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Rabbit Sedation and Anes 2022 Veterinary Clinics of North America Exotic An

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R a b b i t S e d a t i o n an d

Anesthesia
a, b
Sara Gardhouse, DVM, DABVP (ECM), DACZM *, Andrea Sanchez, DVM, DVSc, DACVAA

KEYWORDS
 Rabbit  Oryctolagus cuniculus  Anesthesia  Monitoring  Premedication
 Induction  Local anesthesia  Recovery

KEY POINTS
 Rabbits (Oryctolagus cuniculus) are prey animals with several behaviors that make them
unique anesthetic candidates that require special considerations in the preanesthetic,
anesthetic, and postanesthetic periods.
 As prey animals, the preoperative assessment of the rabbit patient is critical, as they
instinctually hide any signs of illness and disease.
 Multimodal anesthesia (balanced anesthesia) using various drugs and routes of adminis-
tration helps to provide the safest anesthetic plan for rabbits.
 There are various ways to obtain airway access in rabbits, each of which has its advan-
tages and disadvantages.
 The recovery period following anesthesia in rabbits is as critical as the preanesthetic and
anesthetic periods, and should not be ignored for its importance.

INTRODUCTION

Increasingly, rabbits are presented to veterinarians for evaluation, diagnostics, and


treatment, and with them on the rise as one of the most common domestic pets in
North America, owners expect high-level medical and surgical care.1 Deep sedation
is often necessary for procedures requiring restraint, evaluation, or minor medical
needs, and general anesthesia is frequently required for medical and surgical proced-
ures. Successful management of the rabbit anesthetic case requires understanding of
basic anesthetic principles, awareness of the limitations, and the necessary require-
ments to ensure high standards of anesthetic care for the patient.

Disclosure: The authors have nothing to disclose.


a
Department of Clinical Sciences, Kansas State University, 1800 Denison Avenue, Manhattan,
KS 66506, USA; b Department of Clinical Studies, Ontario Veterinary College, 55 Stone Road
East, Ontario N1G 2W1, Canada
* Corresponding author.
E-mail address: sgardhous@vet.k-state.edu

Vet Clin Exot Anim 25 (2022) 181–210


https://doi.org/10.1016/j.cvex.2021.08.012 vetexotic.theclinics.com
1094-9194/22/ª 2021 Elsevier Inc. All rights reserved.
182 Gardhouse & Sanchez

ANAMNESIS

A thorough history and husbandry evaluation is critical to the understanding of rab-


bits.2 Evaluation must include a thorough evaluation of the husbandry and a chrono-
logic report of the presenting complaint.2 Asking detailed questions is key to the
assessment of the patient, and open-ended questions tend to provide better
information.2

PREANESTHETIC ASSESSMENT AND CONSIDERATIONS

Rabbits have a reputation of being difficult or dangerous to anesthetize.3–5 As a prey


species, they are adept at concealing illness, and suitability as an anesthetic candi-
date may not be as ideal as initially perceived on presentation. As a result, a thorough
preanesthetic evaluation is key to a good outcome. A complete physical examination
including cardiac, respiratory, and gastrointestinal assessment (Table 1), and prean-
esthetic bloodwork may reveal underlying disease that has been concealed.2 If there is
suspicion for fluid deficits or gastrointestinal ileus, stabilization should be performed
before sedation or anesthesia. An accurate body weight is critical to successful anes-
thesia and to ensure accurate dosing of drugs.
Overall anesthetic mortality reported in healthy rabbits ranges from 1.39%3 to
4.8%.4 Prevalence is even higher when evaluating anesthetic and sedation-related
deaths in systemically ill rabbits with a 7.37% risk of death in one of these studies’
populations.3 Although the mortality associated with anesthesia is generally consid-
ered to occur during the anesthetic event, this study also revealed that rabbits are
as likely to die in the immediate 3 hours following anesthesia, and that these deaths
can occur up to 48 hours postanesthetically.3
Owing to rabbits’ prey nature, a crucial consideration to reduce stress before anes-
thesia is ensuring suitable accommodations away from cats, dogs, ferrets, and birds
of prey that are their predators in natural settings.6 This can be enhanced with the pro-
vision of privacy shelters and hides, and administration of anxiolytics and/or sedatives
such as benzodiazepines.6 Other strategies to reduce stress include providing a litter
tray and housing with their bonded mate when possible.6
Another important consideration is the large surface-area-to-volume ratio and poor
thermal tolerance that makes small mammals, like rabbits, susceptible to hypothermia
during general anesthesia. Inhalant anesthetics can also alter thermoregulatory
thresholds for compensatory responses in a dose-dependent fashion and also have
a cooling effect on the respiratory membranes.7 Thermoregulatory systems can be
further depressed by other drugs used in the perioperative period such as opioids.8
Hypothermia has the potential to create substantial impairment in cardiovascular
performance, slow recovery from anesthesia, impair coagulation, and decrease meta-
bolism of anesthetic drugs.9,10 A significant association between hypothermia at the
time of admission and mortality has been demonstrated in rabbits.11,12 Therefore,
measurement of body temperature and thermal support during the perioperative
period are critical to improve outcomes.

Table 1
Normal vital parameters in the rabbit13

Parameter Reference Range


Heart rate (beats/min) 200–300
Respiratory rate (breaths/min) 32–60
Temperature ( C [ F]) 38.5–39.5 [101.3–103.1]
Rabbit Sedation and Anesthesia 183

PREOPERATIVE BLOOD TESTS

It is straightforward to obtain a blood sample from most rabbits without the aid of
sedation.6 At a minimum, a packed cell volume (reference interval 34%–43%),13 total
protein (5.0–7.5 g/dL),13 and blood glucose (4.1–8.2 mmol/L; 74–148 mg/dL)13 should
be performed before anesthesia, but ideally, a complete blood cell count and
biochemistry profile should be performed to provide a more complete picture of over-
all health.6 Additional diagnostics such as a urinalysis and diagnostic imaging may be
indicated depending on the reason for anesthesia.6
Blood glucose can be used as a prognostic indicator in rabbits.14 A significant rela-
tionship between blood glucose and food intake, signs of stress, and severity of clin-
ical disease has been demonstrated.14 Stressed rabbits demonstrate a higher blood
glucose than those with no signs of stress, and complete anorexia results in a higher
blood glucose than those with normal food intake or hyporexia.14 Severe hyperglyce-
mia (>20 mmol/L, 360 mg/dL) has been associated with a poor prognosis.14 In addi-
tion, in cases of diagnosed intestinal obstruction, the mean blood glucose was higher
(24.7 mmol/L, 444.6 mg/dL) compared with nonobstructive gastrointestinal ileus
(8.5 mmol/L, 153 mg/dL).14 Based on these results, blood glucose can be used as
an indicator of the severity of a rabbit’s condition on presentation, and aid in differen-
tiation of gastrointestinal ileus versus true gastrointestinal obstruction.14
In addition to blood glucose, cholesterol, non–high-density lipoprotein cholesterol,
and triglycerides are also indicators of disease in rabbits and are associated with ev-
idence of severe infection or sepsis, renal failure, and hepatopathy.15 These parame-
ters should be taken into consideration before anesthesia and included as part of the
conversation with the owner regarding prognosis and risks.

