Clinical characteristics and short-term outcomes for rabbits with signs of gastrointestinal tract dysfunction: 117 cases (2014–2016)

Kimberly M. Oparil 1Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

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Jay N. Gladden 1Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

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Jonathan M. Babyak 1Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

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Christopher Lambert 1Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

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Jennifer E. Graham 1Department of Clinical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA 01536.

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Abstract

OBJECTIVE

To describe the clinical findings and short-term outcomes for rabbits with signs of gastrointestinal tract dysfunction or rabbit gastrointestinal syndrome (RGIS).

ANIMALS

117 client-owned rabbits.

PROCEDURES

The electronic medical records database of a veterinary teaching hospital was searched to identify rabbits that were examined because of altered or absent food intake and decreased or absent fecal output between June 1, 2014, and June 30, 2016. For each rabbit, information extracted from the record included history of prior episodes of gastrointestinal tract dysfunction, signalment, physical examination and diagnostic test results, and outcome.

RESULTS

117 of the 484 (24%) rabbits examined at the hospital during the study period met the inclusion criteria and were enrolled in the study. Fifty-nine and 58 rabbits were managed on an inpatient and outpatient basis, respectively. Gastrointestinal stasis without overt obstruction was diagnosed for 43 rabbits on the basis of abdominal radiographic, ultrasonographic, or necropsy results. Many rabbits had concurrent disease and biochemical abnormalities. Fifteen, 18, and 84 rabbits died, were euthanized, and survived to hospital discharge, respectively. Rabbits that were hypothermic (rectal temperature, ≤ 36.6°C [97.9°F]) during the initial examination were 5 times as likely to die or be euthanized as were euthermic rabbits, after controlling for potential confounders.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that the prognosis was generally good for rabbits with signs of RGIS unless they were hypothermic during initial examination. Prospective studies are warranted to further elucidate and characterize RGIS and assess the efficacy of various treatments and outcomes for affected rabbits.

Abstract

OBJECTIVE

To describe the clinical findings and short-term outcomes for rabbits with signs of gastrointestinal tract dysfunction or rabbit gastrointestinal syndrome (RGIS).

ANIMALS

117 client-owned rabbits.

PROCEDURES

The electronic medical records database of a veterinary teaching hospital was searched to identify rabbits that were examined because of altered or absent food intake and decreased or absent fecal output between June 1, 2014, and June 30, 2016. For each rabbit, information extracted from the record included history of prior episodes of gastrointestinal tract dysfunction, signalment, physical examination and diagnostic test results, and outcome.

RESULTS

117 of the 484 (24%) rabbits examined at the hospital during the study period met the inclusion criteria and were enrolled in the study. Fifty-nine and 58 rabbits were managed on an inpatient and outpatient basis, respectively. Gastrointestinal stasis without overt obstruction was diagnosed for 43 rabbits on the basis of abdominal radiographic, ultrasonographic, or necropsy results. Many rabbits had concurrent disease and biochemical abnormalities. Fifteen, 18, and 84 rabbits died, were euthanized, and survived to hospital discharge, respectively. Rabbits that were hypothermic (rectal temperature, ≤ 36.6°C [97.9°F]) during the initial examination were 5 times as likely to die or be euthanized as were euthermic rabbits, after controlling for potential confounders.

CONCLUSIONS AND CLINICAL RELEVANCE

Results indicated that the prognosis was generally good for rabbits with signs of RGIS unless they were hypothermic during initial examination. Prospective studies are warranted to further elucidate and characterize RGIS and assess the efficacy of various treatments and outcomes for affected rabbits.

Rabbits are often examined on an emergency basis because of clinical signs referable to the digestive system, such as alterations in food intake, anorexia, decreased or absent fecal output, changes in fecal appearance and consistency, bruxism, and abnormal body posture suggestive of abdominal pain. Those clinical manifestations of gastrointestinal tract dysfunction have previously been termed gastrointestinal stasis. Some exotic companion animal clinicians1 have advocated use of the term RGIS to describe rabbits with a range of clinical signs and concurrent pathological conditions that affect the digestive system because they feel it more accurately refects the multifactorial nature of the disease process than the term gastrointestinal stasis. We have adopted that definition of RGIS for the purpose of the study reported here.

Rabbit gastrointestinal syndrome can result from primary gastrointestinal tract dysfunction or secondary etiologies. Primary causes of RGIS include diet changes, dietary indiscretion, inadequate fiber intake, high carbohydrate diets, foreign body ingestion, bacterial or viral infection, parasitosis, toxicosis, or gastrointestinal neoplasia.1–5 Stress and anxiety and environmental changes can also contribute to signs of RGIS. Secondary causes of gastrointestinal tract dysfunction and signs of RGIS include extragastro-intestinal neoplasia, dental disease, pancreatitis, and liver disease such as hepatic lipidosis, torsion, and cholangiohepatitis.1 In a 2014 retrospective study,2 25% (96/382) of rabbits examined at an exotic animal referral hospital had signs of RGIS and presumed primary gastrointestinal tract dysfunction. Although physical examination and diagnostic test findings were not reported for the rabbits of that study,2 idiopathic gastrointestinal stasis was common and frequently affected young adult rabbits (mean ± SD age at onset, 3.1 ± 1.9 years). Despite the fairly high prevalence of RGIS, most of the published veterinary literature1,4,5 focuses on treatment recommendations based on expert opinion rather than those based on clinical research of potential etiologies and patient outcomes. The objective of the study reported here was to describe the clinical findings and short-term outcomes for rabbits with signs of RGIS.

