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J B Glen

Publications and source records attributed to J B Glen.

At least 19 recordsLinked to original sources
PubMed1998

Evaluation of the predictive performance of a 'Diprifusor' TCI system.

The predictive performance of a 'Diprifusor' target controlled infusion system for propofol was examined in 46 patients undergoing major surgery, divided into three age groups (18-40, 41-55 and 56-80 years). Measured arterial propofol concentrations were compared with values calculated (predicted) by the target controlled infusion system. Performance indices (median performance error and median absolute performance error) were similar in the three age groups, with study medians of 16.2% and 24.1%, respectively. Mean values for 'divergence' and 'wobble' were -7.6%.h-1 and 21.9%, respectively. Measured concentrations tended to be higher than calculated concentrations, particularly following induction or an increase in target concentration. The mean (SD) propofol target concentration of 3.5 (0.7) micrograms.ml-1 during maintenance was lower in older patients, compared with higher target concentrations of 4.2 (0.6) and 4.3 (0.7) micrograms.ml-1 in the two younger age groups, respectively. The control of depth of anaesthesia was good in all patients and the predictive performance of the 'Diprifusor' target controlled infusion system was considered acceptable for clinical purposes.

Adolescent↗
PubMed1998

The development of 'Diprifusor': a TCI system for propofol.

The 'Diprifusor' target controlled infusion system has been developed as a standardised infusion system for the administration of propofol by target controlled infusion. A preferred set of pharmacokinetic parameters for propofol was selected using computer simulation of a known infusion scheme with pharmacokinetic parameters described in published literature. The selected model was included in a 'Diprifusor' module that was interfaced with, and later incorporated into, a computer-compatible infusion pump. Clinical trials with such systems led to guidance on appropriate target concentrations for the administration of propofol by 'Diprifusor' target controlled infusion for inclusion in drug prescribing information. Standardisation of the delivery performance (+/- 5%) of commercial systems has been achieved with a laboratory performance specification. Clinical studies indicate that the actual blood concentrations achieved were about 16% greater than the calculated values displayed by the system. In an individual patient, titration of the target concentration is required in the same manner as an anaesthetic vapouriser is adjusted to obtain a specific pharmacodynamic effect.

Anesthesia, Intravenous↗
PubMed1996

Administration of propofol by target-controlled infusion in patients undergoing coronary artery surgery.

OBJECTIVES: To study the predictive performance of a target-controlled infusion (TCI) system of propofol in patients undergoing coronary bypass graft (CABG) surgery, using a referenced pharmacokinetic set derived from healthy patients. Also, to determine the propofol concentrations required for clinically acceptable induction and maintenance of anesthesia when combined with midazolam as premedication and a continuous alfentanil infusion and to study the hemodynamic stability of this technique. DESIGN: Prospective noncomparative study analysis. SETTING: Operating room at a university hospital. PARTICIPANTS: Twenty-on patients with good left ventricular function undergoing coronary artery surgery. INTERVENTIONS: Patients were anesthetized using a continuous infusion of alfentanil (mean infusion rate: 1 microgram/kg/min) and propofol administered by TCI. MEASUREMENTS AND MAIN RESULTS: The predictive performance of the TCI system (212 arterial samples) was measured at specified time points before, during, and after bypass. The TCI system underestimated the measured blood propofol concentrations with a bias of +21.2% and +9.6% during the prebypass and the bypass periods, respectively. The predictive inaccuracy, expressed by the median absolute prediction error, was 23% and 18.5%, respectively. Mean target propofol concentrations required to induce and maintain anesthesia before bypass were 0.92 microgram/mL and 3.64 micrograms/mL, respectively. In the period during and after bypass, the mean target concentrations required to maintain anesthesia was 2.22 micrograms/mL. The administration of propofol by TCI was still associated with some short episodes of hemodynamic instability that were easily controlled by adjusting the target concentration in the majority of the patients. Therefore, the overall quality and ease of control of anesthesia were considered as being good or adequate. CONCLUSIONS: In this group of patients undergoing CABG surgery, the TCI system used underestimated the measured propofol concentrations. However, the predictive performance of the selected mean pharmacokinetic parameters derived from healthy patients was acceptable during the whole surgical procedure.

