Advances in the Clinical Pharmacology of Intravenous Anesthetics

279 Page 1 Figure 1. A surfing analogy as a graphical explanation of how anesthesiologists use a combination of three approaches to administer anesthetics to maintain the anesthetic effect while making rapid recovery possible. Anesthesiologists target the upper portion of the " steep " part of the concentration-effect relationship so that small decreases in concentration translate into large decrements in drug effect at the end of the anesthetic; this can be visualized as a surfer riding the crest of a wave (see text for complete explanation); from Egan and Shafer. 1 Over the last several decades we have witnessed dramatic advances in the scientific underpinnings of intravenous anesthesia. Having been rapidly translated into the clinical domain, the ultimate result of these advances is that total intravenous anesthesia (TIVA), once an impractical fantasy, is now an appealing, workable alternative to the traditional practice of inhalation anesthesia. This refresher course summary is intended to provide a broad overview of recent advances in the scientific foundation of intravenous anesthetic pharmacology. Drawing upon a " surfing " analogy as a theoretical framework, we will briefly review advances in pharmacokinetics and pharmacodynamics, developments in pharmaceutics such as designer drugs, and improvements in intravenous drug delivery technology. THE " SURFING ANALOGY " IN ANESTHESIA DRUG SELECTION AND ADMINISTRATION Anesthesia and reanimation necessitate a standard of precision and accuracy in drug administration not required in most areas of clinical medicine. Anesthetists profoundly depress the central nervous system to maintain the anesthetized state but then must rapidly reanimate the patient after the operation is complete. Although empirically over-dosing every patient is one approach to assuring the patient is adequately anesthetized, it comes at the cost of slow emergence from anesthesia and hemodynamic depression, among others. Anesthetists must therefore target drug levels that are within a relatively narrow therapeutic window to achieve the competing clinical imperatives of adequate anesthesia (without toxicity) and rapid emergence. This " on-off " imperative is unique to anesthesia pharmacology. A surfing analogy is helpful in conceptualizing the approaches that can be applied to the problem of rational drug administration in anesthesia. 1 The anesthesiologist typically targets the upper portion of the steep part of the concentration-effect relationship; that is, the anesthesiologist targets a concentration that produces considerable drug effect but from which drug effect will recover quickly once drug administration is terminated. This can be visualized as a surfer riding near the crest of …