Biomedical Engineering Reference
In-Depth Information
rodents (
Olney et al., 1989; Jevtovic-Todorovic et al.,
2001
). Although the authors are unaware of reports of
ketamine neurotoxicity in adult nonhuman primates, it is
neurotoxic in neonatal rhesus monkeys (
Zou et al., 2009
).
In neuroscience experimental protocols, the use of sedation
protocols that do not employ NMDA antagonists may be
especially desirable. There are also some specific situa-
tions, such as smaller species (see section “Alternatives to
ketamine” below) and sedation of an animal at risk from
cerebral edema (see section “Neurosurgery” below) where
ketamine or
ketamine (3
e
4), and its injection into the relatively small
muscle mass of marmosets. For this reason, pre-medication
with alphaxalone/alphadolone has been recommended
(
Green et al., 1978
). This combination of neuro-active
steroid anesthetics is no longer available, but the more
potent component, alphaxalone, is available and produces
effects ranging from deep sedation to full surgical anes-
thesia in marmosets and other primates. Despite the rela-
tively large volume of injectate, no muscle damage has
been associated with use of alphaxalone/alphadolone, and
initial clinical experience suggests a similar lack of local
tissue irritation when using alphaxalone. An advantage of
this agent is that additional drug can be given intravenously
to deepen and maintain anesthesia (see section “Alpha-
xalone (and Alphaxalone/alphadolone)” below).
As an alternative to the dissociative anesthetics, seda-
tives and tranquillizers can be used for immobilization, but
these are not always effective in preventing aggression.
Diazepam and midazolam are benzodiazepines and can be
used to provide light to moderate sedation but are often
ineffective as sole agents and so are more usefully
combined with other agents (ketamine or alpha-2 adren-
ergic agonists). Medetomidine, an alpha-2 adrenergic
agonist, has been used successfully in a wide range of
laboratory species to produce heavy sedation and immo-
bilization. It must be used with great care in nonhuman
primates as its sedative effects are less predictable, and
some animals may suddenly become alert and attempt to
bite their handlers. It has also been combined with butor-
phanol (
Hampton et al., 2004
) or butorphanol and mid-
azolam (
Williams et al., 2003
; unpublished data from
authors' laboratory) to provide deep sedation and analgesia
in situations where the use of ketamine is undesirable (see
above). The authors are not aware of any suitably
controlled comparisons of the use of nonketamine combi-
nations in primates, but given the anecdotal reports sug-
gesting that butorphanol has more respiratory depressant
effects in nonhuman primates than it has in other species,
its substitution with buprenorphine (also a mixed agonist/
antagonist but longer acting) may be appropriate in these
circumstances. The advantage of medetomidine is that it
can be reversed using a specific antagonist, atipamezole
(see section '“Reversal” agents” below). Other alpha-2
adrenergic agonists include xylazine and dexmedetomidine
(the S-enantiomer of medetomidine). Alpha-2 adrenergic
agonists inhibit insulin release leading to hyperglycemia
and increased urine output; intravenous fluids (see section
“Fluid administration” below) can be used to ensure that
dehydration does not occur. Concerns about the use of
alpha-2 agonists in nonhuman primates include cardio-
vascular effects such as hypotension, bradycardia, and
atrioventricular block. These concerns can be mitigated by
using low doses of alpha-2 agonists, monitoring cardio-
vascular parameters, and having antagonist agents on hand.
tiletamine should be used with extreme
caution.
Ketamine Combinations
The same ketamine combinations that are used for immo-
bilization (to produce deep sedation/light anesthesia) can
also be used for brief surgical procedures, either with repeat
bolus dosing or by continuous intravenous infusion. Ket-
amine should be used in combination with other agents for
surgical procedures because it does not produce muscle
relaxation when used alone. The addition of benzodiaze-
pines produces muscle relaxation and additional sedation,
and combination of ketamine with alpha-2 agonists
produces additional sedation, muscle relaxation, and anal-
gesia. Acepromazine (ACP) has also been used in combi-
nation with ketamine, but because it can cause profound
hypotension, has no useful analgesic properties, and has
been reported to decrease seizure threshold in susceptible
animals of other species, other drugs are often better
alternatives. Although, when in combination with other
agents, ketamine is useful for short surgical procedures,
drug accumulation occurs with repeat administration
leading to prolonged dissociative effects in recovery (for
which there is no reversal agent) and therefore shorter
acting drugs such as propofol or alphaxalone are better
alternatives for such situations (see section “Injectable
anesthetics” below).
A combination of the dissociative anesthetic tiletamine
with the benzodiazepine zolazepam (Telazol, Fort Dodge,
USA) is available for veterinary use and provides dose-
dependent sedation, analgesia, and muscle relaxation with
minimal cardiovascular depression. The greater potency
of Telazol enables lower injection volumes than ketamine
requires, which is particularly useful for very large
primates, such as baboons and chimpanzees. The effects
of zolazepam can be antagonized by administration of
flumazenil at the end of the procedure. Although the
effects of tiletamine still remain, recovery is generally
rapid.
Alternatives to Ketamine
The use of ketamine in marmosets has been associated with
muscle damage. This is probably related to the low pH of