Adult↗
PubMed1996

Total intravenous anaesthesia with propofol or inhalational anaesthesia with isoflurane for major abdominal surgery. Recovery characteristics and postoperative oxygenation--an international multicentre study.

Two hundred and ten adult patients undergoing open cholecystectomy, vagotomy or gastrectomy were included in a randomised multicentre study to compare postoperative nausea and vomiting, oxygen saturations for the first three postoperative nights, time to return of gastrointestinal function, mobilisation, and discharge from the hospital following induction and maintenance of anaesthesia with propofol and alfentanil or with thiopentone, nitrous oxide, isoflurane and alfentanil. Recovery from anaesthesia was significantly faster in the propofol group (mean (SD) times to eye opening and giving correct date of birth of 14.0 (SD 13.8) and 25.5 (SD 29.5) minutes, and 18.5 (SD 14.8) and 35.5 (SD 37.2) minutes in the propofol and isoflurane groups respectively). There was significantly less nausea in the propofol group (15.4%) than in the isoflurane group (33.7%) in the first two postoperative hours (p < 0.003) but not thereafter. There were no significant differences between the groups in any other recovery characteristics. The incidence of hypoxaemia (arterial oxygen saturation less than 93%) was close to 70% in both groups for the first three postoperative nights, indicating the need for oxygen therapy after major abdominal surgery.

Adult↗
PubMed1995

Propofol administered by a manual infusion regimen.

We have evaluated the clinical utility and blood propofol concentrations produced with two different infusion regimens for propofol, given to supplement 67% nitrous oxide-morphine anaesthesia. Patients received a standardized three-step infusion of propofol based either on body weight (weight-corrected group) or on a mean body weight of 70 kg (standard dose group). Both groups showed similar cardiovascular stability and recovery times. In the 48 patients studied, isoflurane was used as a supplement in nine (two in the weight-corrected group). Apparent steady state blood propofol concentrations were 3.41 (SD 0.69) micrograms ml-1 in the weight-corrected group and 3.46 (0.79) microgram ml-1 in the standard dose group. These results suggest that for patients weighing 60-90 kg body weight, a standard dose infusion regimen may be a suitable starting point. In routine clinical practice, the need for isoflurane supplementation may be avoided by subsequent titration of the infusion rate according to clinical response. Computer simulation of the actual infusion rates used in each patient has allowed retrospective comparison of the predictive performance of different pharmacokinetic descriptors for propofol. The variables described by Tackley and colleagues provided a more accurate prediction of the measured blood propofol concentration than did the variable set reported by Gepts and colleagues.

Adolescent↗
PubMed1995

Manual compared with target-controlled infusion of propofol.

We studied 160 ASA I-II patients, anaesthetized with propofol by infusion, using either a manually controlled or target-controlled infusion system. Patients were anaesthetized by eight consultant anaesthetists who had little or no previous experience of the use of propofol by infusion. In addition to propofol, patients received temazepam premedication, a single dose of fentanyl and 67% nitrous oxide in oxygen. Each consultant anaesthetized 10 patients in sequential fashion with each system. Use of the target-controlled infusion resulted in more rapid induction of anaesthesia and allowed earlier insertion of a laryngeal mask airway. There was a tendency towards less movement in response to the initial surgical stimulus and significantly less movement during the remainder of surgery. Significantly more propofol was administered during both induction and maintenance of anaesthesia with the target-controlled system. This was associated with significantly increased end-tidal carbon dioxide measurements during the middle period of maintenance only, but recovery from anaesthesia was not significantly prolonged in the target-controlled group. With the exception of a clinically insignificant difference in heart rate, haemodynamic variables were similar in the two groups. Six of the eight anaesthetists found the target-controlled system easier to use, and seven would use the target-controlled system in preference to a manually controlled infusion. Anaesthetists without prior experience of propofol infusion anaesthesia quickly became familiar with both manual and target-controlled techniques, and expressed a clear preference for the target-controlled system.

Adolescent↗
PubMed1995

Pharmacokinetic model selection for target controlled infusions of propofol. Assessment of three parameter sets.

