We determined the pharmacokinetics and pharmacodynamics of cisatracurium, one of the 10 isomers of atracurium, in 14 patients with end-stage liver disease undergoing liver transplantation and in 11 control patients with normal hepatic and renal function undergoing elective surgery. Blood samples were collected for 8 h after i.v. bolus administration of cisatracurium 0.1 mg kg-1 (2 x ED95). Plasma concentrations of cisatracurium and its metabolites were determined using an HPLC method with fluorescence detection. Pharmacokinetic variables were determined using non-compartmental methods. Neuromuscular block was assessed by measuring the electromyographic evoked response of the adductor pollicis muscle to train-of-four stimulation of the ulnar nerve using a Puritan-Bennett Datex (Helsinki, Finland) monitor. Pharmacodynamic modelling was completed using semi-parametric effect-compartment analysis. Volume of distribution at steady state was 195 (SD 38) ml kg-1 in liver transplant patients and 161 (23) ml kg-1 in control patients (P < 0.05), plasma clearance was 6.6 (1.1) ml kg-1 min-1 in liver transplant patients and 5.7 (0.8) ml kg-1 min-1 in control patients (P < 0.05), but elimination half-lives were similar: 24.4 (2.9) min in liver transplant patients vs 23.5 (3.5) min in control patients (ns). The time to maximum block was 2.4 (0.8) min in liver transplant patients compared with 3.3 (1.0) min in control patients (P < 0.05), but the clinical effective duration of action (time to 25% recovery) was similar: 53.5 (11.9) min in liver transplant patients compared with 46.9 (6.9) min in control patients (ns). The recovery index (25-75% recovery) was also similar in both groups: 15.4 (4.2) min in liver transplant patients and 12.8 (1.9) min in control patients (ns). After cisatracurium, peak laudanosine concentrations were 16 (5) and 21 (5) ng ml-1 in liver transplant and control patients, respectively. In summary, minor differences in the pharmacokinetics and pharmacodynamics of cisatracurium in liver transplant and control patients were not associated with any clinically significant differences in recovery profiles after a single dose of cisatracurium.
I'urpose: To measure the haemodynamic effects of rocuronium in adults undergoing cardiac surgery with cardiopulmonary bypass (CPB). Methods: Twenty patients undergoing elective cardiac surgical procedures with moderate hypothermic nonpulsatile bypass participated in this prospective, observational study. After anaesthetic induction, recovery from succinylcholine, and achievement of baseline haemodynamic stability, patients received 0.6 mg'kg -I rocuronium as an initial rapid intravenous bolus. Maintenance dosing of 0.2 mg'kg -I was continued for the remainder of the procedure. Haemodynamic measurements (heart rate, systemic artedal systolic, diastolic, and mean arterial pressure, pulmonary artedal systolic, diastolic, and mean pressure, pulmonary capillary wedge pressure, central venous pressure, and thermodilution cardiac output measurements) were obtained for the fi~ tire minutes after rocurenium administration, and subjects were observed for histamine-related symptoms. Results: Central venous pressure decreased from baseline at two and five minutes after the rocuronium bolus, and mean pulmonary artery pressure decreased at five minutes. No changes were observed in hearL rate, mean systemic arterial pressure, pulmonary capillary wedge pressure, cardiac index, stroke volume, systemic vascular resistance, or pulmonary vascular resistance, nor did any patient manifest any other histamine-related symptoms. Conclusion: The haemodynamic profile for a 0.6 mg-kg-' bolus of rocuronium is acceptable for patients with cardiovascular disease.Objectif : Mesurer les effets h~modynamiques du rocuronium chez des adultes subissant une chirurgie cardiaque sous CEC. M&hodes : Vingt patients subissant une chirurgie cardiaque sous CEC ~ riot non pulsatile et sous hypothermie mod4r4e ont particil~ ~ cette ~tude d'observation prospective. Apr~s I'inductian de I'anesth&ie, r~cup~ration de I'effet de la succinylcholine et obtention d'une stabilit~ h~modynamique