Gastrointestinal Stasis in the Rabbit

Introduction

Gastrointestinal stasis (GIS) is a common problem in pet rabbits and is a frequent cause of malaise and morbidity. There are myriad of potential causes of GIS. Left untreated, advanced and complicated GIS cases can lead to death.

What is Gastrointestinal Stasis?

Gastrointestinal stasis (GIS) involves a reduction in gastrointestinal motility and subsequent lengthened gastrointestinal transit time. GIS is usually accompanied by partial or complete inappetence.  GIS is also referred to as gut stasis, ileus, gastrointestinal hypomotility, gastric stasis syndrome and rabbit gastrointestinal syndrome (RGIS).

The rabbit gastrointestinal system relies upon complex interactions between diet, caecal microflora, caecotroph ingestion and gut movement to manage their herbaceous ingesta. In patients with GIS, the ingesta can putrify, leading to a die-off of normal microflora and the proliferation of harmful bacteria may give rise to enterotoxaemia leading to a rapid demise, decompensation and death. Secondary effects of reduced gut motility include:

– gastric or gastrointestinal dilation/impaction
– gastric ulceration
– gastric trichobezoar formation
– alterations in water/electrolyte secretion and absorption
– hypovolaemia
– acid-base and electrolyte imbalances
– dehydration

These cause pain which further exacerbates inappetence and GIS.

Anorectic rabbits are prone to developing ketoacidotic states relatively quickly. Rabbits have limited metabolic processes to rectify acid/base imbalances compared to other mammals. Further to this, rabbits are vulnerable to developing hepatic lipidosis (Figure 1) even after a short period of inappetence, further reducing appetite and increasing morbidity and mortality.

In cases of gastrointestinal obstruction, a rapid accumulation of fluid proximal to the obstruction site can occur due to the rabbit’s inability to vomit, continual salival production (and swallowing), water secretion into the stomach and subsequent fermentation of contents. This may lead to marked gastric dilation.

What are the Causes of Gastrointestinal Stasis?

Husbandry and dietary factors as well as stressors may contribute to GIS as can primary disease. Improper diet plays a vital role in development of GIS in many cases (e.g., insufficient fibre, sudden change in diet). Rabbits require high fibre diets for optimal GI motility. Other aetiologies can include obesity, reduced physical activity, dehydration, anaesthesia, toxins, systemic illness and any source of pain. Some primary causes of GIS can include impaction, obstruction (reingested compressed faecal hair pellets in rabbits and foreign material most frequently obstruct the proximal duodenum and distal ileum in rabbits) and peritoneal adhesions. Primary diseases of the gastrointestinal tract, liver and pancreas (e.g., infection, neoplasia) may occur but are relatively rare causes of GIS. Oftentimes the underlying cause of GIS cannot be determined.

Brief Summary of Rabbit Gastrointestinal Physiology

Rabbits are monogastric hindgut fermenters. Rabbits are not able to vomit due in part to a well-developed cardiac sphincter. They produce two types of faeces; hard faecal pellets and caecotrophs (Figure 2). Caecotrophs are reingested as they are passed from the anus and constitute a vital part of their digestive process. Caecotrophs provide the rabbit with energy in the form of volatile fatty acids, amino acids, vitamins and help to repopulate the gut with microflora.

The caecum comprises the largest portion of the gastrointestinal tract, holding 40% of total ingesta. Rabbits harbour a wide variety of non-pathogenic microbes (bacteria, fungi, protozoa) in their caecum, many of which are vital to normal fermentative and digestive processes. The maintenance of an optimal caecal environment is vital to normal gastrointestinal function. An array of elaborate peristaltic and anti-peristaltic movements help separate ingesta in the colon and caecum to allow for passage of digestible fibre into the caecum for fermentation and for non-digestible fibre into the colon to be formed into faecal pellets. Caecal dysbiosis can result from dietary imbalances especially and also from inappropriate antibiotic use.

Normal gastrointestinal motility is under the influence of multiple factors including neuronal and hormonal control. For example, the fusus coli (a highly innervated vascular portion delineating the proximal and distal colons) serves as a pacemaker for the complex change of peristaltic waveforms necessary for the colon to enact depending on the phase of faecal excretion. The fusus coli is innervated by autonomic fibers and its action is influenced by aldosterone, catecholamines and prostaglandins. Both physiologic and underlying disease processes can influence such mechanisms thus aiding in the establishment of reduced gut motility.

