Biomedical Engineering Reference
In-Depth Information
1980
) and later applied in laboratory species (
Cowan et al.,
1977; Flecknell et al., 1989; Hu et al., 1992
). It has been
employed successfully by the authors in nonhuman
primates using buprenorphine. Butorphanol should be
avoided since anecdotal reports suggest that it has more
respiratory depressant effects in nonhuman primates than it
has in other species. It is also important to note that pro-
pofol has a context-sensitive half-time (
Shafer, 1993
)so
that its effects are prolonged as the period of anesthesia
continues. Although much less of a problem than when
using barbiturates, this effect must be taken into account in
longer procedures, or other agents (e.g. volatile agents)
should be considered for procedures that will last more than
a few hours. The most commonly used formulation of
propofol is a 10% soybean oil emulsion which has been
associated with hyperlipemia when used for prolonged
infusion in humans (
Eddleston and Shelly 1991; Mateu and
Barrachina, 1996
) and other species (
Weaver et al., 1996
).
A newer lipid-free micro-emusion formulation of propofol
(PropoClear, Fort Dodge) may prove more appropriate for
such uses.
variable effects on consciousness, and attempting to
maintain general anesthesia in this way can be challenging.
The most commonly used agents predominantly act at mu
opioid receptors. They have minimal effects on cardio-
vascular function but so-called full mu receptor agonist
opioids such as fentanyl, alfentanil, and remifentanil
produce profound respiratory depression, apnea, and
cardiovascular depression at the doses required for general
anesthesia when used as a single agent. They are therefore
more useful when combined with other agents (e.g. section
“Propofol” above) in order to reduce the required dose of
that agent and provide excellent analgesia and balanced
anesthesia. The shorter acting opioids alfentanil and remi-
fentanil are preferable when administering a continuous
infusion because more rapid pharmacokinetics results in
elimination of sedative and respiratory depression effects
during recovery providing the infusion is stopped 15
e
30
minutes before the primary anesthetic agent is ceased.
Further postoperative analgesia can be provided with a less
potent agent, e.g. buprenorphine (see main section “Anal-
gesia” below). When infused as adjuncts to anesthesia,
alfentanil and other opioids may cause mild or moderate
bradycardia. If this causes a fall in blood pressure, then it
can be corrected by administration of low dose atropine.
Sufentanil (a particularly potent opioid) has been used
as a single agent for some nonhuman primate electro-
physiology experimental protocols due to its lower damp-
ing effect on neuronal responsiveness. Isoflurane, for
instance, has been shown to substantially reduce recording
contrast sensitivity of some neurons when compared to
sufentanil (
Solomon et al., 1999
). However, whilst this
rules out isoflurane as a sole agent for such experiments,
recent reports suggest that it can be combined with sufen-
tanil (in order to ensure an appropriate level of anesthesia
e
something that is very much more challenging when using
opioids alone) without a difference in neuronal physio-
logical properties being detected (
McLelland et al., 2010
).
Ventilatory support and a degree of skill is essential when
using opioids as the predominant anesthetic agent to ensure
that anesthesia is produced without hypoxia or hyper-
capnia. It is advisable to carry out any surgical preparation
using a regime that enables rapid control of depth, e.g.
volatile agent or rapidly acting intravenous agent
(e.g. propofol), as the depth of anesthesia required for
surgery will be greater and more variable than that required
for recording.
Alphaxalone (and Alphaxalone/Alphadolone)
Alphaxalone is a neuro-active steroid. As with propofol, its
anesthetic effects predominantly result from action on
GABA
A
receptors. Alphaxalone is one of the agents of
choice for anesthesia of marmosets but has also been used
successfully in other species of nonhuman primate (
Prior
et al., 1978; Whelan et al., 1999; Virley et al., 2004
). An
initial dose may given intramuscularly to immobilize the
animal, however the volume of injection is relatively high
and so ketamine may be preferred for the initial immobi-
lization of larger primates. Once an intravenous cannula is
placed, a loading dose of alphaxalone is given to induce
surgical anesthesia. The loading dose is given slowly and
20
e
30 seconds allowed to lapse before the adequacy of the
dose is judged. Dosing can be repeated in this manner
without the induced respiratory depression leading to apnea
(personal communication,
Windle, 2011
) until surgical
anesthesia is achieved. Anesthesia can then be maintained
by administration of additional doses or preferably by
continuous infusion of the agent. Again, like propofol,
alphaxalone is relatively noncumulative compared to
barbiturates, so recovery following procedures of up to
a few hours is relatively rapid. The short duration of action
of alphaxalone and propofol (approximately 10 min after
a single dose) means that the depth of anesthesia can be
adjusted easily by changing drug infusion rates.
Neuroleptanalgesia
Neuroleptanalgesia refers to the combination of a potent
sedative analgesic agent (an opioid) and a tranquillizer.
Studies evaluating neuroleptanalgesia in nonhuman
primates are absent, but it has been used extensively and
for many years in numerous laboratory animal species
Opioids
Opioids have been used in nonhuman primates to provide
excellent analgesia as components of balanced anesthetic
regimens. When used alone, at high doses, they have very