Materials and Methods

Case selection criteria

The electronic medical record database of a veterinary teaching hospital was searched to identify records for rabbits that were examined because of signs of gastrointestinal tract dysfunction by the exotic animal referral and emergency services between June 1, 2014, and June 30, 2016. Search terms used included “GI stasis,” “anorexia,” and “decreased fecal output.” To be included in the study, rabbits had to have a history of altered or absent food intake and decreased or absent fecal output. Rabbits that were brought to the teaching hospital solely for euthanasia were excluded from the study. For rabbits that were examined multiple times during the study period, only information recorded during the initial visit was included in the analysis.

Medical records review

For each rabbit that met the study inclusion criteria, information extracted from the medical record included history (particularly prior episodes of RGIS), signalment, physical examination and diagnostic test results, and outcome. Breed information was not assessed owing to inconsistent reporting of that data in the medical records. Historical information recorded included housing type (indoor, outdoor, or mixed), diet (hay, pellets, or both), fecal output assessment, previous known episodes of gastrointestinal stasis, recent surgical or anesthetic events, and presence of concurrent medical conditions. Physical examination results recorded included rectal temperature, heart rate, respiratory rate, BCS (on a scale of 1 to 9, where 1 = emaciated and 9 = obese), dental evaluation, gastrointestinal auscultation findings, and presence or absence of bruxism and signs of abdominal pain and distention. Hypothermia was defined as a rectal temperature ≤ 36.6°C (97.9°F). All available diagnostic test results including hematologic and biochemical analyses and abdominal radiographic and ultrasonographic findings were reviewed. Because BUN can be affected by multiple factors, for the purpose of data analysis, azotemia was defined as an abnormally high serum creatinine concentration (> 2.5 mg/dL) only. Abdominal radiographic and ultrasonographic findings were obtained from the original reports issued by the board-certified veterinary radiologists who assessed the images. For each rabbit, the overall assessment of the gastrointestinal tract was categorized as follows: clinically unremarkable, evidence of gastrointestinal stasis or functional ileus only, evidence of gastrointestinal obstruction only, or unable to distinguish between mechanical obstruction and functional ileus. Necropsy data, including the final gross and histologic diagnoses, were obtained from the original pathology report issued by the attending board-certified veterinary pathologist. Serologic status for antibodies against Encephalitozoon cuniculi was also recorded when available. Treatments administered and prescribed and hospitalization status (inpatient or outpatient) were also recorded, as was the short-term outcome (died, euthanized, or survived to hospital discharge).

Statistical analysis

Descriptive statistics were generated. Proportions were reported for categorical variables. Data distributions for continuous variables were assessed for normality by means of the Shapiro-Wilk test. The mean ± SD was reported for normally distributed continuous variables, and the median (range) was reported for nonnormally distributed continuous variables. Age, sex, BCS, housing type, diet type, occurrence of previous episodes of gastrointestinal stasis, fecal output assessment, dental evaluation findings, fluid therapy, medications administered, hospitalization status, and short-term outcome were individually compared between rabbits with and without gastrointestinal stasis by means of χ2, Fisher exact, Student t, or Wilcoxon rank sum tests, as appropriate. Logistic regression was used to assess the association of hypothermia with outcome while controlling for history of gastrointestinal stasis (yes or no), age (< or ≥ 4 years as determined on the basis of lowess spline analysis), presence of gastrointestinal sounds during abdominal auscultation, and diet type. The outcome was modeled as nonsurvival (ie, death or euthanasia), and the model was built in an additive stepwise manner with hypothermia added as the first predictor followed by the other variables, which were selected on the basis of a significant result on univariate analysis or suspected clinical importance. The final multivariable model included only those variables with a value of P < 0.05. All analyses were performed with a statistical software program,b and values of P < 0.05 were considered significant.

Results

Rabbits

Four hundred eighty-four rabbits were examined at the teaching hospital during the study period, of which 117 had signs consistent with RGIS and met the study inclusion criteria. Nineteen rabbits were examined multiple times, but only the first visit for each of those rabbits was included in the analysis. Of the 117 study rabbits, 9 were examined by the exotic animal referral service and 108 were examined by the emergency service.

The study population included 34 (29%) sexually intact males, 31 (26%) neutered males, 33 (28%) spayed females, and 19 (16%) sexually intact females and had a median age of 3.4 years (range, 9 months to 10.8 years). Fifty-seven (49%) rabbits were housed exclusively indoors, 2 (2%) rabbits were housed exclusively outdoors, and 10 (9%) rabbits were housed both indoors and outdoors. Housing information was unavailable for the remaining 48 (41%) rabbits. Eighty-nine (76%) rabbits were fed both hay and pellets, 6 (5%) rabbits were fed pellets only, and 8 (7%) were fed hay exclusively. The diet was unknown for the remaining 14 (12%) rabbits. Among the 97 rabbits that were fed hay, 80 were fed timothy hay, 5 were fed alfalfa hay, and 1 was fed orchard grass hay; the type of hay fed was unknown for the remaining 11 rabbits. All 5 rabbits that were fed alfalfa hay were > 1 year old. The type of pellets fed was not reliably recorded in the medical records; therefore, it was not assessed.

History and clinical findings

Forty-one of the 117 (35%) rabbits had at least 1 previous episode of gastrointestinal stasis as reported by the owners. Among those 41 rabbits, the mean ± SD number of previous gastrointestinal stasis episodes was 2.47 ± 1.9. The owners of all rabbits reported that their pets were anorexic with variable fecal output volume and consistency in the days to hours prior to examination at the teaching hospital. Twelve (10%) rabbits had reportedly normal fecal output, 8 (7%) had diarrhea, 47 (40%) had decreased fecal output, and 27 (23%) had no fecal output. Fecal output history was not recorded for the remaining 23 (20%) rabbits.