FASTING

Rabbits are unable to vomit because of a highly developed and muscular cardiac
sphincter.16 Contrary to other species, long fasting times are contraindicated and it
is typically recommended to provide access to food and water close to the time of
anesthesia to ensure ongoing gastrointestinal motility; however, removing food 1 to
2 hours before anesthesia and after premedication reduces the risk of finding food
in the oral cavity during intubation that could be aspirated into the respiratory tract.17
Following an anesthetic event, food should be available as soon as the rabbit is ambu-
latory and feeding support should be considered when alert and swallowing.17,18

FLUID THERAPY

Preoperative assessment of hydration can be challenging in rabbits and intraoperative


monitoring of blood pressure can also present unique challenges; however, preoper-
ative assessment of packed cell volume, total protein, blood urea nitrogen, creatinine,
and urine specific gravity can provide some assessment with respect to overall hydra-
tion.8 An important consideration is to ensure constant hydration of the gastrointes-
tinal tract to ensure there is normal gastrointestinal motility and function; without
attention to this detail, potential consequences such as a functional ileus can be
fatal.18,19
In human and small animal medicine, it is becoming more widely acknowledged that
intravenous (IV) fluid therapy should not be all encompassing as a volume per hour, but
rather as a goal-oriented therapy titrated to the needs of the individual.20 As significant
as hypovolemia and hypoperfusion can be, overhydration and fluid overload can be as
detrimental.20
184 Gardhouse & Sanchez

Water intake in rabbits is comparatively higher than in other mammals.21,22 The


average daily water intake has been reported to range from 50 to 150 mL/kg of
body weight.2 In addition, with decreased food intake, polydipsia develops and water
intake may increase by as much as 6.5 times, which is an important consideration in
anorexic patients.2 This unique physiologic response, combined with their specialized
gastrointestinal anatomy, makes fluid therapy a critical part of the perianesthetic man-
agement plan.

INTRAVENOUS CATHETERS

Intravenous access should be obtained in any rabbit undergoing anesthesia and can
typically be achieved with adequate premedication/sedation protocols. The use of
topical, local anesthetic creams containing lidocaine 2.5% and prilocaine 2.5% over
the IV site 20 minutes before placement of a catheter can provide vasodilation and
comfort through full-thickness analgesia.23 Common locations for IV catheters include
the cephalic vein, lateral saphenous vein, and in certain situations, the marginal ear
vein.24 It is important to note that there is the potential for ear necrosis and sloughing
if certain medications leak perivascularly when the marginal ear vein is used.24 The
most common size of catheters that are appropriate are 22, 24, or 26 gauge, depend-
ing on the size of the vein and the rabbit (Fig. 1).24

INTRAOSSEOUS CATHETERS

In certain situations, such as very small or severely hypotensive rabbits, IV catheteri-


zation may not be possible. In these scenarios, the placement of an intraosseous (IO)

Fig. 1. Cephalic intravenous catheter placement. (Courtesy of Miranda Sadar, DVM, DACZM,
Colorado State University.)
Rabbit Sedation and Anesthesia 185

catheter may be appropriate.25 Almost all products that can be administered IV can be
given via the IO route including crystalloids, colloids including blood products, various
medications, dextrose, and emergency drugs.25 Common locations for placement of
an IO catheter include the trochanteric fossa of the femur, the greater tubercle of the
proximal humerus, the wing of the ilium, or the tibial tuberosity.24 Details regarding the
placement of IO catheters have been described elsewhere.24

BALANCED MULTIMODAL ANESTHESIA

Multimodal or “balanced” anesthesia is a concept that uses a combination of drugs in


a sufficient amount to produce the desired effect of anesthesia at its optimum degree
but minimizes the undesirable effects that can occur.26 This technique targets the triad
of narcosis, analgesia, and muscle relaxation by acting on each element individually to
avoid deep levels of central brain depression.26

PREMEDICATION

As in small animals, premedication of rabbits is ideal. Anxiety and stress can induce
dyspnea, and result in the release of endogenous catecholamines and cortisol, which
can result in complications during anesthesia and result in a less stable patient.27 In
addition, effective premedication protocols facilitate IV access, decrease induction
drug doses, and often decrease the minimum alveolar concentration (MAC) of inhalant
anesthetics required for anesthetic maintenance.28–32 There are many premedication
protocols that have been successfully used in rabbits and the selection of the protocol
will depend, in part, on the procedure to be performed. In addition, certain breeds and
strains have demonstrated differing responses to sedation protocols, and there is little
information evaluating the influence of age, sex, or health status on drug effects.33
Given the lack of scientific data and the higher anesthetic risks, the preferential use
of reversible drugs should be considered to allow for better control of the depth of
anesthesia and expedite recovery times.

BENZODIAZEPINES

The most commonly used benzodiazepine in rabbits is midazolam. Midazolam is a


short-acting benzodiazepine that is water soluble and can be administered either
intramuscularly (IM) or subcutaneously (SC) for a premedication, or IV during induc-
tion.34 Midazolam is often used as a sole sedative for minor, noninvasive, nonpainful
procedures, but is also commonly used in combination with an opioid, ketamine, or an
alpha-2 agonist for more extensive procedures in the preoperative setting. Midazolam
alone administered at 2 mg/kg IM produces muscle relaxation, mild sedation lasting
for 30 to 60 minutes, and minimal to no respiratory depression characterized by a
decreased respiratory rate but no changes in PO2 or PCO2.35 More profound and longer
sedation is obtained when midazolam is combined with an opioid.35 Flumazenil is the
common reversal agent for benzodiazepines and can be titrated to effect.34 Diazepam
is typically avoided because of the presence of propylene glycol in the injectable for-
mulations that can result in hypotension and thrombophlebitis.36

Partial Opioid Agonists and Agonist/Antagonists


Butorphanol is a m antagonist to partial m agonist and k opioid agonist. It has less anal-
gesic potency than m-pure agonists, a ceiling effect at high doses, and minimal
MAC-sparing effects.37–39 Due to its unique pharmacologic profile, butorphanol admin-
istration is only appropriate to treat mild pain and is an excellent sedative for minor
186 Gardhouse & Sanchez

diagnostic procedures.35 Butorphanol alone causes mild, short-term sedation in healthy


rabbits with minimal cardiorespiratory depression.35 More profound sedation, but also
significant respiratory depression, can be seen when it is combined with other sedatives
such as midazolam or alpha-2 agonists.35,40,41 Butorphanol is often administered IM or
IV, but it is also well absorbed when given intranasally.42
Buprenorphine is a m-partial agonist and an effective analgesic to treat mild to
moderate pain. Used alone, buprenorphine produces mild sedation, no cardiovas-
cular side effects, and mild respiratory depression.35,43 A study examining bupre-
norphine use in rabbits as a single dose demonstrated no adverse effects on
gastrointestinal motility44; however, other multidose studies have demonstrated po-
tential effects of buprenorphine on food intake and gastrointestinal motility.45 The
combination of midazolam and buprenorphine can result in marked sedation lasting
90 to 120 minutes.35

