[Pharmacokinetics of continuous infusion of etomidate in cirrhotic patients]. / Pharmacocinétique de l'étomidate en perfusion continue chez le patient cirrhotique.

The pharmacokinetics of etomidate were studied in 9 control subjects (with normal liver function) and in 5 patients with cirrhosis scheduled for gastro-intestinal surgery. Anaesthetic induction included an initial bolus of etomidate 0.3 mg.kg-1, together with fentanyl 2 micrograms.kg-1, and pancuronium 60 micrograms.kg-1. An etomidate infusion was then started according to one of two following schemes: a (0.03 mg.kg-1.min-1 for 10 min, and then 0.01 mg.kg-1.min-1), or B (0.1 mg.kg-1.min-1 for 10 min, followed by 0.02 mg.kg-1.min-1 for a further 110 min, and 0.01 mg.kg-1.min-1 thereafter). Plasma concentrations of etomidate were determined at regular intervals throughout anaesthesia, and up to four hours afterwards, using inverse phase high pressure liquid chromatography. The infusion was given for 273 +/- 87 min in controls, and for 259 +/- 56 min in the cirrhotic group. Scheme A, only used in 3 controls and 1 cirrhotic in a preliminary study, resulted in very low plasma concentrations: 0.2 to 0.4 micrograms.ml-1. Those measured during the apparent plateau phase (steady state) of infusion protocol B were close to predicted values (0.5 to 0.6 micrograms.ml-1) in controls, whereas higher concentrations (approximately 1.5 micrograms.ml-1) were reached in cirrhotic patients. For all the patients the time interval to spontaneous recovery was 41 +/- 27 min; plasma levels were then 0.199 +/- 0.092 micrograms.ml-1. There were significant alterations in pharmacokinetic parameters in the cirrhotic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemodynamic effects of fentanyl and sufentanil combined with flunitrazepam in coronary artery surgery]. / Effets hémodynamiques du fentanyl et du sufentanil associés au flunitrazépam lors de la chirurgie coronarienne.

Because sufentanil has been reported as being able to prevent or treat peroperative hypertensive crises during aorto-coronary artery graft surgery, a study was carried out to compare the haemodynamic effects of sufentanil with those of fentanyl. 20 patients who were to undergo aortocoronary bypass grafting (CABG) were randomly allocated to two equal groups, sufentanil (Sf) and fentanyl (F) groups. A 1 to 5 dose ratio was used so as to have equipotent doses of sufentanil and fentanyl. Induction doses were 10 micrograms.kg-1 sufentanil and 50 micrograms.kg-1 fentanyl. Up to 20 micrograms.kg-1 sufentanil and 100 micrograms.kg-1 fentanyl were then used between intubation and the setting-up of cardiopulmonary bypass (CPB). A bolus of 10 micrograms.kg-1 flunitrazepam was given if necessary, so as to lower the mean arterial pressure (Pa) to below 100 mmHg after intubation, and under 80 mmHg during CPB. Heart rate, Pa, mean pulmonary arterial pressure, pulmonary wedge pressure (Ppw), central venous pressure and cardiac output were measured before anaesthesia, 2 min after intubation, before incision, 2 min after sternotomy, 10 min after the end of CPB, after chest closure, 30 min and 2h after arrival of the patient in the intensive care unit. The only difference found between the two groups was a more rapid drop in left ventricular preload after induction with sufentanil; 2 min after intubation, there was a 26% fall in Ppw with sufentanil (p less than 0.01) and 8% with fentanyl. Before skin incision, this drop was of 32% (p less than 0.01) and 24% (p less than 0.01) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Analgesia and ventilatory response to CO2 following epidural sufentanil in children.