Thirty (26%) rabbits were anesthetized during the month prior to examination for RGIS. Four rabbits were anesthetized for dental procedures, 23 were anesthetized for ovariohysterectomy or orchiectomy, and 3 were anesthetized for other surgical procedures (laceration repair, femur fracture repair, and cutaneous mass removal). Among the 4 rabbits that underwent dental procedures, 3 had coronal reductions performed and 1 had surgical debridement of an endodontic abscess.

Body condition score was recorded for 95 of the 117 (81%) rabbits. The median BCS was 5 (range, 2 to 8). Median body weight was 2.3 kg (5.0 lb; range, 0.7 to 5.6 kg [1.5 to 12.3 lb]). Median rectal temperature was 37.4°C (993°F; range, 32.3° to 41.1°C [90.1° to 106.0°F]). Thirty-four (29%) rabbits were hypothermic (rectal temperature, < 36.6°C), and 2 rabbits had a rectal temperature > 40.0°C (104.0°F). The median heart rate was 240 beats/min (range, 80 to 330 beats/min). Many rabbits were recorded as sniffing when the respiratory rate was assessed, which made it difficult to calculate the respiratory rate. The median respiratory rate for rabbits that were not recorded as sniffing was 80 breaths/min (range, 16 to 300 breaths/min).

Seventy-nine of 117 (68%) rabbits underwent a dental evaluation as part of the initial physical examination for the study-qualifying event. Among those 79 rabbits, 56 (71%) had no or only mild dental disease, 11 (14%) had moderate dental disease, and 5 (6%) had severe dental disease; dental disease severity was not classified for the remaining 7 rabbits. Categorization of dental disease was subjective and was made by either the attending emergency clinician or an exotic animal specialist.

Results of abdominal auscultation and borborygmi assessment were recorded for only 40 of the 117 (34%) rabbits. Of those 40 rabbits, 12 (30%) were reported to have normal gut sounds and 28 (70%) were reported to have decreased or absent gut sounds. Forty-three of 117 (37%) rabbits had signs of abdominal pain or distension during the initial physical examination. The presence or absence of bruxism was not reliably recorded in the patient records; therefore, it was not assessed in the study.

Fifty-eight of the 117 rabbits were managed on an outpatient basis, whereas the remaining 59 rabbits were hospitalized and managed as inpatients. Among the 58 outpatients, 37 had only a physical examination performed, whereas 21 underwent a physical examination as well as additional diagnostic testing (eg, CBC and serum biochemical analysis, n = 13) and diagnostic imaging (abdominal radiography, 14; abdominal ultrasonography, 2). Twenty of the 58 (34%) outpatients were reexamined because of signs of RGIS during the study period, with 8 rabbits being reexamined multiple times. Among the 59 inpatients, 12 had only a physical examination performed, and 47 underwent a physical examination and additional diagnostic testing (n = 39) and diagnostic imaging (abdominal radiography, 36; abdominal ultrasonography, 10).

Hematologic and serum biochemical results were summarized (Table 1). Blood glucose concentration was recorded for 50 rabbits and was determined by a handheld glucometerc for 3 of those rabbits and an automated biochemical analyzer for the remaining rabbits. Twenty-five of those 50 (50%) were classified as hyperglycemic (glucose concentration, > 155 mg/dL; reference range,6 75 to 155 mg/dL) and had a median glucose concentration of 249 mg/dL (range, 158 to 467 mg/dL). Two rabbits were hypoglycemic (glucose concentration, < 75 mg/dL), whereas the remaining 23 rabbits were euglycemic.

Table 1—

Descriptive statistics for hematologic and serum biochemical variables of 117 rabbits with signs of gastrointestinal tract dysfunction (RGIS) evaluated in a retrospective case-series report.

ValueNo. of rabbitsMeanMedian (range)Reference range*
PCV or Hct (%)4640.1738.5 (28–54)33–50
Total solids or protein (g/dL)466.796.8 (4.5–8.8)5.4–8.3
Lactate (mmol/L)177.615.9 (2.7–25.4)5.5–8.7
Glucose (mg/dL)50190.02150.5 (55–467)75–155
BUN (mg/dL)4436.3028.5 (9–118)13–29
Creatinine (mg/dL)442.261.2 (0.6–13.5)0.5–2.5
ALT (U/L)34160.2043 (37–2,403)48–80
Aspartate aminotransferase (U/L)24186.0036 (10–1,502)14–113
Total bilirubin (mg/dL)350.250.1 (0–2.8)0–0.75
γ-Glutamyltransferase (U/L)2620.429 (1–167)
WBC count (× 103 WBCs/μL)349.077.19 (1.73–28.1)5.2–12.5
Platelet count (× 103 platelets/μL)30393.30369.5 (37–719)250–650
Potassium (mmol/L)444.504.25 (2.6–8.5)3.6–6.9
Sodium (mmol/L)44142.29141.6 (132.3–162)131–155
Ionized calcium (mmol/L)171.431.50 (1.06–1.82)1.60–1.82
Total calcium (mg/dL)3512.312.3 (6.8–15.9)
Phosphorus (mg/dL)364.413.5 (1.8–12.9)4.0–6.9
Albumin (g/dL)162.892.15 (1.2–6.7)2.4–4.6
Fibrinogen (mg/dL)18350300 (100–1,100)

All rabbits were examined at a veterinary teaching hospital because of altered or absent food intake and decreased or absent fecal output between June 1, 2014, and June 30, 2016.

All reference range values were obtained from Mader6 unless otherwise indicated.

Obtained from Langlois et al.7

Obtained from Kamphues et al.8

— = Reference range not established.

