Pharmacological models and their use in clinical anaesthesia

Intravenous agents used in anaesthesia belong to a variety of chemical classes and cover a number of different pharmacodynamic responses. Compared to inhalational anaesthesia the combined administration of intravenous agents offers a greater degree of freedom because different pharmacodynamic effects can be controlled separately. This greater degree of freedom, however, requires a more detailed insight into the pharmacology of the drugs to allow control of drug administration and to meet the therapeutic optimum. This review considers the combination of pharmacokinetics and pharmacodynamics as a pharmacological model. The general principles of these two subunits relevant for dosing of intravenous agents are reviewed. In establishing a model of the non-linear system relating dosing to effect, pharmacokinetics introduces an intermediate step which describes the time course of drug concentrations as a function of dosing. It is thought that incorporating the entire dependence of the effect upon time is, in most cases, linear. Pharmacodynamics relate concentration to effect in a non-linear but time-independent manner. It embodies the entire non-linearity of the system, but is assumed to be a static relation. Special attention is given to those principles which apply to any intravenous agent irrespective of its particularities. The impact of distribution and elimination, hysteresis, and ceiling on the induction, maintenance and recovery of anaesthesia, and on improving anaesthesia techniques and drug delivery are considered.