XI. ANESTHESIA
This chapter provides guidance and information
on anesthesia and relief of pain in experimental animals. It is not meant to
be comprehensive, and non-veterinary users should consult with a veterinary
anesthesiologist or laboratory animal veterinarian when such drugs are to be
administered. Information on common dosages and means of administration of analgesic,
tranquillizing and anesthetic agents are given in the Appendices. The agents
described in this chapter are all prescription and/or controlled drugs. Non-veterinary
users may obtain prescription drugs from a licensed veterinarian, and should
contact the Bureau of Dangerous Drugs, Health and Welfare Canada regarding the
use of controlled drugs in research.
Methods for assessing the depth of anesthesia
vary with the species and the drug, and are discussed in Green (1982).
Specific details are available in the textbooks and review articles listed
in the references.
A. MANAGEMENT OF ANESTHESIA
1. General
Sedatives, analgesics, and general anesthetic
agents must be utilized for the control of pain and distress unless contrary
to the achievement of the objectives of the study. In the latter case,
approval of the institutional Animal Care Committee (ACC) is mandatory.
Anesthetic agents frequently affect the
cardiovascular, respiratory and thermoregulatory mechanisms, in addition
to the central nervous system (CNS). Every effort should therefore be made
to maintain the circulation, respiratory function and the body temperature
of the anesthetized subject within normal physiological limits (Parker
and Adams, 1978). Endotracheal intubation ensures that the airway remains
patent and free from obstruction.
Hypothermia may occur during exposure to
anesthetic gases and during intra-abdominal surgery, particularly in small
animals. This may result in death or a greatly prolonged recovery from
the anesthetic. The degree of hypothermia may be reduced by placing the
animal on a circulating warm water blanket or other device that assists
in conserving body heat (Muir and Hubbell, 1989; Lumb and Jones, 1984;
Flecknell, 1987).
2. Handling the Patient
The animal should always be handled
gently and calmly in order to minimize struggling and fright. Prolonged
excitement will disturb the circulatory and metabolic state of the patient
and induce a degree of shock. Furthermore, attempts to anesthetize a struggling
animal present physical problems in addition to enhancing the likelihood
of an abnormal response to the anesthetic agents. These points are particularly
important when restraining and anesthetizing wild animals (Fowler, 1986).
3. Fasting
Cats, dogs, non-human primates (NHP), ferrets
and pigs should receive no food during the 8-12 hours prior to induction
of anesthesia in order to minimize the risk of vomiting during induction
or recovery from anesthesia (Flecknell, 1987). Very small or immature mammals
should be subjected to a much shorter fast, usually from two to four hours,
due to their higher metabolic rate. Withholding food from ruminants for
12-24 hours may help reduce the incidence of ruminal tympany (bloat); however,
reduction of the volume of digesta in the rumen requires much longer periods
of starvation (36-72 hours). Water should be withheld for 12 hours before
surgery to prevent gorging and increase in the volume of rumen contents.
Pre-anesthetic fasting of small rodents or rabbits is unnecessary since
they do not vomit during induction (Flecknell, 1987). Guinea pigs should
be fasted 6-12 hours before anesthesia to allow time to clear their mouths
of the food bolus commonly carried at the base of the tongue. Small birds
often are not fasted at all, in order to maintain energy during the stress
of the procedure (Muir and Hubbell, 1989; NRC [U.S.], 1977). Fasting pregnant
animals of all species, particularly ruminants, can produce severe metabolic
disturbances. Other than ruminants, every animal should be provided with
drinking water until approximately one hour before induction of anesthesia
(Flecknell, 1987).
4. Anticholinergics
Anticholinergics block parasympathetic
stimulation to the cardiopulmonary system and reduce salivary secretion.
They are used in combination with sedatives and analgesics as pre-medication
to general anesthesia. Anticholinergics are no longer routinely administered
to each animal undergoing anesthesia. They are administered selectively,
after a pre-anesthetic clinical examination of the animal, and according
to the determined needs of the individual patient, the anticipated response
to the anesthetic medication, and the tendency to develop bradycardia or
excessive salivation (Short, 1987).
a) Atropine is the most commonly
used anticholinergic agent; however, routine administration is controversial
due to the high incidence of associated cardiac dysrhythmias (premature
ventricular contractions and sinus tachycardia) (Lumb and Jones, 1984;
Flecknell, 1987). It is most commonly recommended for use in NHP, pigs,
guinea pigs and chinchillas in order to decrease airway secretions, but
should not be given if a marked tachycardia is already present (Green,
1982).
b) Glycopyrrolate is a quaternary
ammonium anticholinergic. Although its mechanism of action is similar to
that of atropine, its effects last longer. Glycopyrrolate seems to be less
likely than atropine to produce sinus tachycardia (Paddleford, 1988). It
does not penetrate the CNS because of its difficulty in crossing the blood-brain
barrier. It is also less likely than atropine to cross the placental barrier,
indicating that it is a selective peripheral anticholinergic agent (Short,
1987).
