Cathy's Critter Corner: A common rabbit condition for review

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Cathy Emery — Associate IndeVet

Associate IndeVet Dr. Cathy Emery has a wealth of knowledge about exotics. Cathy’s Critter Corner is a new column where she takes an in-depth look at common exotics issues. Today, she explores GI stasis in rabbits.

Gastrointestinal issues in rabbits

Rabbits are the third most common pet species in the United States and are frequently presented to veterinarians for gastrointestinal complaints.

“GI stasis” is a commonly used term for any rabbit that is not eating or defecating, but is too simplistic to account for the myriad causes and consequences of altered gastrointestinal function, hence the current move toward the descriptor “Rabbit Gastrointestinal Stasis Syndrome” (RGIS). This phrase, too, is at best a description of the disease process rather than an actual diagnosis.

The unique anatomy and physiology of lagomorphs (rabbits are not rodents!) can make them challenging to work on; a basic understanding of predisposing factors, clinical signs, diagnostic clues, and therapeutic options can help the general practitioner manage these cases more confidently.

Rabbit digestion

The rabbit GI tract is designed for hindgut fermentation, much like that of the horse, which means the majority of their diet should consist of low energy fiber like that found in grass hay. Rabbits chew high fiber foods in a horizontal motion, which helps wear down their open rooted continuously growing teeth, grinding that fiber into particles 0.5mm or larger; this size particle stimulates gastrointestinal motility and is essential for proper gut function.

Particles 0.3mm or smaller (derived from lower fiber foodstuffs) have the opposite effect of slowing down GI motility. Grass hay should be offered in unlimited amounts with plain grass hay-based pellets kept to a minimum (1/4 cup per 5lbs body weight per day in non-reproducing adults) to avoid dental issues, obesity, gastroenteropathies, and metabolic diseases. Excessive protein and simple carbohydrate/sugar intake can alter cecal pH, leading to cecal dysbiosis and subsequent enterotoxemia.

The moisture content of ingesta is also important, facilitating its passage through the GI tract. Rabbits have a high metabolic rate and require 120-150 mL/kg/day of water to maintain a healthy, functioning system. Fresh leafy greens at a rate of 1-2 cups per 5lbs per day provide both moisture and fiber and are preferred to starchy vegetables and fruit, which should be kept to a minimum. Normal GI transit time is around 19 hours; while wild rabbits are crepuscular, domestic rabbits tend to graze continuously.

The rabbit stomach is very thin-walled and distensible; due to the presence of a serrated mucosal rosette at the cardiac orifice and a large muscular gastroesophageal sphincter rabbits are unable to vomit. After approximately 3 to 6 hours in the stomach food passes into the small intestine, which is relatively short with a narrow lumen. This is the primary site of nutrient absorption.

The duodenum passes at an acute angle to the liver, making it susceptible to compression in cases of hepatomegaly and a common site of obstruction. The ileum terminates in the ileocolic cecal junction, a T-shaped junction with a structure unique to rabbits called the sacculus rotundus or ileocecal tonsil. This is the most common site for intestinal impactions.

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Ingesta passes through this junction into the proximal large intestine, which separates food particles based on size. Smaller particles and fluid are passed into the cecum, which comprises 40% of the intestinal tract; it is large, thin-walled, and distensible, coiling on itself three times before ending in the vermiform appendix. The cecum is where microbial fermentation occurs, whereby cellulose and proteins are broken down into volatile fatty acids; some of these VFAs are absorbed, while others are incorporated into cecotrophs that are typically excreted when the rabbit is at rest (hence the term “night feces”).

Cecotrophs are extremely high in nutrients (energy-providing VFAs, vitamins, amino acids, enzymes), softer than normal feces, and coated with mucus; they are usually consumed directly from the anus and the nutrients recycled in the small intestine. Larger indigestible food particles pass into the distal colon for water resorption and are excreted as firm fecal pellets.

The separation of these two types of feces is controlled by another structure unique to rabbits, the fusus coli, which separates the proximal and distal large intestine. Stress and other causes of adrenaline release can inhibit the function of the fusus coli, leading to cecal stasis and abnormal cecotroph production.

Immunological functions of the intestinal tract

In addition to digestion, the rabbit intestinal tract serves an important immunological function. There are Peyers patches throughout the small intestines, while large intestine gut associated lymphoid tissue (GALT) comprises half of the rabbit’s total lymphoid tissue. Large intestinal microbes (mostly anaerobic bacterial and commensal fungal organisms), in addition to releasing nutrients from food, act as a defensive barrier against potential pathogens.

Non-intestinal components of the rabbit digestive system include the liver and pancreas. The pancreas is fairly small and is rarely involved in disease processes.

