Intravenous anaesthesia: a step forward

Although the first recorded use of intravenous anaesthesia goes back more than 100 years, it was the introduction of Althesin and etomidate that lead to a resurgence of interest in its use. However, Althesin has been withdrawn completely and the use of etomidate has been restricted to single bolus dose administration (at least in the UK). Since the mid-1980s, propofol has become established as the most suitable agent currently available for maintenance of anaesthesia by intravenous technique. This is based not only on the superior quality of recovery that is associated with the use of this agent, along with a low incidence of postoperative nausea and vomiting, but also on its desirable pharmacokinetic profile 12345. The advantages of using intravenous anaesthesia employing propofol for maintenance have been demonstrated in several studies. These have shown, with a fair degree of consistency, the earlier recovery associated with the use of this method. The advantages are particularly apparent in surgery of short to intermediate duration 1, 6 but, even in surgery of longer duration, the use of intravenous anaesthesia has some advantages over inhalational anaesthesia, at least in the early postoperative period 3, 7. For some time after the introduction of propofol into intravenous anaesthesia, propofol was used on an empirical basis at doses of 6–12 mg.kg−1.h−1. It was only in the late 1980s that the widely used scheme of ‘ten-eight-six’ was described 8. In this scheme an initial bolus dose of propofol of 1 mg.kg−1 given over 20 s is followed by an infusion run at 10 mg.kg−1.h−1 for 10 min, followed by 8 mg.kg−1.h−1 for the next 10 min, and continued at 6 mg.kg−1.h−1 thereafter. This manual scheme was based on an earlier computer-controlled infusion study, based on the three-compartment pharmacokinetic model, designed to achieve a blood propofol concentration of 3–4 μg.ml−1 within 5 min and then maintain it at a constant level 9. This concentration of propofol was considered to be adequate for maintenance of surgical anaesthesia when supplemented with nitrous oxide and/or an opioid. Although satisfactory in maintaining constant propofol concentration at a particular level, the ‘ten-eight-six’ regimen suffers from some drawbacks. One of the main problems with its use arises when the depth of anaesthesia (translated into blood concentration of propofol) needs to be altered. If the depth of anaesthesia (or propofol concentration) needs to be increased, simply increasing the rate of infusion means that it will take some time before the new steady state concentration is achieved. One either has to run the infusion at a very high rate in the beginning followed by a slower rate, or a bolus dose of propofol would need to be given while increasing the rate of infusion at the same time. The size of this bolus dose may not be easy to judge and the process is inconvenient. Similarly, when the blood concentration needs to be lowered to decrease the depth of anaesthesia, one can stop the infusion but then one needs to remember to re-start it. The consideration of the shortcomings of these infusion schemes led to work starting at a number of academic centres, including the University of Glasgow, on the use of computer-controlled infusions of propofol and the concept of target controlled infusion (TCI) systems that would maintain the blood propofol concentrations at a desired (set) concentration 101112. Collaboration with Zeneca Pharmaceuticals ultimately resulted in the introduction of the ‘Diprifusor’ TCI system late in 1996. Experience with the use of TCI systems, including the ‘Diprifusor’ system, has clearly shown their advantages in terms of versatility and preference for their use by anaesthetists 131415. The anaesthetist using intravenous anaesthesia employing propofol now simply has to change the target concentration and the ‘Diprifusor’ system automatically adjusts the rate of propofol infusion to achieve the required blood concentration of propofol. The advantages are clearly seen when the anaesthetist wants to change the depth of anaesthesia, either in response to surgical stimulation or pre-empting a response to it. The pharmacokinetic variables built into the system ensure that the patient receives an appropriate bolus dose followed by an increased rate of infusion when the target concentration needs to be increased. The system also works well when the target concentration needs to be lowered; the pump stops infusing till the system predicts that the required blood concentration has been reached and then starts, once again, at a lower rate. The system makes the use of infusion anaesthesia by changing the target concentration analogous to that of inhalational anaesthesia where the concentration of the inhalational agent is changed. This clearly makes it much more convenient to administer intravenous anaesthesia using ‘Diprifusor’. This supplement of Anaesthesia, dealing with the theory and practice of using ‘Diprifusor’, also critically examines the safety features of the technology used 16. The use of ‘Diprifusor’ is also advantageous for induction of anaesthesia, which is achieved relatively slowly and smoothly without producing concentrations higher than those desired or set. Induction of anaesthesia is therefore achieved with a lower dose of propofol 15. This may result in greater haemodynamic stability at induction 17. The amount of propofol used during maintenance of anaesthesia, however, is somewhat greater than when using manually controlled infusions 13. Although useful, it is not essential to know the blood concentrations of propofol required for any particular type of surgery. The ‘target concentration’ can be altered easily once the system is running in response to the clinical signs of the depth of anaesthesia. The ‘Diprifusor’ system does not determine how much anaesthesia a patient needs. It is not a monitor of the depth of anaesthesia and control still rests with the anaesthetist, who should be using clinical signs or more sophisticated means of monitoring depth of anaesthesia. Clearly anaesthetists need to gain a lot more experience with the use of ‘Diprifusor’ but once experienced with the technique, anaesthetists find it makes the administration of intravenous anaesthesia much simpler and more versatile. The TCI pumps have undergone modifications since their introduction: the newer models show simulations of the ‘effect-site’ concentration and the time to awakening once the infusions are stopped. At this stage, ‘Diprifusor’ has been evaluated for anaesthesia only in adult and elderly patient populations. Its use is not recommended in children at present. In addition, the kinetic parameters on which the ‘Diprifusor’ system is based at the moment take into account only the weight of the patient. The ‘Diprifusor’ system may need modifications in future for use in children, and in patients with organ pathology. Careful titration of the target concentration setting will be required in such patients. Further studies will be necessary before the system can be recommended for use in children or for the provision of sedation with propofol. Nevertheless, at its present stage of development it is a significant step forward in the use of intravenous anaesthesia.