Tci Overview - CareFusion Alaris PK Plus MK4 8005PK201 Directions For Use Manual

TCI Overview

The dose-response relationship can be divided into three parts: the relationship between administered dose and plasma concentration
(the pharmacokinetic phase), the relationship between effect organ concentration and clinical effect (the pharmacodynamic phase) and
the coupling between pharmacokinetics and dynamics. The ultimate goal when administering a particular dose of a drug is to obtain
the desired clinical effect, for which a specific therapeutic concentration of the drug at the site of action (the receptor) is necessary.
Fig. 1: Schematic representation of the pharmacokinetic and dynamic processes determining the relationship between administered dose
and resulting effect intensity of a drug. Pharmacokinetic factors such as distribution, metabolism, and/or excretion determine the relationship
between drug dose and drug-concentration in the plasma and bio-phase (effect-site). In the bio-phase the drug interacts with the receptor
resulting in the pharmacological effect.
Until recently, when intravenous anaesthetic agents were used for induction or maintenance of anaesthesia, they were administered
either manually (by hand) or by simple infusion pumps (the anaesthetist calculated the infusion according to the body weight
of the patient). Inline measurement of concentrations is not possible, and the polyexponential equations required to predict the
concentrations requires vast computer processing power. Based on the pioneering work of Kruger-Thiemer
TCI concept was developed during the 1980's and early 1990's, as advances in computer technology made inline predictions of drug
concentrations feasible.
The pharmacokinetic behaviour of most anaesthetic drugs can be described mathematically with a 3-compartment model: usually a
central compartment (V1), a vessel-rich compartment (V2) and a vessel-poor compartment (V3) are described. Transfer of drug between
different compartments (distribution) is described by rate constants (k
by the rate constant k (Fig. 2). The aim of TCI techniques is to use pharmacokinetic modelling to calculate the infusion rates required to
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achieve a desired plasma concentration. Thus, instead of specifying an infusion rate, the user specifies a "target" concentration, based on
clinical judgement. When a concentration in the plasma compartment is targeted, this is called "open-loop plasma targeted TCI". When a
certain concentration at the effect compartment is targeted, then this is called "open-loop effect-site targeted TCI".
For anaesthetic agents the effect-site (or bio-phase) is not the plasma
Until the early 1990's it was considered that blood-brain equilibration was virtually instantaneous. Early TCI systems were thus all
plasma-targeted. For many drugs the relationship between plasma concentration and clinical effect was described, usually in terms of
the Cp50 or Cp95 (the concentrations required to elicit a specified clinical effect in 50 or 95% of patients respectively). For an example
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see Ausems et al.
During the 1990's it was increasingly appreciated that after a change in plasma concentration there is a temporal delay in equilibration
between the plasma and effect-site concentrations. The clinical effect changes in parallel with the effect-site concentration, and so
for most drugs the rate of drug transfer into and from the site of action can be characterized by the time-course of drug effect
means that the effect can be transferred to concentrations, thereby resulting in a quantitative approach. The concentration at the site of
action is called "the effect-site concentration" and the corresponding compartment
Because the actual amount of drug entering the brain is very small, the effect-site compartment can be regarded as having no volume,
the rate constant k can be ignored and the rate constant k
1e
effect-site compartments.
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Fig. 2: Schematic representation of the three compartment model used for target-controlled infusions.
can be used to describe the rate of equilibration between the plasma and
eo
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, k , k and k ) or clearances. Drug metabolism is described
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but the brain, where concentrations cannot be directly measured.
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(see Fig. 3) is called "the effect-site compartment".
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Alaris™ PK Plus Syringe Pump
TCI Overview
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and Schwilden et al.
6,7
. This
3
, the