General Topics: Anesthesia, Analgesia, and Sedation of Small Mammals

SECTION SIX
General Topics
CHAPTER 31
Anesthesia, Analgesia, and
Sedation of Small Mammals
Michelle G. Hawkins, VMD, Diplomate ABVP (Avian), and

Peter J. Pascoe, BVSc, Diplomate ACVA, DVA, Diplomate
ECVAA

General Principles and Challenges in Anesthetizing GENERAL PRINCIPLES AND CHALLENGES IN

Small Exotic Mammals ANESTHETIZING SMALL EXOTIC MAMMALS
Balanced Anesthesia/Analgesia There are many challenges to be faced when one is anesthetizing
Preanesthetic Considerations very small patients. It is more difficult to obtain preoperative
Patient Evaluation blood work, secure an airway or intravenous access, monitor
Nutritional Status and Fasting anesthesia, and prevent hypothermia once the animal is anes-
Equipment thetized. Small mammals have higher metabolic rates and
Breathing Circuits smaller glycogen reserves, predisposing them to hypoglycemia.
Ventilators Metabolism and excretion of parenterally administered drugs
Clinical Techniques are faster; therefore they have shorter durations of action. Small
Vascular Access mammals have higher oxygen consumption and may thus suffer
irreversible central nervous system (CNS) injury more rapidly
Intubation
during respiratory arrest. Time becomes critical during anesthe-
Preanesthetic Medications sia; complications occur faster, and the time for intervention is
Injectable Medications shorter. Much dosing information has been established in ter-
Sedatives and Tranquilizers minal studies of young, healthy laboratory animals, so critically
Induction and Maintenance of Anesthesia evaluate the information prior to using it in a sick or debilitated
Injectable Anesthetics pet animal. A recent large-scale prospective study reported an
Inhalant Anesthesia overall perianesthetic mortality rate of healthy pet rabbits and
Local and Regional Anesthesia guinea pigs of approximately 1.39% and 3.80%, respectively,
Epidural Anesthesia/Analgesia values 5 to 10 times higher than those found in dogs and cats.9
Anesthetic Monitoring and Supportive Care There is substantial room to decrease mortality during anesthe-
Emergencies sia in these patients.
Small Mammal Analgesia
Opioids BALANCED ANESTHESIA/ANALGESIA
Tramadol Hydrochloride Isoflurane has been the most common anesthetic used in small
Nonsteroidal Anti-Inflammatory Drugs exotic mammals for the last two decades and is often admin-
Acupuncture istered as the sole agent. Inhalant anesthetics have the advan-
tage of allowing rapid changes in anesthetic depth and rapid
Copyright © 2012 by Saunders, an imprint of Elsevier Inc. 429

430 SECTION VI General Topics
recoveries owing to their low solubility in tissues and elimina- gastrointestinal (GI) transit times and potential for GI stasis.
tion via the respiratory tract. But inhalants also induce dose- Fasting has been advocated to reduce stomach and cecal volumes
dependent cardiopulmonary depression. Clinically, 1.3 to 1.5 in large and obese rabbits, which can theoretically compress
times the minimum alveolar concentration (MAC) of an inhal- their small thoracic cavities, but this generally does not change
ant is required for immobility during surgery, but inhalants do GI volumes enough to be clinically important. Fasting exhausts
not block activation of nociceptive pathways by noxious stimuli. glycogen stores, resulting in hypoglycemia, and may significantly
High inhalant doses (1.5-3 times MAC) are required to block contribute to perianesthetic ileus and potentially exacerbate pan-
undesirable responses to pain, such as changes in heart rate, creatic tumors in ferrets. Fasting reduces regurgitation in ferrets,
blood pressure, and respiratory rate, but the margin of safety at but vomiting/regurgitation is uncommon in most other small
these doses is low and circulatory collapse can occur.121 While mammal species. Rabbits and rats cannot vomit because of their
inhalants are still the main agents used for many procedures, well-developed cardiac sphincter and limiting ridge of the stom-
there are many ways to minimize their use and thus decrease ach, respectively. In general, recommended fasting times are 0 to
their adverse effects. 4 hours, with prudence used to weigh the risks and benefits in the
The concept of “balanced anesthesia” originated to provide specific patient. Schedule procedures early in the day to reduce
the elements of anesthesia (unconsciousness/amnesia, immo- fasting times. Many small rodents store food in their oral cavities;
bility, muscle relaxation, reduced autonomic response to nox- thus the mouth is cleaned out by gently syringing water into the
ious stimuli) by using multiple drugs at lower overall doses so as oral cavity to remove food materials in tolerant awake patients
to minimize the adverse effects of each drug while still provid- or with wet cotton tips immediately after induction. Elevate the
ing appropriate anesthesia and analgesia for the procedure. This head during anesthesia if there is any concern of aspiration.
approach reduces the magnitude of cardiovascular depression
under anesthesia and promotes hemodynamic stability.
EQUIPMENT
Even with balanced anesthesia protocols, morbidity and
mortality increases with increased duration of anesthesia.
BREATHING CIRCUITS
Minimize anesthesia time by preparing the patient as well as
all drugs and equipment in advance and provide close patient Nonrebreathing circuits (Ayre’s T-piece, Mapleson systems,
monitoring so that adjustments in anesthesia are identified and Magill, Jackson-Rees, Norman elbow, and the Bain circuit)
corrected immediately. Morbidity and mortality also occurs dur- are most commonly used for anesthetizing small mammals.
ing recovery, and it is important to continue to monitor animals The nonrebreathing system depends upon high rates of fresh
until they are fully recovered. gas flow to remove carbon dioxide (CO2) and provides rapid
changes in inhalant concentration when the vaporizer setting is
changed. Circle systems are heavier and bulkier, which predis-
PREANESTHETIC CONSIDERATIONS
poses to accidental extubation and difficulty working around
the head region. These circuits also have a greater resistance to
PATIENT EVALUATION
breathing. For these reasons, the nonrebreathing circuit is used
A complete history should be obtained and a physical exami- most commonly in small mammals.
nation performed to assess preexisting clinical problems and In general, the flow rate used for a T-piece or Norman elbow
record baseline values for comparison. Age should be consid- should be two to three times the minute ventilation. But in the
ered, because the margin of safety is wider in younger animals. Bain circuit, a flow rate of 150 to 200 mL/kg per minute appears
Obtain an accurate body weight for fluid and drug dose calcula- effective. Removal of waste gases from the circuit occurs during
tions. Evaluate hydration status, and correct dehydration prior to the pause between expiration and inspiration. Thus if the respi-
anesthesia. Compensatory mechanisms are blunted under anes- ratory rate is high (shorter pause and therefore more mixing of
thesia, exacerbating underlying hypotension and poor peripheral inspired and expired gases), a higher flow rate should be used
perfusion. Whenever possible, preanesthetic noninvasive blood (e.g., if RR >40, increase the flow rate to 300 mL/kg/min).
pressure should be assessed to provide a more objective assess-
ment of perfusion. Ideally, a complete blood count and bio-
VENTILATORS
chemical profile should be performed prior to anesthesia. Severe
anemia should be corrected, because the patient may not be able Ventilators appropriate for small mammals must cope with the
to compensate for decreased oxygen delivery. The packed cell vol- range of tidal volumes in the different species. In very small
ume (PCV) may decrease 3% to 5% during anesthesia because of patients, this may be less than 1 mL; but some giant-breed rab-
vascular hemodynamic changes. In ferrets, isoflurane and sevo- bits might need to be as high as 500 mL. In general the three
flurane are associated with significant reductions in PCV.77-79 things that must be controlled by a ventilator are tidal volume,
Glucose concentration should be monitored and supplemented the rate at which the tidal volume is delivered, and the number
as necessary. The type of surgery to be performed and potential of breaths per minute. The way in which each of these is con-
for blood loss should be assessed for fluid plan preparation. trolled varies from ventilator to ventilator.45
NUTRITIONAL STATUS AND FASTING CLINICAL TECHNIQUES

Prolonged anorexia leads to negative energy balance and
VASCULAR ACCESS
hypoglycemia, requiring nutritional support in the perianes-
thetic period. Nutritional support for the debilitated patient Vascular access is necessary for replacement fluids and to deliver
is discussed in Chapter 38. Overnight fasting prior to anesthe- anesthesia and emergency medications. Sites for intravenous
sia is not performed in small mammals because of their rapid catheterization include the cephalic, lateral saphenous, and
CHAPTER 31 Anesthesia, Analgesia, and Sedation of Small Mammals 431
A B
Fig. 31-1 Catheterization of the cephalic vein is the most common intravenous site used (A),
but the lateral saphenous, jugular, or femoral veins and the superficial lateral tail veins in the rat can
also be used. Catheters can be taped and bandaged for security; additional stability can be provided
with tongue depressors for very small limbs. In cases where intravenous catheterization is not pos-
sible, an intraosseous catheter may be placed in the tibia (B) or femur for short-term use.
femoral veins in larger mammals and the superficial lateral IO catheter; administration of alkaline or hypertonic solutions
tail veins in the rat (Fig. 31-1). Sedation may be necessary for can contribute to osteomyelitis and cause pain.89 Dilute these
intravenous catheter placement. A surgical cut-down procedure solutions before administration and flush the catheter with hep-
under anesthesia is generally necessary for jugular catheter- arinized saline after any drug injection.
ization. Small-bore over-the-needle catheters (≤24 gauge) are Arterial catheterization for the evaluation of blood pressure,
used. The catheter site should be aseptically prepared; cath- blood gas tension, and pH can be performed in many species.
eters are then secured with tape and/or sutured in place and The most common sites include the pedal arteries in most spe-
bandaged for extra security. Jugular catheters, if left indwelling, cies, the central auricular artery in the rabbit, and the ventral
require 24-hour monitoring, as fatal hemorrhage can occur if tail artery in the rat and ferret. The catheters are usually placed
the patient pulls or chews on the catheter and damages the ves- percutaneously, but a cut-down procedure is sometimes used.
sel. Many small rodents, even when severely compromised, are
intolerant of bandaging material and indwelling catheters and
INTUBATION
will attempt to remove them.
Intraosseous (IO) cannulation can be useful in smaller Endotracheal intubation provides a patent airway, reduces
patients or during cardiovascular collapse (see Fig. 31-1).89 Prod- dead space, and facilitates positive-pressure ventilation. Dis-
ucts that can be used as IO cannulas include 18- to 24-gauge 1- to advantages include tracheal mucosal trauma, increased airway
1½-in. spinal needles or 18- to 25-gauge 1-in. hypodermic nee- resistance, and airway occlusion due to mechanical forces or
dles, depending upon the animal’s size. The cannula should be secretions. Increased resistance is of greater importance in very
long enough to extend through one-third to one-half the length small patients because it is inversely related to the fourth power
of the medullary cavity. A wire stylet reduces the potential for a of the tube radius. For example, decreasing the tube radius from
bone core. Prepare several hypodermic needles (25- to 18-gauge) 5 to 3 mm increases the resistance 7-fold, whereas a decrease
with wire stylets (stainless steel suture) and sterilize them for IO from 3 to 1 mm increases it more than 80-fold. Increased resis-
catheterization. Common sites for IO cannula placement include tance can be overcome by positive pressure ventilation.
the trochanteric fossa of the femur and the tibial crest (see Fig. Specialized endotracheal tubes and light sources are avail-
31-1, B). Placement is similar to that of a normograde intramed- able to aid intubation of small mammals. The smallest com-
ullary pin and requires strict aseptic technique during placement mercial uncuffed tubes have an internal diameter (ID) of 1 mm.
and maintenance. Once the cortex is penetrated, the cannula However, tubes of less than 2-mm ID are often highly flexible
should advance easily, with little resistance. Flush the cannula and kink easily. The smallest-diameter cuffed tube is 3-mm ID.
with heparinized saline immediately to prevent clotting. Cover Uncuffed tubes do not provide a sealed airway, so clean the oral
the insertion site with an antibiotic ointment and secure the can- cavity prior to intubation, elevate the head, and monitor during
nula with tape, suture, and a bandage. IO cannulas can remain the procedure. If you are using a cuffed tube, the cuff is care-
patent for 72 hours without flushing but should be flushed with fully inflated with just enough air to prevent leakage when 10
heparinized saline twice daily if fluid therapy is not continu- to 15-cm H2O pressure is applied. Very small mammals may be
ous. Complications associated with IO catheterization include intubated with Teflon IV, red rubber, or urinary catheters (Fig.
penetration of both cortices, failure to properly enter the med- 31-2, A). Care is taken to ensure that no sharp edges are present
ullary cavity, and extravasation of fluids with associated pain.89 at the end. This is achieved by using a small piece of silicone
IO catheters are used primarily for short-term vascular volume tubing over the end of the catheter (see Fig. 31-2, B,C).
expansion until an IV catheter site can be obtained. Many ani- Endotracheal tube obstruction is detected by monitoring for
mals become uncomfortable on limbs supporting IO catheters a prolonged expiratory phase. Anticholinergics reduce the pro-
even after short-term placement. IO catheterization is contrain- duction of mucus and mucous plug formation but also increase
dicated in septic patients and those with metabolic bone disease. mucous viscosity, making it harder to clear secretions. The
Osteomyelitis may occur owing to duration or placement of the use of an endotracheal tube with a Murphy eye decreases the
for intubation (Fig. 31-3). Placement of the tube is confirmed by