Serum creatinine concentration was measured for 44 rabbits, of which 7 (16%) had moderate to severe azotemia (creatinine concentration, > 4 mg/dL; reference range,6 0.5 to 2.5 mg/dL) with a median creatinine concentration of 5.9 mg/dL (range, 4.6 to 13.5 mg/dL). Eight (18%) rabbits had mild azotemia (creatinine concentration, > 2.5 but < 4 mg/dL).

Liver enzyme activities were assessed in 34 of the 117 (29%) rabbits. Hepatic disease was diagnosed in 3 rabbits on the basis of abnormally high ALT activity with or without concurrent hyperbilirubinemia (total bilirubin concentration, > 0.75 mg/dL). Lactate concentration was determined for 17 (15%) rabbits, of which 6 were hyperlactatemic (lactate concentration, > 8.7 mmol/L) with a median lactate concentration of 10.5 mmol/L (range, 9.7 to 25.4 mmol/L; reference range,7 5.5 to 8.7 mmol/L). Among the 6 hyperlactatemic rabbits, 2 with lactate concentrations of 25.4 and 17.0 mmol/L died, 2 with lactate concentrations of 10.6 and 10.0 mmol/L were euthanized, and 2 with lactate concentrations of 10.4 and 9.7 mmol/L survived to hospital discharge.

A CBC was performed for 33 of 117 (28%) rabbits. Six rabbits were leukopenic6 (WBC count, < 5,200 WBCs/μL) and had a median WBC count of 3,610 WBCs/μL (range, 1,730 to 4,900 WBCs/μL). Five rabbits were leukocytotic6 (WBC count, > 12,500 WBCs/μL) with a median WBC count of 16,810 WBCs/μL (range, 13,640 to 28,100 WBCs/μL). One rabbit was thrombocytopenic (platelet count, 37,000 platelets/μL). That rabbit died and underwent a necropsy. The pathology report indicated that the rabbit had evidence of hepatic necrosis, disseminated intravascular coagulopathy, and sepsis.

Serum sodium and potassium concentrations were determined for 44 rabbits. Two rabbits were hypernatremic (sodium concentration, > 155 mEq/L; reference range,6 131 to 155 mEq/L), and no rabbits were hyponatremic (sodium concentration, < 131 mEq/L). Six rabbits were hypokalemic (potassium concentration, < 3.6 mEq/L; reference range,6 3.6 to 6.9 mEg/L), and 2 rabbits were hyperkalemic (potassium concentration, > 6.9 mEq/L). Both hyperkalemic rabbits were also azotemic (creatinine concentration, 9.7 and 4.8 mg/dL), and 1 had evidence of chronic nephropathy during an abdominal ultrasonographic examination.

Ionized and total calcium concentrations were determined for 17 and 35 rabbits, respectively. Twelve of the 17 rabbits for which the ionized calcium concentration was determined were hypocalcemic and had a mean ionized calcium concentration of 1.35 mmol/L (range, 1.06 to 1.59 mmol/L; reference range,8 1.60 to 1.82 mmol/L). Serum phosphorus concentration (reference range,6 4 to 6.9 mg/dL) was determined for 36 rabbits, of which 20 were classified as hypophosphatemic and 6 were classified as hyperphosphatemic.

Serum albumin concentration (reference range,6 2.4 to 4.6 g/dL) was determined for 16 rabbits, of which 7 were hypoalbuminemic and 3 were hyper-albuminemic. Of the 16 rabbits that underwent serological evaluation for antibodies against E cuniculi, 7 were seropositive and 9 were seronegative.

Fifty of 117 (43%) rabbits underwent abdominal radiography. Abdominal radiographs were unremarkable for 5 rabbits. One of those rabbits subsequently underwent an abdominal ultrasonographic examination and was determined to have a gastric trichobezoar. Twenty-one rabbits had radiographic evidence suggestive of gastrointestinal stasis or ileus. Definitive diagnosis of a mechanical gastrointestinal obstruction and differentiation between functional and mechanical gastrointestinal obstructions solely based on radiographic evidence were difficult. For 18 rabbits with radiographic evidence of gastrointestinal stasis, the reviewing radiologist was unable to confidently distinguish between functional ileus and mechanical obstruction, although suspected pyloric obstruction was reported for 11 rabbits. Five of those 11 rabbits subsequently underwent an abdominal ultrasonographic examination. None had evidence of a mechanical obstruction, and all 5 were assigned a diagnosis of gastrointestinal stasis. Additionally, 2 of those 5 rabbits had a small amount of peritoneal effusion, 1 had a cavitated hepatic mass and ultrasonographic changes consistent with a gastric trichobezoar without overt obstruction, and 1 had evidence of urinary bladder debris. A rabbit with marked abdominal tympani during physical examination and suspected functional ileus or a pyloric outflow obstruction died acutely, and a gastric rupture with no overt underlying cause was diagnosed during necropsy. Overall, 43 rabbits were assigned a diagnosis of gastrointestinal stasis or ileus without an overt obstruction on the basis of abdominal radiographic, abdominal ultrasonographic, or necropsy findings.

Twenty-three of the 62 (37%) rabbits that underwent diagnostic imaging had evidence of concurrent abnormalities that did not involve the gastrointestinal tract. Eight rabbits with evidence of gastrointestinal stasis without obstruction on abdominal radiographs also had radiographic evidence of cranial mediastinal masses (n = 2), hypovolemia (1), cystic calculi (1), an intra-abdominal lipoma and suspected cystolith with right kidney irregularities (1), right ischiatic tuberosity fracture (1), hepatomegaly (1), and an aggressive bone lesion in the left hemipelvis, fracture and suspected metastatic lesions involving the T1 and T12 vertebrae, and pulmonary metastases (1).