B. TRANQUILLIZERS
AND SEDATIVES
Tranquillizers produce a calming effect
without sedation (Green, 1982). They have no analgesic properties, and
even at the high doses that cause ataxia (failure of muscular co-ordination)
and depression, animals are easily aroused. Tranquillizers are useful over
a wide range of species, often in combination with other drugs, to lessen
the dose of a general anesthetic and produce a smoother induction and recovery.
Sedatives are used to produce drowsiness and reduce fear and apprehension
(Flecknell, 1987).
The psychological state of the animal prior
to administration of tranquillizers may markedly affect the degree of sedation
achieved. Animals that are vicious, intractable and in a state of excitement
may not become manageable except with very high (incapacitating) doses.
a) Phenothiazines (promazine, acepromazine)
produce
sedation and reduce the dose of drugs needed for general anesthesia, but
also cause moderate hypotension and hypothermia (Lumb and Jones, 1984;
Flecknell, 1987).
b) Benzodiazepines (diazepam, midazolam)
produce
variable sedation depending on the species (Lumb and Jones, 1984; Flecknell,
1987; Green, 1982). They are good muscle relaxants and have no marked undesirable
side effects. Diazepam cannot be mixed with other water soluble agents,
while midazolam can (Flecknell, 1987).
c) Butyrophenones (azaperone, droperidol)
have
similar effects as phenothiazines, but are more potent and cause less hypotension
(Lumb and Jones, 1984; Flecknell, 1987; Green, 1982). Droperidol is used
in combination with an opioid to produce neuroleptanalgesia (Flecknell,
1987).
d) alpha-2-adrenergic agonists (xylazine,
detomidine, medetomidine)
i) Xylazine (Rompun) is a sedative
and analgesic that acts as a CNS depressant and induces muscle relaxation
by inhibiting the transmission of impulses in the CNS. Its major use in
laboratory animal anesthesia is in combination with ketamine to produce
surgical anesthesia. This combination has been used in dogs, cats, NHP,
large farm animals and wild animals (Olson and McCabe, 1986; Lumb and Jones,
1984). It causes respiratory depression and a bradycardia which may progress
to heart block (Flecknell, 1987). It also increases the susceptibility
of the myocardium to circulating catecholamines during halothane anesthesia
(Short, 1987). Vomiting may occur in dogs and cats, and gas accumulation
due to gastrointestinal atony (lack of normal tone or strength) may be
a problem in both large dogs and ruminants (Lumb and Jones, 1984). Xylazine
produces profound physiological changes and its safe use requires knowledge
of these effects which are often species specific. Yohimbine and 4-aminopyridine
reverse most of the effects of xylazine without relapse in many species
(Jernigan, Wilson, Booth et al. 1988), with the exception of NHP
(Lynch and Line, 1985).
ii) Detomidine is marketed for use
in horses, and has the same cardiovascular effects (bradycardia and hypotension)
as xylazine, but is more potent and has a longer-acting effect.
iii) Medetomidine is being evaluated
for use in dogs and cats, and has cardiovascular effects similalr to xylazine.
A medetomidine/ketamine combination in cats has the advantage over xylazine/ketamine
in that a lower dose of ketamine is needed, the duration of action is longer
and the analgesia better (Verstegen, Fargetton, Donnay et al. 1990).
C. GENERAL ANESTHETICS
1. Dissociative Anesthetics
Dissociative anesthetics produce a state
of chemical restraint and anesthesia characterized by muscle rigidity and
dissociation of the mind from the external environment. The eyes remain
open, necessitating use of protective ointment. Various reflexes, including
the blinking reflex and laryngeal reflex, remain intact, and adequate respiration
is normally maintained. An increase in heart rate, blood pressure and intracranial
pressure frequently occurs. Thus, their use is contra-indicated in head
injuries or intra-ocular surgery. While the use of dissociative anesthetic
agents is most common with NHP and cats, they have also been used in most
other mammalian species as well as birds and reptiles (Jones, 1977). Combination
with a tranquillizer is recommended in most species to enhance analgesia
and reduce muscle tone (Flecknell, 1987; Green, 1982).
a) Ketamine hydrochloride is the
most commonly used member of this group. Depth of anesthesia is dose related.
Side effects include excessive salivation which may be controlled with
atropine (Flecknell, 1987), a tendency toward convulsions, and a recovery
characterized by excitement, disorientation, and hallucinations which may
be controlled by tranquillizers and barbiturates (Lumb and Jones, 1984).
In all cases, a smooth recovery will be facilitated if the patient is left
undisturbed in a quiet, darkened environment.
b) Tiletamine is similar to ketamine,
but is longer lasting and more potent; therefore, a smaller dose volume
is needed. It is most commonly sold in combination with the tranquillizer
zolazepam (Telazol), which improves muscle relaxation, CNS depression,
and emergence from anesthesia. It also prevents tiletamine seizures. Cats
may take 12-36 hours to be clinically "normal" following tiletamine anesthesia.
Tiletamine/zolazepam has proven successful in rats and gerbils, but not
in mice or hamsters (Hrapkiewicz, Stein and Smiler, 1989). Tiletamine causes
nephrotoxicity in rabbits (Brammer, Doerning, Chrisp et al. 1991;
Doerning, Brammer, Chrisp et al. 1992).
