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Pharmakokinetische/pharmakodynamische Modelle für Inhalationsanästhetika

Pharmacokinetic-pharmacodynamic models for inhaled anaesthetics

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Zusammenfassung

Pharmakokinetische Modelle können in physiologisch basierte und empirische Modelle unterschieden werden. Traditionell erfolgt die Beschreibung der Pharmakokinetik volatiler Anästhetika mithilfe physiologisch basierter Modelle unter Verwendung der jeweiligen Gewebe-Blut-Verteilungskoeffizienten. Die Kompartimente des empirischen Modells weisen kein anatomisches Korrelat auf, sondern sind durch das mathematische Verfahren der Parameterabschätzung entstanden. Die endexspiratorische Konzentration von volatilen Anästhetika entspricht nahezu der arteriellen Konzentration, daher kommt der Beschreibung des Übertritts zwischen Plasma und Wirkort für volatile Anästhetika eine zentrale Rolle zu. Der wichtigste Parameter ist hierbei der ke0-Wert; dieser ist eine zeitliche Konstante und beschreibt die zeitliche Verzögerung beim Übergang zwischen dem zentralen Kompartiment und dem berechneten Effektkompartiment. Die ke0-Werte für Sevofluran und Isofluran unterscheiden sich nicht; der Konzentrationsausgleich zwischen dem Zentral- und dem Effektkompartiment bei Desfluran hingegen erfolgt doppelt so schnell. In der klinischen Praxis werden volatile Anästhetika in der Regel mit N2O und/oder Opioiden kombiniert. Dabei ergibt sich eine additive Interaktion von volatilen Anästhetika und N2O. Die Interaktion zwischen volatilen Anästhetika und Opioiden ist hingegen synergistisch. Für die klinisch weit verbreitete Dreifachkombination von volatilen Anästhetika, N2O und Opioiden liegen hingegen kaum Interaktionsuntersuchungen vor.

Abstract

Pharmacokinetic models can be differentiated into two groups: physiological-based models and empirical models. Traditionally the pharmacokinetics of volatile anaesthetics are described using physiological-based models together with the respective tissue-blood distribution coefficients. The compartments of the empirical model have no anatomical equivalents and are merely the product of the mathematical procedure for parameter estimation. The end expiratory concentration of volatile anaesthetics is approximately equal to the arterial concentration and, therefore, the description of the transition between plasma and effect site for volatile anaesthetics plays a central role. The most important parameter here is the ke0 value which is a time constant and describes the time delay for the transition from the central compartment to the calculated effect compartment. The ke0 values for sevoflurane and isoflurane are the same but the concentration balance between the end-tidal concentration and the effect compartment occurs twice as quickly with desflurane. In clinical practice volatile anaesthetics are normally combined with N2O and/or opioids. This results in an additive interaction between volatile anaesthetics and N2O but a synergistic interaction of volatile anaesthetics with opioids. However, there are relatively few investigations on the interactions between the clinically widely used combination of volatile anaesthetics, N2O and opioids.

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  1. Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie, Universitätsklinikum des Saarlandes, 66421, Homburg/Saar, Deutschland

    S. Kreuer

  2. Department of Anaesthesiology, UMC St. Radboud, Nijmegen, Niederlande

    J. Bruhn

  3. Klinik für Anästhesiologie und operative Intensivmedizin, Klinikum St.-Marien-Hospital, Lünen, Deutschland

    W. Wilhelm

  4. Klinik und Poliklinik für Anästhesiologie, Inselspital, Bern, Schweiz

    T. Bouillon

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  1. S. Kreuer
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  2. J. Bruhn
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  3. W. Wilhelm
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  4. T. Bouillon
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Correspondence to S. Kreuer.

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Kreuer, S., Bruhn, J., Wilhelm, W. et al. Pharmakokinetische/pharmakodynamische Modelle für Inhalationsanästhetika. Anaesthesist 56, 538–556 (2007). https://doi.org/10.1007/s00101-007-1188-7

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  • DOI: https://doi.org/10.1007/s00101-007-1188-7

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