Radiography reports were unavailable for 8 rabbits. For 6 of those rabbits, the radiographs were obtained prior to examination at the teaching hospital. Abdominal ultrasonography was performed for 6 of the 8 rabbits with unavailable radiology reports. Four of those rabbits had ultrasonographic abnormalities associated with the gastrointestinal tract. One rabbit had fluid-filled intestines without evidence of a concurrent obstruction. Three rabbits (1 with a suspected jejunal obstruction, 1 with an impaction at the distal aspect of the descending colon, and 1 with suspected enteritis and peritonitis at the cranial aspect of the abdomen) had a small amount of peritoneal effusion and evidence of nonspecific hepatopathy. Of the 2 remaining rabbits, 1 had focal peritoneal effusion and 1 had multiple ovoid cystic structures with echogenic foci within the abdomen, which were of unknown clinical relevance; both rabbits also had evidence of urinary bladder debris or sludge but no overt uroliths. The rabbit with ultrasonographic evidence of fluid-filled intestines without an overt obstruction subsequently underwent a full-body CT scan, which revealed changes consistent with gastrointestinal stasis or ileus, dental disease, diffuse SC edema of unknown etiology, testicular neoplasia, acute respiratory distress syndrome and interstitial lung disease, and osteoarthritis of both stifle and elbow joints.

Treatment

Fluid therapy was administered to 101 of the 117 (86%) rabbits. Only 1 of 59 inpatients and 15 of 58 outpatients did not receive fluid therapy. Thirty-three of 59 (56%) inpatients and 39 of 58 (67%) outpatients received fluids by the SC route. The median rate for fluids administered by the SC route was 115 mL/kg/d (52 mL/lb/d; range, 50 to 240 mL/kg/d [23 to 109 mL/lb/d]) for inpatients and 46 mL/kg/d (21 mL/lb/d; range, 12 to 120 mL/kg/d [5.5 to 54.5 mL/lb/d]) for outpatients. Two inpatients received fluids by the IO route at rates of 100 and 130 mL/kg/d (45.5 and 59.1 mL/lb/d). Twenty-eight inpatients and 4 outpatients received fluids by the IV route. The median rate for fluids administered by the IV route was 139 mL/kg/d (63 mL/lb/d; range, 50 to 266 mL/kg/d [23 to 121 mL/lb/d]) for inpatients and 115 mL/kg/d (range, 80 to 150 mL/kg/d [36 to 68 mL/lb/d]) for outpatients. One outpatient received a single IV fluid bolus and then was euthanized. Three outpatients received IV fluids during triage but died before they could be admitted to the hospital. Five rabbits received fluids by multiple routes. One rabbit received fluids by the IO route initially because IV access could not be attained, but the route of administration was switched to the IV route after it was rehydrated and an IV catheter was successfully placed. Some rabbits that initially received fluids by the IV route were subsequently administered fluids by the SC route after their IV catheters were removed owing to the patient chewing on it or some other reason.

Medications were administered to each rabbit at the discretion of the attending clinician. Forty-seven of the 117 (40%) rabbits were administered an opioid for analgesia. Forty-six (98%) rabbits received buprenorphine (0.005 to 0.05 mg/kg [0.0023 to 0.023], IV or IM), and 1 rabbit received tramadol (10 mg/kg [4.5 mg/lb], PO). Thirty-five (30%) rabbits were administered the NSAID meloxicam (0.2 to 0.5 mg/kg [0.09 to 0.23 mg/lb], PO). Seventy-five (64%) rabbits were administered metoclopramide (0.4 to 1 mg/kg [0.18 to 0.45 mg/lb], SC or PO) as a prokinetic. Thirty-seven (32%) rabbits received antimicrobials including enrofloxacin (n = 27), metronidazole (12), trimethoprim-sulfamethoxazole (9), penicillin G procaine (1), and azithromycin (1); some rabbits were administered > 1 antimicrobial. Fifteen (13%) rabbits were administered simethicone. Sixteen (14%) rabbits received no medications (Table 2).

Table 2—

Number of rabbits from Table 1 that received medications of various types on either an inpatient (n = 59) or outpatient (58) basis.

Medication typeInpatientOutpatient
Opioid3710
NSAID1124
Histamine H2-receptor antagonists00
Prokinetic4035
Antimicrobial1918
None79

Short-term outcomes

Of the 117 study rabbits, 15 (13%) died, 18 (15%) were euthanized, and 84 (72%) were alive at the time of hospital discharge. Necropsy was performed on 5 rabbits (1 outpatient and 4 inpatients). The diagnoses for those 5 rabbits as indicated on the necropsy reports included pyogranulomatous bronchointerstitial pneumonia, necrotizing typhlocolitis, lymphohistiocytic myelitis of the spinal cord, lymphoplasmacytic and heterophilic nephritis, and lymphocytic hepatitis (n = 1); multifocal marked subacute myocarditis with myocardial degeneration (1); cystadenocarcinoma with carcinomatosis (1); bicavitary transudate, granulomatous ileitis, heterophilic and lymphoplasmacytic enteritis, and moderate acute multifocal centrilobular necrosis with multifocal fibrin thrombi (1); and gastric rupture (1).

Univariate and logistic regression results

Increasing age (P < 0.001) and the absence of borborygmi (P = 0.017) were positively associated with recurrent episodes of signs of RGIS on univariate analyses. Recurrence of signs of RGIS was not significantly associated with sex, housing (indoor vs outdoor), BCS, heart rate, respiratory rate, or any hematologic or serum biochemical variable assessed. On univariate analysis, rabbits that were hypothermic at the time of the initial examination were approximately 4.6 times as likely to die or be euthanized as were rabbits that were not hypothermic (OR, 4.58; 95% confidence interval, 1.80 to 11.64; P = 0.001). When potential confounding factors (previous episodes of gastrointestinal stasis or ileus, diet type, age, and presence or absence of borborygmi) were controlled, rabbits with hypothermia at the time of the initial examination were approximately 5 times as likely to die or be euthanized as were rabbits that were not hypothermic (OR, 5.1; 95% confidence interval, 1.9 to 13.5; P = 0.001).