2. Barbiturates
Barbiturates differ from tranquillizers
and opioids in that increasing the dose progressively increases the depth
of depression until a state of general anesthesia is reached. They are
poor analgesics. Their primary use is in the induction and/or maintenance
of general anesthesia. Barbiturates are potent respiratory depressants
and their effects on the cardiovascular system are variable. At intermediate
dosages, excitement is sometimes induced (Green, 1982).
The barbiturates are grouped according
to duration of action into long acting (e.g., phenobarbital), short- or
intermediate-acting (e.g., pentobarbital) and ultrashort-acting (e.g.,
thiopental, thiamylal, methohexital) (McLaughlin, 1988). The short- and
ultrashort-acting drugs are commonly used for anesthesia. Anesthetic duration
varies widely with species; however, in general, short/intermediate barbiturates
produce approximately 2-3 hours of anesthesia and ultrashort barbiturates
range from 10 to 20 minutes (McLaughlin, 1988).
Variation in dose response and duration
of effect of barbiturates is extreme within and between species (Olson,
1986a; Green, 1982; McLaughlin, 1988). The following are examples of the
variation found with pentobarbital (intermediate) anesthesia:
i) cats frequently having a considerably
prolonged sleeping time (McLaughlin, 1988);
ii) mice on hardwood bedding take
almost twice as long to recover as mice on softwood bedding, and male mice
sleep longer than female mice (McLaughlin, 1988);
iii) the anesthesia produced in
adult horses and cattle is of relatively short duration; however, the recovery
period is long and difficult (Lumb and Jones, 1984).
Whenever possible, barbiturates should
be administered intravenously, slowly, to effect. Administration by other
routes is far less satisfactory, as dosage is more difficult to judge and
the anesthetic effects are less predictable. Any of the barbiturates can
cause skin sloughing if perivascular injection accidently occurs (McLaughlin,
1988).
Although barbiturates are commonly used,
they are often poor choices for general anesthesia due to poor analgesia,
profound cardiovascular effects, high mortality and numerous external factors
that can affect dose response and sleeping time. Adequate anesthesia can
be obtained by combining a barbiturate with a tranquillizer, sedative or
an opioid (Olson, 1986a; Lumb and Jones, 1984; McLaughlin, 1988).
3. Chloralose
Chloralose may be used for non-survival
experiments requiring prolonged anesthesia and minimal surgical
interference (Flecknell, 1987; Holzgrefe, Everitt and Wright, 1987).
There is disagreement about whether chloralose is a true anesthetic agent
or a hypnotic with little analgesic action. It is used primarily for physiological
studies to preserve the vagal and central baroreceptor reflexes or in acute
cardiovascular studies to preserve myocardial function. While chloralose
is generally considered to have no application in survival studies or in
clinical veterinary medicine (Lumb and Jones, 1984), one recent study used
chloralose repeatedly over a long time period in puppies without any signs
of toxicity (Grad, Witten, Quan et al. 1988).
4. Urethane (Urethan,
Ethyl Carbamate)
Urethane produces long periods of anesthesia,
has a wide safety margin and little effect on normal blood pressure and
respiration. It produces sufficient analgesia to allow surgical manipulations
(Flecknell, 1987). However, the drug should be handled with extreme
care as it is considered to be cytotoxic, carcinogenic and immunosuppressive.
It
also causes profound changes in gastrointestinal function and is stimulatory
to the hypothalamus and pituitary (Olson, 1985). Animals should not
be allowed to recover following urethane anesthesia.
5. Saffan
Saffan is a combination of two steroids,
alphaxalone and alphadolone dissolved in a surfactant (vehicle), Cremaphor
EL, to solubilise it. It is administered intravenously or intramuscularly,
although the latter route gives more unpredictable results. Muscle relaxation
is good, and recovery rapid. It is rapidly metabolized and is an excellent
agent for long-term maintenance (Flecknell, 1987). It has been used for
the cat, pig, large farm animals, small NHP, rodents, birds and exotics
(Lumb and Jones, 1984; Flecknell, 1987; Green, 1982). It is not recommended
in the dog due to the associated massive histamine release caused by the
Cremaphor EL vehicle that often occurs (Flecknell, 1987). Saffan must not
be used with barbiturates (Flecknell, 1987).
6. Tribomoethanol
(Avertin)
The use of Avertin is controversial because
of the wide variation in results between laboratories. Although no longer
available in Canada, it may be introduced in a different formulation. Purchased
as a powder, it must be dissolved in amylene hydrate and then diluted with
distilled water at 40C immediately prior to use. Great care must be taken
to use only fresh solutions as it decomposes very rapidly in light or temperatures
above 40C, producing byproducts that are severe tissue irritants. In rodents,
it is given intraperitoneally (Green, 1982), resulting in good muscle relaxation
and moderate respiratory and cardiovascular depression (Flecknell, 1987;
Green, 1982); however, post-operative fatalities are often high due to
peritoneal adhesions. Even if a freshly prepared solution is used, mortality
is often high after administration of a second anesthetic at a later date
(Green, 1982; Norris and Turner, 1983).
