muscle relaxant administered. Neuromuscular monitoring was established before administration of the muscle relaxant. The time from injection of muscle relaxant until complete ablation of T1 (onset) and recovery of T1 to 25% (duration) were recorded. Tracheal intubating conditions were evaluated, and the presence or absence of fasciculations was noted. RESULTS: Onset times for patients receiving 0.9 mg/kg (75 +/- 28 s) and 1.2 mg/kg rocuronium (55 +/- 14 s), and succinylcholine (50 +/- 17 s) were similar. Onset times for the groups given 0.6 mg/kg rocuronium (89 +/- 33 s) and vecuronium (144 +/- 39 s) were significantly longer. Clinical duration of action was longest with 1.2 mg/kg rocuronium, similar with 0.6 and 0.9 mg/kg rocuronium, and vecuronium, and least with succinylcholine. CONCLUSIONS: There is a dose-dependent decrease in onset time with rocuronium. The onset times for the two larger doses of rocuronium were similar to that for succinylcholine, but clinical duration of action with rocuronium was significantly longer. The brief onset time achieved with rocuronium indicates that administration of 0.9-1.2 mg/kg is an acceptable alternative to succinylcholine for rapid-sequence induction of anesthesia.

Adolescent↗
PubMed1994

Different priming techniques, including mivacurium, accelerate the onset of rocuronium.

Different priming sequences of equipotent doses of rocuronium and mivacurium on the onset of maximum neuromuscular block and intubating conditions were compared with those obtained after succinylcholine. During thiopentone-fentanylnitrous oxide anaesthesia, 70 patients were randomly assigned into seven groups. Group I received mivacurium 0.15 mg.kg-1 as a single bolus dose. Group II received a priming dose of mivacurium 0.015 mg.kg-1 followed three minutes later by mivacurium 0.135 mg.kg-1. Group III received rocuronium 0.6 mg.kg-1 as a single bolus dose, and Group IV received an initial dose of rocuronium 0.06 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group V received a priming dose of mivacurium 0.015 mg.kg-1 followed by rocuronium 0.54 mg.kg-1. Group VI received an initial dose of rocuronium 0.06 mg.kg-1 followed by mivacurium 0.135 mg.kg-1. Group VII received succinylcholine 1.0 mg.kg-1. Groups I, III, and VII received a placebo injection before the administration of the neuromuscular blocking drug. Additional thiopentone 2 mg.kg-1 iv was given 30 sec before intubation. Onset times (mean (95% confidence interval)) after priming a rocuronium block with either rocuronium (73 (57-90) sec) or mivacurium (58 (47-69) sec) were similar to those after succinylcholine (54 (40-68) sec), and were shorter (P < 0.01) than that observed in other groups. Intubating conditions were not different between the groups. The duration of neuromuscular block was shortest with succinylcholine. It is concluded that priming a rocuronium block with either mivacurium or rocuronium resulted in a neuromuscular block comparable to that of succinylcholine in both the onset of action and intubating conditions.

Adult↗
PubMedDate not supplied

Clinical pharmacology of rocuronium (Org 9426): study of the time course of action, dose requirement, reversibility, and pharmacokinetics.

STUDY OBJECTIVE: To evaluate the time course of action, dose requirement, reversibility, and pharmacokinetics of rocuronium (Org 9426) under 3 anesthetic techniques (nitrous oxide-fentanyl supplemented with propofol, halothane, or isoflurane). DESIGN: Prospective, randomized study. SETTING: Operating suite at a university hospital. PATIENTS: 36 ASA physical status I-III patients aged 18 to 65 years who were scheduled for elective surgery. INTERVENTIONS: The time course of action of an intubation dose of rocuronium 600 micrograms/kg was investigated in 36 patients. In 18 of these patients, the maintenance dose requirement of rocuronium and reversibility by neostigmine were evaluated. In the remaining 18 patients, the pharmacokinetics of rocuronium after the intubating dose were studied. Neuromuscular transmission was monitored by mechanomyography. Venous blood samples and urine were analyzed by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: With the exception of a longer clinical duration of rocuronium-induced neuromuscular block in the isoflurane group compared with the propofol group (p = 0.03), time course of action variables were similar in the 3 groups. In patients receiving maintenance doses of rocuronium, the dose requirement until reversal was 636 +/- 191 micrograms/kg/hr, 496 +/- 107 micrograms/kg/hr, and 384 +/- 127 micrograms/kg/hr for the propofol, halothane, and isoflurane groups, respectively (p = 0.02 for the isoflurane group vs. the propofol group). With respect to the reversal of a rocuronium-induced neuromuscular block, there were no differences in the percentage recovery or rate of recovery among the 3 groups. Pharmacokinetic analysis showed no significant differences for rocuronium during the 3 anesthetic techniques. CONCLUSION: Isoflurane potentiates the rocuronium-induced neuromuscular block, resulting in a longer clinical duration and lower maintenance dose requirement. This difference is not explained by differences in pharmacokinetics but is probably due to increased sensitivity of the neuromuscular junction to rocuronium during isoflurane anesthesia.

