9.7 TCI Flashcards
What are the indications of total intravenous anaesthesia (tiVA)?
- During intra- and inter-hospital transfer of patients
- When inhalational agents cannot be used (e.g. bronchoscopy)
- When inhalational agent is contraindicated (e.g. malignant hyperthermia)
- To reduce postoperative nausea and vomiting
- To reduce pollution
- As another mode of maintenance of anaesthesia
What properties make propofol an ideal agent for tiVA?
Physical properties
* Cheap
* Stable
* Safe
* Long shelf life
Pharmacokinetic properties
* Rapid onset and offset
* Small volume of distribution
* Rapid metabolism
* No excitation or emergence phenomenon
Pharmacodynamic properties
* Antiemetic effect
* No comparative toxic effect
A drug with a smaller Vd,
rapid metabolism,
high clearance,
short context sensitive half-life
is ideal for TIVA/TCI
What is TCI
TCI means ‘Target Controlled Infusion’
in which a microprocessor-controlled syringe pump
automatically and variably controls the rate of infusion
of a drug to attain a user-defined target level in an effect site (brain) in the patient.
-
A pharmacokinetic model is a mathematical model that can be used to
predict the blood concentration profile of a drug after a bolus dose or after
an infusion of varying duration.
These models are typically derived from measuring
arterial or venous plasma concentrations after a bolus or infusion
in a group of volunteers,
using standardised statistical approaches and computer software models.
Basically, the components of the system are:
- User interface, which allows the user to enter data such as the patient’s
details and target drug concentration and displays useful numeric and
graphic information regarding the infusion rates - Computer or microprocessor, which implements the pharmacokinetic
model, accepts data and instructions from the user, performs the
necessary calculations, and controls and monitors the infusion device - Infusion device, which is capable of infusing rates
up to 1200 mL/hr with a precision of 0.1 mL/hr
Volume of distribution (Vd)
This is the apparent volume in which the drug is distributed.
Vd = dose/concentration of drug.
Clearance
Clearance represents the
volume of plasma (Vp) from which the drug
is eliminated per unit time
to account for its elimination from the body.
Clearance can also be used to describe how quickly the drug moves between compartments.
Clearance = Elimination × Vp.
From these parameters it is possible to derive three main calculations.
- Loading dose
- Bolus dose to achieve a new concentration
- Rate of infusion to maintain a steady state concentration
- Loading dose
The drug is initially distributed into the central compartment before
distribution to peripheral compartments.
If the initial volume of distribution (Vc) and
the desired plasma concentration for therapeutic effect (Cp)
are known,
it is possible to calculate the loading dose to achieve that concentration.
Loading dose = Cp × Vc
- Bolus dose to achieve a new concentration
It can also be used to calculate the bolus dose required to rapidly
increase the concentration during a continuous infusion.
Bolus dose = [Cnew – Cactual] × Vc
- Rate of infusion to maintain a steady state concentration
Rate of infusion to maintain steady state = Cp × Clearance
Which compartment model better explains the working of a tci?
A 2- or 3-compartment model can be used to mathematically describe the
behaviour of anaesthetic drugs with considerable accuracy.
Conventionally the compartment into which the drug is injected is known as
the
central compartment (1) and its volume of distribution is the initial volume
of distribution (V1).
From the central compartment, drug transfers rapidly to the second
compartment (2) due to its abundance in vessels and
lastly into the third compartment (3), which is the slower,
vessel-poor compartment.
The sum of all these compartments is known as ‘volume of distribution at steady state’.
Define context sensitive half time (CSHt).
Time for the plasma concentration to fall to half after stopping an infusion at
steady state.
It is a comparison between the distribution and elimination clearances.
For example, a high distribution clearance and a low elimination clearance
increase the CSHT.
After 4 hours of infusion,
the ratio of distribution clearance to elimination clearance
for fentanyl is 5:1 and that of propofol is 1:1,
accounting to the CSHT of 250 min and 20 min, respectively.
As remifentanil is degraded by plasma esterases,
distribution clearance is less than elimination clearance,
so CSHT is very short.
Elimination clearance CSHT at 2 hours CSHT at 4 hours for propofol fentanyl and remi
Distribution Clearance:
Elimination clearance CSHT at 2 hours CSHT at 4 hours
Fentanyl 5:1 48 250
Propofol 1:1 16 20
Remifentanil <1 4.5 6
Define rate constant.
A coefficient of proportionality relating the
rate of a chemical reaction at a given temperature
to the concentration of reactant or to the product
of the concentrations of reactants.
It is measured in units of reciprocal time (time–1)
The rate of drug elimination (k) is assumed to be proportional to the
amount of drug in the compartment at any time,
while the concentration (C) decreases with time (t) in a monoexponential manner.
Ct = C0e–kt, where e = 2.718
K10 is the symbol used to denote the rate constant for metabolism or
elimination,
whereas K12, K21, K13, K31 symbolise the rate constants for
drug transfer between respective compartments.
Define half-life.
Half-life is the time required to
reduce the plasma concentration to half of its initial value.
What is time constant?
Time constant is the time taken for the plasma concentration to reach ‘0’ if
the initial rate of decline had continued.