7. Non-specific Injectable
Anesthetic Antagonists
Several agents have the ability to reverse
many of the effects of non-opioid injectable anesthetics through non-specific
antagonistic properties.
a) Yohimbine blocks central alpha-2-adrenoreceptors,
and partially antagonizes barbiturates, xylazine, ketamine, benzodiazepines
and phenothiazines (Fowler, 1986; Lumb and Jones, 1984).
b) 4-aminopyridine (4-AP) partially
antagonizes xylazine, ketamine and barbiturates. Yohimbine and 4-AP are
often combined for a more effective reversal (Lumb and Jones, 1984).
c) Doxapram is a respiratory stimulant
and not a reversal agent
per se; however, it has been used to partially
antagonize the respiratory depression produced by barbiturate anesthesia
in dogs (Hatch, Jernigan, Wilson et al. 1986).
8. Inhalant Anesthetics
Inhalant anesthetics have the advantage
of requiring minimal detoxification by the body, as they are exhaled through
the lungs, and the level of anesthesia can be easily and rapidly controlled.
However, their use requires specialized equipment for administration, and
constant monitoring of the patient (Stimpfel and Gershey, 1991). Some are
explosive or inflammable, or tissue irritants. Chronic exposure to some
agents is hazardous to the health of the operating room personnel (Lumb
and Jones, 1984).
The speed of induction and recovery depend
on the solubility of the anesthetic in blood. Highly soluble anesthetics
(methoxyflurane) are slow to reach an equilibrium in the blood; therefore,
induction and recovery are prolonged. Insoluble anesthetics (halothane)
reach an equilibrium rapidly, making manipulation of anesthetic depth easier,
but also more hazardous due to the potential for rapid overdose (Flecknell,
1987).
The use of inhalation anesthesia requires
the following equipment:
i) a vaporizer for the volatile
anesthetics;
ii) a source of carrier gas (usually
oxygen or air);
iii) a breathing system from which
the anesthetic mixture is inhaled;
iv) a mask or endotracheal tube
for connecting the breathing system to the patient (Sedgwick and Jahn,
1980; Gilroy, 1981). Exceptions are discussed with the individual agents.
Numerous simple systems have been devised and reported in the laboratory
animal literature for use in small laboratory animals (Dudley, Soma, Barnes
et
al. 1975; Skartvedt and Lyon, 1972; Rich, Grimm, Wong et al.
1990; Olson, 1986b; Levy, Zwies and Duffy, 1980; Mulder and Hauser, 1984).
Unnecessary exposure of personnel to gases
from volatile anesthetics must be avoided by use of appropriate scavenger
systems (Muir and Hubbell, 1989). Several reports have suggested a health
risk associated with prolonged and repeated exposure to low concentrations
of halothane (hepatocellular toxicity), methoxyflurane (renal toxicity),
nitrous oxide (neurologic disease and pernicious anemia) and to the chronic
ingestion of chloroform (renal and hepatic tumours in rodents) (Rettig,
1987; Stimpfel and Gershey, 1991). Expired gases should be vented to the
exterior or adsorbed onto activated charcoal (Mitchell, 1976).
a) Ether-based Volatile Agents
i) Diethyl ether is a highly volatile
agent of relatively low potency and wide range of safety. Ether produces
good muscle relaxation and analgesia; however, it is very irritating to
mucous membranes. The vapours are highly explosive, necessitating extreme
caution in its use and storage. Due to the risk of explosion, the use
of ether is discouraged as excellent alternatives are now available (Flecknell,
1987; Stimpfel and Gershey, 1991).
ii) Methoxyflurane (Metofane) is
a highly soluble, potent ether-based anesthetic. Because of its low volatility,
it may be used safely for induction with anesthetic chambers, and nose
cone maintenance. Methoxyflurane produces some respiratory and cardiovascular
depression, but less than halothane at comparable depths of
anesthesia. Myocardial
sensitization occurs, but is not as severe as with halothane. Muscle relaxation
and analgesia are good, and it is neither irritating nor explosive in anesthetic
concentrations. In animals, methoxyflurane anesthesia for less than one
hour is not usually associated with hepatorenal toxicity, especially if
periods of hypoxia and/or hypercapnia are avoided (Stimpfel and Gershey,
1991).
iii) Enflurane provides rapid induction
and emergence from anesthesia. It provides moderate levels of analgesia
and muscle relaxation, the latter decreasing as anesthetic concentrations
increase. It produces profound depression of respiratory functions and
myocardial performance (Short, 1987). It is largely eliminated via the
lungs. Unlike halothane, very little of the drug is metabolized by the
liver. This may offer some experimental advantages; otherwise, there is
little to choose between enflurane and halothane in terms of efficacy (Flecknell,
1987). Enflurane is expensive and requires a special vaporizer.
iv) Isoflurane is less potent than
halothane or methoxyflurane. It is relatively insoluble which leads to
fast inductions and recoveries. It may be used in halothane vaporizers
that have been recalibrated. It produces a slightly more severe respiratory
depression than does halothane, but slightly less depression of the cardiovascular
system (Flecknell, 1987). There is very little myocardial sensitization
to catecholamines; in fact, isoflurane has the greatest margin of safety
with the cardiovascular system of all the inhalant anesthetics. Isoflurane
produces better muscle relaxation than halothane, but has poorer analgesic
properties. It undergoes even less biotransformation than enflurane and
is almost completely eliminated in exhaled air (Flecknell, 1987).
