15. TIVA Flashcards
What is meant by the term ‘total
intravenous anaesthesia’?
> Total intravenous anaesthesia
(TIVA)
refers to anaesthesia that is
provided solely by the intravenous route,
e.g. propofol infusion.
> It is generally administered as a
continuous infusion.
This infusion can be either run at a specific rate
or titrated to achieve a specific concentration
of the agent,
either in the plasma (Cp),
or at the brain, i.e. the effect site
(Ce), by running a ‘target-controlled’ infusion
What are the indications for using TIVA?
1 > When inhalational agents are not available, e.g. ITU, transfers and field anaesthesia.
2
> When administering inhalational agents
is difficult, e.g. during bronchoscopy.
- > When inhalational agents are contraindicated,
e.g. malignant hyperpyrexia.
4
> To reduce post-operative nausea and vomiting.
5
> To reduce exposure of staff to inhalational agents.
6
> To reduce pollution.
What are the properties of an
ideal intravenous anaesthetic
agent?
> Ideal physical properties:
- Cheap
- Stable and non-reactive with plastics, glass and metal
- Long shelf life
- Water soluble and so easy to formulate and store
- Environmentally safe
> Ideal pharmacokinetic properties:
• Rapid onset and offset, i.e. lipid soluble
• Minimal accumulation in body tissues, i.e. small VD
• Rapid metabolism in plasma to
inactive products giving a context
‘insensitive’ half-time
- No excitation or emergence phenomena
- No interaction with other drugs
> Ideal pharmacodynamic properties:
- Painless on injection
- Analgesic, muscle relaxant and antiemetic
- No effect on patient’s physiology
- No toxic effect
- No hypersensitivity reactions or histamine release
What is meant by the term ‘target-controlled infusion’?
> Target-controlled infusion (TCI) refers to an infusion system where the target concentration of the agent in the plasma or the effect site can be chosen.
What are the pharmacokinetic principles used in designing a TCI?
> TCI designs are based on
pharmacokinetic mathematical models
like the three-compartment model
> Pharmacokinetic data sets for the infused drug are incorporated into this mathematical model (e.g. VD, Cl, t½, k).
> Patient data,
e.g. age, weight, height and sex,
are also entered into the model.
> The mathematical model then predicts the plasma and effect site concentration of the drug and adjusts the infusion rate according to these predictions.
What are the limitations of such a pharmacokinetic mathematical model?
x5
> These models are based on several
assumptions as follows:
1 > Tissues only have either a high or a low blood flow with specific rate constants for distribution, redistribution and clearance.
2
> All people have the same proportion
of different tissues.
3
> All people metabolise and
eliminate the drug at the same rate.
4
> All people will become anaesthetised
at the same target concentration.
5
> There is no in vivo measurement of the
actual plasma or effect site
concentration of the drug.
The data produced are merely
predictions based on mathematical models, pharmacokinetic data sets and normograms.
What is context-sensitive half-time?
> Context-sensitive half-time (CSHT)
is applicable to intravenous infusions of drugs.
It is the time taken for the
drug concentration to
reduce by half
once an infusion designed to
maintain a constant plasma concentration
is stopped.
> The term ‘context’ refers
to the duration of drug
infusion prior to stopping.
> CSHT for a specific drug will
vary depending on the
duration of the infusion.
What causes context-sensitive half-times?
> During an infusion, the plasma will have the highest concentration of the drug in the body and therefore the drug will tend to travel down its concentration gradient into various tissues until tissue and plasma concentrations reach equilibrium.
> If the infusion is given for
long enough for
plasma concentration to
reach equilibrium with the tissues,
there will be no net movement of the drug between compartments as long as the rate of infusion matches the rate of elimination of the drug.
> Tissues with a high perfusion
will equilibrate with plasma faster
than those with low perfusion.
Tissues with a high fat content
and poor perfusion will act as a store.
> Once a drug infusion has stopped,
the drug concentration in the plasma
will start to fall as the
drug is metabolised and excreted.
> The tissues will then have a
higher concentration of the drug compared
with the plasma and
hence drug will redistribute
from these tissues into the plasma.
> The longer the duration of an infusion,
the more drug will accumulate in the tissues,
forming a store that can then
replenish and maintain the
plasma levels as the drug
is metabolised and excreted.
> This results in the context-sensitive half-life.
Which drugs lend themselves well to infusion regimes?
> Drugs with a small volume of distribution, rapid metabolism (with no active metabolites), high clearance and short CSHT are ideal for infusions.
> Remifentanil, propofol and alfentanil are the three main anaesthetic agents used in TCI.
Table 15.1 Context-sensitive half-times for various agents @ 2h and 8h Remi PRop Alfentnil Fentanyl
Drug CSHT after
2-h infusion CSHT after 8-h infusion
Remifentanil 4.5 min 9 min
Propofol 16 min 41 min
Alfentanil 50 min 64 min
Fentanyl 48 min 282 min
What is unique about remifentanil infusion?
> Remifentanil is rapidly broken
down by non-specific plasma
and tissue esterases.
> It has a short elimination half-time (t½ = 1.3 min), high clearance (2.5 L /kg/h)
and small volume of distribution (0.35 L /kg),
giving it a relatively constant
context-sensitive half-time of 3–10 minutes.
> Remifentanil is therefore often said to have a context-
‘insensitive’ half-time.