Adolescent↗
PubMed1994

Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis.

BACKGROUND: Rocuronium, like other steroidal nondepolarizing muscle relaxants, may in part be eliminated by the liver. To determine the influence of liver disease on its neuromuscular blocking effect, we studied the pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis. METHODS: Eighteen patients undergoing elective surgery, 10 with cirrhosis and 8 with normal liver function, were studied. Anesthesia was induced with intravenous thiopental 5-7 mg.kg-1 and maintained with 60% nitrous oxide in oxygen and repeated doses of fentanyl 2 micrograms.kg-1. The force of thumb adduction in response to supramaximal ulnar nerve stimulation was monitored and recorded. An intravenous bolus of rocuronium 0.6 mg.kg-1 was administered and venous blood sampled at frequent intervals for 6 h. Plasma concentrations of rocuronium was measured by high-pressure liquid chromatography. Data were fitted to both a pharmacokinetic and a pharmacodynamic model by using a two-compartment open model and an effect compartment model. Data were analyzed by least-squares regression. RESULTS: The onset of neuromuscular blockade was longer (P < 0.01) in patients with cirrhosis (158 +/- 56 s) than in normal patients (108 +/- 33 s). Recovery of the thumb twitch to 75 and 90% of its control value was 77 +/- 25 and 88 +/- 29 min in cirrhotic patients versus 57 +/- 11 and 64 +/- 13 min, respectively, in normal patients (P < 0.05). The central volume of distribution of rocuronium was 104 +/- 21 in cirrhotic patients and 78 +/- 24 ml.kg-1 in normal patients (P < 0.05). No significant difference in elimination kinetics was observed between the two groups. The elimination half-life was 87.5 +/- 17.5 min in normal patients and 96.0 +/- 36.8 min in cirrhotic patients (difference not significant). This increased onset time was linearly correlated to the increased central volume of distribution of rocuronium in cirrhosis. CONCLUSION: Rocuronium onset time is longer in cirrhotic patients than in those with normal liver function; this can be explained by an increase in the volume in which rocuronium initially distributes. Although elimination kinetics are unchanged in patients with cirrhosis, rocuronium recovery time is prolonged in cirrhotic patients.

Androstanols↗
PubMed1995

Pharmacokinetics of rocuronium in children aged 4-11 years.

BACKGROUND: Rocuronium is a new nondepolarizing muscle relaxant with a rapid onset and intermediate duration of action. Although the pharmacokinetics of rocuronium have been determined in adults and the elderly, similar data are lacking in children. Accordingly, rocuronium's pharmacokinetics were determined in children aged 4-11 yr. METHODS: Rocuronium (600 micrograms/kg) was administered to 20 children aged 4-11 yr anesthetized with nitrous oxide and < or = 1% halothane, and four plasma samples were obtained over 4 h to determine rocuronium concentrations. The pharmacokinetics of rocuronium were determined using two sparse-sampling population approaches, mixed-effects modeling, and naive pooled data analysis. RESULTS: With mixed-effects modeling, weight-normalized plasma clearance varied with weight (P < 0.01), being 79.4 ml.min-1 + 3.13 ml.kg-1.min-1. Neither weight-normalized distributional clearance (2.67 ml.kg-1.min-1), weight-normalized central compartment volume (106 ml/kg), nor weight-normalized volume of distribution at steady-state (224 ml/kg) varied with weight, height, or age. Similar results were obtained with the naive pooled data approach. CONCLUSIONS: Maturational changes were observed in rocuronium's weight-normalized clearance but not in its weight-normalized distributional clearance or volume of distribution. Assuming that the duration of rocuronium's neuromuscular effects is influenced by its pharmacokinetics, repeated administration or continuous infusion of rocuronium should result in larger dose requirements and more rapid recovery in younger, compared to older, children.