Isoflurane has a pungent odour which may cause breath holding during induction.
It has no known toxicities, but it is expensive (Raper, Barker, Burwen
et
al. 1987).
b) Halogenated Hydrocarbons
i) Halothane, a halogenated hydrocarbon,
is highly potent and volatile. It should be used only with a finely calibrated
precision vaporizer. It produces dose-dependent depression of the cardiopulmonary
system and hypotension (Flecknell, 1987). There is direct myocardial depression
and sensitization to circulating catecholamines. The analgesia offered
by halothane is reasonable, as is muscle relaxation. The vapours are neither
explosive nor irritating, but can be hepatotoxic to man (Lumb and Jones,
1984).
c) Other Agents
i) Nitrous oxide has very low anesthetic
potency. Induction of a state of general anesthesia or even unconsciousness
is not possible in most animal species (Flecknell, 1987; Mahmoudi, Cole
and Shapiro, 1989). As it exerts minimal effects on the cardiopulmonary
system, it can be used to reduce the required concentration of other agents
and so reduce the degree of depression at a particular depth of anesthesia
(Flecknell, 1987). It has some analgesic properties in animals; however,
the potency is less than half that experienced in humans (Short, 1987).
Following cessation of nitrous oxide administration, 100% oxygen must be
administered to the
animal to prevent hypoxia caused by the
rapid diffusion of the gas from the body (Flecknell, 1987; Short, 1987).
Because it presents numerous occupational hazards, nitrous oxide should
be scavenged. If a carrier gas is required 100% oxygen is effective
and non-toxic as well as being vital to life (Stimpfel and Gershey, 1991).
D. MUSCLE RELAXANTS
1. Glyceryl Guiacolate
Glyceryl guiacolate (guaifenesin) is a
centrally acting muscle relaxant, with its action on the internuncial neurons
of the spinal cord. As the drug has little effect on the diaphragm, it
produces muscle relaxation without respiratory paralysis. A state of sedation
and hypnosis is produced; however, the degree of analgesia is in dispute.
Guaifenesin is most often used as part of induction technique in large
farm animals. It is useful in combination with thiobarbiturate for short
surgical procedures and for intubation prior to the administration of an
inhalant anesthetic (Lumb and Jones, 1984). Guaifenesin has been added
to ketamine and xylazine to produce effective anesthesia in ponies, dogs
and pigs with minimal cardiovascular and respiratory depression. This same
combination has also been used in a continuous infusion for long term anesthesia
in cats (Brown, McCarthy and Bennett, 1991).
2. Neuromuscular
Blocking Agents
Succinylcholine (a depolarizing agent),
curare, pancuronium, gallamine, atacurium and vecuronium (non-depolarizing
agents) are neuromuscular blocking agents which act peripherally at the
neuromuscular junctions. Anticholinesterases such as neostigmine, pyridostigmine
and edrophonium are antagonistic to the non-depolarizing agents, but ineffective
against the depolarizing agents (Lumb and Jones, 1984). Neuromuscular blocking
agents are used as adjuncts to general anesthetics where profound muscle
relaxation is desired.
These agents produce motor paralysis
only. There is no sedation or analgesia. Their use on conscious animals
is prohibited (see also Ethics of Animal Investigation).
The use of neuromuscular blocking agents
abolishes some of the signs used to judge the depth of anesthesia. Autonomic
functions remain intact with the newer agents (atacurium, vercuronium);
therefore, increases in heart rate and arterial blood pressure may indicate
the perception of pain. Animals must be artificially ventilated as the
respiratory muscles are paralyzed. Should neuromuscular blocking agents
be a component of an anesthetic protocol, it is extremely important that
proper equipment and personnel with experience in the use of these agents
be available.
E. LOCAL AND REGIONAL
ANESTHETICS
Local anesthetics such as lidocaine, procaine,
bupivacaine and tetracaine may be used to block the nerve supply to a limited
area for the performance of minor or rapid procedures. Local anesthesia
is also frequently used as an adjunct to various sedative and hypnotic
agents in more prolonged and invasive procedures, such as caesarian section.
Local anesthetic agents may be used for the regional infiltration of a
surgical site, field blocking, nerve blocks, and for epidural and spinal
anesthesia (Green, 1982; Elmore, 1981; Kero, Thomasson and Soppi, 1981;
Gray and McDonell, 1986). Veterinary assistance should be sought in the
initial use of the last three procedures (Lumb and Jones, 1984; Gray and
McDonell, 1986). A combination of lignocaine/prilocaine has also been used
topically for pain-free venipuncture in some laboratory animals (Flecknell,
Liles and Williamson, 1990).
