| 1. |
- Björkman, Sven, et al.
(författare)
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Ketamine and midazolam decrease cerebral blood flow and consequently their own rate of transport to the brain: an application of mass balance pharmacokinetics with a changing regional blood flow
- 1992
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Ingår i: Journal of Pharmacokinetics and Biopharmaceutics. - 0090-466X. ; 20:6, s. 637-652
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Tidskriftsartikel (refereegranskat)abstract
- Mass balance pharmacokinetics, with simultaneous blood sampling from an artery and the internal jugular vein, was used to characterize the cerebral uptake of ketamine, norketamine, and midazolam in normoventilated pigs. Intravenous injections of ketamine or midazolam decreased the cerebral blood flow (CBF) by one third, as measured by intermittent 133Xe washout. By means of pharmacodynamic models, the effects on the CBF could be predicted from the arterial drug concentrations. The high-resolution CBF vs. time curves thus generated allowed the calculation of cerebral drug levels from arterio-venous concentration gradients in spite of a continuously changing regional blood flow. By their effects on the CBF, ketamine and midazolam decrease their own rate of transport to the brain, the immediate 30-35% drops in CBF giving similar reductions in initial net influx of drug. Physiological pharmacokinetic models assuming a constant regional blood flow are therefore not appropriate. Under clinical conditions, the CBF is determined mainly by the effects of the anesthetics and by the arterial CO2 tension. CBF changes in either direction influence the transport of drugs to the brain and may consequently result in impaired or exaggerated drug effects.
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| 2. |
- Åkeson, Jonas, et al.
(författare)
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A porcine model for sequential assessments of cerebral haemodynamics and metabolism
- 1992
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Ingår i: Acta Anaesthesiologica Scandinavica. - 0001-5172. ; 36:5, s. 419-426
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Tidskriftsartikel (refereegranskat)abstract
- We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.
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| 3. |
- Åkeson, Jonas, et al.
(författare)
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Cerebral haemodynamic and metabolic effects of hypnotics and analgesics
- 1992
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Ingår i: Annales Francaise D'Anesthesie et de Reanimation. - 0750-7658. ; 11:6, s. 682-684
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Tidskriftsartikel (refereegranskat)abstract
- Abstract in French La sédation des patients neurochirurgicaux fait appel le plus souvent à une association hypnotique-analgésique. Leurs effets sur l'hémodynamique et le métabolisme cérébraux sont l'un des critères qui président au choix des produits. Les analgésiques utilisés seuls, ont peu d'effets sur le flux sanguin cérébral et la CMRO2. Certaines données de la littérature attribuent aux analgésiques une vasodilatation à la fois cérébrale et systémique, chez les patients atteints de lésions cérébrales expansives. Cette notion est controversée. Concernant la kétamine, plusieurs travaux récents proposent son utilisation à doses infra-anesthésiques en association avec le midazolam, sans élévation de la CMRO2. Le propofol et les benzodiazépines diminuent le flux sanguin cérébral et la CMRO2 de façon dose-dépendante. Les baisses excessives du flux sanguin cérébral rapportées dans la littérature seraient à rattacher à la potentialisation d'autres anesthésiques comme les halogénés ou le protoxyde d'azote. Les effets dépresseurs des barbituriques sur le flux sanguin cérébral et la CMRO2 sont bien connus. Les variations quelquefois observées dans la réponse aux barbituriques seraient en rapport, pour les auteurs, avec le maintien ou non de la réactivité vasomotrice cérébrale.
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