visualizing the movement of water vapor in the tube, by the rab-
bit coughing, by auscultation of breath sounds in the lungs, and
definitively by attaching a capnograph and seeing a characteristic
capnographic trace. Rabbits are obligate nasal breathers and the
patency of both nares must be carefully assessed postextubation,
especially if the animal has been in dorsal recumbency. Reported
complications include postextubation obstruction, respiratory
arrest, and tracheal mucosal injury.38,92 Intranasal intubation or
A catheterization can be used in the rabbit if endotracheal intuba-
tion cannot be performed or for complicated oral procedures,
such as extensive dental procedures. The ventral meatus of the
rabbit’s nasal passage is surprisingly large. A blind intubation
technique with a 2.5- to 3-mm ID endotracheal tube is used, but
these are often stiff for smaller rabbits; standard IV tubing has a
thinner wall and so is more flexible. IV tubing can be cut to the
appropriate length and a bevel fashioned on the distal end; the
B proximal end can be fitted with a 2- to 2.5-mm endotracheal
tube adapter. Administer anticholinergics with nasal intubation,
as vagally mediated bradycardia can be associated with this pro-
cedure. The tube is passed through the ventral meatus with the
head held in a normal or slightly extended position. Because of
the difficulties of intubating rabbits, newer techniques such as
laryngeal mask airways are being evaluated.7,66,111
Rodents also have a long narrow oral cavity, but equipment
C and techniques for intubating small rodents have been devel-
oped.87,117 In guinea pigs and chinchillas, orotracheal intubation
Fig. 31-2 A, Commercial endotracheal tubes are useful for larger is complicated by the fusion of the soft palate to the base of the
mammals, but Teflon intravenous, red rubber, and urinary catheters
tongue, creating the palatal ostium, which is highly vascular and
are often necessary to intubate very small mammals. A small piece
of silicone tubing can be glued over the end of the intravenous cath- easily traumatized (Fig. 31-4, A). Endotracheal tubes of 1.0- to
eter to minimize sharp edges (B, C [inset]). 2.5-mm ID are most often needed for small rodents. Very small
rodents may be intubated with catheters or IV tubing as in the
rabbit, but occlusion with mucous plugs, due to the small inter-
likelihood of mucous occlusion. Humidification of the gases nal diameter of these tubes, occurs frequently. An otoscopic cone,
reduces mucous plug formation. Commercial endotracheal tube modified pediatric blade, commercially available rodent work
humidifiers are available (Humidi-vent Mini Agibeck Product, stands and intubation packs, or endoscopy can help facilitate
Hudson RCI, Temecula, CA). Disadvantages of their use include intubation. Otoscopic cones that have been modified by remov-
increased dead space and plugging of the filter with secretions. ing a section laterally can facilitate visualization of the epiglottis
Care must be taken to minimize head and neck movement and direct placement of the endotracheal tube. A stylet placed
in intubated patients, as movement of the tube and changes first may help facilitate endotracheal tube placement (see Fig.
in positioning may induce mucosal trauma. Sublaryngeal tra- 31-4, B,C). Endoscopy provides the best visualization of the epi-
cheal injury, ulceration, and postintubation tracheal strictures glottis and minimizes trauma during tube placement. Nasal intu-
have been described in rabbits from several institutions that bation/catheterization has also been performed for guinea pigs
were intubated with both cuffed and uncuffed endotracheal and other small rodents with similar issues arising as for rabbits.
tubes.38,92 Other factors that predispose to mucosal injury
include ventilation technique and endotracheal tube disinfec-
PREANESTHETIC MEDICATIONS
tion protocols.
Ferret intubation is straightforward and should be performed Parasympatholytics are most commonly used to minimize
routinely as in the cat. All pet rabbits over 1-kg body weight can salivary and bronchial secretions and vagally induced bradyar-
be intubated, but this is more difficult. Rabbits have large inci- rhythmias, but they can increase secretion viscosity. Many rab-
sors, long narrow oral cavities, and thick tongues, making laryn- bits have high circulating concentrations of atropine esterases,
geal visualization more difficult, and laryngospasm is easily thus reducing the efficacy of atropine and prompting the use
induced. There are a number of tracheal intubation techniques of much higher atropine doses, with redosing as often as every
that have been advocated for use in rabbits: direct visualization 10 to 15 minutes during bradycardia.44 Large doses of parasym-
of the larynx with a laryngoscope and intubation, blind intuba- patholytics can alter GI motility in hind-gut fermenters; there-
tion with the neck in extension, endoscope-guided intubation, fore the lowest doses necessary are used.48 Glycopyrrolate has a
and nasotracheal intubation. Apply topical local anesthetic on longer duration of activity than atropine (Table 31-1). Glycopyr-
the larynx 60 seconds before intubation to decrease laryngo- rolate increased heart rates in rats for 240 minutes, versus 30
spasm. The authors use the blind technique routinely. Guide the minutes with atropine.86 The same study demonstrated that 0.1
tube to the larynx and listen for louder breath sounds, place one mg/kg glycopyrrolate administered to rabbits increased heart
drop of 2% lidocaine via tomcat catheter through the endotra- rate for an equal duration to the rats, but atropine doses ≤2 mg/
cheal tube directly on to the larynx, then use the same approach kg did not increase heart rate for any duration.86
A B C
Fig. 31-3 Intubation of the rabbit using the blind technique. Provide fresh oxygen and anes-
thetic gas through a nasal mask during the procedure. Guide the tube to the larynx, listen for louder
breaths and/or visualize water vapor in the tube (A), place one drop of 2% lidocaine via tomcat
catheter through the endotracheal tube directly onto the larynx (B), wait 60 seconds, then use the
same approach for intubation (C). Placement of the tube is confirmed by visualizing movement of
water vapor in the tube, by the rabbit coughing, by auscultation of breath sounds in the lungs, and
definitively by attaching a capnograph and seeing a characteristic capnographic trace.
A B
Fig. 31-4 In guinea pigs and chinchillas, orotracheal intubation is complicated by the fusion of
the soft palate to the base of the tongue, creating the palatal ostium, which is highly vascular and
easily traumatized (A). Intubation can be accomplished with the use of an otoscope or endoscope
and placement of a stylet (B), then threading the endotracheal tube over the stylet (C).
434
Table 31-1 Injectable Preanesthetic, Sedative, and Tranquilizer Drugs Used in Small Exotic Mammalsa
Rabbit Ferret Guinea Pig Chinchilla Rat Hamster Gerbil Mouse Comments
Preanesthetics
Atropine 0.2-1.0 SC, IM, 0.05 SC, IM, 0.05 SC, IM, 0.05 SC, IM, 0.05 SC, IM, 0.04 SC25 0.04 SC25 0.05 SC, Higher doses may be
SECTION VI General Topics