PURE m AGONISTS

Pure agonists such as morphine, methadone, hydromorphone, and fentanyl are


preferred as part of the premedication regimen when moderate to severe pain is pre-
sent, or before an invasive procedure. Comparison of the sedative effects of morphine
(2 mg/kg SC) and methadone (2 mg/kg SC) demonstrated more profound sedation
with methadone compared to morphine, with a maximum sedation score achieved be-
tween 30 and 60 minutes postinjection.46 Fentanyl is a short-acting potent opioid that
is commonly administered as a constant rate infusion (CRI) to provide analgesia and
MAC-reduction during surgery. At clinical doses, fentanyl has minimal cardiovascular
side effects except for mild to moderate bradycardia.47 In healthy rabbits anesthetized
with propofol, repeated boluses of fentanyl (5 mg/kg IV) caused no changes in cardiac
contractility but significant decreases in heart rate and mean arterial pressures
(MAPs).48 Therefore, high doses should be used with caution in ill patients or when
used concomitantly with drugs that depress the sympathetic system. Pharmacoki-
netics of fentanyl in rabbits after IV and sublingual administration have been described
elsewhere.49
Tapentadol is a novel, atypical opioid that behaves as an agonist at the m-receptor
and is also a norepinephrine reuptake inhibitor.50 Although few studies evaluate the
effectiveness of this drug in small mammals, tapentadol is reported to have similar
analgesic activity to morphine in humans, but lower affinity for the m-receptors.50 In
rabbits, 5 mg/kg IV was administered before sevoflurane induction to perform orchi-
ectomy and demonstrated rapid distribution, elimination, and no evidence of apnea.51
In addition, the pharmacodynamic evaluation of the drug demonstrated that tapenta-
dol provided adequate postsurgery analgesia.51

ALPHA-2 AGONISTS

Commonly used alpha-2 adrenergic receptor agonists include xylazine, detomidine,


medetomidine, and dexmedetomidine. These drugs are advantageous in premedica-
tion protocols because of their ability to provide excellent sedation and muscle relax-
ation, as well as commercially available reversal agents (yohimbine, atipamezole,
tolazoline).52 The cardiovascular effects can be significant and include vasoconstric-
tion, decreased cardiac output, second-degree heart block, and bradyarrhythmias.52
With cardiovascular compromise or concerns for cardiac disease, this class of drugs
should typically be avoided.
Rabbit Sedation and Anesthesia 187

N-METHYL-D-ASPARTATE (NMDA) ANTAGONISTS

Ketamine is a noncompetitive NMDA receptor antagonist that results in the prevention


of central sensitization, provision of analgesia, and induction of dissociative anes-
thesia.53 In healthy patients, ketamine is well tolerated and can be an excellent adjunct
to a premedication or injectable anesthetic protocol for short procedures; however,
ketamine can cause muscle rigidity and should be used with drugs that are potent
muscle relaxants such as alpha-2 agonists or benzodiazepines. Ketamine also has
sympathomimetic properties that can result in an increased heart rate, increased
myocardial contractility, and increased peripheral vascular resistance.53 Ketamine is
commonly used to produce profound sedation, or as an induction agent combined
with midazolam.
Reports of tiletamine-zolazepam in New Zealand white rabbits demonstrated neph-
rotoxicity at certain dosages but provides the advantage of smaller drug volumes
compared to ketamine if given as an IM injection.54,55 This drug should be used
with caution.

ANTICHOLINERGICS

The most common indication for anticholinergics in a premedication protocol include


minimization of salivary and bronchial secretions, and reduction of vagally-induced
bradyarrhythmias56; however, their utility in these scenarios has been questioned in
the human medical field, and controlled studies in rabbits have not been performed.57
In addition, atropine is not recommended because of lack of efficacy and clinical ef-
fects. This has been traditionally explained by approximately 61% of rabbits having
a high level of atropine esterase activity that rapidly hydrolyses atropine from the sys-
temic circulation, with a higher prevalence in males.50,58 Even rabbits with low levels of
atropine esterase activity also metabolize atropine quickly, which results in doses up
to 2 mg/kg having no effect on heart rate.47 Glycopyrrolate has a longer duration of
action than atropine.56 In rabbits, 0.1 mg/kg IM of glycopyrrolate has been demon-
strated to increase heart rate for a period of 60 minutes.56 Owing to the lack of proven
efficacy and the confirmed negative effects on gastrointestinal motility in hindgut fer-
menters,59 the routine use of anticholinergics as part of the premedication protocol is
not recommended. Table 2 lists common premedication protocols and indications for
each protocol.

LOCAL ANESTHETICS

Local anesthetics such as lidocaine and bupivacaine are commonly used in small an-
imals to reversibly inhibit neural transmission.60 Routes of administration of local an-
esthetics include topical, infiltration, intraarticularly, or as a regional nerve block.60

EPIDURAL ANESTHESIA

For abdominal surgeries or painful procedures of the caudal half of the body, epidural
anesthesia and analgesia offer a useful adjunct to pain management. Epidural anes-
thesia offers many avenues for use, including management of surgical cases, obstetric
pain, postsurgical pain, and chronic pain.60 Epidural drugs allow for the achievement
of analgesia without the concern for systemic effects compared to when the same
drugs are given IM or IV.60 In addition, epidurals have been shown to reduce recovery
time and it could be assumed a similar advantage would be seen in rabbits.61
Epidurals also allow a decrease in the amount of gas anesthesia required during the
procedure, allowing for a safer and more stable anesthesia.62 The lumbosacral
188
Gardhouse & Sanchez
Table 2
Injectable preanesthetic sedation and premedication protocols commonly used in rabbits with reversal agents

Drug Dosage Common Uses Reversal Agents


Midazolam 1 Midazolam 0.5–2 mg/kg SC Excellent for sedation for Flumazenil 0.05–0.1 mg/kg IM or SC
butorphanol  or IM 1 butorphanol nonpainful procedures
ketamine 0.5–2 mg/kg SC or IM  such as radiographs,
ketamine 3–5 mg/kg SC or IM computed tomography scan,
and catheter placement
Midazolam 1 Midazolam 0.5–2 mg/kg SC or Excellent for sedation for Flumazenil 0.05–0.1 mg/kg IM or
hydromorphone  IM 1 hydromorphone potentially painful procedures SC 1 naloxone 0.01–0.04 mg/kg IM or SC
ketamine 0.1–0.3 mg/kg SC or IM  or as a premedication
ketamine 3–5 mg/kg SC or IM before surgery
Midazolam 1 Midazolam 0.5–2 mg/kg Useful in young healthy Flumazenil 0.05–0.1 mg/kg IM or
butorphanol 1 SC or IM 1 butorphanol rabbits when moderate to SC 1 atipamezole 0.1–0.5 mg/kg SC or IM
dexmedetomidine 0.5–2 mg/kg SC or IM  profound sedation is necessary (depending on the dose of
dexmedetomidine dexmedetomidine)
0.01–0.05 mg/kg SC or IM
Midazolam 1 Midazolam 0.5–2 mg/kg SC or Useful in young healthy rabbits when Flumazenil 0.05–0.1 mg/kg IM or
hydromorphone 1 IM 1 hydromorphone moderate to profound sedation is SC 1 naloxone 0.01–0.04 mg/kg IM or
dexmedetomidine 0.1–0.3 mg/kg SC or necessary with analgesia in addition SC 1 atipamezole 0.1–0.5 mg/kg SC or IM
IM  dexmedetomidine (depending on the dose of
0.01–0.05 mg/kg SC or IM dexmedetomidine)