F. ANIMAL HYPNOSIS
(Tonic Immobility)
A state of hypnosis or tonic immobility
can be readily induced in a variety of animals including rabbits, birds,
small rodents and reptiles (Prestrude and Crawford, 1970; Danneman, White,
Marshall et al. 1988). It is characterized by a lack of spontaneous
movement or overt response to external stimuli for up to several minutes,
and is usually exhibited under stressful or fearful conditions. There is
evidence that animals remain aware of external events and hypnosis can
be interrupted by mild tactile or auditory stimuli. It is usually induced
by placing the animal on its back and gently extending the neck and hind
legs to place traction on the spine. Recent work indicates that some degree
of analgesia is produced with hypnosis; however, individual animal susceptibility
to hypnosis varies greatly and in consequence hypnosis cannot be recommended
as a suitable alternative to appropriate analgesics when painful procedures
are to be performed (Danneman, White, Marshall et al. 1988).
G. SPECIES CONSIDERATIONS
a) Canine
General anesthesia: sedation, followed
by intravenous induction with an ultrashort-acting barbiturate, intubation
and maintenance with an inhalant anesthetic. Alternatively, intermediate
or long-acting barbiturates may be used but are poor analgesics and can
result in profound respiratory and cardiovascular depression (Flecknell,
1987; Green, 1982). Minor surgical procedures can be carried out using
neuroleptoanalgesics, xylazine combinations and diazepam combinations (Green,
1982).
b) Feline
General anesthesia: sedation, induction
using an injectable agent, intubation and maintenance with an inhalant
anesthetic (Green, 1982). The larynx should be sprayed with a local anesthetic
such as 2% lidocaine (without epinephrine) prior to intubation (Flecknell,
1987). Mask induction with an inhalant anesthetic is also well tolerated
if the cat is sedated previously and handled expertly. Ketamine and ketamine
combinations have proven very useful for restraint and minor surgical procedures
(Flecknell, 1987; Ingwersen, Allen, Dyson et al. 1988). Saffan or
xylazine also produce sedation and anesthesia for minor surgical procedures
(Flecknell, 1987; Green, 1982).
c) Ferrets
Administration of intravenous drugs can
be difficult in the awake ferret; therefore, alternate routes are usually
used. Intramuscular ketamine and ketamine combinations are useful (Muir
and Hubbell, 1989; Moreland and Glaser, 1985), as are fentanyl/ droperidol
and intravenous Saffan (Flecknell, 1987; Green, 1982). For induction with
inhalation anesthetics, a special induction chamber is usually used, with
maintenance by mask or intubation (Poole, 1987; Moody, Bowman and Lang,
1985).
d) Rabbits
Neuroleptanalgesics and ketamine combinations
with xylazine, acepromazine or azaperone have been used successfully (Muir
and Hubbell, 1989; Olson, 1986a; Flecknell, 1987; Lipman, Marini and Erdman,
1990). Ketamine alone does not produce adequate anesthesia or analgesia
(Lumb and Jones, 1984; Flecknell, 1987). The degree of analgesia produced
by Saffan is generally low. At the higher dose rates needed to produce
medium or deep surgical anesthesia, there may be sudden apnea followed
by cardiac arrest (Flecknell, 1987). A technique of continuous intravenous
infusion of ketamine and xylazine has been reported to maintain a light
anesthetic plane for up to 4 hours, although hypoxemia and hypotension
are marked (Wyatt, Scott and Richardson, 1989). Inhalant anesthetics and
mask induction are readily tolerated (Peeters, Gil, Teske et al.
1988). Endotracheal intubation in the rabbit is relatively difficult for
anatomical reasons. Barbiturates alone are not recommended in rabbits,
as the dose required to produce surgical anesthesia is very close to the
lethal dose. Respiratory arrest frequently occurs before the onset of surgical
anesthesia. They may be used, if combined with a sedative or tranquillizer
(Olson, 1986a; Peeters, Gil, Teske
et al. 1988). If atropine is
used it must be at high dose levels to counteract the presence of serum
atropinase (Muir and Hubbell, 1989).
e) Small laboratory rodents (rats, mice,
guinea pigs, gerbils, hamsters and wild rodents)
Withholding food and water is unnecessary
prior to anesthesia, since vomiting normally does not occur (Flecknell,
1987). Anesthetic agents used include barbiturates, ketamine, ketamine
combinations (Muir and Hubbell, 1989; Flecknell, 1987; Wixson, 1987a, 1987b),
neuroleptoanalgesics (Muir and Hubbell, 1989; Green, 1982; Parkes, 1987;
Olson, 1986a), tiletamine/zolazepam (Muir and Hubbell, 1989) and Saffan
(Green, 1982). Ketamine alone produces severe respiratory depression at
doses high enough for surgical anesthesia in small rodents (Flecknell,
1987). Intramuscular ketamine/xylazine causes muscle necrosis in Syrian
hamsters and is not recommended in that species (Gaertner, Boschert and
Schoeb, 1987). The same problem has been noted with fentanyl/droperidol
in guinea pigs (Holmes, 1984). Ketamine combinations and pentobarbital
are poor anesthetics in the gerbil, but fentanyl/metomidate (Flecknell,
John, Mitchell et al. 1983) and tiletamine/zolazepam have proven
effective (Hrapkiewicz, Stein and Smiler, 1989). Barbiturates are still
in common use, but are very poor analgesics, and often cause high mortality,
especially when given intraperitoneally or when full-strength commercial
solutions are used intravenously (dilution is recommended). When combined
with a sedative, tranquillizer or an opioid, adequate anesthesia results
(Olson, 1986a).