The authors studied the effects of epidural sufentanil (0.75 microgram.kg-1) after urologic surgery in 15 children ranging in age from 4 to 12 yr, and in weight from 14 to 47 kg. The onset and duration of analgesia were 3.0 +/- 0.3 and 198 +/- 19 min, respectively (mean +/- SEM). Side effects included pruritus (3/15), nausea and vomiting (5/15), drowsiness (10/15), and urinary retention (1/11). No apnea was observed. Periosteal analgesia and ventilation were studied in eight of the children (mean age 8.6 +/- 0.8 yr). There was significant periosteal analgesia of the tibia (30, 60, 90, and 120 min after injection) and of the radius (60, 90, and 120 min after injection). Resting respiratory rate and tidal volume did not change during the study. Resting minute-ventilation decreased from 6.3 +/- 0.5 l.min-1 preoperatively to 5.6 +/- 0.6 l.min-1 (P less than 0.05) postoperatively, before epidural sufentanil injection; it did not decrease further after epidural sufentanil. Similarly, end-tidal CO2 tension increased significantly from 37.2 +/- 0.7 mmHg preoperatively to 39.9 +/- 1.2 mmHg (P less than 0.05) postoperatively, before epidural sufentanil; epidural sufentanil did not cause a further significant increase in end-tidal CO2 tension. The slope of the CO2 ventilatory response curve decreased significantly from 1.68 +/- 0.12 l.min-1. mmHg-1 preoperatively to 1.10 +/- 0.13 l.min-1.mmHg-1 (P less than 0.01) postoperatively. There were further significant decreases to 0.68 +/- 0.10 and 0.89 +/- 0.16 l.min-1.mmHg-1 30 and 60 min after epidural sufentanil.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of sufentanil and fentanyl to supplement N2O-halothane anesthesia for total hip arthroplasty in elderly patients.

Sufentanil was compared with fentanyl as a supplement to nitrous oxide-halothane anesthesia in a double-blind study of 30 elderly patients undergoing total hip arthroplasty. Comparisons were made with respect to (a) hemodynamic (heart rate and blood pressure) and adrenergic (plasma norepinephrine and epinephrine levels) responses during surgery and recovery; (b) time to extubation after the end of surgery; and (c) postoperative analgesia. No difference was observed between the two groups with respect to demographic data, blood gas tensions, or hemodynamic and adrenergic responses to surgery and recovery. Total doses of opioids used were 0.7 +/- 0.3 micrograms/kg of sufentanil and 6 +/- 2.6 micrograms/kg of fentanyl. Times between end of surgery and extubation were not different (60 +/- 54 min in the fentanyl group and 58 +/- 52 min in the sufentanil group). The number of patients needing postoperative analgesia did not differ between the two groups, but use of analgesia was significantly delayed in the sufentanil group (168 +/- 25 vs 127 +/- 29, P less than 0.05). This study suggests that in elderly patients sufentanil confers a greater residual analgesia than fentanyl in the immediate postoperative period.

The pharmacokinetics of droperidol in anesthetized patients.

A pharmacokinetic study of droperidol was performed in ten anesthetized patients receiving an intravenous bolus dose of 150 micrograms/kg of droperidol. Plasma concentrations were measured using a specific radioimmunoassay method. The pharmacokinetics of droperidol can be described according to a three-compartment open model. The mean (+/- SD) half-life for the rapid (t 1/2 pi) and slow distribution t 1/2 alpha) phases was 1.4 +/- 0.5 min and 14.3 +/- 6.5 min, respectively. The mean elimination half-life, t 1/2 beta was 103.8 +/- 20.2 min. The mean (+/- SD) total body clearance was 14.1 +/- 4.4 ml X min-1 X kg-1, and the total apparent volume of distribution (Vd beta) was 2.04 +/- 0.50 l/kg. The short terminal half-life of droperidol does not correlate with the well-known, relatively prolonged duration of its pharmacologic action.

Pharmacokinetics of phenoperidine in anaesthetized patients undergoing general surgery.

The pharmacokinetics of phenoperidine have been studied in five anaesthetized patients receiving a 2-mg bolus dose i.v. Plasma concentrations were measured using a sensitive radioimmunoassay method. The distribution of phenoperidine was described according to a two-compartment open model. The mean distribution half-life (T1/2 alpha) for the five patients was short (2.2 min); the mean elimination half-life (T1/2 beta) was 193 min. The mean whole body clearance was 22 ml min-1 kg-1 and the apparent steady state distribution volume (VSS) was 5.7 litre kg-1. Secondary concentration peaks occurred in all patients; in two patients these were substantial and occurred 80 min after injection.