26 - Intravenous Drug Delivery Systems

Abstract

Intravenous induction and maintenance of anesthesia is common practice. During anesthesia, stable concentrations of the hypnotic and opioid drugs are desirable and can be achieved by taking into account the pharmacokinetic processes that influence drug concentrations, and the pharmacodynamic factors that determine the clinical effect. The pharmacokinetics of most anesthetic drugs have been described by two or three compartment models. Recently, general purpose models have been developed for propofol and remifentanil, using data from a large number of studies involving a wide variety of patient characteristics. Target-controlled infusion (TCI) systems are drug delivery systems that aim to facilitate accurate drug administration. In plasma targeting mode they use pharmacokinetic models to determine and implement the intravenous anesthetic drug administration rates required to achieve user-specified plasma concentrations. In effect-site targeting mode they use combined pharmacokinetic-pharmacodynamic models to achieve desired effect-site concentrations. TCI systems are commercially available in most of the world except the United States, and are used extensively to administer hypnotics and opioids. Drug requirements are influenced by concurrent drug administration. Response surface modeling has facilitated much of this progress. Display systems have been developed to provide anesthesiologists with real-time information to help them to individualize hypnotic and analgesic drug administration to properly take account of the synergy between coadministered drugs. The availability of electroencephalographic-based measures of clinical effect has facilitated the development of closed-loop anesthesia delivery systems, capable of automatically controlling infusions of one or more drugs. Studies have shown that these systems can provide more stable and accurate anesthesia than human anesthesiologists. Further investigations are required to demonstrate the outcome benefits to patients.