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Section IBasic principlespatients were ventilated. The more usual induction dose of propofol is 2 mg.kg−^1 ,
which is much higher than described in the Bristol regime and can produce adverse
cardiovascular depression. This infusion regime may need adjusting according to
the nature of the surgery either by giving boluses of propofol or by reducing or stop-
ping the infusion altogether to allow the blood level of propofol to fall. Clearly, if
higher plasma concentrations of propofol are needed to maintain adequate anaes-
thesia, then the 10-8-6 algorithm should be adjusted appropriately or an additional
intravenous supplement used, such as a remifentanil infusion.TCI
TCIisatechnique that uses a microprocessor-controlled infusion pump pro-
grammed with a three-compartment model of propofol pharmacokinetics. There
are two types of TCI: one that targets plasma concentration and, more recently intro-
duced, one that targets the effect site. If the target concentration and the patient’s
weight are entered, the pump will infuse propofol at varying rates calculated to keep
that target level constant. For remifentanil it is also important to enter the patient’s
age, since metabolism of remifentanil is significantly reduced in the elderly. There are
also two different pharmacokinetic models for propofol infusion. The better known
is the Marsh model, whereas the newer one is the Schnider model. They differ partic-
ularly in terms of the half-life reflecting equilibration with the effect compartment,
known as the t1/2keo.Inthe original pharmacokinetic model this constant was not
defined, but experimentally it has been suggested that propofol has a t1/2keoof about
2.6 minutes; with the Schnider model, this has been reduced to about 1.5 minutes.
The choice of model depends on the target chosen; in general the Schnider model
is better where effect compartment is targeted whereas the Marsh model appears
to perform better for targeting plasma concentration, particularly for longer proce-
dures.
Atinduction, when the plasma concentration is the target, propofol is delivered at
1200 ml.h−^1 ,giving a bolus calculated to fill the central compartment. The infusion
then continues at a diminishing rate, calculated to match the exponential transfer
and uptake of drug to different compartments. If a higher blood level is required, for
example to cover a highly stimulating point of surgery, the new target is entered and
asmall bolus is automatically delivered to reach the desired level. Similarly, if a lower
level is required, the infusion automatically stops to allow a multi-exponential fall
to the new level, at which point the infusion restarts at a lower rate.
The blood concentration targeted is titrated to clinical effect. For propofol the
target concentration for an adult generally varies between 4 and 8μg.ml−^1 .Inthe
unpremedicated patient an initial target of 5–6μg.ml−^1 can be used, whereas in
the premedicated patient 3–4μg.ml−^1 may be more appropriate. These targets will
be lower if remifentanil is co-infused, with propofol targets as low as 2–2.5μg.ml−^1
commonly used. The target for remifentanil is around 6–10 ng.ml−^1 for induction,
which can be reduced for maintenance to somewhere between 3 and 8 ng.ml−^1.