• H Schwilden and J Schüttler.
• Klinik für Anästhesiologie, Universität Erlangen-Nürnberg, Krankenhausstr. 12, 91054, Erlangen, Germany. Schwilden@kfa.imed.uni-erlangen.de
• Handb Exp Pharmacol. 2008 Jan 1 (182): 425-50.

AbstractIt belongs to the particularities of anaesthesia that the conscious response of the patient to drug therapy is not available for the adjustment of drug therapy and that the side-effects of anaesthetic drug therapy would be in general lethal if no special measures were taken such as artificial ventilation. Both conditions do not allow for a slow, time-consuming titration of drug effect towards the therapeutically effective window, but measures have to be taken to reach a therapeutic target fast (within seconds to a few minutes), reliably, and with precision. Integrated pharmacokinetic-pharmacodynamic models have proved to be a useful mathematical framework to institute such drug delivery to patients. The theory of model-based interactive drug dosing on the basis of common pharmacokinetic-pharmacodynamic (pk-pd) models is outlined and the target-controlled infusion system (TCI) is presented as a new anaesthetic dosing technique that has developed during the last decade. Whereas TCI presents an open-loop dosing strategy (the past output does not influence the future input), current research deals with the model-based adaptive closed-loop administration of anaesthetics. In these systems the past output is used to adapt and individualize the initial pk-pd model to the patients and thus has an influence on future drug dosing which is based on the adapted model.

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