The liver has six lobes: left lateral and medial, right lateral, medial, quadrate, and caudate lobes. The caudate lobe, located near the right kidney, has a loose, stalk-like attachment, making it prone to torsion. Liver lobe torsion is a not uncommon cause of abdominal pain in rabbits and should be a differential for RGIS.

The gallbladder is located between the right medial and quadrate lobes and primarily produces biliverdin, rather than bile. It’s rare for a rabbit to become jaundiced, even with severe liver disease; they can, however, develop hepatic lipidosis quite rapidly when in a negative energy state.

Rabbit gastrointestinal stasis syndrome (RGIS)

Rabbit gastrointestinal stasis syndrome (RGIS) is not a specific disease, rather it encompasses a set of presentations with multiple primary and secondary etiologies.

GI hypomotility is the end result of reduced food intake, thus working up a case entails determining what led to the GI disturbance (the actual diagnosis) while simultaneously treating the rabbit’s clinical signs. Common signs of GI disease include depression, reduced or absent appetite, change in stool quantity and/or quality (abnormally hard or small pellets, diarrhea), lack of cecotroph ingestion (often mistaken as diarrhea), reduced activity, a hunched, painful posture, bruxism, distended abdomen, and failure to groom.

Non-GI conditions that contribute to stasis include stress, recent surgery, pain, dental disease, dehydration, and other disease processes, while primary GI causes include inappropriate diet (high carb/low fiber), intestinal obstructions (trichobezoars or foreign bodies), cecal impaction or tympany, gastric tympany/bloat, liver lobe torsion, adhesions, and neoplasia.

Enteritis characterized by diarrhea and potentially sepsis can also be considered a condition of disordered intestinal motility and may eventually result in stasis due to dehydration and debilitation. Improper antibiotic usage leading to cecal Clostridial overgrowth (oral penicillins, cephalosporins, clindamycin, lincomycin, and erythromycin should never be given to rabbits), toxins, diet, and parasites (coccidia, more common in young animals and overcrowded environments) can all lead to diarrhea of varying severity; treatment is largely supportive and is the rare instance where antibiotics may be indicated therapeutically.

Diagnosing RGIS: History and physical exam

It is vital to obtain a detailed history, especially in regards to basic husbandry/diet, recent surgery, medications, environmental or diet changes, or other stressful events. The duration of illness is also important, as it can impact prognosis.

Try to find out when exactly the rabbit last ate, drank, and defecated. Initial assessment of a sick rabbit should be performed with the goal of classifying the patient as critical versus non-critical and surgical versus non-surgical, as management is determined accordingly.

General practitioners should be able to manage non-critical, non-surgical cases, while stabilizing critical and surgical ones for transfer to a specialist (or recommending euthanasia if proper care cannot be provided).

Clinical findings that indicate a critical patient include extreme depression, hypothermia (temperature <98°F), hypotension (systolic BP < 80 mmHg, MAP <60 mmHg), pale mucous membranes with prolonged CRT, and an extremely bloated, painful abdomen.

These patients should be provided with immediate pain relief, ideally with an opioid (buprenorphine 0.02-0.05 mg/kg, hydromorphone 0.1-0.3 mg/kg, or fentanyl 3-5 mg/kg/h CRI; opioids do not seem to have a clinical impact on rabbit GI motility) and an anxiolytic to reduce stress (midazolam 0.2-0.5 mg/kg); this can be done prior to completing a more comprehensive physical exam. Heat support should be provided to hypothermic animals and antibiotics to those with signs of or at risk of developing sepsis (enrofloxacin 5-15 mg/kg/d IV preferred to SQ/IM and metronidazole 10mg/kg IV BID; both can later be given orally).

On physical exam special attention should be paid to hydration status (evaluated similarly to cats and dogs), heart and respiratory rates (often quite elevated), mentation (a healthy rabbit is alert and curious about its environment; degree of depression usually correlates with severity of illness, as rabbits are very good at hiding signs of illness), abdominal palpation, body temperature (normally 100.5-103.5°F), oral health, and stool quality.

The normal rabbit stomach is located in the left cranial abdomen and contains a moderate amount of ingesta; it may feel full, but should be fairly soft and fluctuant. A distended, painful gas or fluid filled stomach raises concern for an obstructive process; an empty stomach may indicate prolonged anorexia or gastric rupture.

Intestines should palpate soft and non-painful; varying amounts of gas distension and discomfort are present with stasis and obstruction. The cecum can be felt along the ventral body wall and is typically soft, fluidy, and thin-walled; a firm, distended cecum could indicate cecal impaction, while a fluctuant, gassy one could indicate cecal tympany. Formed fecal pellets are usually palpable in the normal rabbit colon. Auscultation of the abdomen can be used to assess gut sounds: reduced or absent with stasis or obstruction, increased with enteritis. Repeatable pain in the right cranial abdomen may signify liver lobe torsion.

