• Mats Enlund.
• Dept of Anaesthesia & Intensive Care, and Centre for Clinical Research, Central Hospital, Västerås, Sweden. mats.enlund@ltv.se
• Ups. J. Med. Sci. 2008 Jan 1;113(2):161-70.

AbstractDifferent 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 microg/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 microg/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 microg/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 microg/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!

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