These are suggested dosages and protocols based on published information and the authors’ clinical experience. Species and individual variation in response to a
drug can be unpredictable and therefore, each dose should be selected with knowledge of clinical status and underlying health concerns.
Rabbit Sedation and Anesthesia 189

junction site is the most commonly used location in rabbits, with a technique similar to
dogs and cats. It is important to note that injection into the lumbosacral space may
result in intrathecal administration of drugs because the dural sac in rabbits extends
into the sacrum.63 The use of a shielded needle and electrical stimulation has been
described to allow for successful entry into the subarachnoid space.64 Successful
needle placement was described when a muscle contraction was noted at
0.3 mA.64 In one study, an epidural consisting of lidocaine and morphine were both
demonstrated to be effective adjunct analgesia when administered to rabbits under-
going pelvic limb orthopedic surgery.65

REGIONAL NERVE BLOCKS

A unique anatomic feature of rabbits is their elodont and hypsodont dentition that re-
sults in frequent presentations of dental disease in some form.66,67 The pain associ-
ated with dental disease and surgical treatment of dental disease can be
substantial. The use of locoregional dental blocks can help provide a multimodal anal-
gesic approach, and various dental blocks have been described in the literature.68–70
Sciatic and femoral nerve blocks have been successfully described in rabbits with
the use of a nerve stimulator and can provide intraoperative and postoperative anal-
gesia after pelvic limb surgery.71,72 Ultrasound-guided axillary brachial plexus nerve
blocks have also been described in rabbits.73
Many other ultrasound-guided blocks have been described in small animals
including paravertebral blocks, radial, ulnar, median, and musculocutaneous nerve
blocks; erector spinae plane blocks; intercostal blocks; transversus abdominis plane
blocks; and quadratus lumborum blocks.74 The details of these blocks are beyond the
scope of this article but are well described elsewhere (DiGeronimo PM, da Cunha A.
Local and regional anesthesia in zoological companion animal practice. Vet Clin Exot
Anim 2022;25:1: in press.].74

INDUCTION

Induction of anesthesia can be achieved through the use of injectable drugs or inhalant
gases. Induction using an inhalant agent is common practice in rabbits, but whenever
possible should be preceded by appropriate premedication. Premedication before
gas induction shortens the excitatory phase and the dose of inhalant agent required.
Preoxygenation via face mask can provide benefits before administration of the
inhalant anesthetic by increasing oxygen stores and delaying arterial hemoglobin
desaturation during apnea (Fig. 2).75 The mask should be loose, but well-fitted with
enough room to allow for escape of carbon dioxide and heat.76 Oxygen flow rates
greater than 100 mL/kg/min are needed with a mask that is well-fit.76 If the mask is
large and poorly fitted, higher oxygen flow rates (300 mL/kg/min) may be needed.76
Benefits of preoxygenation can be achieved in less than 1 minute in a healthy patient,
but may require greater than 5 minutes with compromised respiratory function.17
Induction with an appropriately sized mask allows for better depth control and moni-
toring and is preferred, but commercially available induction chambers can be advan-
tageous in very stressed rabbits that are resistant to facemask induction.77 As soon as
the righting reflex is lost, the patient should be removed and placed on a face mask to
allow for better control of anesthetic depth. A comparison of the advantages and dis-
advantages of face mask versus chamber induction is provided in Table 3. Given the
many benefits of safe injectable drugs available, the use of injectable techniques is
recommended, allowing for reduced anesthetic waste gas, readily available IV and
airway access, and less cardiovascular depression due to easier drug titration.
190 Gardhouse & Sanchez

Fig. 2. Preoxygenation via face mask.

PROPOFOL

Propofol is a substituted isopropylphenol anesthetic. Its use as an injectable induction


agent in rabbits is common because of its ability to provide a rapid, excitement-free
induction and recovery.78 The use of propofol requires IV or IO access, and the ability
to rapidly intubate, as apnea is common after administration.78 Propofol given as a
bolus for induction causes a short-lived, dose-dependent vasodilation, and at supra-
therapeutic doses may decrease cardiac contractility.79–81 These side effects are
dose-related and may be exacerbated by rapid administration, and therefore, it is rec-
ommended to titrate propofol to effect. A calculated propofol induction dose can be
given in one-quarter increments, administered over 30 to 60 seconds, to minimize
side effects.17 Propofol can also be used for anesthetic maintenance with doses of
24 to 36 mg/kg/h reported.82 Pharmacokinetic data for propofol administered as a sin-
gle bolus, and short and long infusion are available in the literature and appear to be
affected by the time of the day with higher doses needed in the morning compared
with the afternoon to reach the same anesthetic depth.83–85

ALFAXALONE

Alfaxalone is a neurosteroid anesthetic that is suitable as an induction agent through IV


administration with a rapid onset and short duration of action.86 Cardiovascular effects
of the newest formulation of alfaxalone have not been well studied in rabbits but an
older formulation of alfaxolone/alfadolone was demonstrated to produce dose-
dependent cardiovascular depression similar to other general anesthetics.87 This
drug can also be administered IM or SC to provide sedation. Doses of 4 mg/kg and
6 mg/kg IM were reported to be well tolerated; however, one rabbit died following res-
piratory and cardiac arrest after a dose of 8 mg/kg was administered.86 In one study, a
combination of alfaxalone (6 mg/kg), dexmedetomidine (0.2 mg/kg), and butorphanol
(0.3 mg/kg) IM produced anesthesia lasting approximately 1 hour with a recovery time
of approximately two and a half hours.88 An additional study examined a dose of 2 and
3 mg/kg IV for induction, and intubation was possible in all rabbits, although apnea
was noted.89 Therefore, as with propofol, preoxygenation and preparation for intuba-
tion is advised when alfaxalone is administered IM and IV.89
Rabbit Sedation and Anesthesia 191

Table 3
Advantages and disadvantages to face mask and chamber induction methods in rabbits17

Method of
Induction Advantages Disadvantages
Face mask Rapid induction Waste gas high
with a well-fitted mask Staff exposure to anesthetic gases
Chamber induction Waste gas lessened Staff exposure to anesthetic
Short induction time gases when patient is removed
from chamber
Inability to assess the depth of the patient
Trauma during the excitement phase

ETOMIDATE

Etomidate is a potent, nonbarbiturate hypnotic agent with a short duration of action


that is commonly used for induction and maintenance of anesthesia in animals and
humans.90 Similar to propofol and alfaxalone, etomidate does not possess analgesic
properties.90 Etomidate has been reported to cause hemolysis, thrombophlebitis, and
pain on injection because of the formulation containing propylene glycol.90 These side
effects have been reduced with the creation of an aqueous formulation of the drug.91
Although etomidate has been reported to have minimal cardiovascular side effects in
other species, both formulations resulted in decreases in MAP and increases in HR
when administered to rabbits.91 Other common adverse effects include laryngeal
reactivity and inhibition of cortisol secretion which preclude its use with adrenal
insufficiency.90
Commonly used injectable induction protocols are listed in Table 4. Table 5 de-
scribes reported combinations of drugs for premedication, induction, and mainte-
nance of anesthesia.

