“Benji”, a 2-year-old intact male rabbit, presents to your facility with a recent history of respiratory signs. On examination you note he is nostril flaring, has conjunctivitis,nasal discharge, and is tachypneic. You place him in an oxygen cage while collecting more information from the owner. She tells you this is not the first time Benji has had similar signs and wants to investigate further. What are your next steps? 

First off, What is Normal?

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While the above chart¹ provides a reference for what to expect when evaluating the vital signs of a rabbit, it is important to remember that they are prey species. As a result, these vital signs will be affected by many factors like stress and handling. For instance, normal rabbit respiratory rate and effort are rare to see during handling in the exam room. They often have rapid, shallow breaths when stressed, so it is best to count a respiratory rate when the rabbit is most relaxed prior to handling. Uniquely, some normal rabbits produce a honking sound when stressed. Body temperature is also impacted by factors including stress, ambient temperature, and body condition, so this is also a value important to collect prior to conducting an extensive exam. 

Based on the above chart, you can see that Benji is relatively young. His signalment, history, and vital signs decrease the potential for conditions such as heart failure and neoplasia, and this along with his current clinical signs makes infectious etiology a higher differential. Similar to other animals, respiratory disease is classified as upper, lower, or both. For the purposes of this article, let’s focus on rabbit upper respiratory disease. 

Signs of Upper Respiratory Distress in a Rabbit

Rabbits are obligate nasal breathers, making open mouth breathing a poor prognostic indicator. Nostril flaring, as noted in Benji, is a sign of respiratory distress in rabbits and other nasal breathers. Keep in mind that diseases of the upper respiratory tract are more stressful and severe in rabbits compared to other species as nasal discharge will occlude the respiratory pathway (Figure 1). During the visual exam of a rabbit in respiratory distress, you will observe an increased respiratory rate and effort. This rate and effort are often more pronounced with exertion.  

Practice tip: always look at the fur on the inside of the forefeet - rabbits are fastidious and usually attempt to remove ocular or nasal discharge with the forefeet, resulting in accumulated debris in this area.

Pathogens associated with rhinitis can cause disease within the nasolacrimal duct and inner ear which can lead to ocular abnormalities and neurologic signs including head tilt. Other signs can include nonspecific findings such as weight loss from decreased appetite, exercise intolerance, and lethargy.² 

Rabbits have a small thoracic cavity compared to other animals.. When the upper respiratory tract is affected, wheezes and other increased respiratory noises may be referred to the thorax making auscultation challenging. Now that we’ve covered some of the basics, let’s discuss differentials for Benji’s presentation.

Differentials for Upper Respiratory Signs in a Rabbit

Bacterial pathogens are the most common cause for upper respiratory infection in rabbits, but it is important to be aware of other etiologies. Outside of bacterial causes , viral, parasitic, and fungal causes of upper respiratory disease are reported in rabbits. Some of the non-infectious differentials include dental disease, neoplasia or other masses including polyps, trauma, foreign body, or congenital and anatomic anomalies. 

What are the top infectious etiologies for Benji’s signs? Differentials include Pasteurella multocida, Bordetella bronchiseptica, E. coli, Pseudomonas sp., Staphylococcus sp., Chlamydia sp., among others. In a survey of 121 rabbits with signs of upper respiratory disease, P. multocida was the most common isolated bacteria in greater than 50% of rabbits. Approximately 50% of rabbits also had B. bronchiseptica, 28% had Pseudomonas sp., and Staphylococcus sp. was isolated from 17.4%.³ A similar report of 171 rabbits with nasal discharge had these bacteria isolated in order of frequency: Pasteurella, Pseudomonas, Moraxella sp., and E. coli.⁴ It is important to note that P. multocida can be isolated from the respiratory tract of normal rabbits as indicated by a study that showed it was isolated in 10% (2) of 20 apparently healthy rabbits.⁵  

Diagnostic Testing for Upper Respiratory Infection in Rabbits

We’ve got a lot to consider when it comes to Benji’s case. We need more information to narrow our differential list and guide appropriate diagnosis and treatment. It is important to always weigh the risk of obtaining diagnostics with the patient’s clinical status. Sedation is beneficial for rabbits with significant respiratory distress as it reduces anxiety, allows for relaxation, reduces dyspnea, and facilitates appropriate positioning for imaging, blood draw, and other diagnostics. A common sedation protocol includes midazolam and butorphanol, but there are many other options.¹ Supplemental oxygen by facemask or oxygen cage throughout diagnostics and recovery is recommended. 

Veterinary blood tests including CBC and chemistry analysis may be within the normal reference range for the species. Although a leukocytosis may not be seen, CBC pathology review may reveal an inverse shift in heterophil/lymphocyte ratio (approx. 2:3).² Diagnostic imaging like radiographs, ultrasound, endoscopy, and advanced imaging including CT can help narrow differentials for rabbits presenting with respiratory distress. But in a case like Benji, with active ocular and nasal discharge, sampling for testing including bacterial culture and sensitivity is important. Let’s consider how to collect meaningful diagnostic samples in this case. Keep in mind that certain culture techniques can enhance isolation of organisms including P. multocida, so consulting with your animal reference lab prior to sample collection may be beneficial. 

