There may be some anaesthetic situations where it is desirable or necessary to avoid the use of inhalational agents. These include concern about pollution of the local and global environment  and the possible effects of inhalational anaesthetics on patients . Total intravenous anaesthesia (TIVA) may be a more suitable option for some surgical procedures such as laryngoscopy, bronchoscopy or thoracic surgery . It is vital that volatile agents are avoided in patients who suffer from malignant hyperpyrexia and TIVA has been reported to be a safe alternative . Postoperative nausea and vomiting had been reported to occur less often after TIVA with propofol compared with volatile anaesthesia .
Propofol has a favourable pharmacokinetic profile for TIVA but the use of intravenous agents for maintenance of anaesthesia requires a different technique compared with the use of volatile anaesthetics delivered from calibrated vaporizers. Multi-step infusion regimens were designed to achieve and maintain indefinitely a certain target concentration in the blood. Stepped manual infusion regimens are simple but inflexible and do not allow drugs to be titrated in a controlled manner to respond to changing anaesthetic and surgical requirements. It is therefore not possible to manipulate the concentration of a drug in a predictable way during surgery  and volatile supplementation may be required to produce satisfactory anaesthesia .
The inflexibility of manual infusion systems and the complexity of the mathematics required for a flexible dosing regimen led to computers being used to control administration of anaesthetic drugs . The computer is programmed with the mathematical solution to the patient's pharmacokinetic model for propofol.  The model operates in real time to generate the infusion rates calculated to achieve and maintain the theoretical target blood concentrations selected by the anaesthetist.
The Diprifusor is a module that contains the pharmacokinetic model and is fitted inside infusion pumps to provide a simple and complete target-controlled infusion (TCI) system. The module contains two different microprocessors that run different software and obtain data from different sources. The outputs from the microprocessors are compared only when each microprocessor has calculated the target blood concentration of propofol. Together with the use of an identification system for propofol, the double processor design considerably enhances the safety of the TCI system.
This type of TCI system allows the anaesthetist to deliver drugs by titrating the predicted blood concentration instead of infusion rates against the response of the patient. The required infusion rates to achieve and maintain the predicted target values of blood concentration are calculated automatically by the microprocessor. In this manner the anaesthetist is able to deliver intravenous drugs with the same degree of control as with inhalational agents employing a vaporizer.
There is nearly always some uncertainty about the pharmacokinetics for any individual patient because of the problem of variable drug handling. It is unlikely that the pharmacokinetic variability can be reduced below a certain minimum level. However, in the clinical situation, the delivery device may not have to achieve the target drug concentration completely accurately since the pharmacodynamic variability of anaesthetic drugs may be several times greater than the variation between the pharmacokinetics of individual patients . In practice, the anaesthetist uses the target-controlled infusion device to achieve proportional changes based on pharmacokinetic principles and then titrates the target blood concentration to achieve the required clinical effect in each patient.
Questionnaire on anaesthetic practice
Thirty-one anaesthetists were supplied with TCI systems for evaluation and to record details concerning their practice of use . Twenty-seven of 30 replies to the questionnaire indicated that the system had changed their use of propofol for maintenance of anaesthesia. The main reasons were greater ease of use and more confidence regarding the predictability of anaesthetic effects compared with a manually controlled infusion. Data obtained from 770 patients anaesthetized with the system showed wide variations in the target concentrations selected and in the number of alterations in propofol concentration . This reflects the need for a flexible infusion system that can be used to titrate the level of anaesthesia for any individual patient against the level of surgical stimulation.
The variability of measured drug concentration compared with the predicted concentration has also been demonstrated for inhalational anaesthetics in that there is considerable variability of blood partial vapour pressures compared with end-tidal partial pressures, especially during periods when there is rapid change in the inspired vapour concentration . A similar degree of alteration in the doses administered during surgery has also been reported for intravenous and inhalational anaesthetics .
The recommended induction dose of propofol frequently reduces blood pressure by 25-35% compared with awake baseline values . In contrast, Chaudhri et al., using a target-controlled infusion of propofol to induce anaesthesia reported reductions of only 14-16% . Arndt et al. found equally minimal adverse cardiovascular effects , with decreases of 6-9% in blood pressure following induction with TCI propofol. Target-controlled anaesthesia may therefore allow more precise control of intravenous agents with benefit in difficult anaesthetic situations [17,18]. It is also evident that the requirements for propofol depend not only on the individual patient but also on the amount of premedication  and the quality of analgesia the patient has received .
Systems are being assessed to measure the level of anaesthesia [21,22]. Future developments include closed-loop systems that titrate the drug directly to the requirements of the patient. A closed-loop anaesthesia (CLAN) system has been developed to administer intravenous anaesthesia automatically in patients breathing spontaneously during surgery . The CLAN systems may not be generally available for clinical use, but demonstrate the reliability of systems for measuring the level of anaesthesia.
As with any new technique, there must be an obvious perceived benefit for the patient and the anaesthetist to consider the use of TCI. The increased requirement for day-case surgery highlights the need for rapid recovery of the patient with minimal postoperative nausea and vomiting. TIVA based on propofol appears to offer better quality of recovery in this respect compared with the use of inhalational agents. Target-controlled infusions offer similar ease of control to that which can be achieved by delivering volatile agents with calibrated vaporizers.
There is no single blood concentration of an anaesthetic agent that will result in satisfactory anaesthesia for all patients and all surgical conditions. It is necessary to titrate the concentration against the clinical response. Target-controlled systems provide the best estimate of the blood concentration of propofol and permit the required target concentration to be achieved as accurately and as rapidly as possible. The use of monitors of anaesthetic depth to provide reliable and automatic closed-loop administration of anaesthesia is a major technical development. However, the real value of such monitors may be that they provide a reliable guide to the effect achieved in individual patients. This is considerably more important for maintaining the correct level of anaesthesia than simply measuring the blood or end-tidal concentration of anaesthetic agents.
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Seventh International Symposium on Intravenous Anaesthesia, Lausanne, Switzerland, 2-3 May 1997
This publication is supported by grants from various pharmaceutical companies. The views in this publication are those of the authors and not necessarily those of supporting companies. Drugs and administration techniques referred to should only be used as recommended in the manufacturers' prescribing information.