Anesthesia: A Discipline That Incorporates Clinical Pharmacology Across the DDRU Continuum

Abstract

he dawn of the modern discipline of anesthesia can be traced to 16 October 1846, when William Morton administered ether to a patient who was undergoing surgical removal of a vascular malformation. The event took place in the surgical amphitheater in the Bullfinch Building of Massachusetts General Hospital, now known as the Ether Dome, and was memorialized by Robert C. Hinckley in a painting that is reproduced on the cover of this issue. Although Crawford Long first administered ether as a general anesthetic in 1842, this operation was not recorded, so official credit went to Morton. By today’s evidentiary standards, Morton’s experiment lacked the statistical safeguards of placebo control, double-blinding, and randomization, but the crowd shown in Hinckley’s painting certainly documents substantial peer review.Subsequent to this demonstration, anesthesia developed slowly as a medical discipline—the American Board of Anesthesiology not being founded until 1937—but it can be argued that anesthesia today stands out as the major primary medical specialty that routinely incorporates clinical pharmacology principles in patient care. In turn, scientists trained in anesthesia or working with compounds used in anesthesia have made major contributions to clinical pharmacology across the entire continuum of drug discovery, development, regulation, and utilization (DDRU). Most notable have been major contributions in the areas of physiological pharmacokinetics, pharmacokinetic–pharmacodynamic (PK-PD) modeling, and pharmacogenetics.