TCI: Target controlled infusion, or totally confused infusion? Call for an optimised population based pharmacokinetic model for propofol

Abstract

Different pharmacokinetic models for target controlled infusion (TCI) of propofol are available in the recently launched open TCI systems. There is also a compelling choice to work with either plasma- or effect-site targets. Knowledge about the clinical consequences of different alternatives is of importance. We aimed to illustrate the potential differences in the actual drug delivery/output between three present commercially available and clinically used pharmacokinetic models: the original Marsh model, which is also implemented in the Diprifusor®, the "modified Marsh-" and the Schnider models. Simulations were made in the TivaTrainer program (eurosiva.com). Firstly, our standard plasma target regimen was simulated, and secondly an effect-site target of 3.5 μg/mL was chosen. Thirdly, real infusors were used for measuring the time to reach defined predicted effect-site concentrations when aiming at a plasma target of 6 μg/mL. Identical patient characteristics were used in all simulations: male, 170 cm, 70 kg, 40 years of age. Resulting predicted effect-site peak concentrations, and used bolus doses were recorded, as were the resulting plasma over-shoot, and time frames. The plasma target regimen gave predicted effect-site peaks in the different models ranging from 3.6 to 7.2 μg/mL, reached after 2 3/4 to 4 minutes. To reach the same effect-site target, the three models used bolus doses ranging from 68 to 150 mg given during 22 to 46 seconds. The predicted plasma concentration over-shoots varied from 5.0 to 13.4 μg/mL. There were obvious differences between the models in the time taken to reach defined effect-site concentrations. We observed clinically significant different results between the models. The choice of model will make a difference for the patient. To eliminate confusion - not necessarily to improve precision - we call for an optimised population based pharmacokinetic model for propofol - a consensus model!