Biomedical Engineering Reference
In-Depth Information
including primates (
Marsboom et al., 1963
). There are no
recent reports of the use of commercially available neu-
roleptanalgesic combinations (fentanyl/fluanisone, fen-
tanyl/droperidol) in primates, although they have been
used for immobilization and to produce light surgical
anesthesia. Combinations of opioids and benzodiazepines,
delivered by continuous infusion, can provide surgical
anesthesia in macaques and marmosets (unpublished data
from author's laboratory). These combinations generally
produce good muscle relaxation as well as analgesia and
less cardiovascular depression than some other combina-
tions, e.g. those with alpha-2 agonists. As with ketamine
combinations, the commerically available neuro-
leptanalgesic combinations, administered as a single
intramuscular injection, are mostusefulforshortproce-
dures. Continuous infusion of opioid and benzodiazepine
combinations is useful for prolonged recovery and non-
recovery procedures, however the infusion rates required
to maintain anesthesia are highly variable so anesthetic
depth must be monitored carefully. At the end of the
procedure a pure opioid antagonist or partial opioid
agonist may be administered to facilitate recovery (see
“Reversal agents” below). A benzodiazepine antagonist,
flumazenil, can be used to speed recovery, but the duration
of action of this agent is short relative to the actions of
midazolam and diazepam. As a result, re-sedation often
occurs unless repeated doses of
by anticholinesterases (e.g. neostigmine) after the
administration of a muscarinic antagonist such as glyco-
pyrrolate, which is
required to eliminate excessive
muscarinic responses.
For a guide to drug doses see
Tables 17.4, 17.5, 17.6
and 17.7
.
Volatile Liquid and Gas Anesthetics
Volatile liquid anesthetics are delivered as vapors following
evaporation in agent-specific vaporizers. They all appear to
have a relatively nonselective mechanism of action, which
includes hyperpolarization of neurons via increasing
potassium conductances as well as modulation of multiple
ligand-gated ion channels (including GABA
A
)(
Evers and
Koblin, 2004
). The use of volatile anesthetics is desirable
because of their rapid onset and offset of action and the
resultant ease with which anesthetic depth can be modified
during the procedure in response to changes in surgical
stimulus and/or physiological condition of the animal. This
can allow for an optimal maintenance of anesthetic depth
according to the demands of the procedure by not over-
anesthetizing the animal or maintaining too light a level of
anesthesia to ensure loss of responsiveness to stimuli. There
are some disadvantages in that they require specialized
equipment for administration, and the dose-dependent
hypotension produced by the majority of volatile agents
may be a concern, particularly when used as the sole
anesthetic agent. In particular contexts such as neurosur-
gery, their effects on cerebral blood flow must be
accomodated (see section “Neurosurgery” below).
However, despite these considerations, volatile agents are
ideally suited to a balanced anesthetic technique and
combination with analgesic agents and or other anesthetic
agents results in an extremely useful anesthetic regime for
a very wide range of procedures and species. Because the
vast majority of elimination of volatile agents occurs via
respiration recovery is relatively rapid, regardless of the
length of anesthesia. This makes them an excellent choice
for long procedures.
The potency of volatile and gas anesthetics is compared
using the minimal alveolar concentration value (MAC).
The MAC, given as a percentage of expired agent, is the
alveolar concentration of the agent required to render 50%
of subjects nonresponsive to a noxious stimulus (equivalent
to the ED
50
). Given that, by definition, 50% of subjects will
respond to a noxious stimulus, a vaporizer setting some-
where between MAC and 1.5
the antagonist are
administered.
“Reversal” Agents
As previously mentioned, some anesthetic/sedative agents
have specific antagonists. Alpha-2 adrenergic agonists can
be antagonized by atipamezole or yohimbine, the benzo-
diazepines (diazepam and midazolam) by flumazenil, and
opioid drugs by naloxone. Such antagonists may be useful
at any point during the perioperative period if inadvertent
overdose has occurred or if the effect of a drug is no longer
required (i.e. during recovery). It should be noted however
that the analgesic effect of alpha-2 adrenergic agonist and
opioid agents will also be antagonized by these drugs and
so alternative forms of analgesia should be administered.
Some opioid agents are classified as partial agonists
(e.g. buprenorphine) and have both agonist (analgesic)
effects at the mu receptor and also antagonize pure mu
agonists. The administration of buprenorphine at the end of
a procedure when neuroleptanalgesia or pure mu opioid
analgesia has been used, for instance, enables recovery
from the sedative effects of the opioid without antagonizing
analgesia (see section “Propofol” above).
Neuromuscular blocking agents may be used to
provide additional muscle relaxation during surgical
procedures (see “Neuromuscular blocking agents” below).
Competitive nondepolarizing agents can be antagonized
MAC (depending on what
other drugs have been given) would usually be required for
surgical procedures. However, required vaporizer settings
vary between individuals and according to the level of
surgical stimulus and so should be tailored accordingly.
The MAC of nitrous oxide (a gas anesthetic) is in excess of
100%; it cannot therefore be used as a sole agent for general
