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At least 397 records · Page 22Linked to original sources
PubMed2003

Target controlled infusion of rocuronium: analysis of effect data to select a pharmacokinetic model.

BACKGROUND: We aimed to evaluate whether area under the curve (AUC) analysis of pharmacodynamic data can be used to compare pharmacokinetic models taken from the literature, during a target controlled infusion (TCI) of rocuronium. METHODS: Seventy-two patients scheduled for orthopaedic surgery received a TCI of rocuronium (Stanpump) based on one of four pharmacokinetic models: those described by Szenohradszky, Alvarez-Gomez, Wierda, and Cooper. The resulting theoretical plasma concentration versus time curve was calculated for all patients based on all four pharmacokinetic models. Predicted effect versus time curves were calculated following the pharmacokinetic-pharmacodynamic link model (Sheiner and colleagues). Neuromuscular block was evaluated acceleromyographically. The difference between the area under the observed effect (AUC(OE)) and predicted effect (AUC(PE)) versus time curves was used for comparison. RESULTS: AUC(PE )differed significantly from AUC(OE) in the Szenohradszky and Alvarez-Gomez models, both with the reference link-pharmacodynamic data and with altered link-pharmacodynamic variables. AUC(PE )and AUC(OE) were comparable for the Wierda and Cooper models. The mean AUC(OE) was 25.1 (SD 11.9)% block x h. AUC(PE)-AUC(OE) was significantly larger in the Szenohradszky model when compared with all other pharmacokinetic models. This difference remained when link or pharmacodynamic variables were modified. The smallest AUC(PE)-AUC(OE) difference was found with the Wierda model. CONCLUSION: It was possible to use AUC analysis for identification of the pharmacokinetic model that best predicted the pharmacodynamic characteristics of our patients.

Adult↗
PubMed2004

Rocuronium for muscle relaxation in two children with Friedreich's ataxia.

Friedreich's ataxia is a rare hereditary neurodegenerative disease caused by a defect in the gene that encodes a mitochondrial protein called frataxin. We report the use of rocuronium 0.6 mg kg(-1) in two adolescent girls with Friedreich's ataxia undergoing propofol-sufentanil-oxygen-air anaesthesia for spinal surgery. Neuromuscular transmission was monitored using acceleromyography, and onset and recovery times were recorded. The clinical duration of rocuronium was comparable to that of children without neuromuscular disease (25% recovery T(1)=44 and 24 min for patients 1 and 2 respectively).

Adolescent↗
PubMed2000

Histaminoid reactions associated with rocuronium.

We describe three histaminoid reactions occurring on induction of anaesthesia. The patients were all resuscitated successfully and subsequent skin testing suggested sensitivity to rocuronium. In this hospital, the incidence of such reactions is of the order of 1 in 3000. This may be coincidental but suggests that there should be close monitoring of the incidence of reactions to rocuronium. Review of the cases suggests that current guidelines on management are not always followed.

Adult↗
PubMed1993

Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia.

The neuromuscular effects of intravenous rocuronium bromide, 0.6 mg.kg-1 or 0.9 mg.kg-1, were studied in four groups of 10 patients during anaesthesia with or without halothane (0.5-0.75% inspired concentration). Neuromuscular block was monitored using mechanomyography and train-of-four stimulation. The mean times to onset of complete neuromuscular block were 58 and 59 s using the 0.6 mg.kg-1 dose in patients anaesthetised with fentanyl and halothane respectively. The times of 34 min and 33 min for 25% recovery of T1 (first response in the train of four), 54 min and 52 min for 90% recovery of T1, 55 min and 60 min for a train of four ratio of 0.7, and 13 and 13 min respectively for the recovery index (25-75% recovery of T1) were not significantly different in these groups. Complete block with the 0.9 mg.kg-1 dose occurred in 47 s and 44 s respectively in the fentanyl and halothane groups. T1 recovered to 25% in 51 min and 58 min, and to 90% in 77 min and 86 min respectively in the two groups. The recovery indices and the times to spontaneous recovery of the train of four ratio to 0.7 were 17 min and 19 min, and 83 min and 93 min respectively. All the parameters were significantly different between the 0.6 mg.kg-1 and 0.9 mg.kg-1 doses. Halothane in the concentrations used did not influence the neuromuscular effects. It is concluded that rocuronium is a rapidly acting non-depolarising muscle relaxant with a duration of action similar to that of vecuronium and may be a useful alternative to suxamethonium for rapid tracheal intubation.

Adolescent↗
PubMed1993

The use of rocuronium (ORG 9426) in patients with chronic renal failure.

