DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

long-term nephrotoxicity following enflurane use, and it is safe to use
in patients with renal impairment, provided that the depth of enflurane
anesthesia and the duration of administration are not excessive.
Liver and GI Tract. Enflurane reduces splanchnic and hepatic blood
flow in proportion to reduced arterial blood pressure. Enflurane does
not appear to alter liver function or to be hepatotoxic.
Desflurane
Desflurane (SUPRANE) is difluoromethyl 1-fluoro-2,2,2-
trifluoromethyl ether (Figure 19–4). It is a highly
volatile liquid at room temperature (vapor pressure =
681 mm Hg) and thus must be stored in tightly sealed
bottles.
Delivery of a precise concentration of desflurane requires the
use of a specially heated vaporizer that delivers pure vapor that then
is diluted appropriately with other gases (O 2
, air, or N 2
O). Desflurane
is nonflammable and non-explosive in mixtures of air or oxygen.
Pharmacokinetics. Desflurane has a very low blood:gas
partition coefficient (0.42) and also is not very soluble
in fat or other peripheral tissues (Table 19–1). For this
reason, the alveolar (and blood) concentration rapidly
rises to the level of inspired concentration.
Indeed, within 5 minutes of administration, the alveolar concentration
reaches 80% of the inspired concentration. This provides
for a very rapid induction of anesthesia and for rapid changes in
depth of anesthesia following changes in the inspired concentration.
Emergence from anesthesia also is very rapid with desflurane. The
time to awakening following desflurane is shorter than with
halothane or sevoflurane and usually does not exceed 5-10 minutes
in the absence of other sedative agents (La Colla et al., 2007).
Desflurane is metabolized to a minimal extent, and
> 99% of absorbed desflurane is eliminated unchanged
through the lungs. A small amount of absorbed desflurane
is oxidatively metabolized by hepatic CYPs. Virtually no
fluoride ions are detectable in serum after desflurane
administration, but low concentrations of trifluoroacetic
acid are found in serum and urine (Koblin et al., 1988).
Clinical Use. Desflurane is a widely used anesthetic for outpatient
surgery because of its rapid onset of action and rapid recovery. The
drug irritates the tracheobronchial tree and can provoke coughing,
salivation, and bronchospasm. Anesthesia therefore usually is
induced with an intravenous agent, with desflurane subsequently
administered for maintenance of anesthesia. Maintenance of anesthesia
usually requires inhaled concentrations of 6-8% (~1 MAC).
Lower concentrations of desflurane are required if it is co-administered
with nitrous oxide or opioids.
Side Effects
Cardiovascular System. Desflurane, like all inhalational anesthetics,
causes a concentration-dependent decrease in blood pressure.
Desflurane has a very modest negative inotropic effect and produces
hypotension primarily by decreasing systemic vascular resistance
(Eger, 1994) (Figure 19–6). Thus, cardiac output is well preserved
during desflurane anesthesia, as is blood flow to the major organ beds
(splanchnic, renal, cerebral, and coronary). Marked increases in heart
rate often are noted during induction of desflurane anesthesia and
during abrupt increases in the delivered concentration of desflurane.
This transient tachycardia results from desflurane-induced stimulation
of the sympathetic nervous system (Ebert and Muzi, 1993).
Unlike some inhalational anesthetics, the hypotensive effects of desflurane
do not wane with increasing duration of administration.
Respiratory System. Similarly to halothane and enflurane, desflurane
causes a concentration-dependent increase in respiratory rate and a
decrease in tidal volume. At low concentrations (< 1 MAC) the net
effect is to preserve minute ventilation. At desflurane concentrations
> 1 MAC, minute ventilation is markedly depressed, resulting in elevated
arterial CO 2
tension (Pa CO2
) (Figure 19–7). Patients spontaneously
breathing desflurane at concentrations > 1.5 MAC will have
extreme elevations of Paco 2
and may become apneic. Desflurane,
like other inhalational agents, is a bronchodilator. However, it also
is a strong airway irritant, and can cause coughing, breath-holding,
laryngospasm, and excessive respiratory secretions. Because of its irritant
properties, desflurane is not used for induction of anesthesia.
Nervous System. Desflurane decreases cerebral vascular resistance
and cerebral metabolic O 2
consumption. Burst suppression of the
EEG is achieved with ~ 2 MAC desflurane; at this level, CMRO 2
is
reduced by ~ 50%. Under conditions of normocapnia and normotension,
desflurane produces an increase in cerebral blood flow and can
increase intracranial pressure in patients with poor intracranial compliance.
The vasoconstrictive response to hypocapnia is preserved
during desflurane anesthesia, and increases in intracranial pressure
thus can be prevented by hyperventilation.
Muscle. Desflurane produces direct skeletal muscle relaxation as well
as enhancing the effects of non-depolarizing and depolarizing neuromuscular
blocking agents (Caldwell et al., 1991).
Kidney. Consistent with its minimal metabolic degradation, desflurane
has no reported nephrotoxicity.
Liver and GI Tract. Desflurane is not known to affect liver function
tests or to cause hepatotoxicity.
Desflurane and Carbon Monoxide. Inhaled anesthetics are administered
via a circle system circuit that permits unidirectional flow of
gas. This systems permits rebreathing of exhaled gases that contain
CO 2
. To prevent rebreathing of CO 2
(which can lead to hypercarbia),
CO 2
absorbers are incorporated into the anesthesia delivery circuits.
These CO 2
absorbers contained either Ca(OH) 2
or Ba(OH) 2
and smaller quantities of more potent alkalis, NaOH and KOH.
Interaction of inhaled anesthetics with these strong alkalis results in
the formation of CO. The amount of CO produced is insignificant as
long as the CO 2
absorbent is sufficiently hydrated. With almost complete
dessication of the CO 2
absorbents, substantial quantities of CO
can be produced. This effect is greatest with desflurane and can be
prevented by the use of well-hydrated, fresh CO 2
absorbent.
Sevoflurane
Sevoflurane (ULTANE, others) is fluoromethyl 2,2,2-
trifluoro-1-[trifluoromethyl]ethyl ether (Figure 19–4).
It is a clear, colorless, volatile liquid at room
temperature and must be stored in a sealed bottle. It is
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CHAPTER 19
GENERAL ANESTHETICS AND THERAPEUTIC GASES