Pharmacokinetic concepts for TCI anaesthesia.

Abstract

The development of new short-acting anaesthetic drugs, improved drug assay techniques and the availability of reliable infusion systems opened the field of clinical pharmacokinetics and pharmacodynamics. The tri-exponential drug concentration decay complicates the definition of therapeutic dosage regiments and prevents straightforward prediction of recovery from drug effects. The context-sensitive half-time, the time required for drug blood concentration to decrease to half its value, provides a useful comparative predictor of drug concentration decline after infusion. The effect-site equilibration time contributes to the delay of drug effect and intensifies the disequilibrium between drug blood concentrations and obtained effect following incremental dosage. The rationale for drug infusion is reduction of fluctuating drug concentrations and drug effects. A variability similar to that observed with the use of inhalation agents, must be achieved by the choice of an appropriate pharmacokinetic model. The use of a target controlled infusion device, delivering proportional changes based on pharmacokinetic principles, allows titration of the concentration against clinical effect in individual patients.