Contributions of PK/PD modeling to intravenous anesthesia.

Pharmacokinetic (PK)/pharmacodynamic (PD) modeling has made an enormous contribution to intravenous anesthesia. PK/PD models have provided us with insight into the factors affecting the onset and offset of drug effect. For example, we are now able to describe the influence of cardiac output on the disposition of intravenous drugs within the first few minutes after administration of the drug. We are able to calculate intravenous loading doses that allow for the delay between the concentration of the drug in the plasma and the rising concentration at the site of drug effect. We are able to achieve and maintain a stable level of anesthetic effect using computerized infusion pumps that target the site of drug effect rather than the plasma. Importantly, on the basis of models of drug interaction and an understanding of how drug offset varies with duration of administration, we are now able to rationally combine hypnotics and opioids.