AIRWAY ACCESS
Nasotracheal Intubation
Nasotracheal intubation can be a useful method of intubation in specific situations,
including the emergency setting when respiration ceases or during dental procedures
where an endotracheal tube can impede the ability to perform the procedure.92,93
Commonly, nasotracheal intubation is used in cases where the oral cavity is the pri-
mary area of interest.94 The tube should be directed ventrally and medially into the
ventral nasal meatus.93 Nasotracheal intubation uses the fact that rabbits are obligate
nasal breathers.93 The epiglottis is entrapped on the dorsal surface of the soft palate,
and thus, facilitates the direct passage of air from the nasopharynx into the larynx and
trachea.93 Resultantly, a tube passed nasally should naturally traverse the pathway
from the nasopharynx, to the larynx, to the trachea.93 The flipped soft palate is one
of the described difficulties with orotracheal intubation and is beneficial when perform-
ing nasotracheal intubation. Contraindications for the use of nasotracheal intubation
include the presence of upper respiratory disease, preexisting edema of the nasal pas-
sages, and preexisting narrowing of the nasal passages, which may occur because of
apical elongation from the teeth associated with dental disease.93,95 Complications
are usually associated with traumatic nasotracheal intubation where repeated at-
tempts result in damage to the soft tissue structures and nasal turbinates which can
result in swelling and nasal passageway obstruction.94 Although there is little evidence
to support introduction of bacteria into the lungs, in cases of known upper respiratory
192 Gardhouse & Sanchez

infection, it may be prudent to avoid the use of nasotracheal intubation.93,95 In very


small rabbits, this technique may not be feasible because of the small size of tube
that would be required. Step-by-step directions on nasotracheal tube intubation are
provided in Box 1.

Oral Endotracheal Intubation


Oral endotracheal intubation is the most common method of securing an airway in rab-
bits and allows for positive pressure ventilation to be performed throughout the anes-
thetic event. Orotracheal intubation presents challenges because of the narrow oral
cavity lined by premolars and molars on both sides, the long tongue with a large
base, decreased jaw opening ability, and potential for laryngospasm.96 Many tech-
niques have been described for intubation including the blind method, modified blind
method, videoendoscopic methods, and direct visualization.96 Complications with
orotracheal intubation include difficult placement, trauma to the oropharyngeal soft
tissue, laryngospasm, tube dislodgement, and postintubation oropharyngeal swelling
after intubation.96,97
For intubation using the blind technique, visualization of airflow through the endotra-
cheal tube, listening for respiration, or monitoring of end-tidal carbon dioxide (EtCO2)
followed by careful manipulation of the tube is required.96 This technique is not useful
in cases of respiratory arrest or prolonged apnea because of the absence of airflow
and the necessity for breathing.96 With inexperience, this technique can result in sig-
nificant laryngospasm and laryngeal trauma.96 Direct visualization of the larynx with a
laryngoscope can also be attempted; however, this technique presents significant
challenges, as often the laryngoscope blade is wider than the narrow oral cavity, pre-
molars, and molars, preventing appropriate visualization and an inability to depress
the tongue.96 Other techniques include the use of a fiberoptic laryngoscope or an
endoscope to visualize the larynx and guide placement of the endotracheal tube.96
The most common endotracheal tube sizes in rabbits range from 2.0 to 3.5 mm in-
ternal diameter.98 The size selected should be the largest possible to reduce airflow
resistance, and allow creation of a good seal to facilitate ventilation, but should also
avoid iatrogenic trauma to the tracheal mucosa. Commercially available tubes are
often too long and should be measured to the thoracic inlet and cut to ensure acci-
dental bronchial intubation does not occur.
It is important to keep in mind that with small diameter tubes, risk of occlusion of the
tube with saliva, or occlusion from kinking of the tube are significant risks and require
close anesthetic monitoring.99 Use of an EtCO2 monitor can be useful to help correct
tube placement and accidental detachments or obstructions.99
Confirmation of tube placement is similar to other species.99 The rabbit may cough
as the tube is passed, condensation may be seen on the inside of the endotracheal
tube or on a glass slide placed at the end of the tube, air movement can be detected
by listening for breath sounds, a wave form can be detected on the EtCO2 monitor, or
movement of the chest can be detected when a breath is provided with the rebreath-
ing bag.99
Although complications of intubation are rare, reports of subtracheal injury, ulcera-
tion, and postintubation tracheal stricture following intubation with both cuffed and
uncuffed endotracheal tubes have been documented.100,101 The clinical presentation
is typically dyspnea and upper respiratory tract obstruction signs, such as moist rales
and cyanosis.100,101 This highlights the importance of taking great care during the intu-
bation process and the consideration for alternatives such as a face mask or laryngeal
mask airway during very short procedures.100,101 Other factors that have been
Rabbit Sedation and Anesthesia 193

Table 4
Commonly used induction protocols and dosages used in rabbits

Drug Dosage Comments


Propofol 2–8 mg/kg IV Apnea is common, especially
when administered rapidly
or at higher dosages
Dose-dependent hypotension
Alfaxalone 1–4 mg/kg IV Apnea is common, especially
when administered rapidly
or at higher doses
Potential dose-dependent
hypotension
Ketamine 1 Ketamine 2.5–5 mg/kg IV 1 Midazolam Apnea is uncommon
midazolam 0.5 mg/kg IV Increases MAP and HR

These are suggested dosages and protocols based on published information and the authors’ clin-
ical experience. Species and individual variation in response to a drug can be unpredictable and
therefore, each dose should be selected with knowledge of clinical status and underlying health
concerns.

implicated in tracheal injury and stricture include ventilation technique and disinfection
protocols for the endotracheal tubes.100,101

Laryngeal Mask Airway Devices and Supraglottic Airway Devices


The laryngeal mask was initially developed to serve as an alternative to mask ventila-
tion for people and also for use in an emergency setting for the management of chal-
lenging airways.102 The pediatric laryngeal mask airway (LMA) device has been used
as an alternative to endotracheal tube placement in rabbits, and may result in easier
placement than an endotracheal tube, especially in the emergency setting.103 It is
important to note that the LMA device results in more gas inhalant waste than when
endotracheal intubation of the rabbit is performed.103 In addition, as pediatric human
devices have not been specifically designed for use in rabbits, complications such as
lingual cyanosis, gastric tympany, and an incomplete airway seal have been docu-
mented with the use of these devices.103–105
More recently, a supraglottic airway device (SGAD), specifically designed to mirror
the pharyngeal airway anatomic structures of the rabbit (v-gel ADVANCED, DocsInno-
vent Ltd, Hemel Hempstead, UK), has been created. This device allows for rapid man-
agement of the airway and when properly placed can also allow for the application of
positive pressure ventilation (Fig. 3).106 This SGAD is beneficial in certain scenarios
because of its ease of placement by a novice clinician using EtCO2 guidance com-
bined with minimal to no airway trauma.106 Placement time is rapid, ranging from 14
to 38 seconds.106 In one study evaluating the placement of a v-gel compared to
oral endotracheal intubation, the longest time for placement was 38 seconds
compared to 171 seconds with an endotracheal tube.106 The combination of the
unique shape of the v-gel with the soft gel-like material allows for creation of a strong
seal with minimal trauma to the airway.106 In addition, it is suggested by the manufac-
turer that it does not result in narrowing of the airway which is seen with an endotra-
cheal tube and thus, may resultantly decrease work of breathing.107 The rabbit v-gel is
available in a wide variety of weights (0.6 kg to 4.51 kg).107 When positive pressure
ventilation is required, especially for an extended duration, placement of an endotra-
cheal tube is a recommended safer option due to potential for complications such as
194
Gardhouse & Sanchez
Table 5
Drug combination studies reported in rabbits for premedication, induction, and maintenance of anesthesia

