KEY POINTS

1. Anesthetic drugs are described by multicompartmental models. Accurate intravenous drug delivery requires adjusting the dose for drug accumulation in peripheral tissues.
2. The biophase is the site of anesthetic drug action. Initiation, maintenance, and titration of intravenous anesthetics must account for the delay in equilibration between plasma and the site of drug effect.
3. Some drug effects directly reflect the concentration of drug in the biophase (direct effect models). Other drug effects reflect the alteration of feedback systems by anesthetics (indirect effect models). The influence of opioids on ventilation reflects the dynamic influence of opioids on the feedback between ventilation and carbon dioxide and is thus an example of an indirect drug effect.
4. The target concentration in the effect site is the same as the target concentration in plasma at steady state. The target concentration is influenced by patient physiology, surgical stimulation, and concurrent drug administration. Typically, one must set a target concentration for the hypnotic (volatile anesthetic or propofol) and the analgesic (opioid) that properly accounts for the synergy between them.
5. To achieve a target effect concentration, the conventional teaching of administering a loading dose calculated as the target concentration times the volume of distribution, followed by a maintenance rate calculated as the target concentration times clearance, is inaccurate. The initial loading dose may be calculated as the target concentration times the volume of distribution at peak effect. Maintenance rates must initially account for distribution of drug in peripheral tissues and are only turned down to the target concentration times clearance after equilibration with peripheral tissues.
6. The terminal half-life says nothing about the clinical time course of drug concentration. Context-sensitive decrement times are the times for given decrements in drug concentration as a function of the infusion duration for an infusion that maintains a steady plasma concentration. Context-sensitive decrement times properly incorporate the multicompartmental behavior of intravenous anesthetics. The context-sensitive half-time is the time for a 50% decrement in concentration.
7. Alfentanil, fentanyl, sufentanil, remifentanil, propofol, thiopental, methohexital, etomidate, ketamine, and midazolam can all be given by intravenous infusion. Specific caveats, infusion rates, and titration guidelines are given in the text.
8. Target-controlled infusions use pharmacokinetic models to titrate intravenous anesthetics to specified plasma or effect-site drug concentrations. The Diprifusor is a propofol target-controlled infusion system that is available worldwide except in North America.
9. The utility of target-controlled infusions has been demonstrated in 20 years of research experience, well over 100 research publications, and over 8 years of clinical experience with the Diprifusor in millions of patients. Improved patient outcomes have been demonstrated with target-controlled drug delivery.
10. Closed-loop drug delivery systems have used the median EEG frequency, bispectral index, and auditory evoked potentials to control intravenous anesthetic delivery. These systems have generally performed well clinically but remain investigational.