Age Factors↗
PubMed1996

[The effects of age on onset and recovery from atracurium, rocuronium and vecuronium blockade].

UNLABELLED: Elderly patients may show an age-related decline in physiologic functions, which may be responsible for the prolonged duration of some neuromuscular blocking agents. Previous studies have yielded conflicting results as to the effects of these drugs in the elderly. METHODS: After obtaining informed consent and approval of the Ethics Committee, we compared onset and recovery times of single IV doses of atracurium, rocuronium, and vecuronium given to 108 patients divided into three groups according to age (18-50, 51-64, > or = 65 years). Following oxazepam premedication and fentanyl and thiopentone induction, patients were randomly allocated to receive atracurium, rocuronium or vecuronium (0.5, 0.6, or 0.1 mg/kg, respectively) in < or = 0.8 vol.% enflurane (end-tidal)-nitrous oxide anaesthesia. Muscular relaxation was assessed by electromyographic (EMG) recording of the adductor pollicis muscle after supramaximal single-twitch stimulation of the ulnar nerve every 10 s. Onset time and recovery to 25%, 75% and 90% of twitch control values (DUR25, 75, 90) were recorded. Creatinine clearance predicted from serum creatinine (Ccr) was correlated with recovery from neuromuscular block. RESULTS: Onset time was not different among groups or relaxants. The results showed a prolonged duration of action for atracurium (DUR75, DUR90), rocuronium (DUR25, DUR75), and vecuronium (DUR25) in the elderly. A number of patients did not reach DUR75 or DUR90. There was a significant relationship between age and failure to return to control values during recovery from neuromuscular block, especially after atracurium and rocuronium. Ccr showed a negative correlation with age for all relaxants, but a negative significant correlation between Ccr and recovery was found only for rocuronium. CONCLUSIONS: This study suggests that onset time for atracurium, rocuronium and vecuronium is not age-dependent. Recovery was prolonged in the elderly for all three relaxants. This effect appears to be secondary to changes in body composition and function accompanying the aging process. Neither atracurium nor vecuronium depends significantly on the kidney for elimination, but the negative correlation between Ccr and rocuronium suggests an appreciable role for the kidney in the elimination of this relaxant. The long recovery times observed in this study could also be related to enflurane anaesthesia. We suggest that failure of EMG responses to return to baseline values during recovery from neuromuscular block may be related to age, especially for atracurium and rocuronium.

Adolescent↗
PubMed1994

Onset and duration of rocuronium and succinylcholine at the adductor pollicis and laryngeal adductor muscles in anesthetized humans.

BACKGROUND: Rocuronium, a new nondepolarizing muscle relaxant, has a rapid onset of activity and may be suitable as a component of a rapid-sequence induction of anesthesia. We evaluated a range of doses on onset and duration of effect at the larynx and the adductor pollicis and compared these characteristics with those of succinylcholine. METHODS: Forty-eight patients aged 18-70 yr, of ASA physical status 1-3, were randomly allocated to receive succinylcholine (1 mg/kg) or one of three doses of rocuronium (0.4, 0.8, or 1.2 mg/kg) during surgery. Anesthesia was induced and maintained with propofol and fentanyl. The trachea was intubated without the use of muscle relaxants, and the cuff of the endotracheal tube placed between the vocal cords. Neuromuscular transmission was monitored by mechanomyography at the laryngeal adductor and adductor pollicis muscles. Muscular activity was evoked with supramaximal stimuli in a train-of-four sequence every 12 s to the anterior branch of the recurrent laryngeal nerve and the ulner nerve. RESULTS: At the laryngeal adductors, peak effect exceeded 99% in all patients given succinylcholine and in none (0%), five (42%), and ten (83%) of those given rocuronium 0.4, 0.8, and 1.2 mg/kg, respectively. At the adductor pollicis, peak effect exceeded 99% in all study patients except two who received rocuronium 0.4 mg/kg (peak effects 91% and 97%). Onset of effect with succinylcholine was significantly more rapid at the laryngeal adductors (34 +/- 12 s, mean +/- SD) than at the adductor pollicis (56 +/- 15 s); this was true also for rocuronium 0.4 mg/kg (92 +/- 29 s and 155 +/- 40 s for the laryngeal adductors and adductor pollicis, respectively). Onset times were similar at the two muscle groups with rocuronium 0.8 and 1.2 mg.kg-1: 96 +/- 29 and 74 +/- 36 s with 0.8 mg/kg and 54 +/- 30 and 65 +/- 21 s with 1.2 mg/kg at the laryngeal adductors and the adductor pollicis, respectively. CONCLUSIONS: The laryngeal adductors are more resistant to the action of rocuronium than is the adductor pollicis. Consequently, the onset of effect of rocuronium, in doses greater than 0.8 mg/kg, is similar to that of succinylcholine at the adductor pollicis but is significantly delayed compared with that of succinylcholine at the laryngeal adductors.