Drug Protocol Purpose of Protocol Dosage Comments


Ketamine 1 xylazine149 Injectable anesthesia K 35 mg/kg 1 X 5 mg/kg IM Addition of butorphanol to protocol
Ketamine 1 xylazine 1 K 35 mg/kg 1 X 5 mg/kg 1 resulted in a prolonged reflex loss
butorphanol149 B 0.1 mg/kg IM (palpebral reflex, pedal reflex, righting
reflex), as well as mild alterations in
physiologic changes
Ketamine-propofol Induction K 1, 3, or 5 mg/kg 1 P 1 mg/kg Time to loss of righting reflex shortest
admixture150 and duration of action longest with
the highest dose of ketamine
Mild to moderate sedation only achieved
in the lowest dose ketamine group
Hypoxemia observed at highest doses
Medetomidine 1 Induction 1 maintenance of anesthesia Med 0.2 mg/kg IM 1 Propofol at 0.5 mg/kg/min maintained
midazolam 1 Mid 0.5 mg/kg IM 1 general anesthesia with few side
atropine IM 1 atropine 0.5 mg/kg IM 1 effects to the cardiopulmonary system
propofol IV82 P to effect IV apart from mild hypotension,
hypercapnia, and respiratory acidosis
Smooth recovery
Two rabbits died within 24 h of the
procedure
Ketamine 1 Induction K 15 mg/kg 1 Mid 3 mg/kg IM Time to loss of righting reflex was shorter
midazolam151 K 15 mg/kg 1 with medetomidine
Ketamine 1 Med 0.25 mg/kg IM Intubation was not possible with 3
medetomidine151 rabbits in the medetomidine protocol
and 4 rabbits in the midazolam
protocol
Mean heart rate, SPO2, and vaporizer
setting (isoflurane sparing) were lower
in the medetomidine group
Medetomidine rabbits were more prone
to laryngospasm
Ketamine 1 midazolam152 Injectable anesthesia K 25 mg/kg 1 Mid 2 mg/kg IM Faster time to loss of righting reflex and
Ketamine 1 midazolam 1 K 25 mg/kg 1 Mid 2 mg/kg 1 to standing with inclusion of tramadol
tramadol152 T 4 mg/kg IM Inclusion of tramadol did not provide
additional analgesia in the protocol
Ketamine 1 medetomidine153 Injectable anesthesia K 35 mg/kg 1 Med 0.25 mg/kg Surgical anesthesia induced in most
Medetomidine 1 fentanyl 1 Med 0.2 mg/kg 1 F 0.02 mg/kg 1 animals receiving medetomidine-
midazolam153 Mid 1 mg/kg based protocols
Xylazine 1 ketamine153 X 4 mg/kg 1 K 50 mg/kg Apnea was noted in the fentanyl
protocol and endotracheal intubation
is essential
Supplemental oxygen needed for all
protocols
Quality of surgical anesthesia greatest
with the medetomidine 1 ketamine
protocol
Ketamine 1 medetomidine SC154 Injectable anesthesia K 15 mg/kg 1 Med 0.25 mg/kg SC All groups lost righting reflex and ear
Ketamine 1 medetomidine IM154 K 15 mg/kg 1 Med 0.25 mg/kg IM pinch response with time to loss of
Ketamine 1 medetomidine 1 K 15 mg/kg 1 Med 0.5 mg/kg 1 reflexes similar among all groups
butorphanol SC154 B 0.4 mg/kg SC Higher dose of medetomidine and
Ketamine 1 medetomidine 1 K 15 mg/kg 1 Med 0.25 mg/kg 1 B addition of butorphanol produced a
butorphanol IM154 0.4 mg/kg IM greater duration of loss of ear pinch
response

Rabbit Sedation and Anesthesia


Moderate hypoxemia and moderate
bradycardia in all rabbits
SC and IM administration were
equivalent
Addition of butorphanol increased the
duration of anesthesia with a slight
increase in the degree of respiratory
depression

These are suggested dosages and protocols based on the published information. Species and individual variation in response to a drug can be unpredictable and
therefore, each dose should be selected with knowledge of clinical status and underlying health concerns.

195
196 Gardhouse & Sanchez

Box 1
Step-by-step instructions for the placement of a nasotracheal tube in the rabbit
To place a nasotracheal tube, adequate muscle relaxation and appropriate anesthetic depth
are required. Supplemental oxygen via face mask or flow by should be provided over the dura-
tion of the procedure. A 2% lidocaine solution (1–2 mg/kg) can be infused into the nasal pas-
sages with a syringe or catheter 60 seconds before tube placement. Correct positioning is
critical for successful intubation allowing for optimal alignment of the nasopharynx with the
trachea. The rabbit is positioned in sternal recumbency with hyperextension of the head and
neck. The diameter of the nasal passage, even in large individuals, is small, and therefore it
is usually not possible to pass a tube larger than 2.0 to 2.5 mm. In small rabbits, it may not
be feasible. Conservative application of sterile lubricant should be applied on the end of the
tube before placement. Excessive lubricant can result in obstruction of the Murphy eye of
the tube. The bevel of the endotracheal tube is inserted into the ventral nasal canal and
directed in a ventromedial direction. A small degree of resistance is considered normal because
of the nasal passageway anatomy, but if significant resistance or a “crunching” sound is
encountered, it may be indicative of a tube that is too large or it is passing in the wrong direc-
tion through the nasal turbinates and requires redirection.95 The rabbit often coughs when the
tube enters the trachea.95

lingual edema and cyanosis, gastric tympany, and v-gel dislodgement.108 A common
challenge is dislodgement when the head is shifted. When performing surgical pro-
cedures, or an anesthetic event that may require substantial movement of the head,
endotracheal intubation should be considered. A recent study demonstrated that
the v-gel is a practical alternative to both endotracheal tubes and laryngeal masks.109

MAINTENANCE OF ANESTHESIA

Once the airway is secured, the maintenance stage of anesthesia begins. At this point,
the most important considerations include monitoring the depth of anesthesia,
providing supportive care to the rabbit as needed, and ensuring adequate monitoring
is in place.
Active warming should occur after premedication and should continue until the rab-
bit is fully recovered, alert, and normothermic. Active warming options include
warmed IV fluids, warmed anesthetic gases, warmed air beds, hot water bottles,
circulating water blankets, or heat pads. In rabbits breathing a heated anesthetic
mixture, the average body temperature was shown to be 1.01 C (1.8 F) higher than
breathing a nonheated anesthetic mixture.110 With any warming device, caution
should always be used to ensure there is no direct contact that could result in thermal
burns. Constant monitoring of temperature with either an esophageal probe or rectal
thermometer is critical throughout the anesthesia.
In select situations (short-term procedure), maintenance of anesthesia with a face
mask can be considered. Examples include a brief incisor trim or simple dental pro-
cedure, a biopsy for histopathological analysis, or endoscopic evaluation of the oral
cavity; however, though face masks are easily placed, significant leakage occurs dur-
ing controlled mechanical ventilation.109

ISOFLURANE, SEVOFLURANE, AND DESFLURANE

In most situations, maintenance of anesthesia is performed with an inhalant gas, either


isoflurane, sevoflurane, or desflurane.111 Sevoflurane has a less noxious smell and
may be better tolerated for mask induction.112 Very little of the anesthetic gases are
metabolized, which reduces the impact on hepatic and renal function.112
Rabbit Sedation and Anesthesia 197

Fig. 3. Appropriate placement of a commercially available rabbit-specific supraglottic


airway device.