Signs of Gastrointestinal Stasis

Inappetence is featured in most cases of GIS and may be one of the main presenting signs. A decreased food intake may be reported as gradual or sudden in onset. A lack of or scant faecal production may be noted and faeces may be firmer and smaller than normal. Other signs may include weight loss, lethargy, weakness, perineal faecal soiling and diarrhoea. Pain is often a feature of GIS and can be readily masked by rabbits. Signs of pain include:

– Adoption of a hunched position
– Reluctance to move
– Partially closed eyes
– Facial grimacing
– Bruxism

At physical examination vital signs may be normal or altered depending on the underlying cause and duration of GIS. These findings aid in establishing further work-up and degree of immediate intervention required. A thorough physical examination may allude to an underlying cause of GIS, though this is not always the case. With elodont (continuously growing teeth) species such as rabbits, a thorough dental exam is always warranted at every physical exam.

Careful abdominal palpation is imperative. An appreciation of the stomach size and the presence of tympany, gas, relative firmness and pain elicited in any part of the abdomen should be appreciated. A dilated stomach may indicate gastrointestinal obstruction. An increase in gastric or caecal firmness (‘doughiness’) may be detected and may provide an indication of dehydrated ingesta.

Determination of the absence or presence of gut sounds is not a reliable indication of gut movement as borborygmus may or may not be present in the healthy rabbit.

Diagnostic Aids in Gastrointestinal Stasis

The decision to carry out any further diagnostics should be weighed up against any additional stress that may be placed upon the patient. At times, the poor status of a GIS patient warrants initial supportive measures before any diagnostics are performed.

Radiographic imaging offers the most useful diagnostic aids in cases of GIS, in both initial and ongoing evaluation. Imaging should focus on the abdomen (two orthogonal views) but preferably involve full body imaging to capture the thorax and pelvic structures to the distal tip of the urethra. Radiographic studies of the skull for investigation of dental disease should be considered. Serial radiography can serve an important role in monitoring distension of the gastrointestinal tract, gas patterns and formation of faeces. The stomach and small intestines normally contain small amounts of gas. In hypomotile states, accumulated gastric ingesta may be crowned by a gas halo in a ‘crescenteric’ shape (Figure 3a). Gas accumulation may also be evident in the intestines, especially the cecum (Figure 3a & 3b). In acute gastrointestinal obstruction, severe gastric dilation may result comprising air and fluid and the intestines may have little gas accumulation, though a small intestinal gas pattern suggestive of foreign body obstruction may be evident (Figures 4a & 4b). Gastrointestinal contrast studies (e.g., pneumogastrography, barium sulfate) are not recommended due to procedural risks and difficulty with interpretation. Non gastrointestinal anomalies may be found such as hepatomegaly (e.g., hepatic lipidosis) and urogenital disease (e.g., urolithiasis, uterine enlargement).

Abdominal ultrasonography may be hindered by the presence of large amounts of gastrointestinal gas though may be useful to delineate gastrointestinal disease such as obstructions, intussusception, mass effects (abscessation, neoplasia etc), extraluminal compression and the structure of other organs.

Other clinical pathology (haematology, blood biochemistry, urinalysis) may be useful in evaluation of patient status and guide therapy, but is mostly non-specific for gastrointestinal disease. One exception is the measurement of blood glucose (BG) levels in rabbits. A recent clinical study revealed that totally anorexic patients had higher BG levels than those that were eating normally or had reduced food intake. In the same study it was noted that rabbits with BG>20mmol/L had conditions carrying a poorer prognosis. Rabbits with confirmed intestinal obstruction had a mean BG of 24.7mmol/L (n=18) which was significantly higher than rabbits with confirmed gut stasis (8.5mmol/L, n=51). Hence BG measurement has the potential to help assess clinical severity and aid in differentiation of gut stasis and intestinal obstruction in anorexic rabbits¹.

Treatment of Gastrointestinal Stasis

The mainstay of treatment of GIS is supportive care. Treatment should be carried out expediently. Surgical intervention in GIS cases is rarely indicated and may exacerbate hypomotile states. The exception is gastrointestinal obstructive disease that does not respond to medical therapy. This may be indicated by worsening gastric dilation seen on serial radiographic studies (taken over the course of several hours).