BACKGROUND: Computer-assisted target controlled infusions (TCI) result in prediction errors that are influenced by pharmacokinetic variability among and within patients. It is uncertain whether the selection of a propofol pharmacokinetic parameter set significantly influences drug concentrations and clinical acceptability. METHODS: Thirty patients received similar propofol TCI regimens after being randomly allocated to one of three parameter sets. Arterial and venous concentrations were measured and prediction errors calculated from pooled and intrasubject data. RESULTS: Arterial propofol concentrations in the Dyck group revealed greater bias (mean 43%) than did those in the Marsh (-1%) and Tackley (-3%) groups. The Dyck group also showed greater inaccuracy (mean:47%) than the Marsh (29%) and Tackley (24%) groups. There was little tendency for measured concentrations to vary from targeted values over time (divergence). Variability about an observed mean in individual patients (wobble) was low. Venous propofol concentrations were initially much less than arterial concentrations, but this difference decreased over time. CONCLUSIONS: Although it may be preferable to administer propofol TCI by using a locally derived parameter set, it is acceptable to use a model from elsewhere. The Marsh and Tackley models produced equally good performance and are appropriate for propofol TCI within the range of 3-6 micrograms/ml. The Dyck model was less accurate at maintaining anesthetic concentrations, possibly because it was derived from low concentrations. Concentrations in blood, the most sensitive indicators of performance, demonstrated differences among the parameter sets. Clinically, TCI worked well, and by clinical criteria, the choice of pharmacokinetic model did not appear to make a difference.

Adult↗
PubMed1992

Pharmacodynamic stability of a mixture of propofol and alfentanil.

We studied 40 patients undergoing body surface surgery in a double-blind manner to compare the pharmacodynamic stability of either mixed or separate infusions of propofol and alfentanil. No differences were found between the two groups in respiratory or cardiovascular variables during operation, or in requirements for analgesia after operation. The power of the study to determine a difference of 10 mm Hg in mean arterial pressure with a probability of 0.05 was 0.82 and for a difference of 1 kPa in end-tidal carbon dioxide partial pressure 0.89. We conclude that propofol and alfentanil may be administered by infusion from a single syringe without diminished or delayed effect of the opioid during anaesthesia and the first 4 h after operation.

Adult↗
PubMed1992

Effect of graded infusion rates of propofol on regional and global left ventricular function in the dog.

We have studied the effects of graded infusion rates of propofol (0.2-0.5 mg kg-1 min-1) on left ventricular global and regional function, in eight acutely instrumented dogs. Global function was assessed by measurement of aortic and left ventricular pressure, LV dP/dtmax, aortic blood acceleration and stroke volume. Regional function was assessed by measurement of systolic shortening and the end-systolic pressure-length relationship. The response of the coronary circulation to short periods of occlusion was also assessed. Administration of propofol significantly reduced left ventricular preload, as indicated by reductions in end-diastolic pressure and length; contractility was depressed, the depression being greater in the apex than in the base of the left ventricle. High infusion rates impaired relaxation. Regulation of coronary blood flow was not disrupted. Reductions in preload and contractility contributed to the propofol-induced hypotension. After 60 min, recovery from the greatest infusion rate was incomplete.

Animals↗
PubMed1992

Disposition and pharmacology of propofol glucuronide administered intravenously to animals.

1. Propofol glucuronide (PG) is the major human metabolite of the i.v. anaesthetic propofol, 2,6-diisopropylphenol. 2. Bolus i.v. doses of 14C-PG (1 mg/kg) to rat and dog were eliminated in urine (40 and 66% respectively) and faeces (48 and 19%); 25 and 48% of the dose were excreted unchanged in urine. 3. In dog, PG was distributed from plasma (t 1/2 4 min) into a volume equivalent to extracellular water and eliminated with t 1/2 80 min. Total body clearance was 1.8 ml/min per kg, and renal clearance about 20% GFR. In rat, plasma 14C concentrations were about one-tenth those in dog, thus PG levels were not quantified. 4. Propofol was not detected in the plasma showing that PG is hydrolytically stable. Enterohepatic circulation of PG occurred in rat and to a lesser extent in dog. Metabolites, mainly side-chain hydroxylation products, were evident in both species from 4 h after dosing. 5. Bolus i.v. doses of PG (200 mg/kg) showed no hypnotic activity in mice.