Finally, every rabbit exam should include a dental evaluation: palpate the cheeks and chin for lumps, pain, or draining tracts and use an otoscope with attached cone to perform an intraoral exam (keep in mind rabbits can have perfectly normal appearing clinical crowns while still harboring significant reserve crown/root pathology, making skull radiographs essential for ruling out dental disease).

GI Stasis in rabbits: An algorithm

RGIS bloodwork and imaging

A complete diagnostic database should include, at a minimum, two view abdominal radiographs, PCV/TS, blood glucose, and ALT. A full CBC and chemistry panel are recommended if enough blood can be obtained, especially in critical cases. Fecal flotation may be more useful in younger rabbits or those with diarrhea.

The need for abdominal ultrasound and skull films (five views for evaluating dentition) is dependent on the results of initial testing and response to therapy (ultrasound can be difficult due to the large amount of gas in the rabbit GIT and is most useful for identifying discrete obstructions, masses, adhesions, free fluid, and liver lobe torsion).

Normal abdominal radiographs reveal small round gas bubbles scattered throughout the intestines with an ingesta and gas bubble-filled stomach of moderate size that should not extend past the last rib and a cecum in contact with the ventral body wall filled with heterogenous sponge-like gas bubbles.

Abnormal radiographs may show a distended stomach and tympanic intestinal loops in the case of an obstruction; often the cecum will be unusually small and devoid of gas in these cases.

Diffusely dilated intestines may indicate generalized ileus or a more distal obstruction; small intestinal dilation of less than two times the diameter of the second lumbar vertebral body is more consistent with ileus, whereas larger dilation (especially if focal) raises concern for obstruction. With cecal impactions the cecum appears denser and dilated with gas and ingesta, whereas cases of cecal tympany show a diffusely gas-dilated organ.

CBC results are usually normal in cases of RGIS. Increased heterophils (the rabbit neutrophil) and decreased lymphocytes may indicate inflammation or enterotoxemia. Anemia can be seen in cases of liver lobe torsion; these cases may also have an elevated ALT (although a normal ALT doesn’t rule out a torsion due to the enzyme’s short half life).

Other altered chemistry values could include elevations in BUN and creatinine consistent with prerenal azotemia/dehydration, hypercalcemia (not always pathologic in rabbits), and hypochloremia in cases of obstruction.

The most important chemistry value for attempting to discern obstructed rabbits from non-obstructed ones is glucose: blood glucose values over 360mg/dL are correlated with gastrointestinal obstruction (normal rabbit glucose can run up to 250mg/dL with stress). Hypoglycemia (glucose < 75mg/dL), on the other hand, could indicate sepsis. Glucose can be easily checked with an Alphatrak glucometer using the dog setting.

Exam and basic diagnostic findings should allow the practitioner to fit a rabbit patient into two broad classifications: critical (surgical or non-surgical) and non-critical (surgical or non-surgical).

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Managing critical cases

The exam criteria mentioned earlier, delays in diagnosis and treatment, the presence of underlying disease, glucose greater than 360mg/dL or less than 75mg/dL, PCV < 15%, and severe metabolic derangements all put an animal in the critical category and warrant a poorer prognosis. These patients need hospitalized and/or immediately transferred to a specialized facility if owners wish to pursue treatment.

In addition to opioid pain medication and sedation/anxiety relief, intravenous fluid therapy should be instituted early on. An initial crystalloid (LRS, Plasmalyte, ideally warmed) bolus of 10 mL/kg should be given to hypovolemic patients, followed by a fluid rate of 10 mL/kg/h (add dextrose if hypoglycemic). Adjustments are then made based on clinical response.

In cases of sepsis or persistent hypotension the vasopressor of choice is norepinephrine at 0.5-2 mg/kg/min. Once the rabbit is rehydrated and normal kidney function is ascertained, meloxicam may be administered for pain at a dose of 0.5-1 mg/kg/d.

Any animal suspected to have an obstructive process should not be treated as an outpatient, given oral medication, syringe fed, or given prokinetics. Thankfully, medical management with fluids, pain control, and supportive care can be successful in relieving an obstruction in 80% of cases.

Those who show no signs of improvement, have a documented unpassable foreign body, or continue to deteriorate could be considered for surgery, but the high anesthetic complication rate and tendency to develop abdominal adhesions often lead to a poor outcome (<50% survival rate). Liver lobe torsions are also surgical candidates (lobectomy of the affected lobe), but surgery can be delayed if the patient is stable and not bleeding internally. Rarely a torsion may be managed medically with acceptable, albeit prolonged, resolution.