de base, les patients ont regu par voie IV rapide un bolus initial de 0,6 mg-kE "l de rocuronium suivi de doses de malntien de 0,2 mg.kg -~ durant route la dur6e de la procfidure. Durant les premi&es cinq minutes apr~s radministration de rocuronium, les mesures h~modynamiques suivantes ont ~t4 obtenues : rythme cardiaque, pression art&ielle syst~mique et pulmonaire, systolique, diastolique et moyenne, pression capillaire bloqu~e, pression veineuse centrale et mesures du d~bit cardiaque par thermodilution. On a aussi recherch6 chez les patients de sympt6mes li~s ~ la lib&ation d'histamine. R~sultats : Apr& un bolus de rocuronium, on a observ~ une diminution de la pression veineuse centrale apr~s deux et cinq minutes. Les autres variables, rythme cardJaque, pression art&ielle moyenne, pression capillaire bloqu6e, index cardiaque, volume d'~jection, r&istance vasculaire pulmonaire et syst~mique, n'ont pr&ent~ aucun changement. Aucun patJent n'a d~montr~ de sympt6mes li& ~ la lib6ration d'histamine. Conclusion : Une dose bolus de 0,6 mg-kg "l de racuronium poss~de un profil h4modyn...
When compared with GA without an induction room for outpatients undergoing anterior cruciate ligament reconstruction, RA with an induction room was associated with the lowest anesthesia- controlled time. Managers must weigh the costs and time required for anesthesiologists and additional personnel to place nerve blocks or induce GA preoperatively in such a staffing model.
The purpose of this study was to determine whether short-term tolerance develops to GABA-agonist-induced changes in saccadic eye movements (SEMs), and whether the time course for GABA-agonist induced onset and offset of impairment is similar for SEMs and for psychomotor function. An additional goal was to determine whether there are differences in sensitivity between SEMs and psychomotor function. Six healthy volunteers participated in this balanced double-blind, three-way crossover, single-dose study of placebo and two different dosage forms of the GABA-agonist alprazolam: a rapidly absorbed oral 1.5-mg compressed tablet (CT) and a 3.0-mg sustained release (SR) tablet. Treatments were separated by a 7-day washout period. Peak concentrations did not differ between CT and SR treatments, although area under the concentration-time curve (AUC) of alprazolam was greater after administration of SR than after CT, because plateau concentrations were attained after SR. Both SEM and psychomotor tests showed time-dependent responses consistent with the development of tolerance. SEMs discriminated the differences in rate of drug input of the CT and SR formulations, with impairment evident at low concentrations during absorption. SEM impairment also persisted longer than did psychomotor impairment. Peak saccade velocity is a more sensitive indicator of pharmacologic effects mediated by the GABA-benzodiazepine receptor complex than are psychomotor responses. This is probably the result of the very high GABA dependency of SEMs, along with their limited sensitivity to motivation.
The effects of bolus administration of large doses of vecuronium on the onset and duration of neuromuscular blockade and histamine release were studied during fentanyl-nitrous oxide anesthesia. Forty adults were randomly assigned to receive a bolus injection of either 0.1, 0.2, 0.3, or 0.4 mg/kg of vecuronium. The evoked electromyogram of thumb adduction to train-of-four stimulation was monitored. The time of onset and clinical duration (mean +/- SEM) after each dose were as follows: 0.1 mg/kg, 164 +/- 27 s and 42 +/- 5 min; 0.2 mg/kg, 120 +/- 17 s and 68 +/- 8 min; 0.3 mg/kg, 88 +/- 17 s and 111 +/- 19 min; 0.4 mg/kg, 78 +/- 19 s and 115 +/- 19 min. Both time of onset and duration after doses of 0.3 or 0.4 mg/kg were significantly different from values after the lower doses. No dose-related changes in blood pressure, heart rate, or histamine release were observed. The authors conclude that large bolus doses of vecuronium can be safely used to speed the onset of blockade, but with a significantly prolonged duration of action.
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