Direct high-performance liquid chromatography determination of propofol and its metabolite quinol with their glucuronide conjugates and preliminary pharmacokinetics in plasma and urine of man.

Propofol (P) is metabolized in humans by oxidation to 1,4-di-isopropylquinol (Q). P and Q are in turn conjugated with glucuronic acid to the respective glucuronides, propofol glucuronide (Pgluc), quinol-1-glucuronide (Q1G) and quinol-4-glucuronide (Q4G). Propofol and quinol with their glucuronide conjugates can be measured directly by gradient high-performance liquid chromatographic analysis without enzymic hydrolysis. The glucuronide conjugates were isolated by preparative HPLC from human urine samples. The glucuronides of P and Q were present in plasma and urine, P and Q were present in plasma, but not in urine. Quinol in plasma was present in the oxidised form, the quinone. Calibration curves of the respective glucuronides were constructed by enzymic deconjugation of isolated samples containing different concentrations of the glucuronides. The limit of quantitation of P and quinone in plasma are respectively 0.119 and 0.138 microg/ml. The limit of quantitation of the glucuronides in plasma are respectively: Pgluc 0.370 microg/ml, Q1G 1.02 microg/ml and Q4G 0.278 microg/ml. The corresponding values in urine are: Pgluc 0.264 microg/ml, Q1G 0.731 microg/ml and Q4G 0.199 microg/ml. A pharmacokinetic profile of P with its metabolites is shown, and some preliminary pharmacokinetic parameters of P and Q glucuronides are given.

The influence of the concentration of volatile anesthetics on the stapedius reflex determined intraoperatively during cochlear implantation in children.

OBJECTIVE: The goal of this study was, first, to determine the effect of the concentrations of volatile anesthetics (halothane and isoflurane) on the intraoperative elicited electrical stapedius reflex threshold (ESRT) and, second, to evaluate the relation between the ESRTs and postoperative C-levels. STUDY DESIGN: This was a prospective clinical study in a single subject design. SETTING: The study was conducted at University Hospital Nijmegen, which is a tertiary care and cochlear implant center in The Netherlands. PATIENTS: The study population comprised 13 deaf children (6 males and 7 females) undergoing cochlear implantation. RESULTS: In most of the children, increasing the concentration of volatile anesthetic agent resulted in higher stapedius reflex threshold. After correction for this effect, a good relation was found between ESRT and C-level in all children, except for one. CONCLUSIONS: The outcome of this study supports the determination of intraoperative ESRTs for programming of the speech processor postsurgery.

[Sluder's adenotonsillectomy: with or without endotracheal intubation?]. / Adenotonsillectomie volgens Sluder: met of zonder endotracheale intubatie?

OBJECTIVE: To assess differences in results and complications of adenotonsillectomy according to Sluder in children anaesthesized with or without endotracheal intubation. DESIGN: Retrospective descriptive study. SETTING: Ear, Nose and Throat department, Academic Hospital Nijmegen, the Netherlands. METHOD: The medical records were reviewed of 1011 children (511 non-intubated, before 1992, 500 intubated), and a questionnaire was sent to the parents regarding the postoperative period. RESULTS: The total proportion of postoperative haemorrhage was 4.35%; 5.1% in the non-intubated group, 3.6% in the intubated group (p > 0.05). In the intubated group there were more patients with postoperative fever (p < 0.01) but fewer with tonsillar remnants (p < 0.005). The procedure with intubation anesthesia took significantly more time (18 min versus 11 min). CONCLUSION: In a training situation the intubated procedure is advised because of available time. This does not apply to experienced specialists, who may even have fewer complications.

Anaesthesia for laparoscopy. A comparison of five techniques including propofol, etomidate, thiopentone and isoflurane.

This is a report about five anaesthetic techniques for laparoscopy. Propofol and etomidate were used for total intravenous anaesthesia. Propofol, etomidate and thiopentone were used as induction agents prior to inhalational anaesthesia with isoflurane and nitrous oxide. Fentanyl was used for analgesia. Induction with propofol and thiopentone was rapid. Etomidate induction was characterised by myoclonus. Maintenance was smooth with inhalational anaesthesia. Of the groups that received total intravenous anaesthesia, propofol provided stable anaesthesia but required extra bolus doses. Recovery was the most rapid following total intravenous anaesthesia with propofol. Postoperative side effects were much lower after propofol. No difference was observed between the groups with regard to changes in arterial blood pressure and heart rate.