The pharmacodynamics of an initial dose of 0.6 mg.kg-1 rocuronium followed by three maintenance doses of 0.15 mg.kg-1 were studied during nitrous oxide/oxygen/isoflurane anaesthesia in patients with normal renal function (n = 12) and chronic renal failure (n = 12). The mean (SD) duration (min) of block after the initial dose was 28.0 (5.5) and 25.6 (11.7) respectively. The mean (SD) duration (min) of the effect of the three maintenance doses was 15.3 (4.0) and 14.2 (7.0); 17.3 (3.2) and 17.4 (8.7); 18.1 (2.8) and 19.1 (10.1) for the normal and renal failure patients respectively. The induced and spontaneous recovery indices were 3.7 (0.7) and 17.1 (6.9) in the normal group compared with 3.9 (0.5) and 19.0 (12.5) in the renal failure group and these values did not differ between the two groups. In this small study rocuronium appears to be suitable for patients with chronic renal failure. There is no evidence of prolonged block even when the drug is given in repeated doses for maintenance.

Adolescent↗
PubMed1997

Prediction of infusion rates of rocuronium using the bolus test dose technique.

Twenty-four patients were given a loading dose of rocuronium 1.0 mg.kg-1 intravenously followed by boluses of 20 mg (n = 19) and 10 mg (n = 24) after return of T1 of the train-of-four to 5% of control. Neuromuscular function was assessed using a Relaxograph. The time was recorded for the return of T1 to 5% after the administration of the boluses and subsequently an infusion of rocuronium was started. The aim was to maintain T1 between 3% and 7% of control for at least 40 min without a change of infusion rate. The correlations between the duration of the test doses and the infusion rates were -0.94 (10 mg) and -0.86 (20 mg). The predictive accuracy of the 10 mg bolus was assessed in a further 10 patients. At the termination of the infusion three patients had a T1% that was outside the desired range of 3-7%. A 10 mg bolus that lasts 6 min indicates a need for an infusion of at least 60 mg.h-1, 8 min (50 mg.h-1), 10 min (40 mg.h-1), 15 min (30 mg.h-1), 24 min (20 mg.h-1) and 34 min (15 mg.h-1).

Adolescent↗
PubMed1997

A comparison of acceleromyography and mechanomyography for determination of the dose-response curve of rocuronium in children.

In order to compare an acceleromyograph (TOF-Guard) with a mechanomyograph (Grass FT03), the dose-response relationship of rocuronium was simultaneously determined in both arms of 15 children aged 3-11 years during anaesthesia with thiopentone, alfentanil and nitrous oxide. Three subgroups of five children received rocuronium 120, 180 or 240 micrograms.kg-1 randomly. The effective doses to produce 50% and 95% depression of the first twitch of the train-of-four determined by acceleromyography were 206 and 337 micrograms.kg-1, respectively, while these values determined by mechanomyography were 151 and 331 micrograms.kg-1, respectively. The dose-response curve obtained by acceleromyography was steeper and shifted to the right compared with that obtained by mechanomyography (p < 0.0001). The difference between the effective dose producing 50% twitch depression determined by the two devices was highly significant (p < 0.0001). In 13 out of 15 children, the acceleromyograph control train-of-four ratio was significantly greater than unity. Although there was a good correlation (r = 0.85) between simultaneous pairs of measurements of neuromuscular block, the acceleromyograph exhibited a bias of -25% relative to the mechanomyograph with wide limits of agreement (-62 to +12%). We conclude that acceleromyographic and mechanomyographic measurements should not be used interchangeably when determining the potency of muscle relaxants.

Androstanols↗
PubMed1993

Evaluation of the time course of action of maintenance doses of rocuronium (ORG 9426) under halothane anaesthesia.

The time course of action of rocuronium was compared using three different sizes of maintenance doses after at least three subsequent administrations of the same repeat dose in each patients under halothane anaesthesia. Following endotracheal intubation facilitated with 0.6 mg.kg-1 rocuronium (ORG 9426), muscle relaxation was maintained in three groups each consisting of ten patients, using increments of equal repeat doses of either 75 micrograms.kg-1, 150 micrograms.kg-1 or 225 micrograms.kg-1 equivalent to 1/4, 1/2 and 3/4 of the ED95 of this new compound, respectively. Maintenance doses were administered when the twitch height depression induced by the previous dose returned to 25% of its control value. The clinical duration of the intubating dose averaged 27 +/- 7.5 min (mean +/- s.d.). The time course of action of the various maintenance doses depended on their size, but not on the number of administrations. The durations of repeat doses averaged 8-9 min, 14-16 min and 19-23 min after the low, medium and high maintenance doses, respectively. No overt cumulative effects were observed.