Induction of anesthesia with an inhalational
agent is best accomplished with an induction chamber. Anesthesia may be
maintained with a face mask. Endotracheal intubation is difficult in small
rodents and requires purpose-made laryngoscopes (Flecknell, 1987).
The safe administration of general anesthesia
to the guinea pig is notoriously difficult, since they often maintain their
pedal reflex and make squirming movements even when deeply anesthetized
(Holmes, 1984). Their response to many injectable anesthetics is very variable.
Post-anesthetic complications such as respiratory infections, digestive
disturbances, and generalized depression, are seen (Flecknell, 1987). Spinal
anesthesia offers a useful alternative (Green, 1982).
Very brief procedures (e.g., orbital blood
sampling) may be performed on rodents by using a 50:50 mixture of carbon
dioxide and oxygen, if the animal is removed from the gas chamber as soon
as the pedal reflex has disappeared (Green, 1982; Fenwick and Blackshaw,
1989).
Hypothermia may be used to anesthetize
neonatal mice and rats (1-2 days old). The pup is placed in an ice water
slush for 20-30 minutes (Green, 1982).
f) Non-human Primates
Ketamine and its combinations are most
often used for restraint, particularly where rapid recovery is desired.
Neuroleptanalgesics have also been used, and Saffan is useful for small
species such as marmosets. The NHP can be intubated and inhalation anesthesia
administered using techniques similar to those used for the human (Flecknell,
1987; Sainsbury, Eaton and Cooper, 1989).
g) Horses
Both induction and recovery from anesthesia
may be associated with excitement. Due to their size and strength, special
facilities are required for induction and recovery in horses. Veterinary
consultation should be sought. Xylazine and acepromazine are most commonly
used as pre-anesthetics, followed by an induction agent (thiamylal sodium,
guaifenesin, etc.) and inhalation anesthesia (Muir and Hubbell, 1989; Green,
1982).
h) Ruminants
Many surgical procedures can be performed
under local or regional anesthesia (Muir and Hubbell, 1989; Green, 1982;
Gray and McDonell, 1986). The greatest problems with sedation and general
anesthesia are regurgitation, hypoventilation and bloat. The use of atropine
in ruminants is controversial, as it induces bloat and increases the viscosity
of the saliva, while not decreasing the quantity. Xylazine is given at
one-tenth the dose of horses, and usually results in recumbency. It is
probably best to administer xylazine by slow intravenous injection in sheep
and goats as results produced by intramuscular administration are unpredictable.
It should be noted that some goats appear particularly sensitive to xylazine
(Hall and Clarke, 1991). Bloat is often a problem following xylazine administration,
and abortion can be induced in the last trimester (Muir and Hubbell, 1989).
Xylazine/ketamine with or without guaifenesin can be combined for shorter
surgical procedures (Coulson, Januszkiewicz, Dodd et al. 1989).
Other recommended injectables for sheep are Saffan and ketamine/diazepam
(Flecknell, 1987).
Although thiopental is useful for induction,
pentobarbital is not recommended, especially in goats, due to respiratory
depression. Animals less than three months old metabolize barbiturates
very poorly (Muir and Hubbell, 1989).
Mask induction with an inhalant anesthetic
such as halothane or isoflurane is particularly useful with the smaller
species. Sheep should always be intubated to prevent aspiration if regurgitation
occurs. Intubation is accomplished with the use of a laryngoscope in small
ruminants and by direct palpation of the larynx in large ones. A lidocaine
spray should be used on sheep vocal cords prior to intubation to prevent
laryngospasm (Flecknell, 1987).
i) Swine
Pigs should be fasted 12 hours before surgery
to prevent vomiting; however, water can be offered until the pre-anesthetic
is given (Muir and Hubbell, 1989). As respiratory depression is a frequent
sequela to general anesthetics in pigs, reversible drugs such as xylazine
or opioids are recommended (Green, 1982; Muir and Hubbell, 1989). Epidural
anesthesia is also commonly used (Muir and Hubbell, 1989). Ketamine in
combination with xylazine, diazepam, acepromazine or fentanyl/droperidol
have produced good results as general anesthetics (Muir and Hubbell, 1989;
Green, 1982; Swindle, 1985), as have other injectable anesthetic such as
Saffan (Flecknell, 1987) and tiletamine/zolazepam (Muir and Hubbell, 1989;
Bauck, 1984; Cantor, Brunson and Reibold, 1981). Barbiturates are generally
used only in combination with a sedative (Muir and Hubbell, 1989). Azaperone
produces sedation, but has no analgesic effect (Flecknell, 1987).
Inhalation agents are well tolerated and
mask induction can be carried out on small pigs with ease (Becker, 1986).
Intubation of the trachea is difficult for anatomical reasons (Lumb and
Jones, 1984; Flecknell,1987; Green, 1982), and a lidocaine spray on the
vocal cords is used to prevent laryngospasm (Green, 1982).