Adolescent↗
PubMed1996

Neuromuscular and cardiovascular advantages of combinations of mivacurium and rocuronium over either drug alone.

We investigated isobolic mixtures of mivacurium and rocuronium to determine if the combination offered any advantages over either drug alone. We used five dose regimens to achieve ED95 x 2: [(1.5 x ED95 mivacurium) + (0.5 x ED95 rocuronium); (1 x ED95 mivacurium) + (1 x ED95 rocuronium); (0.5 x ED95 mivacurium) + (1.5 x ED95 rocuronium); (2 x ED95 mivacurium); (2 x ED95 rocuronium)]. We studied onset time, duration of block, recovery of block, arterial blood pressure and heart rate. Mivacurium alone produced the block of shortest duration (p < 0.001). Onset time was shortest in the rocuronium alone group and was significantly faster in all the rocuronium treated groups compared to mivacurium alone (p < 0.001). Arterial blood pressure and heart rate decreased transiently in the mivacurium alone group but not in the other groups. These results demonstrate increased cardiovascular stability and more rapid onset of block with combinations of mivacurium and rocuronium without significant prolongation of the block.

Adult↗
PubMed1993

Rocuronium onset of action: a comparison with atracurium and vecuronium.

The onset, maximal neuromuscular block, and duration of rocuronium were compared with atracurium and vecuronium during enflurane anesthesia. Sixty patients received rocuronium (80, 100, 120, or 160 micrograms/kg). Enflurane enhanced a rocuronium neuromuscular block in a dose-related manner; the ED50 was 104 +/- 11 and 83 +/- 7 micrograms/kg (SEM) during 1% and 2% enflurane anesthesia, respectively. Patients receiving atracurium (0.12 mg/kg) or vecuronium (0.02 mg/kg) were studied during 1% enflurane anesthesia until seven in each group qualified by achieving a maximal block between 85% and 97%. These patients were matched with each other and with patients who had received rocuronium. Seven groups of three patients (rocuronium, vecuronium, and atracurium) were obtained. The average difference in maximal block was less than 2% between matched patients. The ratio of dose used to achieve a similar final block suggests potency ratios of 1, 8.5, and 1.2 for rocuronium, vecuronium, and atracurium. Rocuronium's onset time (time from drug administration to 50%, 75%, and 90% of final block) was significantly faster than either of the other two muscle relaxants (P < 0.01). Time to 90% of final block was 1.35 min for rocuronium, 3.06 min for atracurium, and 3.71 min for vecuronium. Using these equipotent doses, atracurium also had a shorter time to develop neuromuscular block than vecuronium (P < 0.05). For these three intermediate duration neuromuscular blockers, speed of onset was inversely related to their potency, confirming a relationship that had been demonstrated for the long-acting drugs pancuronium, d-tubocuranine, and gallamine.

Adult↗
PubMed1992

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.

Adult↗
PubMedDate not supplied

The effect of isoflurane versus balanced anesthesia on rocuronium's pharmacokinetics and infusion requirement.

STUDY OBJECTIVE: To compare the effects of two anesthetic techniques, balanced and isoflurane anesthesia, on the response to an intubating dose and an infusion of rocuronium, and on rocuronium's pharmacokinetics. DESIGN: Randomized, open-label study. SETTING: A university-affiliated hospital. PATIENTS: Twenty-two healthy adults undergoing elective surgery. INTERVENTIONS: The patients were anesthetized with a balanced technique (nitrous oxide, fentanyl, midazolam) or isoflurane (nitrous oxide, isoflurane 0.5-1.0%). Rocuronium was administered initially as a 500-micrograms/kg bolus, then by infusion to maintain approximately 86-94% depression of twitch tension. Plasma samples to determine rocuronium concentrations were obtained before, during, and after the infusion. Pharmacokinetics were determined using a population-based approach. MEASUREMENTS AND MAIN RESULTS: Onset time and initial recovery after the bolus dose were similar for the two groups. Infusion requirements also were similar. Plasma clearance was greater during isoflurane than during balanced anesthesia (4.48 vs 3.49 ml/kg/min). Distribution clearances and volumes of distribution were similar for the two groups. CONCLUSIONS: The similarity of response to an intubating dose and an infusion of rocuronium suggests that clinicians need not alter the dose or rate of rocuronium administration during isoflurane anesthesia with a of duration less than 1 hour. However, the greater clearance of rocuronium, in light of the similarity of infusion requirements, suggests that isoflurane potentiates rocuronium compared with balanced anesthesia.

