Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 5 ANESTHETIC AGENTS
● high environmental temperatures
● high concentrations of sevoflurane
● the use of baralyme rather than soda lime
● low fresh gas flows
● the use of absorbent that has been previously
exposed to sevoflurane.
While compound A causes renal failure in rats at relatively
low concentrations, its toxicity in humans and
other species, including dogs, has not been established.
Despite the lack of evidence most authors recommend
that a minimum fresh gas flow of 2 L/min be used when
sevoflurane is delivered via a rebreathing system.
Solubility
Sevoflurane has a very low blood:gas partition coefficient
associated with a rapid onset of action. This is an
added advantage if sevoflurane is to be used for mask
induction. Recovery is also rapid but may be slowed
slightly by a relatively high solubility in tissues, particularly
fat.
Sevoflurane has a lower oil:gas partition coefficient
than isoflurane and is therefore less potent, having a
MAC value of approximately 2.3% in the dog.
Metabolism and elimination
Approximately 3% of sevoflurane is metabolized in the
liver, inorganic fluoride being the main product. Intrarenal
metabolism to fluoride is minimal (compare
methoxyflurane).
Adverse effects
Many of the pharmacological effects of sevoflurane are
qualitatively and quantitatively similar to those of
isoflurane.
Central nervous system effects
Sevoflurane reduces cerebral metabolic rate but also
causes cerebral vasodilation, thereby increasing intracranial
pressure. The responsiveness of the cerebral
vasculature to carbon dioxide is maintained.
Cardiovascular effects
Sevoflurane, like isoflurane, produces mild depression
of myocardial contractility, systemic vascular resistance
and arterial blood pressure. It may be less likely to
increase heart rate than isoflurane and vasodilation may
not be so prominent. However, these differences are not
marked. Sevoflurane has low arrhythmogenicity.
Hepatic effects
As for isoflurane, sevoflurane decreases hepatic portal
vein blood flow but increases hepatic arterial flow.
Although sevoflurane has two -CF 3 groups, trifluoroacetic
acid is not an important metabolite (free fluoride is
generated instead) and sevoflurane-induced hepatitis
has not been reported.
Renal effects
Increased serum concentrations of fluoride, approaching
nephrotoxic levels, have been documented in people
anesthetized with this agent. However, renal damage
has not been reported despite the now widespread use
of sevoflurane in human anesthesia. Intrarenal production
of fluoride may be a more significant cause of
nephrotoxicity than fluoride generated by hepatic
metabolism (compare methoxyflurane).
Generation of potentially nephrotoxic compound A
is an additional concern when rebreathing anesthetic
systems are used.
Although sevoflurane-induced renal damage has not
been documented it would seem sensible to avoid this
agent in patients with pre-existing renal impairment.
Desflurane
Clinical applications
Desflurane was first synthesized in the 1960s, along
with enflurane and isoflurane. It was not pursued further
at that time, since its low potency was considered a
disadvantage. Its properties have since been reexamined
and desflurane is a relatively recent introduction
to the field of human anesthesia, where it has
gained favor as an anesthetic for day-case surgery. As
yet it is not widely used in veterinary anesthesia.
Pharmacokinetics
Chemical and physical properties
Desflurane is a fluorinated ether (see Fig. 5.1). Its structure
is similar to that of isoflurane, differing only in the
substitution of a fluorine atom for chlorine. It is nonflammable
and stable.
The vapor pressure of desflurane is exceptionally
high; in fact, its boiling point (22.8°C) is close to room
temperature. Standard vaporizers are unable to deliver
a predictable concentration of desflurane and an electronic,
temperature-controlled, pressurized vaporizer
must be used to ensure a reliable output.
Volatile anesthetics that possess an -O-CHF 2 group,
i.e. desflurane and isoflurane, can react with the carbon
dioxide absorbent soda lime to generate carbon monoxide.
This reaction is most likely with desflurane. Recommendations
to limit carbon monoxide production
include regular replacement of used soda lime and flushing
of rebreathing circuits with oxygen for a couple of
minutes prior to use, especially if the circuit has not
been used for a couple of days.
Solubility
Desflurane has the lowest blood:gas partition coefficient
of the volatile anesthetics currently available, i.e. it is
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