Respiratory sampling

In cases where bacterial disease is the leading differential, isolation of the organism must be achieved to reach a definitive diagnosis. Although culture and sensitivity classically provide this information, the success of this diagnostic effort is dependent on sampling technique and bacterial isolation methods.

Deep nasal swabs and nasal flushes are recommended over external nare culture as external sampling identifies environmental organisms. A very small culturette carefully introduced 2-3 cm ventromedially into both nares along the nasal septum samples the pathogens in the nasal cavity. Alternatively, a Teflon intravenous catheter with stylet removed, open ended tomcat or red rubber catheter can be used to flush and aspirate a small amount of preservative free sterile saline for cytologic examination and culture. A head-down position protects the airway. If endoscopy is available, rhinoscopy is an ideal procedure in an anesthetized rabbit to facilitate sample collection in a sterile fashion. 

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Nasolacrimal duct sampling (Figures 2-3)

After instilling a topical ophthalmic anesthetic such as proparacaine, insert a 23-gauge lacrimal cannula or a 22- to 24-gauge Teflon intravenous catheter with the stylet removed into the nasolacrimal puncta in the medial aspect of the lower eyelid to flush the duct with preservative free sterile saline. A sterile bowl can be used to collect the flush as it leaves the nostrils. Although this is not a sterile sample, it can be evaluated cytologically with a culture performed if warranted. A monomorphic bacterial population with accompanying inflammatory cells is suggestive of active infection while a mixed population without inflammation may represent environmental contamination.

Molecular and serologic diagnostic testing are available for multiple pathogens in rabbits including pasteurella, bordetella, and treponema. 

Rabbit Upper Respiratory Infection Treatment

Pathogen identification and disease localization will help facilitate successful treatment. Antibiotic choice should be based on culture and sensitivity information whenever possible.  Fluoroquinolone antibiotics are generally effective in managing many upper respiratory infections in rabbits, including pasteurellosis. Other antibiotics for rabbit respiratory infection such as chloramphenicol, doxycycline, sulfa drugs, azithromycin, and parenteral penicillin can be effective. It is imperative to avoid use of antibiotics that can cause enteritis and fatal dysbiosis including enteral penicillins, erythromycin, and clindamycin, among others. Additional therapies include nebulization and nasolacrimal duct flushing with installation of medication into the duct. NSAIDs and mucolytic agents can also be used. Deep nasal flushing in anesthetized patients with a protected airway can help clear nasal passages in cases of severe nasal discharge. Although more invasive, rhinotomy with surgical debridement has been suggested as an option to manage granulomatous disease of the nasal cavity that is refractory to antibiotic therapy. 

When setting recovery goals for your patient, remember that despite visible clinical control, certain respiratory pathogens will not be completely cured. Organisms like Pasteurella can remain dormant resulting in recrudescence and need for life-long management. 

Benji’s Outcome

Diagnostics including radiographs and nasal flush with culture were facilitated with sedation and supplemental oxygen in Benji. Culture revealed a heavy growth of P. multocida. Benji responded well to systemic and topical fluoroquinolone antibiotics based on sensitivity testing. Further investigation suggested poor air quality in Benji’s environment so dusty bedding was removed and air circulation was improved. Benji’s owners were advised that treatment would likely not institute a cure from infection as he had previous problems and Pasteurella infections are generally life-long with treatment aimed at control of clinical signs. 

References

1. Fisher P, Graham J. Rabbits. In: Carpenter J, Harms C (eds). Carpenter’s Exotic Animal Formulary, 6th ed. St. Louis, MO: Elsevier, 2023: 605-606.
2. Lennox A, Mancinelli E. Respiratory Disease. In: Quesenberry K, Orcutt C, Mans C, and Carpenter J (eds). Ferrets, Rabbits, and Rodents: Clinical Medicine and Surgery, 4th ed. St. Louis, MO: Elsevier, 2021: 188-200.
3. Rougier S, Galland D, Boucher S, et al. Epidemiology and susceptibility of pathogenic bacteria responsible for upper respiratory tract infections in pet rabbits. Vet Microbiol. 2006;115:192–198.
4. Pellet S, Harcourt-Brown F, Pinborough M. Bacterial and fungal culture and sensitivity from rabbits presenting with nasal discharge. Proc Brit Small Anim Vet Asso. 2016;553.
5. Quinton JF, Lennox A, Guillon L, et al. Results of bacterial culture and sensitivity testing from nasolacrimal duct flushes in one hundred and three both healthy and clinically ill pet rabbits (Oryctolagus cuniculus). Intern J Appl Res Vet Med. 2014;12(2):107–120