Pharmacokinetic–pharmacodynamic modeling in anesthesia

Abstract

The so-called “anesthetic state” is a dynamic combination of hypnosis, amnesia, analgesia, neuromuscular and neurohumoral blockade. To achieve this state, different combinations of drug effects must be induced in the patient undergoing the surgical procedure under anesthesia. Patients are routinely and exhaustively monitored during anesthesia. This makes it easy to observe and quantify the effects of anesthetic drugs, and also to attempt to establish the relations between drugs administered, degree of effect and the factors that can influence this relation. Based on the above, important concepts like the “effect compartment model” have been developed. In this case, anesthesia has served clinical pharmacology to describe and validate the concept of the effect compartment. This relation works also in the other way. The effect compartment model has been routinely used to study the profile of different drugs used in anesthesia like opioids (fentanyl, alfentanil, sufentanil and remifentanil), hypnotics (propofol, barbiturates), benzodiazepines (diazepam, midazolam) and neuromuscular blocking agents (pancuronium, vecuronium, atracurium). Based on this approach, it has been possible to develop rational dosing guidelines according to the specific characteristics of the patient for most of the drugs used in anesthesia. More sophisticated modeling techniques, as well as improved designs of clinical trials, made possible to investigate the effect of covariate factors in the PK/PD model. Using this approach has allowed the study of how altered physiologic states as well as the presence of disease can affect the relation between drugs and effect in a particular patient. In addition, different models can be used to study more complex relations like the pharmacokinetics of inhaled anesthetics or the pharmacodynamics of intraspinally administered local anesthetics. The model has been recently described for the interaction between two or three different intravenous agents, enabling the clinician to assess how the use of another drug can influence the effect profile of a given one. Anesthesiology is a very safe medical specialty in terms of morbidity and mortality directly derived from the effect of drugs. The more we know about the relations between drugs, drug effects and the factors that can affect them, the best it will be for the patients. The application of quantitative modeling in pharmacokinetics and pharmacodynamics enables the clinician to use rationally the anesthetics and, hence, to provide more benefit to the patient undergoing anesthesia.