Thiopentalkinetik bei hochdosierter Anwendung

Taeger, K.; Murr, R.; Schmiedeck, P.; Jensen, U.; Peter., K.

doi:10.1055/s-2007-1002476

Cited by 6 publications

(4 citation statements)

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“…aureus (31), and arterial concentration 60-80 pg/ml after an induction dose of 4-5 mg/kg fat-free tissue (32), but the exposure time of granulocytes at these concentrations is less during induction with thiopental than the 60 min used in this study. However, during surgical thiopental anaesthesia plasma concentrations are 39-42 pg/ml with a longer exposure time (33) and during barbiturate treatment for cerehral protection thiopental concentrations may persist at 60-100 pg/ml for days (34,35). Our study suggests that some of the chemiluminescence depression found in the peripheral blood samples of anaesthetized patients may be due to thiopental exposure.…”

Section: Discussionmentioning

confidence: 64%

“…Our study suggests that some of the chemiluminescence depression found in the peripheral blood samples of anaesthetized patients may be due to thiopental exposure. 'The fact that 75-80% of plasma thiopental is protein bound, with free thiopental plasma levels of 5.9-6.3 pg/ml during surgical anaesthesia (33) or 9-12 pg/ml during cerebral protection (35) can be disregarded, since the test medium also contained human plasma. By contrast, it is not known whether the thiopental tissue concentrations are also so high at the site of infection or injury as to inhibit granulocyte chemiluminescence responses.…”

Section: Discussionmentioning

confidence: 99%

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Effects of thiopental on granulocyte oxidative microbicidal capacity

Salo

Perttilä

1989

Acta Anaesthesiol Scand

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Some anaesthetics are known to depress granulocyte chemiluminescence responses in the phagocytosis of zymosan as a measure of their oxidative microbicidal capacity. In this study the effects of thiopental were measured on chemiluminescence responses in the phagocytosis of Staphylococcus aureus and Escherichia coli, which are the commonest bacteria causing postoperative infections. Granulocytes from 14 healthy volunteers (mean age 35 +/- 9 (s.d.) years) were tested in vitro in the presence of clinical thiopental concentrations 0, 5, 10 and 25 micrograms/ml (0, 18, 36 and 91 mumol/l, respectively). During a 60-min exposure period, decreased chemiluminescence responses occurred to Staph. aureus at 5 micrograms/ml (P less than 0.01) and higher thiopental concentrations and to E. coli at 10 micrograms/ml (P less than 0.01) and higher concentrations, as a sign of depressed oxidative microbicidal activity.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Effects of thiopental on granulocyte oxidative microbicidal capacity

Salo

Perttilä

1989

Acta Anaesthesiol Scand

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“…On the other hand, when thiopental is used in high dosages for several days as a neurological therapeutic modality, its accumulation and elimination characteristics are not clearly defined and there have been only a very small number of relevant publications [18][19][20][21][22]. Thiopental is used in a very large range of dosages, and non-linear kinetics have been shown after therapeutic doses [20,22].…”

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confidence: 99%

Pharmacokinetics of thiopental after single and multiple intravenous doses in critical care patients

Russo

Brès²,

Duboin³

et al. 1995

Eur J Clin Pharmacol

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Thiopental was administered to neurosurgical patients for cerebral protection and its pharmacokinetic parameters were determined after a single bolus of 540, 1000 or 1500 mg (3 subjects) or after multiple doses of 250 mg (5 subjects) and 500 mg (2 subjects) every two hours for up to 7 days. The data were analysed by a two- or three-compartment model and linear kinetics. After a single iv bolus, the mean initial volume of distribution (V1) was 0.481 l.kg-1, and the steady-state volume of distribution (Vss) was 2.16 l.kg-1. The distribution (t1/2 alpha) and elimination (t1/2 beta) half-lives were 0.590 and 5.89 h, respectively, and the mean residence time (MRT) was 7.44 h. The clearance was 5.41 ml.min-1.kg-1. With repeated injections, the pharmacokinetic parameters for each patient were estimated taking into account all administered doses and blood samples, which were taken whenever possible daily at steady state and after the last dose. The variability observed in the pharmacokinetic parameters of thiopental reflected by the coefficient of variation (CV%) was wide but was of similar magnitude within patients (CVintra) as it was between patients (CVinter). The steady-state trough plasma concentration (Cmin obs) ranged from 4.8 to 30 mg.l-1 (mean 16.0 mg.l-1 and median 14.3 mg.l-1). Peak concentrations (Cmax obs) ranged from 8.35 to 45 mg.l-1 (25.4 mg.l-1, and median 23.3 mg.l-1). The values of V1 and Vss were similar to those obtained after a single dose. For V1, the mean was 0.333 l.kg-1. The mean Vss was 2.68 l.kg-1, with a CVintra of 12.6 to 56% and a CVinter of 13.2%. A shorter distribution half-life t1/2 alpha was noted on multiple dosing; the mean value was 0.122 h. The elimination half-life t1/2 beta and the mean residence time became longer due to a decrease in clearance. For t1/2 beta the mean value was 16.3 h. The mean MRT was 21.9 h, CVintra 9.19 to 48.5%, and the CVinter 35.3%. The mean clearance was 2.16 ml.min-1.kg-1, CVintra 7.28 to 25.5%, and the CVinter 20.4%. This value is 50% lower than after a single dose. Identification of the kinetic parameters of thiopental allows simulation of the effects of doses on subsequent plasma levels and will permit a priori prediction of day to day adjustment of drug dosage.

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“…Das Verfahren der Extraktion und Reinigung entspricht einer Modifikation der von Van Hamme (38) beschriebenen Methode. Details dieser Methode und die zur Berechnung der Plasmaproteinbinderate und der Plasmawasserkonzentration verwendeten Formeln finden sich in einer anderen Mitteilung(35). Der relative Säureanteil (S) an der Plasmawasserkonzentration wurde nach Reynolds (3 1) berechnet:…”

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