Malignant hyperthermia has been observed
in response to inhalation anesthetics (especially halothane), depolarizing
muscle relaxants and stress in swine. A predisposition to hypothermia is
probably inherited (Basrur, Bouvet and McDonell, 1988), and is commonest
in the Landrace and Poland China breeds. Dantrolene is effective therapy
for malignant hyperthermia (Muir and Hubbell, 1989).
j) Avian
Hypothermia is a frequent problem in general
anesthesia, especially for small birds. Small birds are also prone to handling
shock, and small friable vessels make intravenous injection difficult (Green,
1982). Ketamine is an effective pre-anesthetic, and ketamine/xylazine (Muir
and Hubbell, 1989) or ketamine/diazepam (Fowler, 1986) are two of the safest
injectable anesthetics. Tiletamine/zolazepam is an alternative to ketamine/xylazine
(Muir and Hubbell, 1989; Green, 1982). Diazepam combined with chloropent
(chloral hydrate, sodium pentobarbital, magnesium sulfate) provides surgical
anesthesia for 60-90 minutes in the domestic fowl (Christensen, Fosse,
Halverson et al. 1987). Saffan has been used in a variety of avian
species (Lumb and Jones, 1984). However, it should only be administered
intravenously, and even then used with great caution due to associated
cardiac arrhythmias (Green, 1982; Short, 1987).
Inhalant anesthesia with mask induction
can be used fairly safely and effectively; however, because of the efficiency
of the avian respiratory system, changes in anesthetic depth tend to occur
very rapidly, especially in small birds (Muir and Hubbell, 1989; Lumb and
Jones, 1984; Green, 1982). Resuscitation is complicated due to accumulation
in the air sacs (Fowler, 1986; Ludders, Mitchell and Schaefer, 1988). Inhalants
cannot be used for thoracic procedures because the gas leaks through the
opened air sacs (Christensen, Fosse, Halverson et al. 1987), and
positive pressure ventilation is necessary for abdominal procedures due
to an incomplete diaphragm. Restraint must allow free movement of the sternum
for respiration. Isoflurane is the safest inhalation anesthetic, followed
by halothane (Muir and Hubbell, 1989).
k) Cold Blooded Animals
Agents commonly used include tiletamine/zolazepam,
ketamine, Saffan, tricaine methanesulfonate (MS-222) and inhalant anesthetics.
Dosage varies widely between species. Absorption and excretion of injectable
anesthetics are directly related to environmental temperature.
Fish should be fasted 24-48 hours to prevent
vomiting (Green, 1982). They are commonly anesthetized by immersion or
use of a recirculation system that passes an anesthetic solution over the
gills. Tricaine methanesulfonate (MS-222) (Brown, 1987), and benzocaine
(Green, 1982) are recommended, although numerous other anesthetics including
carbon dioxide, ether, chloral hydrate, halothane and Saffan have also
been used (Muir and Hubbell, 1989; Lumb and Jones, 1984; Green, 1982).
Benzocaine is as effective as MS-222, equally safe for personnel and much
less expensive (Green, 1982). Exposure of benzocaine to direct sunlight
causes breakdown and releases highly toxic chlorine (Poole, 1987).
Reptiles and amphibians can be effectively
anesthetized with local anesthetics, immersion in a solution containing
an anesthetic agent, injectable or inhalation anesthetics (Muir and Hubbell,
1989). Hypothermia should only be used for restraint in non-painful procedures,
as it is not known whether or not analgesia is induced. Secondary tissue
damage also results from the practice. Hypothermia is not a suitable anesthetic
for major surgery (Muir and Hubbell, 1989). Amphibians can be anesthetized
by immersion in MS-222, which provides excellent muscle relaxation and
analgesia (Muir and Hubbell, 1989; Green, 1982). Preferred injectable anesthetics
for reptiles include ketamine and tiletamine/zolazepam, although Saffan
and etorphine have also been used successfully (Muir and Hubbell, 1989;
Fowler, 1986).
Inhalation anesthesia is induced by soaking
a cotton ball with a volatile anesthetic and placing it with the animal
in a box or bag, or using an induction chamber or face mask (Muir and Hubbell,
1989). Halothane, isoflurane and methoxyflurane are preferred to ether
(Muir and Hubbell, 1989). Reptiles are relatively easy to intubate, as
the larynx is readily visualized. Their slow respiratory rates and ability
to breath-hold constitute complicating factors (Muir and Hubbell, 1989).
Inhalants are not recommended for turtles (Green, 1982).
Johnson (1992) warns that in administering
anesthetics to amphibians and reptiles, one must consider the structure
of the reptilian respiratory system. Respiratory movements are different
in snakes, which have one lung, crocodiles which have diaphragms, and lizards
which have pleuroperitoneal cavities. He suggests that, because their respiratory
movements may be weak, if a volatile anesthetic is used, one may have to
assist respiration because they have a poor way of expelling air. Johnson
also notes that, if anesthesia is to be done for a long period of time,
amphibians must be kept moist; as they are all poikilotherms, keeping them
at their preferred optimum temperature zone will have an effect on the
absorption and excretion of the anesthetic.
l) Invertebrates
Volk (1986) discusses methods of evaluating
anesthetic depth in various invertebrates and includes a complete list
of anesthetics.
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