Animals↗
PubMed1985

Interaction studies and other investigations of the pharmacology of propofol ('Diprivan').

The anaesthetic properties of propofol ('Diprivan') have been described previously. This report summarizes additional studies designed to investigate some aspects of the general pharmacology of propofol. Following recovery from anaesthesia with propofol there was no evidence of any central anticholinergic or anticonvulsant effect in mice. An anti-convulsant effect followed thiopentone anaesthesia. In mice anaesthetized with propofol 24 h after the last of 4 daily doses of phenelzine, amitriptyline, diazepam or alcohol, no marked potentiation of anaesthesia was found. Pretreatment with alcohol on the day of anaesthesia potentiated thiopentone but not propofol anaesthesia. Oral doses of propofol up to 300 mg/kg failed to induce anaesthesia in mice. The acute administration of the beta-adrenoceptor antagonists, atenolol or propranolol was well tolerated during anaesthesia with propofol in pigs. In the cat the arrhythmia threshold to adrenaline was greater than that in cats anaesthetized with halothane and no ganglion blocking or alpha-adrenoceptor antagonist properties were demonstrated. No potent or specific agonist or antagonist properties were detected in the range of in vitro systems examined. Neither propofol nor thiopentone had any effect on ADP-induced platelet aggregation or whole blood clotting time. Bronchomotor tone and gastrointestinal motility were unaffected by propofol. Tests of renal function indicated only a slight reduction in sodium excretion, similar to that seen with thiopentone. A normal corticosterone response to ACTH was seen in rats anaesthetized for 90 min with an infusion of propofol.

Adrenergic beta-Antagonists↗
PubMed1985

Effects of propofol ('Diprivan') on histamine release, immunoglobulin levels and activation of complement in healthy volunteers.

This randomized study compared the effects of the emulsion formulation of propofol with those of the Cremophor-containing agent Althesin. Plasma histamine concentration, immunoglobulin levels, total complement C3 and complement C3 conversion were measured prior to and following induction of anaesthesia in 32 male volunteers with either 2 mg/kg propofol or 0.05 ml/kg Althesin. In only one volunteer, in the Althesin group, was an increase in plasma histamine to a value greater than 1 ng/ml associated with a relatively large increase over the base line value. Cutaneous signs, such as flushing, did not correlate with the plasma concentrations of histamine. No changes consistent with a propensity to produce anaphylactoid reactions could be seen from measurements of immunoglobulin levels, complement C3 or plasma histamine concentration in the propofol treated subjects.

Adolescent↗
PubMed1984

Pharmacology of an emulsion formulation of ICI 35 868.

Studies with an emulsion formulation of ICI 35 868 (2,6- diisopropylphenol ) indicate that this new formulation has anaesthetic properties in rats and mice, and haemodynamic effects in the mini-pig which are similar to those of the previously available Cremophor formulation. Administration of the emulsion formulation to dogs produced no untoward effect, whereas the Cremophor formulation produced a marked increase in plasma histamine concentration. In the mini-pig, no adverse response was produced by the repeated administration of the emulsion formulation of ICI 35 868, whereas the Cremophor formulation produced anaphylactoid responses when a second injection was given 1 week after an uneventful first exposure to this formulation. Behavioural responses in the rat suggest that the emulsion formulation may produce less discomfort on i.v. injection.

Anaphylaxis↗
PubMed1980

Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents.

Following our discovery of the intravenous (iv) anesthetic activity of 2,6-diethylphenol in mice, a series of alkylphenols was examined in this species and the most active analogues were further evaluated in rabbits. The synthesis of compounds which were not commercially available was accomplished by adaptations of standard ortho-alkylation procedures for phenols. Structure-activity relationships were found to be complex, but, in general, potency and kinetics appeared to be a function of both the lipophilic character and the degree of steric hindrance exerted by ortho substituents. The most interesting compounds were found in the 2,6-dialkyl series, and the greatest potency was associated with 2,6-di-sec-alkyl substitution. In particular, 2,6-diisopropylphenol (ICI 35 868) emerged as a candidate for further development and has subsequently been shown to be an effective iv anesthetic agent in man.

Anesthesia, Intravenous↗