Presenting problem: Dyspnea in Rabbits

Introduction

Respiratory difficulty can occur as a result of upper respiratory tract disease, disease of the lower respiratory tract, pulmonary parenchyma, or pleural space as well as disease of the chest wall or diaphragm. There are also cardiovascular, metabolic and neurologic conditions that can lead to respiratory difficulty.

It is critical to approach the dyspneic rabbit (Oryctolagus cuniculus) quietly, carefully, and gently. Many rabbits with respiratory disease are unstable upon presentation, given the stress of their condition compounded by the stress of transport and the strange smells, sights and sounds of the veterinary clinic. In many cases, it is prudent to delay handling the patient. Transfer the rabbit to an oxygen-rich environment in dark, quiet, room for a period of time instead.

Clinical tip: Rabbits are obligate nasal breathers, therefore open-mouth breathing is a particularly poor prognostic indicator in this species.

Case management

Signalment

Respiratory disease is a common problem in domestic rabbits of all ages. Your patient’s age may provide important clues to the underlying cause of disease (Box 1).

Box 1. Causes of dyspnea may vary with the rabbit’s age

All Ages	Middle-aged to older
Bacterial infection	Neoplasia Congestive heart failure, atherosclerosis

Metastatic uterine adenocarcinoma is an important problem in middle-aged to older does (Woodhouse 2011). Even after ovariohysterectomy, metastatic disease must remain a differential diagnosis for female rabbits that develop lung masses (Brown 2010).

Bacterial infection may be seen in rabbits of all ages, and pasteurellosis has been reported in rabbits as young as 3 months (Geertsema 2008).

Reports of thymoma causing respiratory signs have been described in rabbits ranging from 5 to 10 years of age (Clippinger 1998, Sanchez-Migallon 2006). There are also rare reports of congestive heart failure with pleural effusion in middle-aged rabbits (Lord 2011).

 

Clinical picture

Using the principles of “all-one-medicine”, respiratory disease in the rabbit often looks like respiratory disease in any other animal. However here are also species-specific clues or clinical signs more common in the rabbit such as dried nasal discharge (Box 2). The fastidious nature of the normal rabbit means that early evidence of oculonasal discharge may be limited to matted fur on the medial surface of the forelimbs. Coughing is extremely rare in rabbits.

Box 2. Signs of respiratory disease in the rabbit (Oryctolagus cuniculus)

All one medicine	Species-specific clues
Oculonasal discharge Sneezing, congestion Tachypnea Dyspnea: increased respiratory effort, open-mouth breathing, anxiety, glazed look, extended head and neck Non-specific signs of illness: anorexia, lethargy, weight loss	Rubbing nose on ground or with forepaws Dried nasal discharge on medial surface of forelimbs Inferior vena caval syndrome (see thymoma below)

Differential diagnoses

Upper respiratory tract disease in the rabbit is most commonly caused by bacterial infection due to pasteurellosis and other bacteria such as Bordetella bronchiseptica. The most important differentials for lower respiratory tract disease are bacterial infection and pulmonary metastases of uterine adenocarcinoma. The most common sign of metastatic uterine carcinoma is serosanguinous vaginal discharge (Woodhouse 2011). Additional signs may include intermittent or cyclic hematuria, non-specific signs of illness (such as anorexia, lethargy, weight loss), as well as pallor and dyspnea.

Other potential causes of respiratory distress in the rabbit include:
Degenerative disease:

• Congestive heart failure is an infrequent, but growing, problem in the pet rabbit (Lord 2011).

Neoplastic disease:

• Malignant thymoma is relatively uncommon in rabbits, however the thymus persists into adulthood in the rabbit so this tumor is seen more frequently in rabbits than many other species (Dirven 2009). Thymoma creates a mass effect in the cranial thorax.
• Lymphosarcoma is also relatively rare, but has been reported in juvenile rabbits (Cloyd 1978).

Infectious disease:

• Viral infections such as myxomatosis or rabbit calicivirus (also known as viral hemorrhagic disease or VHD) may also cause respiratory signs. In the United States, sporadic cases of myxomatosis are typically restricted to the northwest. Outbreaks of VHD have been seen and eradicated in the United States, most recently in 2005 (USDA APHIS 2005).