Fluid therapy

Fluid therapy is one of the most important therapies to initiate and maintain. Similar principles apply to fluid therapy in these species as in canine/feline patients. Fluid therapy is provided to replace deficits and then to rehydrate and maintain. Fluid therapy is best provided by the intravenous route rather than subcutaneous route (unless the patient’s status is fair to good). Choice of fluids (crystalloids, colloids, blood replacement products) depend on the status of the patient, associated disease states and clinical pathology. Maintenance fluid rates are 100mL/kg/day. Oral rehydrative solutions (e.g. Lectadeâ) may also be used but not in obstructive or gastric dilation cases. An underestimated benefit of fluid therapy in GIS cases is the rehydration of the gastrointestinal tract and its contents that may subsequently promote gastrointestinal function and motility.

Nutritional support

Nutritional support should be implemented as soon as possible in all cases except for those with suspect obstruction or marked gastric dilation. In most cases, assist feeding is carried out via careful syringe feeding directly into the mouth. The provision of food offers critical energy to the GIS patient as well as providing valuable fodder for gut motility. Commercial herbivore enteral diets are available (e.g. Oxbow critical care feeding formulaâ and Emeraid Herbivore Elemental Dietâ). Both of these products can also be utilised in nasogastric (NG) tube feeding protocols. Typically, rabbits may be assist fed 5 to 20mL in one sitting via the oral or NG tube routes. Feeding frequency will depend on volume fed at each time and aimed at achieving at least 80% of the manufacturer’s recommended daily requirement. Regardless, tempting the patient with their usual diet and other foods should be encouraged.

Medical management

The approach to medical management of GIS appears to vary geographically and in part may be due to the variation in drug availability. Much of the medications used are based on anecdotal reports, although some evidence based reports exist. Table 1 offers common medications and doses used in the treatment of GIS.

Drug	Dose	Comments
Analgesics – Should be implemented in most cases due to the likelihood of underlying pain. Opioids are used most commonly. Despite their potential for reducing GI motility, the benefit of pain relief appears to outweigh this. The author favours buprenorphine or low-dose fentanyl constant rate infusions (CRI). Opioids are often used with prokinetics.
Buprenorphine	0.01-0.03mg/kg SC q6-8h
Fentanyl		Can be used as a CRI.
Meloxicam	0.3-0.5mg/kg PO, SC q12-24h	Do not use NSAIDs in dehydrated/hypovolaemic, hypotensive or azotaemic patients.
Carprofen	2-4mg/kg PO, SC q24h
Gut Prokinetics – Likely to be beneficial in managing GIS, but are contraindicated in suspect cases of obstruction.
Ranitidine	3-5mg/kg PO q12h	Stimulates gastrocolonic motility by inhibiting anticholinesterase. Also useful as a gastric antacid. Synergistic with cisapride.
Cisapride	0.5mg/kg PO q8h	Promotes gastric emptying and increases both gastrointestinal and colonic motility by enhancing acetylcholine release.
Metoclopramide		May only be useful if used in a CRI. Its efficacy at promoting gastrointestinal motility in rabbits has been questioned when given by oral or subcutaneous routes. Regardless of its prokinetic effect it still reduces ‘nausea’ with its effect on the chemoreceptor trigger zone.
Gastric Antacids – Gastric ulceration may occur in rabbits with prolonged anorexia. Ranitidine may thus serve a useful dual purpose for rabbits with GIS. Proton pump inhibitors such as omeprazole may also be beneficial and may be superior to H2 antagonists in reducing gastric acid secretion. Note: The author routinely uses ranitidine as his first choice prokinetic. If concerned about the length of anorexia the author may include omeprazole.
Ranitidine	As above	Used first
Omeprazole	0.5-1mg/kg PO/IV	Can be used with ranitidine
Anti-enterotoxemic agents – Rabbits experiencing GIS may be vulnerable to developing enterotoxemia.  The main pathogen responsible is Clostridium spiroforme (and subsequent production of iota toxin). Once enterotoxemia has developed, treatment is difficult and prognosis is often poor. Cholestyramine and Crospovidone can be given orally and may serve to bind bacterial toxins and aid in their elimination.
Cholestyramine	0.5g/kg PO q8h
Crospovidone	250mg/rabbit
Antiflatulents – In humans it aids in the passing of gastrointestinal gas by coalescing smaller air bubbles into larger ones.
Simethicone	70mg/kg PO	Benefits in rabbits is uncertain
Appetite stimulants – Inappetent rabbits should be assist fed. Pharmacotherapy alone should not be relied upon to encourage eating. Anecdotal use of intravenous benzodiazepines, oral cyproheptadine and nandrolone parenterally have been reported. B complex vitamin supplementation may help promote appetite in GIS patients.
Benzodiazepines		Any promotion of appetite stimulation is uncertain in rabbits
Cyproheptadine
Nandrolone
Lubricant Laxatives
Liquid paraffin	Contraindicated.	Do not use. Unlikely to be beneficial and risk of aspiration
Vitamin Supplementation – Rabbits may require increased levels during periods of stress (especially Vitamin C).
Vitamin C	50mg/kg PO/SC q24h
Vitamin B group	Utilise multi-B formulations according to manufacturer guidelines (e.g. B-Complex injection, TROY Australiaâ)	Lack of caecotrophy may reduce B vitamin intake
Oral Enzyme Supplements
Bromelin/Papain		Purported hair digestion properties over-rated. The ‘pineapple-juice’ effect is unlikely to be any more beneficial than providing hydration and simple sugars. Assist feeding is better achieved with commercial feeding formulas designed for this process.
Probiotics – Theoretically useful, however most commercial products lack the flora typically found in rabbit gut. Unlikely to be harmful if used. Consider the anorexic rabbit’s lack of ingestion of its own caecotrophs. Caecotrophy normally aids in caecal floral recolonisation. GIS patients should be encouraged (and not hindered) to perform caecotrophy. The process of transfaunation (collecting caecotrophs from a healthy animal and offering them to an anorectic patient) can be considered in some circumstances.
Antibiotics- Appears to be no clear rationale for their routine use in GIS management. Reserve use for known primary or secondary GIT infections or enterotoxaemia.
Corticosteroids – No reported benefits in GIS patients. More likely to be harmful than useful. Can exacerbate hepatic lipidosis and induce immunosuppression. No reported benefits in GIS patients.

