Targeting the effect site with intravenous anaesthetics:
what is the effect of plasma peak concentration limitation on time to target?
G van Poucke1, L J C Brandon Bravo2, F Marest3
Introduction:
Controlling the anaesthetic effect requires controlling the anaesthetic concentration at the effect site. To perform target controlled infusion the calculation of the effect site concentration of the anaesthetic using a PKPD model is needed. Based on these calculations the infusion rate is adjusted in such a way, that a pre-set target (CeT) of the effect site is reached in the shortest possible time (TCI-E). When using TCI-E it becomes apparent that very high initial plasma concentrations (Cpmax) are produced. Limiting these initial plasma concentrations without losing control over the effect site concentration is possible. However, at the cost of an increase in the time necessary to reach the target (ttt).
Our study goal was to investigate the effect of peak plasma concentration limiting on the efficiency of controlling the effect site in TCI-E with different anaesthetics.
Material and methods:
Peak plasma concentration limiting was expressed as a ratio (R) of the difference between Cpmax and the selected target concentration (CeT).
This concept of peak reduction was programmed in a computer algebra system (Maple V release 4, Waterloo Maple Inc.) and in an infusion program (“Multifusor" written in Visual Basic, Microsoft Inc), using different algorithms. There were only minor differences in the results for the calculations of ttt at 25, 50 and 75% peak reduction between the algorithms used in “Multifusor” and the Maple program. Subsequently Maple output for ttt at 20 different levels of peak reduction (ranging from 0 to 95%) for five different anaesthetics (propofol, alfentanil, fentanyl, remifentanil and sufentanil) was compared.
Results:
The results for ttt for remifentanil, propofol, alfentanil, fentanyl and sufentanil are almost similar: up to 60 – 70% peak reduction ttt increases only marginally.
Summary and conclusion:
In summary we have shown that effect site targeting without extreme initial plasma concentrations is possible. Interesting is that peak reduction has hardly any effect on the efficacy to control the effect site as indicated by ttt: from zero up to 60 – 70% of peak reduction the ttt does not increase significantly.
1 Anaesthesiologist, Department of anaesthesiology, Ziekenhuis Zeeuws-Vlaanderen, Terneuzen, The Netherlands.
2 Anaesthesiologist, Department of
anaesthesiology, Ziekenhuis Walcheren, Vlissingen, The Netherlands.
3 Process engineer, Alcaltel, Belgium.