Discussion

The present retrospective case series was the first to describe the clinical characteristics, clinicopathologic and diagnostic imaging findings, and short-term outcomes for client-owned rabbits that were examined because of signs of gastrointestinal dysfunction, or RGIS. In the present study, 117 of the 484 (24%) rabbits treated by the emergency and exotic animal referral services of a veterinary teaching hospital during an approximately 2-year study period were examined because of signs of RGIS. This finding was similar to the overall proportion of rabbits examined because of signs of RGIS (96/382 [25%]) at another exotic animal referral hospital.2

In the present study, 84 of 117 (72%) rabbits examined because of signs of RGIS survived to hospital discharge, which suggested that the short-term prognosis was good for rabbits with RGIS. Given the retrospective nature of this study and the emergent nature of many of the cases evaluated, the long-term outcome for rabbits with RGIS remains unknown. Twenty of the 58 rabbits that were managed as outpatients were reexamined because of signs of RGIS during the 2-year study period, and 8 of those rabbits were reexamined multiple times. Unfortunately, it was not possible to determine whether those rabbits were at greater risk for RGIS because of underlying systemic factors or simply needed additional treatment to completely ameliorate their clinical signs.

For the rabbits of the present study, hypothermia (rectal temperature, < 36.6°C) was strongly associated with death. In rabbits, hypothermia is often an indicator of severe underlying disease. In another study,9 rabbits that were hypothermic (rectal temperature, < 37.9 [100.2°F]) at the time of hospital admission were 3 times as likely to die as were rabbits that were normothermic at the time of hospital admission, and for each 1°C (1.8°F) decrease in rectal temperature at the time of hospital admission, the odds of death doubled. Although the rectal temperature cutoff used to define hypothermia in that study9 differed from that used in the present study, the results of both studies clearly indicated that hypothermia was strongly associated with death in rabbits. Measurement of rectal or body temperature is an important part of any clinical evaluation, especially for rabbits.

Abdominal radiographs were obtained for 50 of the 117 (43%) rabbits evaluated in the present study. Radiographic findings were unremarkable for only 5 of the 50 (10%) rabbits, and 23 (46%) rabbits had radiographic evidence of concurrent abnormalities that did not involve the gastrointestinal tract. Among the rabbits with radiographic evidence of gastrointestinal disease, functional gastrointestinal stasis or ileus was more common than pyloric or intestinal obstruction. Nevertheless, ruling out a mechanical obstruction was challenging, even for the board-certified veterinary radiologists who interpreted the radiographs. Five of 18 rabbits with inconclusive radiographic findings subsequently underwent an abdominal ultrasonographic examination, and none were identified as having a gastrointestinal obstruction. Given that results of the present study and a previous study10 indicated that most rabbits with gastric dilatation respond to medical management, it may be prudent to initiate medical treatment in rabbits with signs of RGIS and inconclusive radiographic and ultrasonographic findings despite the remote possibility of a gastrointestinal obstruction.

None of the hematologic and biochemical variables assessed were significantly associated with the short-term outcome for the rabbits of the present study. However, 4 of 7 rabbits with moderate to severe azotemia (creatinine concentration, > 4 mg/dL) died or were euthanized. The lack of a significant association between azotemia (creatinine concentration, > 2.5 mg/dL) and short-term outcome was likely affected by the small number of azotemic rabbits. For rabbits, clinical outcomes on the basis of serum creatinine concentration have not been well described and acute kidney injury has not been clinically defined. Therefore, it was unclear whether the extent of hypercreatinemia in azotemic rabbits was sufficient to affect the short-term outcome. In another retrospective study,d the short-term (15-day) mortality risk for rabbits with azotemia (defined as a BUN concentration > 55.7 mg/dL) was 3 times that for rabbits without azotemia. Because the BUN concentration can be affected by multiple factors, we chose to define azotemia as simply an abnormally high serum creatinine concentration for this study.

Three of 34 rabbits for which serum ALT activity was evaluated had abnormally high activities of the enzyme, which we considered indicative of hepatic disease. One of those rabbits had evidence of hepatitis with neutrophilic inflammation on cytologic evaluation of a hepatic aspirate specimen. Necropsy reports for the remaining 2 rabbits indicated that 1 had moderate, multifocal, acute, centrilobular hepatic necrosis with multifocal fibrin thrombi and 1 had a gastric rupture. Results of another retrospective study11 suggest that rabbits with liver lobe torsions often have abnormally high liver enzyme activities and clinical signs consistent with RGIS. Although liver lobe torsion was not diagnosed in any of the rabbits of the present study, it could not be definitively ruled out for all rabbits.

Twenty-five of 50 rabbits evaluated in the present study were hyperglycemic. This finding was not unexpected because results of another study12 indicate that blood glucose concentration increases with anorexia, stress, and disease severity in rabbits with signs of gastrointestinal tract disease. Despite the fairly high prevalence of hyperglycemia, blood glucose concentration was not significantly associated with the short-term outcome for the rabbits of the present study.

Twelve of 17 (71%) rabbits for which the serum ionized calcium concentration was determined were classified as hypocalcemic on the basis of a previously reported reference range,8 which was substantially higher than the proportion of critically ill dogs with ionized hypocalcemia (22/141 [16%]) in another study.13 A reference range for ionized calcium in rabbits has not been established for the blood gas analyzer used in the present study; therefore, the true incidence of ionized hypocalcemia for the rabbits of this study was unknown. The 2 rabbits with the lowest ionized calcium concentrations (1.06 and 1.08 mmol/L) were both severely azotemic (creatinine concentration, > 4 mg/dL), and 1 died (ionized calcium concentration, 1.06 mmol/L) while hospitalized. Although ionized hypocalcemia is common in critically ill dogs and cats,14 it needs to be investigated further in rabbits, especially those with anorexia or signs of gastrointestinal tract disease.