Inhalant anesthetic can result in cardiovascular and respiratory depression. Most in-
halants act in a dose-dependent manner to reduce systemic vascular resistance and
cause decreases in stroke volume as a result of decreased myocardial contractility.
Both these undesirable side effects result in dose-dependent hypotension.111 Rabbits
appear to be more sensitive to the vasodilatory effects of inhalant anesthetics than
other species, with hypotension occurring at levels as low as 1 MAC and may be a
contributing factor to the higher anesthetic mortality seen.113,114 The underlying cause
is unclear but a lower systemic vascular resistance and substantially lower arterial
blood pressures have been reported at equipotent doses of inhalants.115
The negative effects of inhalant gases can be minimized by using a balanced anes-
thetic approach and the administration of sympathomimetics. Dopamine is commonly
used to combat isoflurane-induced hypotension but has been ineffective in rabbits,
where phenylephrine was only minimally effective at 2 mg/kg/min114 Norepinephrine
0.5 to 1.0 mg/kg/min has been demonstrated as a potentially effective treatment to
combat isoflurane-induced hypotension.116
Various drugs and drug combinations have been reported to reduce MACs, and
should be considered (Table 6).

TOTAL AND PARTIAL INTRAVENOUS ANESTHESIA

Intravenous CRIs of anesthetic drugs have been used to provide total intravenous
anesthesia (TIVA) in rabbits. These medications can be titrated to effect and support
a balanced anesthetic approach by reducing other drug dosages. These techniques
require IV or IO access. Studies examining propofol and fospropofol continuous IV
infusion for anesthetic maintenance in rabbits demonstrated prolongation of recovery
time with increasing infusion time for both drugs.117 Fospropofol, the water-soluble
prodrug of propofol, demonstrated greater prolongation of recovery time compared
to propofol.117 An additional study compared the physiologic effects of sufentanil-
midazolam TIVA to sevoflurane for surgical anesthesia in premedicated rabbits.118
This study demonstrated that both protocols provided similar quality of anesthesia
and required mechanical ventilation.118
198 Gardhouse & Sanchez

Table 6
Anesthetic drugs with clinically significant minimum alveolar concentration sparing effects in
rabbits

Minimum Alveolar
Concentration Commonly Used Clinical
Drug Dose Reduction Doses
Fentanyl114 Plasma concentration up to 63% Loading dose: 3–10 mg/
2  0.1 ng/mL to (Isoflurane) kg
36.8  2.4 ng/mL Intraoperative rate: 5–
20 mg/kg/h
Postoperative rate: 2–
5.0 mg/kg/h
Ketamine120 1 mg/kg loading dose 35% (Isoflurane) Loading dose: 0.5–2 mg/
IV 1 40 mg/kg/min IV kg
Intraoperative rate: 0.5–
3 mg/kg/h
Postoperative rate:
0.25–1 mg/kg/h
Lidocaine125 50–100 mg/kg/min 10.5% to 21.7% Loading dose:1–2 mg/
(Isoflurane) kg
Intraoperative rate: 50–
100 mg/kg/min
Postoperative rate: 10–
50 mg/kg/min
Butorphanol39 0.4 mg/kg IV 2.30% to 2.33% Significantly reduced
(Isoflurane) MAC alone or in
combination with
meloxicam (more
significant reduction
with combination)

Both tramadol (4.4 mg/kg IV) and meloxicam (0.3 mg/kg IV, 1.5 mg/kg IV) have also been evaluated
for MAC reduction in rabbits and did not show clinically significant effects.39,155

CRIs can be used to supplement inhalant anesthesia and provide analgesia. Keta-
mine as a CRI is useful for intraoperative analgesia, MAC reduction, and the benefit of
minimal respiratory depression.119 A ketamine CRI of 9 mg/kg/h resulted in a signifi-
cant decrease in the MAC of isoflurane in rabbits.120 m-Receptor agonist opioids are
also commonly used as CRIs during anesthetic maintenance, with fentanyl citrate be-
ing one of the more common. An IV fentanyl CRI resulted in a reduction of the MAC of
isoflurane by up to 63% in rabbits, depending on the plasma concentrations that were
evaluated.121 In addition, the higher concentrations of fentanyl caused increases in
blood pressure with no change in cardiac output.122 Another study examined the
use of sufentanil in combination with midazolam for use as TIVA, and demonstrated
similar quality surgical anesthesia to sevoflurane anesthesia in ovariohysterectomized
rabbits with both protocols requiring mechanical ventilation.123
Lidocaine as an IV infusion has the potential for multiple benefits including visceral
analgesia, promotion of gastrointestinal motility, MAC reduction, and an increase in
visceral perfusion.124,125 In rabbits, lidocaine CRI (100 mg/kg/min for 2 days)
decreased pain behavior; increased gastrointestinal motility, food intake, and fecal
output, and decreased heart rate compared to buprenorphine (0.06 mg/kg IV q 8 h
for 2 days) in the postoperative period following ovariohysterectomy.126 Commonly
used drugs for CRIs are listed in Table 7.
Rabbit Sedation and Anesthesia 199

Table 7
Commonly used constant rate infusions in rabbits

Drug Dose Comments


Ketamine17,120 Loading dose: 2–5 mg/kg Less respiratory depression was
Perioperative rate: 1–2 mg/kg/h noted compared to opioids that
Postoperative rate: 0.25–1 mg/kg/h are administered as a CRI
Fentanyl citrate17,122 Loading dose: 5–10 mg/kg Apnea is common and ventilation
Perioperative rate: 10–40 mg/kg/h of the rabbit is often necessary
Postoperative rate: 1.25–5.0 mg/kg
h
Lidocaine126 50–100 mg/kg/min

These are suggested dosages and protocols based on the published information. Species and indi-
vidual variation in response to a drug can be unpredictable and therefore, each dose should be
selected with knowledge of clinical status and underlying health concerns.

MONITORING OF ANESTHESIA

Common anesthetic complications in rabbits include hypothermia, respiratory


depression, hypotension, and bradycardia.