Adolescent↗
PubMed2002

Population pharmacodynamic modeling without plasma concentrations of rocuronium in children.

Using the pharmacodynamic model without plasma concentrations described by Bragg et al, an individual approach resulted in highly variable parameters for rocuronium. Using a population approach of the model, the time course of the effect of an IV bolus dose of 400, 600, and 800 microg/kg of rocuronium was studied. Response was measured by accelerometry (TOF-Guard) in 45 low-risk surgical children, ages 2 to 14 years, who were receiving general anesthesia with isoflurane. Using a Bayesian approach and the software P-PHARM, response (the first twitch of the TOF) was modeled. The apparent rate constant of elimination, the rate constant for equilibrium between plasma and the effect compartment, the sigmoidicity factor of the relationship between drug concentration in the effect compartment and the effect, and the infusion rate that produces 50% of the effect at steady state were obtained. Population and individual post hoc parameters were similar among groups and variability was reduced.

Adolescent↗
PubMed1997

Evaluation of the onset time and intubation conditions of rocuronium bromide in children.

We have assessed, in children aged three to eight years, the intubating conditions after administration of rocuronium 0.6 mg/kg at 50 or 60 seconds, in groups of 15 patients. Intubating conditions were excellent in 11, good in 3 and fair in 1 patient at 50 seconds and excellent in 12 and good in 3 patients at 60 seconds. The mean onset time, for all patients, to when the first twitch of the train of four (T1), measured at the adductor pollicis, was depressed to less than 30% and 5% of control was 50 (SD 11.4) seconds and 94 (SD 31.7) seconds respectively. Depression of T1 to less than 30% of control, measured at the adductor pollicis in children, appears to indicate that intubating conditions will be clinically acceptable when using rocuronium.

Androstanols↗
PubMedDate not supplied

The effect of midazolam pre-medication on rocuronium-induced neuromuscular blockade.

We investigated the effect of midazolam pre-medication on rocuronium-induced neuromuscular blockade during sevoflurane anaesthesia. Twenty-two patients scheduled for elective surgery were randomly divided to receive either no pre-medication (control group) or pre-medication with 0.1 mg/kg midazolam intramuscularly (midazolam group). Anaesthesia was induced with fentanyl and propofol, and maintained with sevoflurane and nitrous oxide in oxygen. Neuromuscular responses were monitored using acceleromyography. The onset and clinical duration of action, time to recovery of first twitch of train-of-four (TOF) response to 75% of control, recovery index and time for TOF recovery to 25% and 50% were recorded. Patient-related data were similar in both groups. The parameters recorded were not significantly different between the groups. Midazolam pre-medication does not influence the time-course of action of rocuronium during sevoflurane anaesthesia.

Adjuvants, Anesthesia↗
PubMed2005

The effect of nitrous oxide on the dose-response relationship of rocuronium.

It has been generally assumed that nitrous oxide (N(2)O) enhances the effects of nondepolarizing muscle relaxants only weakly if at all. More recent evidence suggests that drug potency may be more intense under N(2)O anesthesia compared with total IV anesthesia (TIVA). However, the magnitude of this effect has not been well defined. We measured the 50% effective dose of rocuronium in 35 patients receiving N(2)O-propofol-opioid anesthesia and a comparable group receiving TIVA. A single dose of rocuronium was given to each patient and drug potency was calculated for each individual from the Hill equation assuming a log-dose/logit slope of 4.5. In both groups, the relaxant was administered 15 min after induction of anesthesia. Neuromuscular function was measured using electromyography with single stimuli at 0.10 Hz. We measured a 50% effective dose of 0.209 +/- 0.051 mg/kg during TIVA and of 0.166 +/- 0.041 mg/kg during N(2)O anesthesia, a decrease of 20% (P < 0.001). The clinical importance of this effect must be considered modest; however, estimates of potency that are usually obtained during N(2)O anesthesia may underestimate drug requirements at the time of induction of anesthesia.

Adolescent↗
PubMed2006

Long-lasting potentiation of a single-dose of rocuronium by amikacin: case report.

We report for the first time to our knowledge long-lasting (4 hours) potentiation of single intubating dose of rocuronium by a single bolus of amikacin given 55 minutes later in a woman having no precipitating factor (renal failure, hepatic failure, ionic disorder, other drugs influencing neuromuscular function). This patient had received the same rocuronium dose one month sooner in similar circumstances (without aminoglycoside antibiotic drug) and had not presented any prolonged neuromuscular blockade at this time. Neuromuscular blockade should be monitored in every patient receiving aminoglycoside antibiotic with even a single intubating dose of neuromuscular blocking drug.