The blood lactate concentration was determined for only 17 of the 117 (15%) rabbits evaluated in the present study. Only 6 of those rabbits were hyperlactatemic (lactate concentration, > 8.7 mmol/L), of which 2 died, 2 were euthanized owing to disease severity, and 2 survived to hospital discharge. Results of univariate analysis indicated that blood lactate concentration was not significantly associated with survival to discharge; however, the small number of rabbits with recorded lactate concentrations likely limited the power to detect a significant association. In another study,15 the mean blood lactate concentration did not differ significantly between healthy rabbits and rabbits with various clinical conditions or severe hematologic and biochemical abnormalities. Unfortunately, the authors of that study15 did not compare the blood lactate concentration among specific groups of critically ill rabbits. Further investigation of the relationship between blood lactate concentration and disease severity or outcome for rabbits with signs of RGIS is warranted.

Fluid therapy was administered to 101 of the 117 (86%) rabbits of the present study, and only 1 of 59 inpatients and 15 of 58 outpatients did not receive fluid therapy. The route (SC, IV, or IO) of fluid therapy administration was not significantly associated with short-term outcome. The majority (72/101 [71%]) of rabbits were administered fluids by the SC route. Thirty-two rabbits received fluids by the IV route, including the 2 rabbits that initially received fluids by the IO route. The rationale for the route of fluid administration could not be assessed because of the retrospective nature of the study. Factors that might have influenced whether rabbits received fluid therapy and the route by which that therapy was administered include owners' financial constraints, technical abilities of after-hours staff to perform IV or IO catheterization, and perceived patient fluid deficit or extent of dehydration.

In the present study, the majority (82/117 [70%]) of rabbits received analgesics, most commonly the opioid buprenorphine (n = 46) or the NSAID meloxicam (35). Neither analgesic was associated with the short-term outcome. That may have been because rabbits were not subjectively assessed for pain (ie, were not assigned a pain score) or the fact that the rabbits had multiple underlying disease processes. Because so many rabbits received some form of analgesia, it was not possible to compare short-term recovery between rabbits that did and did not receive analgesia. Further research into the effects of analgesics in rabbits with signs of RGIS is necessary.

Seventy-five (64%) rabbits of the present study were administered metoclopramide as a prokinetic. Metoclopramide administration was not significantly associated with the short-term outcome, likely because the rabbits were affected by various disease processes. In another study,10 130 of 145 (90%) rabbits with gastric dilatation that were medically managed with metoclopramide, metamizole (a nonopioid analgesic), fluid therapy, and syringe feedings survived to hospital discharge. Metoclopramide may be beneficial for rabbits with signs of RGIS regardless of the presence of mechanical obstruction, but additional research is necessary to further elucidate the efficacy of metoclopramide for the treatment of RGIS.

Other medications administered to the rabbits of the present study included various antimicrobials and simethicone. None of those medications were significantly associated with the short-term outcome. Simethicone is a polydimethylsiloxane and hydrated silica gel used as an antifoaming agent. Little is known about the mechanism of action or efficacy of simethicone in rabbits or other exotic species.16 In an experimental crossover study,17 healthy rabbits underwent abdominal ultrasonography with and without having food withheld for a period of 4 to 6 hours and with and without simethicone administration. Results indicated that withholding food for 4 to 6 hours in combination with simethicone administration facilitated dissipation of gas in the gastrointestinal tract and improved ultrasonographic visualization of abdominal organs.17 Although it is unknown whether simethicone might be beneficial for rabbits with signs of RGIS, no adverse effects have been associated with administration of simethicone to rabbits.16

All rabbits of the present study were pets, and there was no chance that any of them would subsequently be used for human consumption. However, some rabbits are destined for human consumption, and it is important that all regulations regarding drug use in food-producing animals be followed when treating such animals. For example, the FDA prohibits administration of metronidazole and extralabel use of enrofloxacin in all animals destined for human consumption.

Neither diet type nor husbandry was significantly associated with the short-term outcome for the rabbits of the present study. Because of the retrospective nature of the study, it was difficult to determine whether rabbits were fed appropriate diets. The diet histories recorded in the medical records were often incomplete, lacking information regarding the percentages and types of hay, pellets, and treats fed. Diet and husbandry are often thought to be important contributing factors to signs of RGIS,1,4,5 and prospective research into the role of diet and husbandry on the pathogenesis of RGIS is warranted.

Only 8 of 117 (7%) rabbits evaluated in the present study had diarrhea as diagnosed by the attending clinician, which suggested that diarrhea was fairly uncommon in rabbits with signs of RGIS. Clinicians or owners might have misinterpreted normal cecotropes as diarrhea, which would have falsely increased the prevalence of diarrhea within the study population. Diarrhea was not associated with the short-term outcome for the rabbits of this study, but the small number of diarrhetic animals likely limited the power to detect a significant association.

Limitations of the present study were typical of those for retrospective studies. The historical information recorded for rabbits was not standardized and often incomplete. Only a small number of rabbits underwent all diagnostic tests (eg, CBC, serum biochemical profile, serological analysis for antibodies against E cuniculi, and abdominal radiographic and ultrasonographic examinations), which limited our ability to assess associations among variables. Additionally, long-term follow-up information was not available for the rabbits.