Inflammatory disease:

• Potential respiratory irritants include cigarette smoke, chemical fumes, or the high ammonia levels and dust that can accumulate with poor cage sanitation.
• Allergic rhinitis and bronchitis have also been proposed in the rabbit (Meredith 2006).
• There are also reports of fatal iatrogenic tracheitis 2-3 weeks post-endotracheal intubation. Proposed causes of focal chronic tracheal inflammation included trauma from the bevel of the tube when turning patients or chemical burns from incorrect disinfection or inadequate rinsing of tubes (Grint 2006).

Traumatic disease:

• Nasal foreign bodies, such as grass seeds or pieces of hay, may be associated with paroxysmal sneezing, nose rubbing, unilateral nasal discharge, and congestion. If the condition is allowed to progress, open-mouth breathing and dyspnea sometimes develop.

Physical examination

Rabbits that present severely dyspneic with open-mouth breathing and/or cyanosis should first be provided with supplemental oxygen in a darkened room.
Respiratory rate: Before initiating a brief physical examination, carefully observe the patient’s breathing pattern.

• The normal respiratory rate is 30-60 breaths per minute (bpm), but will vary widely with patient size and circumstances.
• A normal rabbit that is under stress can display a rapid respiratory rate exceeding 200 bpm, however do not be confused by nose twitching as this is not directly associated with breathing (Meredith 2006).
• Slow, deep respirations are abnormal.

Eyes-ears-nose:

• Check the patient for evidence of oculonasal discharge.

Clinical tip:

The fastidious nature of the normal rabbit means that early evidence of oculonasal discharge may be limited to matted fur on the medial surface of the forelimbs.

• Examine the eyes for evidence of conjunctivitis or dacryocystitis. Nasolacrimal duct inflammation and/or obstruction can lead to epiphora and white discharge at the medial canthus. Pressure applied to the lacrimal sac can cause white material to pass from the nasolacrimal punctum.
• Gently evert the lower eyelid to expose mucous membrane color.
• Also note any evidence of exophthalmia. Bilateral exophthalmos is one of the most conspicuous features of inferior caval vein syndrome in rabbits with malignant thymoma (Dirven 2009).
• Perform an otoscopic exam since upper respiratory infection can spread to the middle ear [Otitis in rabbits] via the Eustachian tube.
• Auscultation: Rabbits have relatively small lungs, and auscultation can be challenging. Use a pediatric or infant stethoscope to increase your chances of detecting abnormalities.
• Are breath sounds audible dorsally and ventrally?
• Are breath sounds symmetrical?
• What is the heart rate? Is there a murmur or muffled heart sounds?
• To distinguish between upper and lower respiratory noise, determine if sounds are loudest over the sinuses and/or trachea instead of over the chest.
• In larger rabbits, percussion of the chest can detect solid areas caused by mass lesions or consolidation.

Also evaluate chest wall compliance, which can be reduced with an intrathoracic mass such as thymoma.
Additional physical exam clues:

• Palpate facial bones for asymmetry or swelling. Dental disease can lead to dacryocystitis.
• Evaluate the rabbit’s body condition. Weight loss is a common finding in does with metastatic uterine adenocarcinoma.
• Also palpate the abdomen. A uterine tumor may be detected as a firm, tubular mass in the caudoventral abdomen.

If at any time it appears your patient is becoming overly stressed, return the rabbit to a quiet, dark room. Provide supplemental oxygen as needed.

 

Diagnostics

Carefully weigh the benefits and risks of any diagnostic test undertaken in the dyspneic rabbit. Will the results significantly alter your therapeutic plan? Even if the answer is yes, monitor the patient carefully and perform tests in stages to minimize stress. Begin testing only after the patient has had a chance to rest quietly in a dark room with supplemental oxygen when indicated.

Blood collection for CBC/biochemistry panel testing is often delayed until the patient is more stable. Use of a topical local anesthetic such as EMLA cream (AstraZeneca) may be helpful.

• Heterophilia can be seen with acute bacterial infection.
• Chronic disease is often associated with leukopenia.
• Results with metastatic uterine adenocarcinoma may include anemia, if hemorrhage is severe, as well as leucopenia and monocytosis. Serum liver enzymes (including alkaline phosphatase ) are often elevated as well (Brown 2010, Woodhouse 2011).
• Test results can be unremarkable in rabbit with thymoma (Sanchez-Migallon 2006).