Amikacin↗
PubMed1994

Early and late reversibility of rocuronium bromide.

A computer simulation has been developed based on pharmacodynamic-pharmacokinetic modelling of the effect of neostigmine on rocuronium-induced neuromuscular blockade. The results of a previous study involving 60 patients were used as a test of the model. The model predicts that administration of neostigmine 40 micrograms kg-1 within 20 min of the administration of rocuronium does not decrease the duration of the block until 90% recovery has taken place. The optimum dose of neostigmine depends on the degree of block at the time of administration: for a more intense block the optimum dose is 80 micrograms kg-1 and for a less intense block is about 30 micrograms kg-1. The pharmacokinetic behaviour rather than the potency of the relaxant determines its reversibility.

Androstanols↗
PubMed1994

Evaluation of the onset and intubation conditions of rocuronium bromide.

Rocuronium 0.6, 0.75, or 0.9 mg kg-1, was given after supramaximal train-of-four stimulation of the ulnar nerve, measuring the compound action potential of the hypothenar muscles, Intubation conditions, onset time, recovery to 25% and recovery index of the three doses of rocuronium bromide were determined in 60 ASA I or II consenting patients, who were receiving propofol, alfentanil and N2O/O2 for ophthalmic surgery. Intubation conditions were randomly assessed either 45 s or 60 s after injection. In general, intubation conditions were excellent or good; in only three patients were poor conditions obtained, always at 45 s. For total intubation score a borderline difference was found in favour of the 60 s subgroups. No difference could be shown between the three dose groups. The onset time was longer (P < 0.01) in the 0.6 mg kg-1 group, compared to that in the 0.9 mg kg-1 group. The recovery to 25% and spontaneous recovery index were shorter in the 0.6 mg kg-1 group (P < 0.01).

Action Potentials↗
PubMed1994

Pharmacokinetics and pharmacodynamics of rocuronium bromide in adult patients.

In seven patients (M/F: 4:3) rocuronium 0.6 mg kg-1 was given after the induction of anaesthesia with propofol, and during maintenance with N2O/O2, halothane 0.5% and alfentanil 60-90 micrograms kg-1 h-1. Intubation conditions were scored at 60 s and lag time, onset time, maximal block achieved, recovery to 25% of T1, and Recovery Index, were measured using a Relaxograph. Blood samples were taken over a 300 min period and analysed for rocuronium. Intubating conditions at 60 s were excellent in all patients. Mean clearance was 5.2 ml kg-1 min-1, the terminal half-life was 69 min and distribution volume at steady state was 0.22 litre kg-1. Cumulative urinary excretion was around 18% within 24 h.

Adult↗
PubMed1994

Evaluation of the effects of rocuronium bromide on haemodynamics and left ventricular function in patients undergoing abdominal aortic surgery.

In an open study of 26 patients undergoing abdominal aortic surgery, the effects of rocuronium 0.6 mg kg-1 (eight patients) and 0.9 mg kg-1 (nine patients) were compared with those of pancuronium 0.085 mg kg-1 (eight patients) on haemodynamic parameters and transoesophageal echocardiography. The anaesthetic technique was based on a benzodiazepine and low dose fentanyl (6 micrograms kg-1). Pancuronium was associated with a significant increase in mean arterial pressure, end-diastolic area and heart rate, none of which were seen after rocuronium at either dose level.

Androstanols↗
PubMed1994

Interaction between rocuronium bromide and some drugs used during anaesthesia.

In cats anaesthetized with i.p. chloralose and pentobarbitone, neuromuscular blockade produced by various doses of rocuronium was measured and dose response curves constructed in the presence of halothane, enflurane, nitrous oxide, propofol, alfentanil, thiopentone, ketamine, diazepam, chlorpromazine, morphine or streptomycin. In general, when a shift in the dose response curve was produced, it was a parallel shift to the left, indicating potentiation. Both halothane and enflurane produced a left shift and a small increase in the time from maximum block to 90% recovery. Nitrous oxide had no effect on the depth of block but delayed recovery. Thiopentone and ketamine potentiated the blocking effect of rocuronium but propofol and alfentanil had no effect. Chlorpromazine and morphine caused potentiation which took 1-1.5 h to develop. Streptomycin had a potentiating effect in four cats but not in two others. Diazepam displaced the dose-response curve to the right in four cats. Prior treatment with suxamethonium had no effect.

Androstanols↗