The effect of altered physiological states on intravenous anesthetics

This chapter begins with the rationale for the intense interest in how altered physiologic states change the effect seen following administration of similar doses of intravenous anesthetic drugs. It then traces the development of two types of pharmacokinetic models that have been used to understand the relationship between pharmacokinetics and cardiovascular physiology. Physiologic pharmacokinetic models are constructed from detailed knowledge of tissue blood flow, tissue weight, and blood: tissue partitioning characteristics. The invasive methods involved are often destructive of the subjects being studied. Rodent models are developed and scaled to simulate human subjects under a variety of physiologic conditions. Traditional pharmacokinetic models, based on drug concentration versus time data from easily obtained blood samples, can also be plumbed for physiologic information. Whereas the physiologic estimates obtained are less detailed than those from physiologic models, they do represent the actual pharmacokinetics for the subjects studied and give sufficient physiological detail to delineate the basis for the changed pharmacokinetics of intravenous pharmacokinetics.