Adult↗
PubMed1996

[The effects of cimetidine on the pharmacodynamics of rocuronium].

UNLABELLED: Cimetidine is a commonly used H2-receptor antagonist that has been recommended for the prevention of acid aspiration syndrome and has been shown to potentiate vecuronium-induced neuromuscular block. The present study was designed to investigate the influence of a single IV dose of cimetidine on the neuromuscular effects of rocuronium, an analogue of vecuronium with a short onset time. METHODS: Twenty adults aged 18-65 years were included in the study with their informed consent and approval of the Ethics Committee. Following oxazepam premedication, 10 patients were randomly allocated to receive cimetidine 400 mg IV 30 min before anaesthesia. After fentanyl and thiopentone induction, single-twitch stimulation of the ulnar nerve was performed every 10 s. Following stabilisation of control responses, patients received rocuronium 0.6 mg/kg for intubation. Anaesthesia was maintained with enflurane < or = 0.8 vol.% (end-tidal) and 65% nitrous oxide. Onset time and recovery times to 25% and 75% of the twitch control values were recorded. RESULTS: Onset and recovery times did not differ between groups. CONCLUSIONS: The results of the present study demonstrate that cimetidine does not increase the duration of rocuronium neuromuscular blockade. Inhibition of the cytochrome P450 system or a direct effect at the neuromuscular junction have been suggested as the mechanisms of drug interaction associated with cimetidine. Impairment of hepatic microsomal drug metabolism results in a prolonged duration of action of vecuronium, which appears to be eliminated primarily via the liver. Data on the elimination pathway of rocuronium in humans are not available. The fact that cimetidine does not alter the recovery from rocuronium-induced neuromuscular block confirms a previous suggestion that rocuronium may not be eliminated principally by the liver. A direct effect of cimetidine on the neuromuscular junction could not be confirmed by this study. Therefore, cimetidine can be given as premedication without a risk of prolonged rocuronium block.

Adolescent↗
PubMed1996

A mixture of mivacurium and rocuronium is comparable in clinical onset to succinylcholine.

STUDY OBJECTIVES: To compare the clinical onset and duration of a combination of mivacurium and rocuronium with succinylcholine, and to determine the efficacy of this mixture for rapid tracheal intubation. DESIGN: Observer-blind prospective study. SETTING: Teaching hospital. PATIENTS: 70 ASA status I and II patients having general anesthesia for elective surgery. MEASUREMENTS AND MAIN RESULTS: After induction of general anesthesia, patients randomly received succinylcholine 1.0 mg/kg, rocuronium 0.6 mg/kg, or a combination of rocuronium 0.6 mg/kg and mivacurium 0.15 mg/kg. Evoked muscular response at the adductor pollicis was measured by mechanomyography. The time from injection of muscle relaxant(s) to ablation of T1 (clinical onset) and recovery of T1 to 25% of control height (clinical duration) was recorded. Intubating conditions 45 seconds after administration of muscle relaxants were assessed. There was no significant difference in clinical onset time between succinylcholine (mean +/- SD, 47.4 +/- 6.5 seconds) and the combination of mivacurium-rocuronium (51.2 +/- 13.4 seconds). Intubating conditions with mivacurium-rocuronium were comparable to those of succinylcholine. The clinical duration of rocuronium 0.6 mg/kg (38.9 +/- 12.3 minutes) was prolonged by the addition of mivacurium (49.0 +/- 9.6 minutes). CONCLUSIONS: This combination of mivacurium and rocuronium is comparable to succinylcholine in both clinical onset time and quality of intubating conditions. When rapid onset of dense neuromuscular blockade and intermediate clinical duration is desirable, this mixture may be an acceptable alternative to succinylcholine.

Adjuvants, Anesthesia↗