CARDIOVASCULAR SYSTEM

Thoracic auscultation should be performed throughout anesthesia to allow for evalu-


ation of the heart rate, rhythm, and presence of abnormal cardiac sounds. The normal
anatomy of the heart, including the differences from common domestic species has
been well described.127–129 Pulse strength can be evaluated with the femoral artery,
the dorsal pedal artery, and the auricular artery.130,131 Mucous membrane color and
capillary refill time should be assessed as part of a thorough evaluation of the cardio-
vascular system throughout the anesthetic procedure.132
Doppler evaluation of the cardiovascular system is useful to evaluate the rate and
rhythm of the heart.130 The Doppler transducer can be placed directly on a superficial
artery such as the carotid, radial carpal artery (medial aspect of forelimb), auricular,
dorsal pedal (dorsal aspect of hindlimb), or femoral.131,133–136
Blood pressure measurement in rabbits can be challenging. Arterial blood pressure
is evaluated as a function of heart rate, blood volume, stroke volume, and arterial
compliance.137 The evaluation of blood pressure should be used in conjunction with
other diagnostics as part of the cardiovascular assessment and evaluation of tissue
perfusion.138 A low blood pressure can be indicative of reduced blood flow and
impaired oxygenation of major organs.138 Blood pressure can be measured directly
or indirectly.130 Direct arterial blood pressure monitoring can be reliable and accurate
when an over-the-needle catheter is placed in the central auricular artery (Fig. 4).134 In
small rabbits, less than 2 kg, the arterial wave may be overdamped, making interpre-
tation challenging, and are also at increased risk of thromboembolism.139
Indirect blood pressure measurement is more commonly used and is less inva-
sive.130 There are 2 main methods of indirect blood pressure: oscillometry and
Doppler ultrasonic sphygmomanometry.130 In other species, systolic arterial pressure
is measured by the Doppler technique, although in cats, there is evidence that Doppler
blood pressure may be more reflective of MAP.140 Regardless, the cuff width to limb
circumference ratio should be 30% to 40%.141 Typically, Doppler is recommended
over oscillometric monitoring in rabbits for several reasons. Oscillometric techniques
200 Gardhouse & Sanchez

Fig. 4. Placement of a catheter in the central auricular artery for invasive blood pressure
monitoring.

can fail to obtain accurate measurements in animals with rapid heart rates (>200 bpm),
of small size, and with hypothermia.133,134
Attempts to validate noninvasive blood pressure monitors in rabbits have been
made with mixed results. One study (n 5 17) found good agreement between Doppler
measurements at the dorsal carpal branch of the radial artery and those that directly
obtain auricular systolic pressures; in addition, the same study found that Doppler
measurements below 80 mm Hg were a reliable indicator of arterial hypotension.133
On the contrary, a second study with a smaller sample size (n 5 6) concluded that
both oscillometric and Doppler blood pressure measurements were poor substitutes
for carotid blood pressure measurement because of changing bias and large limits of
agreement.115
When using oscillometric devices, the forelimb is preferred because measurements
from the pelvic limb have a poor correlation with the abdominal aorta (criterion stan-
dard) readings, but measurements from the forelimb appear to correlate well at low
and normal pressure ranges.134

Electrocardiograms
Cardiac muscle cells produce electrical activity and this can be monitored with the use
of an electrocardiogram (ECG) tracing.131 The ECG tracing is composed of 3 primary
complexes, which includes the P wave, QRS complex, and T wave.142 An ECG eval-
uation is useful when detection of arrhythmias occurs, which is common with acid-
base and electrolyte abnormalities. Given that rabbits have rapid heart rates, low-
voltage machines and fast recording speeds (up to 100 mm/s) are
Rabbit Sedation and Anesthesia 201

recommended.136,143 Rabbits have very delicate skin and the standard alligator clips
can tear it. It is preferred that the clips be attached to small-gauge hypodermic nee-
dles placed through the skin. Adhesive pads can be used but may tear the skin on
removal. These pads do not work well on the feet of rabbits as they require the protec-
tive fur on the plantar and palmar aspect of the feet to be shaved, which can lead to
severe pododermatitis because of a lack of protective foot pads.

Pulse Oximeter
Pulse oximetry is commonly used in rabbits, but with limited information available
about its accuracy. Pulse oximetry measures oxygen saturation of the blood through
illumination of the skin and detection of changes in light absorption between oxygen-
ated blood (oxyhemoglobin) and deoxygenated blood (reduced hemoglobin).144 The
pulse oximeter determines the ratio of absorbance between these wavelengths with
calibration against direct measurements of arterial oxygen saturation (SaO2) to deter-
mine the measurement of arterial saturation (SpO2) by the pulse oximeter.144 In
humans, the difference between SpO2 and SaO2 is less than 2% when the SaO2 value
is above 90%; however, the precision of the reading worsens when the SaO2 is lower
than 90%.144 The use of pulse oximetry has been validated in rabbits, with accuracy at
hemoglobin saturation values greater than 85%.145 The pulse oximeter can be placed
in various locations, working most effectively on unpigmented regions of the skin (toe,
ear, perianal region). Pulse oximeters may also provide valuable information on heart
rate.

Capnograph
Capnography is a useful tool in anesthetized rabbits that are intubated.146 Capnome-
try measures the maximum value of carbon dioxide that is measured at the end of
expiration, which in turn is a reflection of the amount of CO2 that is present in the alve-
olar gas.146 Measurement of the EtCO2 has demonstrated utility in determining the
arterial concentration of carbon dioxide (PaCO2).146 Normocapnia in mammals is asso-
ciated with an EtCO2 of 35 to 45 mm Hg.147 Values less than 35 mm Hg are hypo-
capnic, and values from 65 to 75 mm Hg are hypercapnic.147 Both hypoventilation
and hypercapnia are concerns for rabbits under general anesthesia.146 The capno-
graph wave is useful for assessing the adequacy of ventilation and perfusion to the
lungs as it has been well correlated with arterial CO2.146 Capnography has been
demonstrated to provide useful estimations of the PaCO2 in rabbits.148

THE POSTANESTHETIC PERIOD

The recovery period following an anesthetic event requires equally intense monitoring
as the preanesthetic and intra-anesthetic periods. As previously noted, many anes-
thetic deaths occur in the postanesthetic period.3–5 If the endotracheal tube is
removed too soon, there is risk of airway obstruction, hypoventilation, and hypoxemia.
As a result, rabbits should be maintained on oxygen until spontaneous respiration and
movement returns. Even after extubation, maintain the rabbit on a face mask or in an
oxygen cage until they are fully alert and aware of their surroundings.
Following extubation, it is critical to continue close monitoring and provide any
necessary supportive care. Once sufficiently recovered, the rabbit should be placed
into a stress-free, warm, dark, recovery cage. Given that many anesthetic deaths
occur in the postanesthesia recovery period, ongoing monitoring of body temperature,
heart rate, respiratory rate, and comfort should be assessed on a regular basis, with
issues addressed as needed.
202 Gardhouse & Sanchez

Once the rabbit can stand and move confidently about the cage, provision of food
and water is critical, to not only preserve energy requirements but also to ensure resto-
ration of gastrointestinal motility. If hyporexia, anorexia, or reduced or lack of fecal
output is noted, supplemental feeding and analgesia should be instituted.

SUMMARY

Rabbits are increasingly presented to their veterinarian for evaluation and treatment.
Owners frequently expect high-level medical and surgical care, which often results
in the need for intensive and thorough anesthetic management. Successful anesthetic
management requires knowledge of general anesthetic principles, awareness of the
limitations and risks of anesthesia, and knowledge of the current literature to all for
continuation of provision of high standards of care.

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