The recently introduced open-target-controlled infusion (TCI) systems can be programmed
with any pharmacokinetic model, and allow either plasma- or effect-site targeting.
With effect-site targeting the goal is to achieve a user-defined target effect-site
concentration as rapidly as possible, by manipulating the plasma concentration around
the target. Currently systems are pre-programmed with the Marsh and Schnider pharmacokinetic
models for propofol. The former is an adapted version of the Gepts model, in which
the rate constants are fixed, whereas compartment volumes and clearances are weight
proportional. The Schnider model was developed during combined pharmacokinetic-pharmacodynamic
modelling studies. It has fixed values for V1, V3, k(13), and k(31), adjusts V2, k(12),
and k(21) for age, and adjusts k(10) according to total weight, lean body mass (LBM),
and height. In plasma targeting mode, the small, fixed V1 results in very small initial
doses on starting the system or on increasing the target concentration in comparison
with the Marsh model. The Schnider model should thus always be used in effect-site
targeting mode, in which larger initial doses are administered, albeit still smaller
than for the Marsh model. Users of the Schnider model should be aware that in the
morbidly obese the LBM equation can generate paradoxical values resulting in excessive
increases in maintenance infusion rates. Finally, the two currently available open
TCI systems implement different methods of effect-site targeting for the Schnider
model, and in a small subset of patients the induction doses generated by the two
methods can differ significantly.