IV IV IV IV IV, IP IM, IP necessary in rabbits
Glycopyrrolate 0.01-0.02 SC, 0.01-0.02 SC, 0.01-0.02 0.01-0.02 SC, 0.02-0.5 SC, 0.5 IM25 − 0.02-0.5 SC, −
IM, IV IM, IV SC, IM, IV IM, IV IM, IV25 IM25
Sedatives/
tranquilizers
Acepromazine 0.25-1.0 SC, IM 0.1-0.2 SC, 0.5-1.0 SC, 0.5-1.0 SC, 0.5-2.5 SC, IM, − 3 IM25 2-5 SC, May induce seizures in
IM25 IM25 IM IP25 IM, IP25 gerbils
Atipamezole ≥ 1 SC, IM, ≥ 1 SC, IM, IV ≥ 1 SC, IM, ≥ 1 SC, IM, 0.1-1.0 SC, IM, − − ≥ 1 SC, IM, 1:1 volume reversal
IV68,88 IV IV54 IV, IP25 IV, IP of medetomidine or
dexmedetomidine
Dexmedetomidine 0.05-0.125 IM 0.04-0.1 IM 0.05 SC 0.05 SC 0.015-0.5 SC, − − 0.015-0.5 Half the dose of
0.05-1.0 μg/kg 0.05-1.0 μg/kg IP SC, IP medetomidine;
IM, IV IM, IV Microdoses
combined with
benzodiazepines
and opioids for
sedation, induction
Diazepam 0.5-2.0 IV 0.5-2.0 IV 0.5-3.0 IV 0.5-3.0 IV 2.5-5.0 IV, IP 5 IM, IP25 5 IM, IP25 3-5 PO, IP25 Significant irritation if
given IM
Flumazenil 0.05-0.1 SC, 0.05-0.1 SC, 0.05-0.1 SC, 0.05-0.1 SC, 0.1-1.0 IM, IV, − − − Reversal of
IM, IV IM, IV IM, IV IM, IV54 IP25 benzodiazipines
Medetomidine 0.1-0.25 SC, IM 0.01-0.2 SC, 0.1 SC 0.1 SC 0.03-0.1 SC, 0.03-0.1 SC, 0.1-0.2 IP25 0.03-0.1 SC, Light sedation, rarely
1-2 μg/kg IM, IV IM25,70 IP25 IP25 IP25 used alone; variable
1-2 μg/kg IM, − − − − − − effects in guinea
IV pigs
Microdoses combined
with benzodiazepine
and opioid for
induction
Midazolam 0.25-2.0 SC, 0.25-0.5 SC, 0.5-2.0 SC, 1-2 SC, IM, IV 1.0-2.5 SC, IM, 5 IP25 5 IM, IP25 1-5 SC, Lower doses for
IM, IV IM, IV IM, IV IV; 5 IP25 IM, IV25 premedication
Xylazine 2-5 IM, IV25 0.1-0.5 SC, 2-10 IM, IV 2-10 IM, IV 1-5 IM, IV, IP 1-5 IM, IP25 2 IM25 5-10 IP25 Seldom used
IM25
Yohimbine 0.2-0.4 IV 0.2-1.0 IM, IV 0.5-1.0 IM, 0.5-1.0 IM, IV 0.2 IV; 0.5 IM25 − − 0.5-1.0 Reversal for xylazine
IV IM, IV
aThese are suggested doses based on published information and the authors’ clinical experience. Species and individual variation in response to a given drug can be uncertain so adjust the
dose depending on the clinical response of the animal. All doses are in milligrams per kilogram unless specified otherwise.
been used as a sole sedative for minor, nonpainful procedures

INJECTABLE MEDICATIONS
in rabbits and rodents. Lower doses are most often used for pre-
A considerable increase in the use of injectable anesthetic anesthetic sedation. Flumazenil will reverse midazolam, but
combinations in small exotic mammals has recently been because its half31-life is shorter than that of midazolam, reseda-
documented.* Certain breeds or even strains of small mammals tion may occur. Titrate the flumazenil dose to avoid the rever-
have differing responses to injectable anesthetics.5 There is little sal of the beneficial anxiolysis, sedation, and muscle relaxation.
published work evaluating different injectable combinations Benzodiazepines coupled with opioid medications provide
for common surgical procedures in pet animals of differing age, sedation and preoperative analgesia.
sex, breed, and health status in the clinical setting,40,88 and so
use caution when extrapolating injectable doses from labora- Alpha-2 Agonists
tory animal studies. Using reversible injectables provides better Xylazine, medetomidine, and now dexmedetomidine are the
control of anesthetic depth, less hypothermia, less cardiopul- most commonly used alpha-2 adrenergic receptor agonists in
monary depression, and shorter recovery times.54-56,98 small exotic mammals (see Table 31-1). Their major advantages
Muscle necrosis and cutaneous reactions can occur in any are that they provide good muscle relaxation and can be reversed
patient administered IM injections, depending on the drug for- with yohimbine, atipamezole, or tolazoline (see Table 31-1). If
mulation or volume delivered. Drugs are often not uniformly all analgesic components are reversed, postoperative analgesia
absorbed when administered SC, resulting in erratic and unpre- should be provided before reversal of anesthesia. These drugs
dictable anesthesia. The intraperitoneal (IP) route of injection can have significant cardiopulmonary effects, including respira-
is commonly used in laboratory medicine, but errors during tory depression, second-degree heart block, bradyarrhythmias,
administration (intravisceral, SC, or intra-adipose tissue) can and increased sensitivity to catecholamine-induced cardiac
result in organ damage or delayed onset of action. Injections are arrhythmias (xylazine).53,54 Because of the many adverse effects
usually performed into the lower left quadrant of the abdomen reported for this class of drugs, their use is not recommended in
with the rodent restrained in dorsal recumbency and the cranial small exotic mammal patients with evidence of cardiopulmo-
end of the rodent directed downward. Supplemental oxygen and nary compromise. Supplemental oxygen and assisted ventilation
assisted ventilation should always be available when injectable should always be available when these drugs are being used.
anesthetics are used, regardless of their route of administration. Xylazine/ketamine given over multiple anesthetic episodes
and detomidine alone or in combination with ketamine or
diazepam have been associated with myocardial necrosis and
SEDATIVES AND TRANQUILIZERS
fibrosis in rabbits.61,80 Significant breed and strain differences in
Acepromazine response to medetomidine sedation doses have been reported
In ferrets, acepromazine provides adequate sedation for simple for rabbits and rats.5,6,48 In rabbits, ketamine/medetomidine
procedures such as ear cleaning,71 however, one author discour- allowed for more rapid intubation, a greater isoflurane-sparing
ages its use in ferrets owing to its vasodilatory effects (see Table effect, and less esophageal temperature loss than with ketamine/
31-1).64 Acepromazine has been used extensively in rabbits and midazolam, but the rabbits thus treated were more prone to
rodents and reported doses vary widely.4,48,120,122 The peak effect laryngospasm.40 Medetomidine/ketamine provided better qual-
in rabbits is often not seen for 30 to 40 minutes, even when ity and duration of surgical anesthesia (38.7 ± 30.0 minutes)
given IV. It is used in laboratory rabbits specifically for blood in healthy rabbits than medetomidine/midazolam/fentanyl
collection because of the drug’s vasodilatory effects. Vasodila- (MMF). Arterial pH and PaO2 were significantly decreased in
tion occurs at very low doses of acepromazine, therefore low both groups and apnea occurred postintubation with MMF.53
doses will not avoid this effect. Animals that are hypovolemic, Atipamezole (10%-20% of calculated dose) may reduce these
anemic, or hypotensive before anesthesia should not receive adverse effects without reversing their anesthetic and analgesic
acepromazine. Acepromazine has also been shown to decrease effects, but supplemental oxygen must be available.
tear production in rabbits.35 Acepromazine is not recommended The effects of alpha-2 agonists with ketamine seem to be less
for use in gerbils because it may lower the seizure threshold.49 uniform in guinea pigs, and they may not become sufficiently
anesthetized.96 Chinchillas administered MMF IM had well-
Benzodiazepines controlled anesthesia for 1.5 hours, but the heart rate (HR) and
Diazepam can be administered PO or IV, but if used IV, the respiratory rate (RR) were decreased and recoveries were pro-
patient must be monitored for hypotension caused by the prolonged without reversal.54 Chinchillas receiving medetomidine/
pylene glycol found in many diazepam formulations (see Table ketamine had greater HR and RR depression, and recovery was
31-1). IM and SC absorption is erratic because of the solution’s longer than with MMF combinations (Table 31-2).54 Alpha-2
high osmolality, which is due to an increased pH with this car- agonists are combined with ketamine for IP injection for surgi-
rier. Because parenteral formulations of diazepam are available, cal anesthesia with good muscle relaxation in rats and mice.4,96
large volumes must often be given. Transient lameness after
IM injection has been reported in ferrets.72,74 Diazepam can
INDUCTION AND MAINTENANCE
be used alone in rabbits to provide preoperative anxiolysis and
OF ANESTHESIA
sedation,15 but it is most commonly used in combination with
other drugs to enhance their activity or decrease muscle rigidity. Preoxygenation should be performed routinely, and always
Midazolam is a short-acting benzodiazepine that is water- when there is potential for hypoxemia. Preoxygenation can pro-
soluble, so it can be given IM (see Table 31-1). Midazolam has duce an oxygen reservoir and the benefits are achieved in ≤1
minute of high inspired oxygen concentration in the healthy
patient but may take ≥5 minutes in a patient with compromised
*References 4, 40, 53-55, 72, 74, 88, 120, 122. respiratory function. Preoxygenation is accomplished with an
436
Table 31-2 Injectable Anesthetic Drugs and Drug Combinations Used in Small Exotic Mammalsa
SECTION VI General Topics

Rabbit Ferret Guinea Pig Chinchilla Rat Hamster Gerbil Mouse Comments
Injectable Anesthetics/Analgesics
Etomidate 1-2 IV 1-2 IV 1-2 IP20 Administer 15-20
minutes after
benzodiazepine
Ketamine 5-50 SC, IM, IV25 5-50 SC, IM, 5-40 SC, IM, 5-40 IM, IV 10-40 IM, IV; 50-100 IP25 100-200 100-200 IM, Lower doses for
IV70 IV 50-100 IP25 IM, IV25 IV25 induction; can
cause muscle
necrosis in guinea
pigs
Ketamine (K)/ 10-25 K/1-5 D 10-25 K/1-3 100 K/5 D 20-30 K/1-2 40-100 K/3-5 70 K/2 D 50 K/5 D25 100 K/5 D Poor analgesia
diazepam (D) IV25,48 D IV25,70 IM25; 20-30 D IV D IP33 IP25 IP25,33
K/1-2 D IV
Ketamine (K)/ − 15 K/3D/0.2 − − − − − − Provided 20-25
diazepam (D)/ B IM, IV70 minutes anesthesia
butorphanol (B) in ferrets
Ketamine (K)/ 5-35 K/0.25-0.5 M 4-8 K/0.08- 5-40 K/0.05- 5 K/0.06 M 45-75 K/0.3- 100 K/0.25 75 K/0.5 50-75 K/0.1- −
medetomidine IM17,39,40,50,53,68,88 0.1 M 0.5 M IM25 IM54 0.5 M IM, M IP25 M IV25 1.0 M
(M) IM25,70 IP42,51 IP25,42
Ketamine (K)/ 5-15 K/0.1-0.5 5 K/0.08 − − − − − − −
medetomidine M/0.4-0.5 B SC, M/0.1-0.2
(M)/butorphanol IM50 B IM70
(B)
Ketamine (K)/ 5 K/0.25-1.0 Mi 5 K/0.1-0.3 5 K/0.5 Mi 5 K/0.5 Mi − − − − −
midazolam (Mi) IM, IV Mi IM, IV IM, IV IM, IV
Induction
Anesthesia 10-40 K/1-3 Mi IM, 5-10 K/0.25- 20-50 K/0.5- 20-50 K/0.5- 40-150 K/3.0- − − 40-150 K/3.0- Lighter anesthesia at
IV39,40,48 0.5 Mi IM, 5.0 Mi IM, 5.0 Mi IM, 5.0 Mi IV, 5.0 Mi IP25 lower dosages of
IV70 IV IV IP25 ketamine
Ketamine (K)/ 10-50 K/3-5 X 25 K/1-2 X 20-40 K/1-2 20-40 K/1-2 40-100 K/5-10 200 K/10 X 50 K/2 X 35-100 K/2.5- −
xylaxine (X) IM17,53 IM25 X IM X IM X IM, IP25,33 IP25 IP25 15.0 X
IP25,42
Medetomidine (M)/ 0.25 M/0.02 F/1 Mi − − 0.05 M/0.02 − − − − Must be prepared to
fentanyl (F)/ IM53 F/1 Mi IM54 intubate because
midazolam (Mi) apnea, respiratory
depression
common; complete
reversal with
atipamezole,
flumazenil,
naloxone
Propofol 3-6 IV 3-6 IV 3-6 IV 3-6 IV 3-10 IV10 − − 3-25 IV25 Doses for routine
induction
Tiletamine/ 5-15 IM, IV18 3-10 IM, IV70 − − 40-80 IV, 50-80 IP25 − 40-80 IP25,96 Avoid higher doses in
zolazepam IP25,96,104 rabbits due to renal
injury18
Local Anesthetics
CHAPTER 31 Anesthesia, Analgesia, and Sedation of Small Mammals

Bupivacaine (local, <2 <2 <2 <2 <2 − − <2 Short duration of
regional blocks) 20-30 min in rats
Dosages for local
blocks; can extend
to 2 mg/kg as
maximum dose
Lidocaine (local, <4 <4 <4 <4 <4 − − <4 Short duration of
regional blocks) 20-30 min in rats
aThese are suggested dosages based on published information and the authors’ clinical experience. Species and individual variation in response to a drug or combination of drugs can be
uncertain, so the dosage should be adjusted depending upon the clinical response of the animal. All doses are in milligrams per kilogram unless specified otherwise.
437
oxygen cage or an induction chamber in the unrestrained ani- and found to have a dose-dependent effect on the duration of
mal or with a face mask in the physically restrained patient. Lev- anesthesia (59-124 minutes), but not much change in cardio-
els rise more slowly in an unprimed oxygen cage or induction respiratory effects was seen over this high dose range.104 Much
chamber. It is expected that PaO2 will decrease rapidly if oxygen smaller doses of tiletamine-zolazepam (1.5-3.0 mg/kg) are used
delivery is interrupted and the animal begins to breathe room in ferrets with xylazine (1.5-3.0 mg/kg) or with xylazine (1.5
air again. Supplemental O2 should be supplied throughout mg/kg)/butorphanol (0.2 mg/kg) with a dose-dependent dura-
the anesthesia, and intubation should be performed whenever tion of effect.70 Tiletamine-zolazepam has been reported to
possible. cause nephrotoxicity, related to the tiletamine, in New Zealand
white rabbits, and this appears to be dose-dependent.18 The
advantage of this combination over ketamine is that much
INJECTABLE ANESTHETICS
smaller volumes of drug are needed, so it is less likely to cause
Ketamine muscle damage if given IM.
Ketamine is a noncompetitive n-methyl-d-aspartate (NMDA)
receptor antagonist that can prevent central sensitization, pro- Propofol
vide analgesia, and cause dissociative anesthesia (see Table 31-2). The need for IV access and ventilatory support limits the use of
Ketamine is generally well tolerated in the stable patient but it propofol. Rapid, excitement-free induction and recovery occur
has sympathomimetic properties that can cause increases in HR, at clinically relevant doses in most mammals (see Table 31-2).
myocardial contractility, and peripheral vascular resistance. It is Early studies evaluating propofol anesthetic maintenance as
a negative inotrope; therefore patients that are highly stressed the sole anesthetic agent in rabbits demonstrated a very nar-
(especially rabbits and chinchillas) may become hypotensive row therapeutic window,2 but balanced anesthesia may produce
following ketamine injection because they have maximized their propofol-sparing effects, thus reducing its respiratory disadvan-
sympathetic output, thus “unmasking” the negative inotropic tages.73,81 The authors suggest a calculated propofol induction
effect of the drug. Patients with hypertrophic cardiomyopathy dose be given in one-quarter increments, each administered
may be at an increased risk of cardiac failure, as they may not be over 30 to 60 seconds, to allow more accurate dosing and mini-
able to cope with the increased myocardial demand caused by mize apnea and hypotension during induction. The effects of
sympathetic stimulation. Renal impairment can markedly pro- propofol given IP in small rodents are unpredictable; very little
long recovery. The authors do not recommend using ketamine information is available on using this drug via this route in
for patients with cardiac or renal disease or in severely stressed small exotic mammals.83 New formulations of propofol have
small mammal patients. Salivation is increased and secretions been developed that may change some of the uses in these spe-
can obstruct the airway. In small rodents, higher IM doses have cies. A clear solution of nanoparticulate propofol in an aque-
been associated with muscle necrosis at the injection site. Ket- ous base eliminates the addition of other solvents and gives this
amine has a very short duration of clinical effect in rabbits and agent a much longer shelf life after the container is opened.95
varies within strains of rabbits, partly owing to redistribution
and renal elimination.5 Another disadvantage is the potential Etomidate
for the development of apneustic ventilation, a pattern charac- Etomidate is a potent short-acting hypnotic induction and
terized by a prolonged pause after inspiration. Despite these dis- maintenance agent (see Table 31-2). It has a rapid onset, a short
advantages, ketamine combined with one or more drugs is still recovery period, and minimal cardiopulmonary effects.82 As an
considered a first-choice injectable anesthetic.97 IV induction agent, etomidate has minimal depressive effects on
Ketamine is commonly combined with alpha-2 agonists or the sympathetic nervous system but may stimulate sympathetic
benzodiazepines as induction agents to improve relaxation and outflow at low doses.3 Etomidate is sold as a hyperosmolar solu-
anesthetic depth (see Table 31-2).* Ketamine/alpha-2 agonist tion with propylene glycol and can cause hemolysis, thrombo-
combinations, particularly at higher doses, produce mild-to- phlebitis, and pain on injection. An aqueous formulation has
severe dose-dependent hypotension and bradyarrhythmias; been developed, which may be safer than the current commer-
ketamine/benzodiazepine combinations produce less cardio- cial product.82 It is usually administered IV, but in rats and mice
pulmonary depression and analgesia but provide good mus- it has been shown to be readily absorbed IP.20 In order to reduce
cle relaxation.40 Low-dose ketamine/midazolam IV is used by the impact of the hyperosmolarity, IV crystalloid fluids are given
the authors to induce anesthesia in rabbits, ferrets, and small simultaneously. The larynx is often reactive with this drug, so
rodents; it is given IP in very small rodents. Opioids added to topical laryngeal lidocaine is helpful.
ketamine combinations further reduce the dose and minimize
the adverse effects of each drug. Reversal of other drugs in ket- Constant-Rate Infusions
amine combinations allows for its specific undesirable effects to Intravenous constant-rate infusions (CRIs) of anesthetic and
become apparent. analgesic drugs are being evaluated in small mammal balanced
anesthesia/analgesia protocols (Table 31-3).14,37,85 Analge-
Tiletamine-Zolazepam sic medications administered IV CRI can be titrated to effect,
In mice, tiletamine-zolazepam (Telazol, Fort Dodge, IA) alone potentially reducing other drug doses within the anesthetic
appears to produce poor analgesia, but in combination with protocol. Disadvantages to the use of CRIs in small mammals
xylazine (7.5 mg/kg tiletamine-zolazepam and 45 mg/kg xyla- are the need for patient IV access and for a syringe pump to
zine) this improved, with an anesthetic time of 30 to 90 minutes accurately deliver low IV dosages. Plasma drug concentrations
(see Table 31-2). In rats, doses of 30 to 60 mg/kg were tested increase slowly when used as a CRI, so a loading dose of the
drug is commonly given prior to initiation of the CRI.
Microdose ketamine via IV CRI can be an effective analge-
*References 17, 40, 52-54, 69, 88, 107, 120. sic (see Table 31-3). It is very useful in patients that cannot be
Table 31-3 Injectable Drugs Administered as Constant-Rate Infusions (CRIs) Used for Perioperative and Postoperative
Analgesia in Small Exotic Mammalsa
Injectable
Analgesics Rabbit Ferret Guinea Pig Chinchilla Rat Mouse Comments
Butorphanol Loading dose, Loading dose, Loading dose, Loading dose, Loading dose, − Less
0.2-0.4 0.05-0.2 0.2-0.4 mg/kg; 0.2-0.4 0.2-0.4 respiratory
mg/kg; mg/kg; maintenance, mg/kg; mg/kg; depression
maintenance, maintenance, 0.2-0.4 mg/ maintenance, maintenance, than with
0.2-0.4 mg/ 0.1-0.4 mg/ kg/h 0.2-0.4 mg/ 0.2-0.4 mg/ fentanyl
kg/h kg/h kg/h kg/h
Fentanyl citrate Loading dose, Loading dose, Loading dose, Loading dose, − 1.25 µg/ The authors
Perioperative 5-10 μg/ 5-10 μg/kg IV; 5-10 μg/kg IV; 5-10 μg/ kg/h have used
CRI kg IV; maintenance, maintenance, kg IV; IV33 up to 40
maintenance, 10-30 μg/ 10-30 μg/kg/h maintenance, μg/kg/h in
10-30 μg/ kg/h IV IV 10-30 μg/ rabbits;
kg/h IV kg/h IV apnea
common,
expect to
ventilate
patient
Postoperative 1.25-5.0 μg/ 1.25-5.0 μg/ 1.25-5.0 μg/kg/h 1.25-5.0 μg/ − − Combine with
analgesia kg/h kg/h kg/h ketamine
CRI to
reduce
overall doses
Ketamine Loading dose, Loading dose, Loading dose, Loading dose, − − More useful
Perioperative 2-5 IV mg/kg; 2-5 IV mg/kg; 2-5 IV mg/kg; 2-5 IV mg/kg; when
CRI maintenance, maintenance, maintenance, maintenance, intubation is
0.3-1.2 mg/ 0.3-1.2 mg/ 0.3-1.2 mg/ 0.3-1.2 mg/ not possible
kg/h IV kg/h IV kg/h IV kg/h IV because
there is less
respiratory
depression
than opioids
given CRI
Postoperative 0.1-0.4 mg/ 0.1-0.4 mg/kg/h 0.1-0.4 mg/kg/h 0.1-0.4 mg/ 0.1-0.4 mg/kg/h − Can be
analgesia kg/h kg/h combined
with fentanyl
to reduce
overall
doses of
both drugs
Oxymorphone − − − − 0.03 mg/kg/h − −
Perioperative IV36
CRI
aThese are suggested dosages based on published information and the authors’ clinical experience. If using for postoperative analgesia only, a
loading dose should be used. Gradually wean from postoperative CRI over 12-24 hours. Species and individual variation in response to a drug
or combination of drugs can be uncertain, so the dosage should be adjusted depending on the clinical response of the animal.
intubated, as it has a low potential for respiratory depression at these drugs via this route in small mammals. Remifentanil is an
these doses. Opioid medications can also be used for CRI. All ultra-short-acting μ agonist opioid, making it very suitable for
mu (μ) receptor agonists can cause respiratory depression; thus CRI.14,37 It is metabolized by esterase hydrolysis in the blood
they should be used only when an airway is secure and venti- and tissues, not via the liver or kidneys, and accumulation is
lation is available.14 These have also historically been avoided prevented even when given at high doses over prolonged peri-
in small hind-gut fermenters for fear of inducing GI stasis, but ods. Because of its very short half31-life, undesirable respiratory
when used as low-dose IV CRIs, these drugs can be part of bal- and cardiovascular effects are not expected to last for more than
anced anesthesia and analgesia protocols.14 Fentanyl citrate is a 10 to 15 minutes after discontinuation. Acute tolerance can
μ receptor agonist that is used as a single-agent CRI (see Table develop with remifentanil,37,47 which may require increasing
31-3),14 or it can be combined with ketamine in the clinical set- doses to maintain intraoperative analgesia. Butorphanol has
ting; to date, however, there are no published studies evaluating also been used successfully as a CRI in the clinical setting, but
there are no published data for small exotic mammals. Anes- minimize its size to reduce movement and trauma. Gas flow
thesia has been maintained with doses of propofol at 0.4 to 0.6 rates are adjusted to chamber size to provide an optimum rate
mg/kg/min, but been deaths have reported rabbits following of rise of the anesthetic concentration. The flow rate can be cal-
propofol infusions.2,67,103 culated using the formula: f = V/t ln (S/(S-C), where f = the O2
flow rate, V = chamber volume, t = time to reach the desired
concentration, S = concentration being put out by the vapor-
INHALANT ANESTHESIA
izer, and C = desired concentration.58 The patient is promptly
Inhalant anesthetics offer rapid induction and recovery and the removed after the righting reflex is lost. The final phase of induc-
ability to rapidly change anesthetic depth; moreover, their use tion is accomplished using a mask to facilitate monitoring.
does not require an accurate determination of body weight. Very
little is metabolized, reducing the impact on hepatic and renal
LOCAL AND REGIONAL ANESTHESIA
function, and recovery is independent of either. Small mam-
mals require approximately the same concentration of inhaled Local anesthetics are ideal for use in preemptive analgesic
anesthetic for an equivalent amount of stimulation as other combinations. Although local anesthetics provide sufficient
mammals. But inhalant anesthetics can induce cardiovascular analgesia for some procedures without the addition of another
and respiratory depression, which may be life-threatening. All anesthetic, the stress of handling and restraint generally pre-
inhalants currently in use are potent negative inotropes; there- cludes their sole use. Local or regional nerve blocks are com-
fore a dose-related decrease in cardiac output is expected, which monly used, as are epidural or spinal administration (see
is reflected as a decrease in blood pressure. Thus the primary “Epidural Anesthesia/Analgesia,” below).19,27,60,84 Regional
function of the anesthetist using inhalants is to maintain the infiltration of incision lines and specific peripheral nerve blocks
lightest plane of anesthesia possible, allowing for minimal car- (i.e., brachial plexus, sciatic) are used; dental nerve blocks are
diopulmonary depression and completion of the procedure. In very useful in performing dental extractions. Intratesticular
some cases these goals may not be achieved by simply reduc- blocks can be used for castration; the authors use 1 mg/kg of
ing the inhalant; balanced anesthetic/analgesic protocols or 2% lidocaine per testicle. The toxic dose of local anesthetics in
the addition of dopamine or dobutamine (only in the volume- small exotic mammals clinically appears to be similar to that
loaded patient) may be necessary to offset inhalant-induced in cats and dogs. Toxic signs may include depression, drowsi-
hypotension. ness, muscle tremors, vomiting, hypotension, and arrhythmias
Isoflurane, sevoflurane, and desflurane are the currently as well as CNS signs such as ataxia and nystagmus. Toxicity is
available inhalants. Their speed of onset and offset is largely prevented by using appropriate concentrations and volumes.
determined by their solubility and isoflurane > sevoflurane > For example, the commercial lidocaine (2%) solution often
desflurane. Despite these physiochemical differences, the clini- must be diluted to achieve a suitable injection volume while
cal differences overall may be fairly small (e.g., induction and not exceeding a total dose of 4 mg/kg. Dilution can decrease
recovery times, heart rate, and indirect blood pressure mea- duration of action and drug effectiveness, but clinical studies
surements were not different between sevoflurane and isoflu- are lacking on dilution limits in small mammals. Bupivacaine
rane in ferrets).77 All three agents appear to have many of the is used conservatively because of concerns that its toxic effects
same dose-dependent cardiovascular effects. Sevoflurane has a may take longer to resolve. New long-acting local anesthetic
less pungent odor than other inhalants and therefore is gener- formulations have been shown to produce nerve blocks for 5
ally better tolerated during mask induction. Many practitioners days without toxic effects in rats.119 Eutectic mixture of local
induce using sevoflurane and then maintain anesthesia with the anesthetics (EMLA, AstraZeneca, Wilmington, DE) is a mix-
more cost-effective isoflurane. ture of 2.5% lidocaine and 2.5% prilocaine used topically to
desensitize skin for catheter placement or superficial biopsies.
Mask or Chamber Induction Reported optimal contact time requires application and occlu-
Induction with inhalants is performed with either a mask or sion with a bandage for 30 to 60 minutes. EMLA toxicity is
an induction chamber. Commercially available masks for dogs associated with application to large or traumatized areas and
and cats can be used, but appropriate-sized masks and nose prolonged contact time. Systemic uptake may occur in smaller
cones are also commercially available or can be fashioned from patients if the skin is damaged during shaving. Blanching of the
syringe cases or other materials (Fig. 31-5, A). The mask should skin and local erythema have also been reported, in addition
have minimal dead space and a diaphragm, so that a seal can be to the typical toxic effects of local anesthetics. Prilocaine can
achieved on the animal’s nose or neck and a piece of suture can induce methemoglobinemia.
be placed around the upper incisors and through the breathing
circuit for security (see Fig. 31-5, B,C). Commercially available
EPIDURAL ANESTHESIA/ANALGESIA
induction chambers sized for mice to small dogs can be used,
especially for very stressed patients that may resist face-mask Epidural anesthesia/analgesia can be an extremely useful
induction. Advantages of appropriately sized chambers are less adjunct to a balanced anesthesia/analgesia protocol and can
waste gas and shorter induction times. In stressed patients, the significantly reduce the concentration of inhalant anesthet-
chamber is darkened by covering it with a towel. Alternatively, ics for surgical procedures (Table 31-4). Anesthetic/analgesic
for induction of large or stressed patients, an animal carrier or effects are achieved with little to no systemic drug effects, thus
the front of a hospital cage can be sealed with a plastic bag and further reducing the use of other cardiopulmonary depressant
inhalant anesthetic administered into the enclosure. Disad- anesthetics in the protocol. Epidural anesthesia is more com-
vantages of induction chambers include inability to assess the monly used in the larger exotic mammals,19,60 but it can be
patient, gas pollution when the chamber opened, and trauma performed routinely in smaller species as well.22,84 The lumbo-
during the excitement phase of anesthesia. Pad the chamber and sacral junction site is most commonly used, and the techniques
A B
Fig. 31-5 A, Appropriate-sized masks and nose cones are commercially available or can be fash-
ioned from syringe cases or other materials for induction and to maintain anesthesia. The mask
should have minimal dead space and a diaphragm so that a seal can be achieved on the animal’s
nose or neck (B). A piece of suture can be placed around the upper incisors and secured between
the mask and breathing circuit (B,C).
Table 31-4 Injectable Drugs Used for Epidural Anesthesia/Analgesia in Small Exotic Mammalsa
Injectable Epidural
Drugs Rabbit Ferret Guinea Pig Chinchilla Rat Mouse Comments
Buprenorphine 12 μg/kg 12 μg/kg 12 μg/kg 12 μg/kg − − −
Bupivacaine (0.125%) 1 1 1 1 1 1 Concentrations of
0.125% or less
minimize motor
block
Morphine 0.1 0.1 0.1 0.1 0.1 0.1 Little evidence of
(preservative-free) systemic uptake
aThese are suggested dosages based on published information and the authors’ clinical experience. Species and individual variation in response
to a drug or combination of drugs may be uncertain, and doses should be adjusted for the needs of each patient. All doses are in milligrams
per kilogram unless specified otherwise. All drugs should be diluted with preservative-free saline only. Total volumes for epidural administration
should not exceed 0.33 mL/kg regardless of drug or drug combination. Opioid and local anesthetics can be administered in combination to
reduce the dosage needed of each drug.
A B
C D
Fig. 31-6 Landmarks for epidural analgesia are the wings of the ileum bilaterally and the depres-
sion between the last lumbar and first sacral vertebrae (A). Sterile technique is used throughout.
Appropriate-sized spinal or hypodermic needles are introduced with a firm rotating motion until a
“pop” is felt (B). Placement is confirmed by lack of resistance to air introduced with a glass syringe
(C) before analgesics are delivered (D). Only half the calculated dose is delivered if spinal fluid is
identified in the needle hub.
for administration are similar to those in dogs and cats (Fig. Withdrawal reflexes that are used in small mammals include
31-6). Morphine is the most commonly used opioid because it toe pinch, stimulation of the interdigital tissue, tail pinch, and
has a high potency and long duration of analgesic action (18- rectal pinch. The toe pinch does not always reliably measure
24 hours), but oxymorphone and buprenorphine have similar anesthetic depth in guinea pigs, as involuntary leg movements
effects and duration (see Table 31-4). Bupivacaine at concentra- sometimes occur under anesthesia. Slight corneal and palpebral
tions ≤0.125% appear to have the least motor effect while pro- reflexes are commonly maintained at a surgical plane of anes-
ducing good sensory block, which is important for minimizing thesia; absence of these reflexes indicates an excessively deep
recovery stress and potential trauma (see Table 31-4). Epidural plane of anesthesia.
bupivacaine in rats provided potent antinociceptive effects for Heart rates vary widely between species. Base knowledge of
only 20 to 30 minutes.84 There appears to be synergism in the expected heart rates for the species is important, but absolute
epidural space between local analgesics and opioids; drug com- trends in rate during anesthesia are of the utmost importance.
binations reduce doses and minimize potential adverse effects The anesthetic concentration is decreased with any sudden HR
of each drug. In general, the total epidural administration vol- reductions and supportive care is provided. Auscult the HR and
ume for all drugs combined should be ≤0.33 mL/kg. record the rate and any arrhythmias. Because of the rapid HR of
many small rodents, ECG complexes can be difficult to assess at
the standard sweep speed of 25 mm/sec. Sweep speeds of 100
ANESTHETIC MONITORING
and 200 mm/sec are available on some ECG machines and can
AND SUPPORTIVE CARE
allow for more accurate assessment. Needle ECG leads are ideal
Effective monitoring requires minute-to-minute patient assess- for small rodents, as they provide excellent conduction without
ment. Regardless of the anesthetic used, the eyes should be well the use of gels. Alternatively, metal alligator clips attached to a
lubricated often to prevent corneal dessication and ulceration. hypodermic needle or a saline-soaked cotton ball or adhesive
Covering the eyes with damp gauze sponges helps maintain the pad can be used (Fig. 31-7). Peripheral pulse quality can be
moisture provided by the eye lubrication. subjectively assessed by changes in pulse loudness gauged with
A B
Fig. 31-7 Monitoring and supportive care equipment for surgery including Doppler and non-
invasive blood pressure equipment, capnography, electrocardiography (ECG), esophageal/rectal
temperature probes, intravenous catheters, and temperature support with pads and forced-warm-air
blankets can be used even on small patients (A). ECG pads can be cut and taped to the footpads
of many rodents (B).
a Doppler ultrasonic probe placed over an artery. This is quite produces little to no noise. Whistling, wheezing, or harsh
insensitive, but a change in Doppler loudness should alert the sounds may indicate obstruction.
anesthetist to reevaluate the patient. Noninvasive blood pres- Both injectable and inhalant anesthetics cause dose-depen-
sure monitoring can be performed using a Doppler probe, a dent respiratory depression; this and the increased resistance to
pressure cuff, and a sphygmomanometer (see Fig. 31-7). Oscil- breathing imposed by the endotracheal tube provide compelling
lometric devices can be unreliable in the small hypotensive or reasons to ventilate these animals. Sick or debilitated patients
hypothermic patient with a high heart rate. In rabbits, oscillo- may not be able to accommodate these physiologic changes and
metric readings from the forelimb correlated well with arterial thus require intermittent positive-pressure ventilation (IPPV).
blood pressures at low and normal pressures, but hind-limb The authors recommend initial inspiratory pressures of 5 to 10
readings did not.125 The size of the blood pressure cuff should cm H2O and rates of 6 to 10 breaths per minute. Thoracic excur-
approximate 40% of the limb circumference. Cuffs that are too sions are assessed and the tidal volume is adjusted to achieve
large can give falsely decreased pressures. The cuff is placed over appropriate thoracoabdominal expansion. In general, the aver-
the radius/ulna, humerus, tibia, or femur, or a tail cuff can be age tidal volume for many species is 10 to 15 mL/kg; however
placed over the base of the tail. The Doppler probe is placed there is variation. Inspiration should take 1 to 1.5 seconds. If a
between the carpal/tarsal pad and pads of the feet, above the mechanical ventilator is not available, hand ventilation deliv-
carpus on the ventromedial aspect, or on the ventral surface ered from the reservoir bag provides assisted ventilation.
of the tail over the ventral tail artery; shaving of these areas is End-tidal carbon dioxide (PETco2) monitoring using
sometimes necessary. The pressures determined with a Doppler a capnograph is useful to assess ventilation (see Fig. 31-7).
and sphygmomanometer are taken as systolic pressures, whereas Mainstream capnographs have a sampling device that reads
oscillometric devices can provide systolic, diastolic, and mean directly from the gas in the airway, whereas sidestream cap-
arterial pressures. Normal systolic blood pressure measure- nographs pull gas along a tube to the measuring device in the
ments obtained with the Doppler range from 90 to 120 mm Hg. machine. Mainstream capnographs may add an unacceptably
Perfusion is assessed by evaluating the color and capillary refill large dead space in small patients (<500 g), and the weight
time of the oral, rectal, or vaginal mucous membranes, femoral of the detector on the end of the endotracheal tube may pre-
pulse quality, heart rate, and blood pressure. Fluid types, uses, dispose to inadvertent extubation. With sidestream sampling,
and volume calculations are provided in Chapter 38. the port should be located inside the endotracheal tube; but it
Respiratory rate and character should be monitored closely. is important that this not take up excessive volume and lead to
Visual monitoring of the respiratory rate can be complicated by an increased resistance to breathing. Sidestream capnographs
surgical drapes, especially in small rodents. Ventilation is moni- draw samples at a rate of 50 to 200 mL/min. Instruments with
tored by watching the frequency and degree of movement of a sample rate of 50 mL/min provide more accurate measure-
the chest or movement of the reservoir bag on the anesthesia ments in small patients.96 Evaluation of the capnograph trac-
machine. Small reservoir bags, such as balloons, can be used to ing can provide important information regarding trends in
visualize small movements. High respiratory frequency can be PETco2.
misleading and does not mean that the patient is necessarily Pulse oximetry (SpO2) is used in many species to evalu-
light and hyperventilating. High respiratory rates can be asso- ate arterial hemoglobin oxygen saturation, but the high nor-
ciated with small tidal volumes, resulting in more dead-space mal heart rates in these species may exceed the upper limits of
ventilation than pulmonary ventilation. Lighten the plane standard monitors. Pulse oximeters that can detect high heart
of anesthesia and institute manual ventilation for any period rates and low signal strengths are now available. SpO2 probes
of apnea greater than 10 to 20 seconds. Respiratory monitors are placed on the tongue, ear, toe, tail, or vaginal/rectal mucous
that are triggered by a thermistor in the airway function well in membranes. Smaller probes are available through laboratory
patients weighing more than 500 g, but they may not respond animal supply companies. An angled probe placed into the
to small respiratory movements and lower tidal volumes in ani- mouth has proven reliable.25 Since many anesthetized animals
mals weighing less than 200 g. In general, normal ventilation are breathing high concentrations of oxygen, the usefulness of
SpO2 is very low unless the procedure is expected to cause desat- to minimize anesthetic time. Postprocedural recovery should
uration (e.g., thoracotomy). have the patient connected to the circuit or on a face mask with
To reduce potential anesthetic-associated morbidity and 100% O2 for as long as possible in a quiet area. Animals wet
mortality, it is mandatory to monitor core body temperature from the procedure are gently dried with a loose towel or with
and to provide thermal support (see Fig. 31-7). Most anesthet- warm air. Always monitor the character of respiration during
ics depress thermoregulatory function, and this is exacerbated towel restraint to ensure that chest movement is not impaired.
in small patients prone to heat loss because of their high body Once recovery is considered to be of minimum potential for
surface-to-volume ratios. Hypothermia certainly depresses car- self-trauma, place the patient in a warm, quiet, darkened, well-
diopulmonary function, and arrhythmias and disturbances of oxygenated environment for continued recovery. Respiratory
coagulation can occur with deep hypothermia in mammals depression can continue into the postanesthetic period, so
(<86°F; <30°C). Hypothermia decreases the anesthetic require- supplemental oxygen should be continued. Use thermal sup-
ment and metabolism and prolongs recovery. port in the recovery areas, but do so with caution, because many
Supplemental heat sources should be used regardless of the small mammals are susceptible to heat stress. Chinchillas are
length of the procedure. Core body temperature is most accu- particularly prone to be stressed by temperatures greater than
rately monitored with an esophageal temperature probe, but 75°F (24°C) and should be monitored closely. Food and water
rectal temperatures can also be obtained if necessary. Most heat are provided as soon as the patient has recovered to a point of
is lost via radiation, so the most effective technique to prevent minimal to no ataxia, and the patient is encouraged to eat. The
heat loss is to minimize the temperature gradient between the GI transit times are very rapid for virtually all small mammals;
patient and the room. This can be done by increasing room tem- therefore carefully consider the patient’s nutritional plane in
perature; insulating the patient with clear plastic drapes, bubble advance. To minimize the potential for GI stasis after the anes-
wrap, or foil; and wrapping nonsurgical fields. Surgical time and thetic period, administer nutritional support to small mammals
the time the body cavities are open are minimized, as are the exhibiting anorexia of concerning duration. Replacement fluid
time for hair clipping and alcohol/water use for skin prepara- therapy plays a role in nutritional support, as the GI tract must
tion. Latex gloves, empty fluid bags, or plastic bottles can be filled be hydrated to facilitate motility and function. If IV fluids were
with water, warmed in a hot-water bath, and placed next to the not provided during surgery, administer warm SC fluids at this
patient. Water bottles are wrapped in a towel to prevent burns. time.
Circulating-warm-water blankets insignificantly diminish the
rate of heat loss in small patients. Radiant heat lamps are effec-
EMERGENCIES
tive at maintaining core body temperature, but the optimal dis-
tance between the heat source and the patient differs with patient Emergencies during anesthesia should be anticipated and
size, heat lamp strength, and the heat setting. Forced-air warmers planned for in advance. Most are averted by careful monitoring
are more effective at minimizing hypothermia during anesthe- of HR, RR, blood pressure, and body temperature. Endotracheal
sia than other methods and are particularly effective when set tubes, oxygen, IV catheters and materials for securing them,
up to have warm air rising around the patient either by wrap- ventilatory support, and emergency drugs should be close by
ping the patient in the blanket or by using a perforated table (see and ready for use. Emergency drug doses should be calculated
Fig. 31-7). Lubricate the eyes well to prevent corneal ulceration and predrawn before induction (Table 31-5). Treat respiratory
due to drying from the warm air. Warm the replacement fluids depression and arrest by turning off the anesthetic machine and
prior to administration. Heated, humidified anesthetic gases also controlling ventilation. The standard approach of maintaining
help to reduce or prevent the development of hypothermia. airway, breathing, and circulation (ABC) should be followed.
One of the most important ways in which to reduce the Cardiac massage can be performed and in many of these small
potential for complications during anesthesia and recovery is species, in which the heart is palpable through the thoracic wall.
Table 31-5 Emergency and Cardiopulmonary Resuscitative/Supportive Drug Dosages Commonly Used in Small Exotic
Mammalsa
Drug Dosea Route of Administration Indications
Atropine 0.04-0.1 SC, IM, IV, IO, IT In all small animals except the rabbit where much higher
doses are required (0.2-1.0); bradycardia, CPR
Diazepam To effect IV Seizures; slow delivery due to propylene glycol carrier
Dobutamine 5 μg/kg/min IV CRI Nonhypovolemic hypotension during surgery
Dopamine 5-20 μg/kg/min IV CRI Nonhypovolemic hypotension during surgery
Doxapram 1-10 IV, sublingual Ineffective during cardiac arrest or severe hypoxia
Epinephrine (1:1000) 0.01-0.1 IM, IV, IO, IT Cardiac arrest; dilute to 1:10,000 before IV use
Glycopyrrolate 0.01-0.05 IM, IV Bradycardia; slower onset than atropine but may provide
longer benefit
Lidocaine 1-2 IV Antiarrhythmic
Midazolam 0.1-2.0 IM, IV Seizures, sedation
CPR, cardiopulmonary resuscitation.

aNote that these are suggested doses based on the authors’ clinical experience. Species and individual variation in response to a given drug can
be uncertain, so adjust the dose based on clinical response. All doses are in milligrams per kilogram unless specified otherwise.
If this is not immediately successful, then administration of epi- studies provide more clinically relevant information about dose
nephrine IV, transpulmonary, or intracardiac is recommended intervals and route of administration but are often carried out
(in that order of preference). Treat severe bradycardia, assuming in the laboratory setting with healthy animals. There is a paucity
that it is due to increased parasympathetic tone, with atropine. of information for many of the drugs used clinically in small
mammals; thus doses and dose intervals are often extrapolated
from experience in other species. Therefore published doses
SMALL MAMMAL ANALGESIA
and dosing frequencies should be critically evaluated for each
The recognition and alleviation of pain in small mammals is an patient prior to clinical use.
essential component of every animal’s evaluation. Recent sur- Balanced analgesia should be considered for every patient,
veys evaluating veterinarians’ use of analgesics in companion as combinations of drugs acting at different points in the noci-
exotics have shown that many small mammals are still under- ceptive system may be more effective and less toxic than one
treated and are less likely to receive analgesics than are dogs drug given alone. For example, synergy has been demonstrated
or cats.76,118 For example, postoperative analgesia was given to in laboratory animals between opioids, which act mainly in the
50% to 70% of dogs and cats but to only 21% of rabbits and CNS, and NSAIDs, which act mainly peripherally to decrease
rodents after the same procedures.76 inflammation and peripheral sensitization. “Preemptive anal-
Recognition of pain (see Chapter 39) is critical for provid- gesia” with opiates, NSAIDs, and/or local anesthetics admin-
ing timely selection of analgesia and pain relief. Human pain is istered before a painful procedure can block noxious sensory
mostly assessed by verbal statements, whereas in animals pain stimuli from onward transmission to the CNS, thus reducing
is assessed by observed behaviors. Pain assessment is complex the overall potential for pain and inflammation.
because it requires consideration of differences in age, gender,
species, breed, strain, individual behaviors, and environment. It
OPIOIDS
must also take into consideration the different types and sources
of pain, such as acute versus chronic pain and visceral versus Opioids are most commonly used for moderate to severe pain,
somatic pain. To assess pain in the small mammal, become such as fractures and traumatic or surgical pain. The most com-
familiar with the normal and abnormal behaviors of each spe- mon adverse effects reported with opioids are respiratory or
cies as well as those of the individual. Many clinical signs have cardiac depression and constipation/GI dysmotility. Changes in
been associated with pain, including change in temperament GI motility are concerning but can be overcome by providing
(either aggressive or passive), restlessness, reduction in mobil- excellent hydration and assisted feeding during drug adminis-
ity or a reluctance to stand, lethargy, hunched appearance, con- tration. Most opioids can be reversed with antagonists, but this
stipation/GI stasis, increased respiratory rate, and lameness. will also terminate analgesia if the antagonist crosses the blood-
A reduction in food consumption may occur with animals in brain barrier. Opioid antagonists that do not cross the blood-
pain. Monitoring body weight in exotic animals fed ad libitum brain barrier can be used to minimize the effects on the GI tract
is extremely important because of their small body size, and in without reversing analgesia. Methylnaltrexone has been investi-
some, such as the rabbit and guinea pig, it may help to recognize gated in horses and humans and has been shown to minimize
disturbances in GI motility and function before these become GI effects associated with μ agonists.8 Pure antagonists such as
critical. Rabbits, ferrets, and some rodents will often grind their naloxone and naltrexone at high doses are most effective. These
teeth with abdominal pain. As with other species, exotic ani- antagonists compete for the receptor but have minimal effects
mals with abdominal pain may exhibit abdominal tensing with at the receptor themselves. They reverse both μ and kappa (κ)
a “tucked up” or “hunched” appearance to the abdomen. Ani- receptor agonists but will reduce or eliminate any analgesic
mals may avoid a painful area of the body, or they may bite or effect of the agonist. Nalbuphine is a κ agonist; it can be used to
chew at the site. Decreased grooming in small mammals may reverse μ agonists and has some residual analgesic effect via the
be exhibited by a dull or greasy appearance or, conversely, the κ receptors (Table 31-6). Butorphanol can be used in the same
animal may overgroom a painful site. Porphyrin staining is a way, but it is a much weaker antagonist and may increase seda-
nonspecific clinical sign of stress in rodents, but it can alert the tion. Buprenorphine has a very strong affinity for μ receptors
clinician that the animal may be in pain. Some species respond and is difficult to reverse. Antagonists should be given carefully,
to strong pain stimuli with tonic immobility. preferably titrating the dose slowly IV to the desired effect.
Because there are few reliable and consistent indicators of The effects of opioids can be variable between species and
pain in exotic species, there is tremendous room for error in our within species at the same dose. Most opioids are used parenter-
assessment of their pain. To provide some standards for deter- ally because of their poor oral bioavailability associated with the
mining whether to provide analgesics, a set of universal ques- first-pass effect. Buprenorphine at 8 to 10 times the parenteral
tions is used to determine whether a patient is in pain: dose has been incorporated into gelatin and administered orally
1. Would the lesion or procedure be painful to any species? to rats.27 Most parenteral routes of administration are effective
2. Is the lesion or procedure damaging to tissues in any species? and the lipid solubility of some opioids leads to routes not nor-
3. Does the patient display any abnormal behavioral responses? mally effective with other drugs. Oral transmucosal buprenor-
If the answer to any of these questions is yes, we must assume phine has been used successfully in cats, and anecdotal use via
that the patient is in pain and that an analgesic plan must be this route in ferrets has been reported.65 Transdermal fentanyl
developed. Ideally the use of drugs in any species is based on and buprenorphine are available in some countries, but dos-
knowledge of the drug’s pharmacokinetics and pharmacody- ing studies in small mammals are limited or have not been
namics. Pharmacokinetic predictions are useful if the plasma performed.
concentration is reflective of the effect site activity, but this is Morphine, hydromorphone, and oxymorphone are μ recep-
often not the case (e.g., buprenorphine and most of the nonste- tor agonists with similar durations of action (see Table 31-6).
roidal anti-inflammatory drugs [NSAIDs]). Pharmacodynamic Both hydromorphone and oxymorphone have been used by the
Table 31-6 Analgesic Drug Dosages Used in Small Exotic Mammalsa