The purpose of the present study was to describe the clinical characteristics, clinicopathological abnormalities, diagnostic imaging results, and short-term outcomes for rabbits with RGIS. Results indicated that the short-term prognosis for rabbits with signs of RGIS was generally good, as evidenced by the fact that 84 of 117 (72%) rabbits evaluated survived to hospital discharge. There was a strong association between hypothermia (rectal temperature, < 36.6°C) at initial examination and risk of death. Many of the rabbits that underwent abdominal radiography or ultrasonography had evidence of abdominal abnormalities, and some of those abnormalities did not involve the gastrointestinal tract. Evidence of functional gastrointestinal stasis or ileus was more common than evidence of a physical pyloric or intestinal obstruction. Prospective studies are warranted to further elucidate and characterize RGIS and assess the efficacy of various treatments and outcomes for affected rabbits.

Acknowledgments

No third-party funding or support was received in connection with this study or the writing or publication of the manuscript. The authors declare that there were no conflicts of interest.

The authors thank Amy Bell, Maria Oparil, and Elizabeth Rozanski for assistance with statistical analysis and manuscript revision.

ABBREVIATIONS

ALT

Alanine aminotransferase

BCS

Body condition score

IO

Intraosseous

RGIS

Rabbit gastrointestinal syndrome

Footnotes

a.

Schwartz Z, Lichtenberger MK, Thamm DH, et al. Lactate normals in healthy rabbits comparing three different analyzers (abstr). J Vet Emerg Crit Care 2006;16(suppl s2):17–18.

b.

R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. 2016. Available at: www.R-project.org. Accessed Dec 27, 2017.

c.

AlphaTrak2, Zoetis Inc, Parsippany, NJ.

d.

Zoller G, di Girolamo N, Huynh M. Biochemical predictor of short-term outcome in rabbits with urologic disorders (abstr) in Proceedings. ExoticsCon 2015;335.

References

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    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Huynh M, Vilmouth S, Gonzalez MS, et al. Retrospective cohort study of gastrointestinal stasis in pet rabbits. Vet Rec 2014;175:225.

  • 3. Huynh M, Boyeaux A, Pignon C. Assessment and care of the critically ill rabbit. Vet Clin North Am Exot Anim Pract 2016;19:379409.

  • 4. DeCubellis J, Graham J. Gastrointestinal disease in guinea pigs and rabbits. Vet Clin North Am Exot Anim Pract 2013;16:421435.

  • 5. Harrenstein L. Gastrointestinal disease of pet rabbits. Semin Avian Exot Pet Med 1999;8:8389.

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    • Search Google Scholar
    • Export Citation
  • 7. Langlois I, Planché A, Boysen SR, et al. Blood concentrations of d- and l-lactate in healthy rabbits. J Small Anim Pract 2014;55:451456.

  • 8. Kamphues J, Carstensen D, Schroeder D, et al. Effects of increasing calcium and vitamin D supply on calcium metabolism of rabbits. J Anim Physiol Anim Nutr (Berl) 1986;56:191208.

    • Search Google Scholar
    • Export Citation
  • 9. Di Girolamo N, Toth G, Selleri P. Prognostic value of rectal temperature at hospital admission in client-owned rabbits. J Am Vet Med Assoc 2016;248:288297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Schuhmann B, Cope I. Medical treatment of 145 cases of gastric dilatation in rabbits. Vet Rec 2014;175:484.

  • 11. Graham JE, Orcutt CJ, Casale SA. Liver lobe torsion in rabbits: 16 cases (2007 to 2012). J Exot Pet Med 2014;23:258265.

  • 12. Harcourt-Brown FM, Harcourt-Brown SF. Clinical value of blood glucose measurement in pet rabbits. Vet Rec 2012;170:674.

  • 13. Holowaychuk MK, Hansen BD, DeFrancesco TC, et al. Ionized hypocalcemia in critically ill dogs. J Vet Intern Med 2009;23:509513.

  • 14. Holowaychuk MK. Hypocalcemia of critical illness in dogs and cats. Vet Clin North Am Small Anim Pract 2013;43:12991317.

  • 15. Hupfeld C. Lactate concentration in blood of healthy and ill rabbits. Tierarztl Prax Ausg K Klientiere Heimtiere 2009;37:244249.

  • 16. Watson MK. Therapeutic review: simethicone. J Exot Pet Med 2014;23:415417.

  • 17. da Silva KG, de Andrade C, Sotomaior CS. Influence of simethicone and fasting on the quality of abdominal ultrasonography in New Zealand White rabbits. Acta Vet Scand 2017;59:48.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 1. Lichtenberger M, Lennox A. Updates and advanced therapies for gastrointestinal stasis in rabbits. Vet Clin North Am Exot Anim Pract 2010;13:525541.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. Huynh M, Vilmouth S, Gonzalez MS, et al. Retrospective cohort study of gastrointestinal stasis in pet rabbits. Vet Rec 2014;175:225.

  • 3. Huynh M, Boyeaux A, Pignon C. Assessment and care of the critically ill rabbit. Vet Clin North Am Exot Anim Pract 2016;19:379409.

  • 4. DeCubellis J, Graham J. Gastrointestinal disease in guinea pigs and rabbits. Vet Clin North Am Exot Anim Pract 2013;16:421435.

  • 5. Harrenstein L. Gastrointestinal disease of pet rabbits. Semin Avian Exot Pet Med 1999;8:8389.

  • 6. Mader DR. Basic approach to veterinary care. In: Quesenberry K, Carpenter J, eds. Ferrets, rabbits, and rodents: clinical medicine and surgery. 2nd ed. St Louis: Saunders, 2004;147154.

    • Search Google Scholar
    • Export Citation
  • 7. Langlois I, Planché A, Boysen SR, et al. