Page 458 - Basic _ Clinical Pharmacology ( PDFDrive )

444 SECTION V Drugs That Act in the Central Nervous System

1
Nitrous oxide
1.0 Ventilation (L/min) Desflurane
8 Nitrous oxide
Sevoflurane
2 Isoflurane

F /F
A I Halothane
0.5
F /F Halothane
A I
0.5 8

2
0
0 10 20 30
0 Time (min)
10 20 30 40 50
Time (min) FIGURE 25–4 The alveolar anesthetic concentration (F A )
approaches the inspired anesthetic concentration (F I ) fastest for the
FIGURE 25–3 Effect of ventilation on F A /F I and induction of least soluble agents.
anesthesia. Increased ventilation (8 L/min versus 2 L/min) accelerates
the rate of rise toward equilibration of both halothane and nitrous
oxide but results in a larger percentage increase for halothane in the
first few minutes of induction. 3. Cardiac output—Changes in the flow rate of blood through
the lungs also affect the uptake of anesthetic gases from the alveolar
space. An increase in pulmonary blood flow (ie, increased cardiac
of administration but increases the F /F ratio for nitrous oxide output) will increase the uptake of anesthetic, thereby slowing the
I
A
by only 15%. Thus, hyperventilation increases the speed of rate by which F /F rises and decreasing the rate of induction of
A
I
induction of anesthesia with inhaled anesthetics that would anesthesia. Furthermore, one should consider the effect of cardiac
normally have a slow onset. output in combination with the tissue distribution and uptake of
anesthetic into other tissue compartments. The increased uptake
2. Solubility—As described above, the rate of rise of F /F is an of anesthetic into the blood caused by increased cardiac output
I
A
important determinant of the speed of induction, but is opposed will be distributed to all tissues. Since cerebral blood flow is well
by the uptake of anesthetic into the blood. Uptake is determined regulated, the increased anesthesia uptake caused by increased
by pharmacokinetic characteristics of each anesthetic agent as well cardiac output will predominantly be distributed to tissues that are
as patient factors. not involved in the site of action of the anesthetic.
One of the most important factors influencing the transfer of
an anesthetic from the lungs to the arterial blood is its solubility 4. Alveolar-venous partial pressure difference—The anes-
characteristics (Table 25–1). As described above, the blood:gas thetic partial pressure difference between alveolar and mixed
partition coefficient is a useful index of solubility and defines venous blood is dependent mainly on uptake of the anesthetic by
the relative affinity of an anesthetic for the blood compared the tissues, including nonneural tissues. Depending on the rate
to the affinity for inspired gas. Desflurane and nitrous oxide, and extent of tissue uptake, venous blood returning to the lungs
which are relatively insoluble in blood, display low partition may contain significantly less anesthetic than arterial blood Anes-
coefficients. When an anesthetic with low blood solubility parti- thetic uptake into tissues is influenced by factors similar to those
tions between gas in the lung and pulmonary capillary blood, that determine transfer of the anesthetic from the lung to the
equilibrium is quickly established and the blood concentra- intravascular space, including tissue:blood partition coefficients
tion rises rapidly (Figure 25–4, top; nitrous oxide, desflurane, (Table 25–1), rates of blood flow to the tissues, and concentration
sevoflurane). Conversely, for anesthetics with greater solubility gradients. The greater this difference in anesthetic gas concentra-
(Figure 25–4, bottom; halothane, isoflurane), more molecules tions, the more time it will take to achieve equilibrium with brain
dissolve in the blood before partial pressure changes significantly, tissue.
and arterial concentration of the gas increases less rapidly. A During the induction phase of anesthesia (and the initial
blood:gas partition coefficient of 0.47 for nitrous oxide means phase of the maintenance period), the tissues that exert greatest
that at equilibrium, the concentration in blood is less than half influence on the arteriovenous anesthetic concentration gradient
the concentration in the alveolar space (gas). A larger blood:gas are those that are highly perfused (eg, brain, heart, liver, kidneys,
partition coefficient causes a greater uptake of anesthetic into the and splanchnic bed). Combined, these tissues receive over 75%
pulmonary blood flow and therefore increases the time required of the resting cardiac output. In the case of volatile anesthetics
for F /F to approach equilibrium (Figure 25–4). with relatively high solubility in highly perfused tissues, venous
I
A