Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

INHALATION ANESTHETIC AGENTS
pass from the liquid into the gaseous state, while others
return to the liquid. The former transition is known as
vaporization. In a closed container and at a constant
temperature, vaporization of liquid will proceed until
an equilibrium is reached at which there is no further
net movement of molecules between phases. At equilibrium,
the gaseous phase is said to be saturated and the
pressure exerted by the molecules of vapor is termed the
saturated vapor pressure. Thus, vapor pressure gives an
indication of the ease with which a volatile anesthetic
evaporates. The higher the vapor pressure, the more
volatile the anesthetic.
The saturated vapor pressure also dictates the
maximum concentration of vapor that can exist at a
given temperature. The higher the saturated vapor pressure,
the greater the concentration of volatile agent that
can be delivered to the patient. To determine the
maximum concentration, vapor pressure is expressed as
a percentage of barometric pressure at sea level, i.e.
760 mmHg. For example, halothane has a saturated
vapor pressure of 244 mmHg at 20°C; therefore the
maximum concentration of halothane that can be delivered
at this temperature is 32% (244/760 × 100 = 32%).
Desflurane has the highest vapor pressure (664 mmHg
at 20°C) of the agents currently used and the maximum
achievable concentration of this agent approaches 90%.
Anesthetic gases such as nitrous oxide do not need to
undergo vaporization and can therefore exist over the
full range of concentrations, i.e. 0–100%.
In theory, a low saturated vapor pressure might
restrict the usefulness of a volatile anesthetic, if therapeutic
concentrations cannot be achieved. However,
this is not a limitation for the volatile agents in current
use.
Solubility
Molecules of anesthetic gas and vapor are able to dissolve
in liquids and solids. Thus, if molecules of anesthetic
are present in a mixture of gases overlying a liquid
they will diffuse into the liquid, i.e. they will dissolve.
This process will continue until an equilibrium is reached
at which there is no net movement of anesthetic molecules
between the two phases. At equilibrium, the partial
pressure exerted by the anesthetic in the gas phase will
equal the partial pressure of anesthetic in the liquid
phase. However, the total number of anesthetic molecules
in each compartment will not be equal.
The number of particles or volume of an individual
gas in a mixture of gases is simply proportional to its
partial pressure. However, the number of particles or
volume of gas that dissolves in a solvent at a given
temperature is dependent also on solubility.
According to Henry’s law:
V = S × P
A
B
Alveolar air
Blood
Alveolar air
Blood
Equilibrium
Equilibrium
Alveolar air
Blood
Alveolar air
Blood
Fig. 5.2 Partition of anesthetic molecules between
alveolar air and blood. (A) For an anesthetic agent that
is poorly soluble in blood, equilibrium is reached when
relatively few molecules have dissolved. The partial
pressure of anesthetic at equilibrium will be relatively
high. (B) For an anesthetic agent that is highly soluble
in blood, equilibrium is not reached until a large
number of molecules have dissolved. In this case the
partial pressure of anesthetic at equilibrium will be
relatively low.
where:
V = volume of gas
P = partial pressure of gas
S = solubility coefficient of gas in solvent.
For an anesthetic gas or vapor that is poorly soluble in
a solvent such as blood, equilibrium will be reached
when relatively few molecules have dissolved. The
partial pressure at which equilibrium occurs will be
relatively high. Conversely, for an agent that is highly
soluble in blood there will be a large number of
molecules in the liquid phase at equilibrium and partial
pressure will be relatively low (Fig. 5.2).
Partition coefficients
Partition coefficients are used to describe the solubility
of inhalation anesthetics in a variety of different solvents.
A partition coefficient is simply the ratio of the
concentration of anesthetic in one phase or solvent compared
to another. The coefficients of most clinical relevance
are the blood:gas and oil:gas partition coefficients.
The blood:gas partition coefficient is an important
determinant of the speed of anesthetic induction and
recovery. It describes the partition of an agent between
a gaseous phase, such as alveolar air, and the blood.
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