Author
Dr David Vella BSc BVSc (Hons) DABVP (Exotic Companion Mammals)
Principal veterinarian
Sydney Exotics and Rabbit Vets (SERV)

Dr David Vella is the Director of Sydney Exotics and Rabbit Vets. He graduated from the University of Sydney with a Bachelor of Science (1992) and a Bachelor of Veterinary Science (1996).

In 2009, David became a Diplomate of the American Board of Veterinary Practitioners (DABVP) in Exotic Companion Mammals, one of the first vets worldwide and the first and only Australian vet to achieve these credentials.

David has extensive clinical experience in treating exotic pets in both the United Kingdom and Sydney.

Currently volunteering for NSW WIRES (Wildlife Information Rescue & Education Service), David is involved in reptile and amphibian rescue. He also trains volunteers in handling, rehabilitation, foster care and rescue. Pets at home include Leonard, the shingleback lizard, and several long-necked turtles. When not working, he enjoys family time, gardening, music and running their ‘escape’ room (The Cipher Room) with his wife Marise.

References

1. Harcourt-Brown FM, Harcourt-Brown SF. Clinical value of blood glucose measurement in pet rabbits. Veterinary Record 2012; 170(26): 674.
2. Harcourt-Brown FM. Gastric dilation and intestinal obstruction in 76 rabbits. Veterinary Record 2007; 161: 409–414.
3. Gastrointestinal physiology and Nutrition (Rabbits). Campbell-Ward ML. In: Ferrets, Rabbits, and Rodents: Clinical medicine and surgery. 3rd edition. Eds. Quesenberry KE, Carpenter JW, Saunders (Elsevier), USA, 2012: 183-192.
4. Langer JC, Branlett G. Effect of prokinetic agents on ileal contractility in a rabbit model of gastroschisis. Journal of Pediatric Surgery 1997; 32(4): 605–608.
5. Lichtenberger M, Lennox A. Updates and advanced therapies for gastrointestinal stasis in rabbits. Veterinary Clinics of North America: Exotic Animal Practice 2010; 13(3): 525-541.
6. Li C, Qian W, Hou X. Effect of four medications associated with gastrointestinal motility on Oddi sphincter in the rabbit. Pancreatology 2009; 9(5): 615–620.
7. Rabbits: Gastrointestinal diseases. Jenkins JR. In: Ferrets, Rabbits and Rodents: Clinical medicine and surgery, 2nd edition. Eds. Quesenberry KE, Carpenter JW, Elsevier, USA, 2004: 161-171.
8. Textbook of rabbit medicine. Harcourt-Brown F. Butterworth-Heinemann, Oxford, UK, 2002.