Abstract
Control of anesthesia requires the determination of quantities assessing the depth or adequacy of anesthesia. The well-known scheme of Guedel for assessing depth of ether anesthesia is not valid when applied to techniques using neuromuscular blocking agents, opiods and other intravenous anesthetic agents.
Pharmacokinetics and pharmacodynamivs constitute the clinical pharmacological framework within which the time course of i.v. anesthetic drug action in man has been investigated in the past. The common understanding is that virtually all i.v. anesthetics obey linear pharmacokinetics if used in the therapeutic range. Common to all anesthetic agents is their ability to induce EEG frequency slowing. Median EEG frequency has been used to quantitate such slowing. It is shown that median EEG frequency is concentration dependent and is a sigmoid function of drug concentration. In addition median EEG frequency correlates with clinical signs of anesthesia. The interval between 2-3Hz has been identified as that range which minimizes the probability of occurrence of signs of undue light or deep levels of anesthesia. On the basis of these findings i.v. drug delivery devices have been developed for the computer assisted titration of intravenous anesthesia using the pharmacokinetic model of the drug while EEG monitoring is suggested as a noninvasive approach to the therapeutic monitoring of anesthetic drug action.
In most recent times the combined use of computer assisted drug delivery and EEG monitoring was further developed to a closed-loop feedback control system for i.v. anesthetic drug delivery. Such system has been applied to the delivery of methohexitone and propofol in total intravenous anesthesia in volunteers and surgical patients as well as to anesthetic techniques using alfentanil and nitrous oxide. In clinical research such feedback systems allow for an efficient investigation of dose-effect relationships in that they inverse the common approach of such investigations. Instead of giving a dose and observing the emerging effects a feedback systems allows to fix a desired effect and to observe the dose necessary to obtain and maintain this action.