Manging non-critical cases

Once a patient is stabilized (normalization of hemodynamic parameters and body temperature, reduced pain) additional supportive therapies can be instituted. This is also the starting management point for stable, more mildly affected rabbits that do not have an obstructive process (these patients could also receive SQ fluids instead of IV at a rate of 50-100mL/kg/d, ideally divided).

In normotensive animals a lidocaine CRI is useful for managing pain and stimulating intestinal motility (loading dose 2mg/kg, then 100 mcg/kg/min). The most important prokinetic is high fiber food, so it’s important to get these critters eating as soon as possible (again, do not force feed a dehydrated, hypothermic, or obstructed rabbit).

Luckily, rabbits are fairly tolerant of syringe feeding and there are multiple formulas on the market designed for this (Oxbow Critical Care, Emeraid Herbivore, both available OTC); in a pinch one could blenderize grass pellets with water and/or higher fiber vegetable baby food, but this should not be given long term. Rabbits should be fed 50-80 mL/kg/d of formula divided into approximately 4 feedings.

Early return to feeding is also important to reduce the risk of hepatic lipidosis. Other foodstuffs, along with fresh water, can be provided buffet-style for the rabbit in case it wants to start eating again on its own.

Prokinetic drugs are often used as an aid in managing GI stasis, but there is little evidence that they work. Nevertheless, metoclopramide (0.5 mg/kg SQ/IM/PO q8-12h) and cisapride (0.5 mg/kg PO q12h) are unlikely to cause harm in a non-obstructed animal and anecdotally seem to help some cases.

Exercise is an overlooked enhancer of intestinal function; sick rabbits should be provided with a large space to roam and encouraged to move around. Rabbits with GI disease also benefit from antiulcer therapy with ranitidine (1-2mg/kg PO q12h), which may act synergistically with cisapride to enhance motility.

Newer medications that are being used in anorectic rabbits with some success include Cerenia (1 mg/kg/d SQ) and Entyce (2-3 mg/kg/d PO). Probiotics like Benebac can be a useful adjunctive therapy and should definitely be a part of enteritis treatment. Antidiarrheals like Biosponge can be used as needed to firm up very loose stool.

In rabbits prone to trichobezoars petroleum-based hairball preventives for cats can be given to try to limit recurrences (malt flavor is typically preferred to tuna). Finally, any comorbid conditions or husbandry deficits that could have led to RGIS should be addressed to prevent relapses.

In very rare cases it may be necessary to pass an orogastric (preferred to nasogastric) tube (10-14 French red rubber catheter with the tip cut off at an angle) for the purpose of decompressing a stomach on the verge of rupture or inhibiting respiration or hemodynamic return. This procedure should be considered a last resort and is more effective for removing gas than solids.

Patients must be sedated prior, as it is extremely stressful and could send a critical patient over the edge. Insertion of the tube is similar to that of dogs, followed by aspiration with a 60cc syringe and/or mild lavage; too often the effectiveness of this technique is limited by thick ingesta clogging the tube.

RGIS recovery

Even with intensive therapy it can take several days for affected rabbits to improve.

Serial radiographs can be used to monitor those suspected to have an obstructive pattern (look for redistribution of abnormal gas patterns and reduction of stomach/intestine/cecum size), but perhaps the best indicators of improvement are behavioral: brighter demeanor, eating, defecating, maintaining body temperature, reduced pain on abdominal palpation.

Abnormal biochemical parameters may also be tracked, especially glucose in the presence of hyper- or hypoglycemia (glucose typically returns to normal once an obstruction resolves). In cases of prolonged anorexia it may take up to five days for a rabbit to produce stool, which may appear abnormally hard or soft at first.

Medications can be transitioned from injectable to oral after initial improvement (it is often at this point that hospitalized patients are sent home) and then tapered off completely when eating and defecation are back to normal.

Conclusion

In conclusion, with a bit of added anatomical and physiological education, most general practitioners have the skills to determine whether or not a rabbit with RGIS is critical/surgical, and thus in need of urgent stabilization and/or referral, as well as to manage more stable cases of stasis.

Fluid resuscitation/support, pain management, heat support, restoration of gastrointestinal motility and function, and prevention of complications are the mainstays of therapy, and the majority of non-surgical cases make a full recovery with early intervention.

Most importantly, the factors that contribute to RGIS need to be identified and addressed to limit the (re)occurrence of disease. Proper diet, stress management, dental care, and cautious antibiotic use go a long way toward safeguarding a rabbit’s intestinal health, and thus the health of the entire rabbit.

Cathy Emery, DVM, is an Associate IndeVet practicing in Maryland and Virginia.