Propofol emulsion for induction and maintenance of anaesthesia. A combined technique of general and regional anaesthesia.

To provide general anaesthesia with endotracheal intubation during regional blockades, three dose regimens of propofol emulsion were studied: induction 2 mg kg-1, infusion rate 9 mg kg-1 h-1 (Group 1); induction 2.5 mg kg-1, infusion rate 12 mg kg-1 h-1 (Group 2); induction 2.5 mg kg-1, infusion rate 9 mg kg-1 (Group 3). Each group comprised 10 healthy (ASA class 1 or 2) unpremedicated patients. The induction times measured from the start of injection until counting ceased (+/- 50 s) and until eye-lash reflex disappeared (+/- 80 s) showed no statistical differences between groups. In five patients in Group 1 and one patient in each of Groups 2 and 3 the induction dose was too low for intubation. Pain on injection was seen in 13 cases (mild 6, moderate 6 and severe 1). Cough accompanied by hypersalivation was the most important side-effect. Recovery times varied widely and showed no statistical differences. Answering simple questions was possible after 14 min in Group 1, 23 min in Group 2 and 19 min in Group 3. Apart from a short period of euphoria, recovery was uneventful. There was no tendency to fall asleep again. None of the combinations of induction doses and infusion rates provided good anaesthesia conditions for an acceptable number of patients.

Comparison of etomidate and propofol for anaesthesia in microlaryngeal surgery.

Propofol and etomidate were compared as hypnotics in total intravenous anaesthesia for microlaryngeal surgery combined with jet ventilation. Two groups of 15 patients were studied. In group 1, propofol 2.0 mg/kg was used for induction. For maintenance a continuous infusion of 12 mg/kg/hour was used for the first 10 minutes, followed by 9 mg/kg/hour for the next 10 minutes and 6 mg/kg/hour thereafter. In group 2, the induction dose of etomidate was 0.3 mg/kg followed by continuous infusion of 1.8 mg/kg/hour for 10 minutes, 1.5 mg/kg/hour for the next 10 minutes and 1.0 mg/kg/hour thereafter. Alfentanil was given for analgesia and suxamethonium for muscle relaxation. The propofol group showed better surgical conditions, more stable anaesthesia and better recovery according to the Steward score. Recovery times to opening eyes on command were comparable for both groups.

Lack of effects of emulsified propofol ('Diprivan') on vecuronium pharmacodynamics--preliminary results in man.

The possible interaction between vecuronium and propofol or thiopentone has been investigated. Cumulative dose response curves for vecuronium and the pharmacodynamic variables measured were similar with both anaesthetic agents. Patients were intubated following the topical application of lignocaine to the larynx and before the administration of vecuronium. A greater degree of relaxation of the vocal cords was noted in patients anaesthetized with propofol.

Propofol ('Diprivan') emulsion for total intravenous anaesthesia.

Propofol as an hypnotic in combination with fentanyl and vecuronium was used for total intravenous anaesthesia in 30 healthy unpremedicated patients undergoing elective surgery scheduled to last no longer than 1 h. Induction with propofol 2 mg/kg and fentanyl 1.875 micrograms/kg resulted in cessation of counting after 39 s and the loss of the eyelash reflex after 57 s. Mean recovery times, measured from the end of the infusion of propofol (9 mg/kg/h) and fentanyl (7.5 micrograms/kg/h) until eyes opened on command and questions answered correctly were 10.5 and 11.5 min, respectively. Trieger test, performed 3 h postoperatively, showed no difference in comparison with the preoperative score. During longer procedures there was evidence of accumulation in that propofol utilization rate decreased as the duration of anaesthesia increased. The results obtained are similar to those described with the previous Cremophor formulation although greater variability in induction and recovery times was noted with the emulsion formulation.