Drug Rabbit Ferret Guinea Pig Chinchilla Rat Mouse Comments
NSAIDs
Carprofen 1.5-5.0 PO, 2-5 PO, SC 2-5 PO, SC 2-5 PO, SC 2-5 PO, SC 2-5 PO, SC −
SC q12-24h q12-24h q12-24h q12-24h q12-24h30,99,102 q12-24h
Ketoprofen 1-3 IM 1-3 SC 1-2 SC, IM 1-2 SC, IM 2-5 SC, IM 2-5 SC, IM −
q12-24h26 or IM q12-24h q12-24h q12-24h30,99 q12-24h
q12-24h26
Meloxicam 0.1-0.3 0.1-0.3 PO, 0.1-0.3 PO, 0.1-0.3 0.5-2.0 PO, SC 1-5 PO, SC −
PO, SC SC q24h SC q24h PO, SC q24h101,106 q24h105
q24h114,115 q24h 1-5 IP105
Opioids
Buprenorphine 0.01-0.05 0.01-0.03 0.01-0.05 0.01-0.05 0.05-0.1 SC, IM 0.05-0.1 SC −
SC, IM, IV SC, IM, IV SC, IM, IV SC, q6-12h62,102,113 q6-12h26
q6-12h29,62 q6-12h q6-12h26 IM, IV
q6-12h
Butorphanol 0.2-2.0 SC, 0.05-0.4 0.2-0.5 IM, 0.2-2.0 IM, 1-2 SC, IM, IV 1-2 SC, IP Lower doses
IM, IV q2-4 SC, IM, IV q4h IV q2-4h q2-4h26 q2-4h26 used in pre-
h50,94,115 IV q2-4h medication
combinations
Fentanyl citrate − − − − − 0.025-0.223
Hydromorphone 0.05-0.2 SC, 0.1-0.2 SC, 0.2-0.5 SC, 0.2-0.5 0.2-0.5 SC q6-8h 0.2-4.0 SC
IM q6-8h IM q6-8h IM q6-8h SC, IM q6-8h
q6-8h
Morphine 0.5-2.0 SC, 0.2-2.0 SC, 2-5 SC, IM 2-5 SC, IM 2-5 SC, IM q4h32 2-10 SC, IM Most commonly
IM q4h IM q2-4h q2-4h28 q4h q4h32 used as a
single dose
pre-operatively
Nalbuphine 1-2 IM, IV 0.5-1.5 IM, 1-2 IM q2-4h26 − 1-2 SC, IM 2-4 SC, IM −
HCl q2-4h IV q2-4h q2-4h26 q2-4h26
Naloxone 0.01-0.1 SC, 0.01-0.1 0.01-0.1 SC, 0.01-0.1 0.01-0.1 SC, 0.01-0.1 Opioid
IM, IV SC, IM, IM, IV SC, IM, IM, IV25 SC, IM, antagonist
IV IV54 IV, IP
Oxymorphone 0.05-0.2 SC, 0.05-0.2 0.2-0.5 SC, 0.2-0.5 1.2-1.5 SC 0.2-4.0 −
IM q6-8h SC, IM IM q6-8h SC, IM SC13
q6-8h q6-8h
Other medications
Tramadol 2-5 PO q4-8h − − − 5-20 PO, SC, IV,16 5-40 SC, Little is known
IP26,41 IP24,26 about this drug
to date in small
mammals;
higher dosing
frequency
necessary
to maintain
therapeutic
concentrations
of other species
aThese are suggested dosages based upon published information and the authors’ clinical experience. Species and individual variation in
response to a given drug can be uncertain, so the dosage should be adjusted depending upon the clinical response of the animal. Although
there is no good data available for hamsters and gerbils, extrapolation from rat dosages clinically appears to be appropriate. Many published
dosages are based upon laboratory animal data; differences in pet breeds of these animals are unknown. Doses are in milligram per kilogram
unless specified otherwise.
authors in ferrets and anecdotally by others in rabbits as pri- an effect for only approximately 30 minutes after a single IV
mary analgesics for the treatment of moderate to severe pain, injection and is thus most commonly used as a CRI during the
but they are also useful for preemptive analgesia and postop- perianesthetic and postoperative periods (see “Constant-Rate
erative pain. In ferrets, these drugs cause profound sedation, Infusions,” above, and Table 31-3).14 As with all μ receptor ago-
making assessment of analgesia difficult.65 Fentanyl citrate has nists, fentanyl can cause respiratory depression; thus a secure
airway and ability to ventilate are required when using it as a the O-desmethyl metabolite (M1) is a much more potent ago-
CRI. Systemic uptake of transdermal fentanyl in rabbits with the nist. The conversion to the M1 metabolite is variable among
25-mcg/h patch was highest, with the longest duration of activ- species, but it is known that it is produced in rats, mice, and
ity (3 days) when the hair was clipped at the patch site. But the rabbits.90,112,123 In the United States, only the PO formulation
rabbits were more sedated and had shorter plasma concentra- is available. In humans, less respiratory depression and con-
tions when the hair was chemically depilated, and no systemic stipation are seen with tramadol than with μ-agonist opioids,
concentrations were identified when hair was present at the but tramadol caused a significant decrease in guinea pig intes-
patch site.31 Although extrapolated effective therapeutic plasma tinal motility in vitro.57 The pharmacokinetics of tramadol
concentrations were obtained, loss of body weight occurred in have been evaluated in rats34,90,127 and rabbits,112 but analge-
this study. If this method of analgesia is to be used, appetite and sic plasma concentrations have not yet been established. Clini-
fecal/urine output must be monitored very closely. Remifentanil cally insignificant isoflurane-sparing effects have been shown in
is an ultra-short-acting μ receptor agonist, making it very suit- both rats and rabbits administered 10 and 4.4 mg/kg tramadol
able for CRI (see “Constant-Rate Infusions,” above). PO, respectively.16,21 Significant decreases in HR and transient
Buprenorphine is a slow-onset, long-acting partial μ opioid decreases in systolic arterial pressure were identified in rabbits
(see Table 31-6).1 It is the preferred opioid in small mammals after a single 4.4-mg/kg IV dose.21 Results of several studies in
for postoperative analgesia because of its longer duration of rats have shown that tramadol can be an effective analgesic for
effect.100 It can antagonize the effects of other pure μ agonists acute pain.12,41,43 In rats, tramadol provided analgesia for osteo-
and is also described as a κ-receptor agonist and antagonist.1 arthritis,12 but its efficacy decreased with increased duration of
Buprenorphine may exhibit a plateau or “ceiling” analgesic pain, and its antinociceptive mechanism changed over time,
effect; administration of additional doses produces either det- which may partially explain its inconsistent efficacy in patients
rimental effects,62 no additional analgesia, or prolonged anal- with chronic pain.43 Anecdotally, doses of 2 to 5 mg/kg PO have
gesia.29,62 Analgesic effects at the same dose can also be variable been well tolerated in rabbits and rats. In one study, there was
among different strains of rodents.62 GI effects are the most evidence of tolerance in rats with chronic use, so dosing may
commonly reported adverse effect with buprenorphine. “Pica need to be adjusted based on individual needs.116 While this
behavior” may occur when rats are housed on certain types analgesic holds great promise for use in small mammals, much
of bedding, especially sawdust or wood chips. Buprenorphine work is still needed to evaluate its appropriate dosing, efficacy,
is most commonly administered SC, IM, or IV; however other and safety in different species.
routes have also been evaluated. Buprenorphine is considered
safe and effective when administered at 0.01 to 0.05 mg/kg par-
NONSTEROIDAL ANTI-INFLAMMATORY DRUGS
enterally, but higher doses are sometimes necessary in smaller
mammals. For example, 0.5 mg/kg provided 6 to 8 hours of Nonsteroidal anti-inflammatory drugs (NSAIDs) are the
analgesia in rats, while 2 mg/kg provided 3 to 5 hours of anal- most commonly prescribed analgesics in veterinary medi-
gesia in mice.32 Buprenorphine administered PO in gelatin to cine. Reported adverse effects include GI ulceration and renal
rats was effective at 8 to 10 times the parenteral dose.27,91 Oral damage.108 Cyclo-oxygenase-2 (COX-2) has been shown to be
transmucosal buprenorphine is used in cats and anecdotally in constitutively expressed in the kidney in all mammalian spe-
ferrets. Epidural administration in rats shows consistent mild to cies studied and is highly regulated in response to alterations
moderate antinociception for at least 2 hours.84 Buprenorphine in intravascular volume. In conditions of relative intravascular
administered as a preanesthetic may not provide timely analge- volume depletion and/or renal hypoperfusion—such as dehy-
sia for surgical procedures and may prolong recoveries, so it is dration, hemorrhage, hemodynamic compromise, heart failure,
most commonly administered for postoperative pain.110 and renal disease—interference with COX-2 activity can have
Butorphanol is a mixed agonist/antagonist with low intrin- deleterious effects on maintenance of renal blood flow and glo-
sic activity at the μ receptor and strong agonist activity at the merular filtration rate. NSAIDs are generally well absorbed after
κ receptor (see Table 31-6). Butorphanol is commonly used in PO, SC, and IM administration. All NSAIDs are highly protein-
small mammals to circumvent the potential for GI disturbances bound, some greater than 99%, which explains their extended
and generally does not produce dose-related respiratory depres- therapeutic activity in inflamed tissues. Plasma half-life there-
sion. The half31-life of butorphanol in rabbits administered 0.5 fore may not be the most important factor in determining
mg/kg IV was shown to be 1.6 hours and 3.2 hours when given NSAID dosing intervals.
SC, consistent with results from other pharmacokinetic studies Ketoprofen is a potent nonselective COX inhibitor (see Table
of this drug.94 In rabbits administered 0.4 mg/kg butorphanol 31-6). Ketoprofen is used parenterally in exotic patients because
SC, ketamine/medetomidine, anesthesia was prolonged, but of limited oral pharmacokinetic data and difficulty in accu-
only minor anesthetic-sparing effects were seen.50 Butorpha- rately dosing oral formulations. Ketoprofen administered at 5
nol (0.4 mg/kg IV) significantly reduced the MAC of isoflurane mg/kg SC preoperatively in rats undergoing exploratory lapa-
in rabbits.115 Butorphanol has also been used as a CRI in the rotomy showed an effect for at least 5 hours, but this dose was
clinical setting, although to date there are no published studies not effective PO, suggesting that higher doses may be needed
evaluating this in small exotic mammals. for PO administration.30 Ketoprofen is available as a 2.5% topi-
cal gel in some countries, but systemic uptake may occur if it is
ingested.
TRAMADOL HYDROCHLORIDE
Carprofen is available in both injectable and PO forms (see
Tramadol hydrochloride is an analgesic that has become Table 31-6). It is a weak COX inhibitor and may achieve its thera-
popular recently despite minimal evidence of its efficacy (see peutic effects, at least partially, through other pathways. The half-
Table 31-6). It is active at opiate, alpha-adrenergic, and sero- life of carprofen varies considerably among mammalian species,
tonergic receptors.109 Tramadol is a very weak μ agonist, but which may affect dosing intervals. Very little work has been done
to date evaluating this drug in exotic animal species.30,46,101 Car- 4. Arras M, Autenried P, Rettich A, et al. Optimization of intra-
profen administered at 5 mg/kg SC provided postlaparotomy peritoneal injection anesthesia in mice: drugs, dosages,
analgesia for at least 5 hours,30 but an equivalent effect was found adverse effects, and anesthesia depth. Comp Med. 2001;51:
using only 2.5 mg/kg in another study.101 Postoperative food and 443-456.
5. Avsaroglu H, Versluis A, Hellebrekers LJ, et al. Strain differ-
water consumption were improved when rats were administered
ences in response to propofol, ketamine and medetomidine
5 mg/kg SC but not PO, suggesting that higher doses may be nec-
in rabbits. Vet Rec. 2003;152:300.
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carprofen enantiomer predominates in rabbit plasma, which in response to anaesthetics and analgesics between inbred rat
may have significant therapeutic and safety implications.46 The strains. Lab Anim. 2007;41:337-344.
authors have used 1 to 4 mg/kg PO, SC, and IM q12-24h short- 7. Bateman L, Ludders JW, Gleed RD, et al. Comparison between
term (<7 days) in many small mammal species. facemask and laryngeal mask airway in rabbits during isoflu-
Meloxicam is a COX-2 selective oxicam NSAID (see Table rane anesthesia. Vet Anaesth Analg. 2005;32:280-288.
31-6). In recent years, meloxicam has become the most widely 8. Boscan P, Van Hoogmoed LM, Farver TB, et al. Evaluation of
used anti-inflammatory medication in pet exotic animal practice. the effects of the opioid agonist morphine on gastrointestinal
tract function in horses. Am J Vet Res. 2006;67:992-997.
It is currently available as an oral suspension and an injectable
9. Brodbelt DC, Blissitt KJ, Hammond RA, et al. The risk of
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death: the confidential enquiry into perioperative small ani-
reduced acute postlaparotomy pain behaviors in rats, but a dose of mal fatalities. Vet Anaesth Analg. 2008;35:365-373.
0.5 mg/kg SC was not effective.101 The pharmacokinetics of single 10. Cantwell SL. Ferret, rabbit and rodent anesthesia. Vet Clin
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13. Clark MD, Krugner-Higby L, Smith LJ, et al. Evaluation of
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General Topics: Anesthesia, Analgesia, and Sedation of Small Mammals

