23.2 TCI propofol Flashcards
An adult patient is to receive a target controlled infusion (TCI) of propofol.
a) Detail how TCI devices ensure a steady-state blood concentration. (50%)
> > TCI devices and programmes rely on the concept
of a three compartmental model of the way in which a specific drug behaves within the body.
> > V1, the central compartment,
is the plasma into which the drug is injected
and any tissues that behave like plasma in
respect to that particular drug.
To achieve a particular drug concentration rapidly,
a bolus is given that is equal to the desired concentration multiplied by this volume of distribution (Cp × V1).
> > Drug leaves this central compartment
down its concentration gradient
initially to vessel-rich tissues (V2)
and then to tissues with
poorer blood supplies (V3).
There are therefore two superimposed
reducing infusion rates that
allow for this loss from the central compartment.
> > Once equilibrium has occurred
between all three compartments, the only
loss of drug from the central compartment is via
**metabolism (to inactive metabolites)
and
elimination from the body.
The final steady-state infusion
rate therefore matches this removal rate.
> > The sizes of the different compartments
and the rate constants between
them depend upon the model and drug being used.
The size of the compartments,
according to these models,
depends on certain patient
characteristics such as height,
weight and age, which will require
inputting into the administration
device being used.
> > In summary,
a steady-state blood concentration
is achieved by a bolus dose followed by three superimposed infusion rates,
two that exponentially reduce and
one that is constant to match elimination.
b) What additional pharmacokinetic data is required to allow effect-site targeting? (20%)*****
> > Targeting the effect-site concentration
aims to eliminate the hysteresis
observed between plasma concentration
and actual drug effect that takes place in the brain.
> > The effect-site compartment volume
is negligibly small and so the rate
constant determining movement of
drug to effect site (Keo) is one way
only, from plasma to effect site,
unlike the rate constants determining
movement between other compartments.
Keo is not known and must be
determined through experiment.
> > Peak drug effect will occur when the
curve of the declining plasma
concentration of the drug after
bolus injection crosses the curve of the
rising effect-site concentration.
Different, hypothetical, Keo values are
used to plot effect-site concentration curves, and the one that results in a concentration matching plasma concentration at peak observed drug
effect is then determined as the actual Keo.
c) What are the advantages of a TCI device compared to a manual propofol infusion regime? (30%)
> > Bolus dose and infusion rate
determined by computer model based on
patient and drug characteristics, not guess-work.
> > Theoretically, can achieve steady state
more rapidly.
If a propofol infusion is initiated at a fixed rate,
it takes 5 half-lives to reach steady state
> > Theoretically, correct dosing
therefore reduces risk of awareness,
on one hand, and excessive cardiovascular and respiratory effects on the other.
> > Changing infusion rate with TCI results
in pause or bolus as well,
to achieve desired effect more rapidly –
not so with manual.
> > Using TCI is less labour-intensive
than repeatedly checking and changing
the rate manually.
> > More rapid wake-up at end of surgery by avoiding excessive dosing during the preceding infusion.
