Intravenous Infusions for Sedation: Rationale, State of the Art, and Future Trends

When sedation outside of the operating room is required, possible routes of administration of the agents include the inhalational, oral, intranasal, intramuscular, and intravenous routes. Although administration of low doses of volatile anesthetic agents by inhalation can provide adequate sedation (and analgesia if nitrous oxide is also used), this mode of sedative administration is often not feasible outside the operating room. With oral or enteral, transnasal, rectal, or intramuscular administration, the administered drug forms a depot that is absorbed slowly. Agents administered by the oral or enteral route are then subjected to significant first-pass metabolism. This problem is avoided with intramuscular injection, but this route is seldom used because it is painful. For all these routes, the rate at which the drug reaches the systemic circulation is highly variable, since it also depends on factors such as gastric emptying, peristalsis, local pH, other contents of the gut, cardiac output, and mucosal or muscular blood flow. The problems of variable absorption and first-pass effects are avoided by intravenous administration as the entire administered dose reaches the systemic circulation. There remains considerable inter-and intra-individual variability in the relationship between administered dose and the blood concentration profile achieved (i.e., pharmacokinetics), but this variability is far less than with other routes of administration.