Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 5 ANESTHETIC AGENTS
The greater the blood:gas partition coefficient, the
greater the solubility in blood. The oil:gas partition
coefficient has been correlated to anesthetic potency –
the higher the coefficient, the more potent the agent.
The solubility of anesthetics in other tissues or in
components of a breathing system, such as rubber, may
also be relevant.
General pharmacokinetics
The aim in using inhalation anesthetics is to achieve
a partial pressure of anesthetic in the brain sufficient
to depress central nervous system (CNS) function and
induce general anesthesia. Thus, anesthetic depth is
determined by the partial pressure of anesthetic in the
brain. To reach the brain, molecules of anesthetic gas
or vapor must diffuse down a series of partial pressure
gradients, from inspired air to alveolar air, from alveolar
air to blood and from blood to brain.
Inspired air → Alveolar air → Blood → Brain
At each interface, diffusion proceeds until equilibrium
is reached and the partial pressures equalize. Gas
exchange at the level of the alveoli is an efficient process
and molecules of anesthetic rapidly equilibrate between
alveolar air and blood. Equilibration between the blood
and the brain is equally rapid. Thus, the partial pressure
of anesthetic in the brain closely follows the partial
pressure of anesthetic in arterial blood, which in turn
closely follows the partial pressure of anesthetic in the
alveoli. Expressed in a different way, this means that
anesthetic depth is largely determined by the partial
pressure of anesthetic in the alveoli.
The rate of change of anesthetic depth
Factors that produce a rapid change in alveolar partial
pressure of anesthetic will produce a rapid change in
anesthetic depth, appreciated clinically as a rapid induction
and recovery. The most important factors are listed
below and can be broadly divided into those that affect
delivery of anesthetic to the alveoli and those that affect
removal of anesthetic from the alveoli:
● inspired concentration
● alveolar ventilation
● solubility of anesthetic in blood
● solubility of anesthetic in tissues
● cardiac output.
Certain pathophysiological factors such as mismatching
of ventilation and perfusion may also influence the
uptake of anesthetic by altering the alveolar-to-arterial
partial pressure gradient.
Inspired concentration of anesthetic
A high inspired concentration of anesthetic is associated
with rapid induction of anesthesia, since increased
delivery of anesthetic to the alveoli induces a rapid rise
in alveolar partial pressure of anesthetic. Conversely,
the lower the inspired concentration, the more rapid the
recovery.
A number of factors may influence the inspired concentration.
The saturated vapor pressure of an agent
imposes a limit on the maximum concentration that can
be delivered at a given temperature. However, for most
inhalation agents, this limit far exceeds the concentrations
required for clinical use. Some inhalation anesthetics
are soluble in rubber or plastic and may therefore be
absorbed by components of the breathing system, effectively
reducing the inspired concentration.
For the volatile agents, the setting on the vaporizer is
an important determinant of inspired concentration,
although other factors such as the fresh gas flow and
the nature and volume of the anesthetic breathing
system will also exert an influence. For rebreathing
anesthetic systems such as the circle, fresh gas flow is
low relative to system volume. In addition, expired
gases contain variable amounts of anesthetic. These
factors serve to delay changes in inspired concentration
instigated by altering the vaporizer setting.
Alveolar ventilation
An increase in alveolar ventilation is associated with a
more rapid induction of anesthesia. As for a high
inspired concentration, delivery of anesthetic to the
alveoli is increased and the rise in alveolar partial pressure
is rapid. Conversely, hypoventilation will slow
both induction and recovery.
Many analgesic and anesthetic drugs, including the
inhalation agents, will depress ventilation and thereby
influence subsequent anesthetic uptake. Similarly,
increases in physiological dead space associated with
rapid shallow breathing serve to reduce alveolar ventilation.
On the other hand, intermittent positive pressure
ventilation tends to increase alveolar ventilation, allowing
for more rapid changes in alveolar partial pressure
of anesthetic.
Solubility in blood
Inhalation agents that are poorly soluble in blood, i.e.
have low blood:gas partition coefficients, produce more
rapid induction of anesthesia. More rapid recovery and
more rapid rate of change of anesthetic depth are also
features of such agents.
The rise in alveolar partial pressure of anesthetic at
induction can be described by plotting a graph of alveolar
partial pressure, expressed as a percentage of inspired
partial pressure, against time (Fig. 5.3). For an agent of
low blood solubility (Fig. 5.3A), equilibration between
alveolar air and blood occurs rapidly when relatively
few molecules of anesthetic have diffused into the blood.
Furthermore, since the majority of anesthetic molecules
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