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SECTION SIX

Michelle G. Hawkins, VMD, Diplomate ABVP (Avian), and

General Principles and Challenges in Anesthetizing GENERAL PRINCIPLES AND CHALLENGES IN

Copyright © 2012 by Saunders, an imprint of Elsevier Inc. 429

NUTRITIONAL STATUS AND FASTING CLINICAL TECHNIQUES

for intubation (Fig. 31-3). Placement of the tube is confirmed by

SECTION VI General Topics

been used as a sole sedative for minor, nonpainful procedures

SECTION VI General Topics

CHAPTER 31 Anesthesia, Analgesia, and Sedation of Small Mammals

CPR, cardiopulmonary resuscitation.

Table 31-6 Analgesic Drug Dosages Used in Small Exotic Mammalsa

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General Topics: Anesthesia, Analgesia, and Sedation of Small Mammals

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General Topics: Anesthesia, Analgesia, and Sedation of Small Mammals

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Copyright

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General Topics: Anesthesia, Analgesia, and Sedation of Small Mammals

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SECTION SIX

Michelle G. Hawkins, VMD, Diplomate ABVP (Avian), and

General Principles and Challenges in Anesthetizing GENERAL PRINCIPLES AND CHALLENGES IN

Copyright © 2012 by Saunders, an imprint of Elsevier Inc. 429

NUTRITIONAL STATUS AND FASTING CLINICAL TECHNIQUES

for intubation (Fig. 31-3). Placement of the tube is confirmed by

SECTION VI General Topics

been used as a sole sedative for minor, nonpainful procedures

SECTION VI General Topics

CHAPTER 31 Anesthesia, Analgesia, and Sedation of Small Mammals

CPR, cardiopulmonary resuscitation.

Table 31-6 Analgesic Drug Dosages Used in Small Exotic Mammalsa

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Table 31-6 Analgesic Drug Dosages Used in Small Exotic Mammalsa