Cytology and bacterial culture of nasal discharge in upper respiratory tract disease or nasolacrimal flush in dacryocystitis may also be indicated.

• To perform a deep nasal swab, insert a sterile, moistened cotton-tipped applicator ventromedially and deeply (1-4 cm). Swab the nasal cavity bilaterally.
• Nasolacrimal flush material may also be collected into a sterile container.

Survey radiographs may provide helpful diagnostic and prognostic information.
Sedation is preferable, but may not be possible in rabbits with severe respiratory compromise.

• Obtain skull radiographs to evaluate tooth roots, nasal turbinates (and tympanic bullae) in rabbits with upper respiratory disease.
• Use chest radiographs to look for consolidation, parenchymal masses, pleural effusion, or even increased soft tissue density within the mediastinum.
• Chest films may be unremarkable with uterine adenocarcinoma. Abdominal radiographs often reveal ascites and a tubular, soft tissue opacity in the caudal abdomen that extends into the pelvic inlet on both views (Woodhouse 2011).

Interpretation of chest radiographs can be difficult even in the normal rabbit:

• The heart sits relatively craniad close to the thoracic inlet.
• A large amount of intrathoracic fat is often present.
• The lung fields and pleural cavity are small making it difficult to obtain inspiratory films. The cranial lung lobes are particularly small.

To minimize the risk of superimposition over the cranial lung fields, draw the forelimbs as far forward as possible.

Thoracic ultrasound is very useful in identifying pulmonary and pleural masses or confirming pleural effusion. Echocardiography and electrocardiography may also be indicated in select cases. Use ultrasound guided fine needle aspiration to collect samples for cytologic evaluation of intrathoracic mass lesions.
Advanced diagnostics will vary but may include a tracheal wash or bronchoalveolar lavage under sedation or general anesthesia, CT or MRI, and endoscopy of the nasal passages. Serology, such as Pasteurella titers, is rarely helpful in clinical practice.

 

Therapy

As in other species, remember to avoid prolonged exposure (> 24h) to high levels of oxygen (Macintire 2006). After the patient is initially stabilized with 100% oxygen, reduce the level of fractional inspired oxygen in increments. Inspired concentrations less than 50% are considered safe (Macintire 2006). Avoid 60% O2 for more than 48 hours.

Although it is desirable to establish intravenous access as soon as possible in the dyspneic patient, this is not always possible or practical in the dyspneic rabbit. Use your own clinical judgment to determine if your patient will tolerate the necessary restraint.

For many conditions, drugs and drug dosages are frequently extrapolated from what is used in cats. For instance, furosemide, nitroglycerin and an anxiolytic may prove therapeutic in congestive heart failure.

If bacterial infection is suspected, begin systemic antibiotics. Most strains of Pasteurella multocida are sensitive to enrofloxacin, sulfa-trimethorpim, tetracycline, chloramphenicol, and penicillin G (Deeb 2003). Remember that penicillins must be administered parenterally in rabbits to prevent the development of potentially fatal dysbiosis. Collect samples for culture/sensitivity testing whenever possible before starting antibiotics. Prescribe antibiotics for a minimum of 7-14 days and recommend follow-up within that time frame so the prescription may be refilled. Antibiotics are often required for much longer in rabbits with chronic disease.

Do not neglect supportive care. Provide fluid therapy to break up respiratory secretions and to support the patient. Once the rabbit has been rehydrated, assist feed if anorectic.

Also consider recommendations that may be targeted at underlying factors or stressors such as substandard husbandry, inadequate sanitiation, poor ventilation, overcrowding, and even concurrent disease.

Long-term or advanced treatments will vary with the definitive diagnosis. Surgical removal is the treatment of choice for thymoma and has been succesfully performed in the rabbit. Little is known about the long-term post-operative prognosis (Clippinger 1998, Dirven 2009). Radiation therapy and chemotherapy have also been described (Sanchez-Migallon 2006).

Prognosis

Prognosis varies with the underlying cause of disease, but is grave for rabbits with uterine adenocarcinoma as this tumor is extremely slow-growing and insidious. It may take 1-2 years for there to be detectable evidence of metastasis (Brown 2010), and by this time disease is often quite advanced.

 

References