Another Look at Acute Tolerance to Thiopentone

Toner, W. T.; Howard, P. J.; Mcgowan, W.A.W.; Dundee, John W.

doi:10.1093/bja/52.10.1005

Cited by 31 publications

(5 citation statements)

References 2 publications

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“…Acute tolerance has been reported for other i.v. anaesthetics, including thiopentone [1] although this was questioned when pharmacodynamic modelling was applied by means of power spectral analysis of the EEG [6]. In both dogs and humans, greater infusion rates of propofol were associated with greater wakening blood concentrations of the drug [2,3].…”

Section: Commentmentioning

confidence: 99%

“…Development of tolerance to central nervous system depression has been reported for several anaesthetic agents [1]. Propofol has not been investigated for development of tolerance, except for the observations made in the course of two pharmacokinetic studies, one during continuous infusion of the drug in humans [2], the second during a bolus injection or a continuous infusion of propofol in dogs [3].…”

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confidence: 99%

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Does tolerance develop to the anaesthetic effects of propofol in rats?

Fassoulaki

Farinotti

Mantz

et al. 1994

British Journal of Anaesthesia

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We have studied the development of tolerance to the anaesthetic effects of propofol in rats. In the first set of experiments, three groups of rats (A, B and C) received i.v. propofol 10 mg kg-1, 15 mg kg-1 and 20 mg kg-1, respectively. The durations of anaesthesia were recorded, the rats were killed and blood was collected to measure the concentrations of propofol. In a second set of experiments, rats received propofol 10 mg kg-1 i.v. repeated 24 h (group D), 48 h (group E) or 72 h (group F) later. Sleeping times were recorded after the first and the second administration and concentrations of propofol at awakening were measured after the second dose, when rats were killed. Sleeping times were significantly longer in groups B (22.4 min) and C (25.9 min) compared with group A (13.7 min) (P < 0.001 for both). Durations of anaesthesia in groups D, E and F were 14.7, 14.5 and 14.3 min, respectively, after the first dose of propofol and 11.6, 12.1, and 14.9 min, respectively, after the second dose. The rats in groups D and E exhibited shorter sleeping times after the second dose of propofol than after the first (P < 0.01 for both). Concentrations of propofol at awakening did not differ between groups A, B and C or between groups D, E and F. The results suggest lack of changes in susceptibility of the CNS to the anaesthetic effects of propofol.

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Section: Commentmentioning

confidence: 99%

mentioning

confidence: 99%

Does tolerance develop to the anaesthetic effects of propofol in rats?

Fassoulaki

Farinotti

Mantz

et al. 1994

British Journal of Anaesthesia

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“…For example, Toner et al 2 observed that the plasma concentrations of thiopentone on recovery from anaesthesia increased with increasing dosage. However, blood samples were taken from an antecubital vein and the correlation between dosage and waking plasma concentrations may be due, at least in part, to sampling site.…”

Section: Discussionmentioning

confidence: 99%

The Influence of Sampling Site upon the Distribution Phase Kinetics of Thiopentone

Barrett

Graham

Torda

1984

Anaesth Intensive Care

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In six sheep anaesthetised with ketamine blood was sampled from the jugular and femoral veins and the femoral artery at frequent intervals for 12 minutes following the intravenous administration of 5 or 10 mg/kg sodium thiopentone. Samples were also taken from cubital veins and radial arteries of five patients who received 5 mg/kg thiopentone. The plasma concentration of thiopentone was determined by an HPLC assay. The time course of plasma concentration of thiopentone showed considerable variation according to sampling site as well as variation between individuals. Such sampling site-dependent variation may result in the appearance of acute tolerance.

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“…Tolerance to Thiopentone Reports from Brodie et al (1951), Dundee et al (1956), andToner et al (1980) first suggested the concept of acute tolerance in reporting that subjects receiving larger doses of thiopentone had higher plasma thiopentone concentrations at the time of awakening than did those receiving smaller doses. Hudson et al (1983b), however, were unable to demonstrate evidence of acute tolerance to thiopentone's EEG effects.…”

Section: Spectral Edge Analysismentioning

confidence: 99%

Intravenous Anaesthetic Agents

Swerdlow

Holley

1987

Clinical Pharmacokinetics

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The number and variety of intravenous anaesthetics available has increased dramatically in recent years. In order to administer these agents safely and rationally in the operating theatre, the anaesthesiologist needs to have a detailed understanding of their dose-response behaviour. The pharmacokinetic and pharmacodynamic profiles of these anaesthetics underlie this behaviour. In understanding and applying this information, an integrated approach involving combined pharmacokinetic and pharmacodynamic modelling has proved tremendously helpful. This approach has provided significant insight into the pharmacology of these drugs under conditions of normal and abnormal physiology. Intravenous anaesthetics may be classified as hypnotics, narcotics, or muscle relaxants. Through quantitative measures or drug effect, as provided by the electroencephalogram (EEG) in the former two classes or electromyography in the latter class, precise measures of end-organ (brain or neuromuscular junction) sensitivity have been generated using integrated modelling techniques. These values not only allow for dose potency comparisons within an anaesthetic class but, furthermore, may explain changes in drug response with ageing and disease. Incorporation within these models of an effect compartment, characterised by a rate constant for equilibration with plasma (keo), has proved to be essential in accurately describing the temporal lag between drug administration and effect. Quantitating the size of this lag has direct implications for the design of anaesthetic bolus and infusion regimens. Combined pharmacokinetic and pharmacodynamic modelling of intravenous anaesthetics provides a precise, rational basis for the clinical use of these classes of drugs.

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Another Look at Acute Tolerance to Thiopentone

Cited by 31 publications

References 2 publications

Does tolerance develop to the anaesthetic effects of propofol in rats?

Does tolerance develop to the anaesthetic effects of propofol in rats?

The Influence of Sampling Site upon the Distribution Phase Kinetics of Thiopentone

Intravenous Anaesthetic Agents

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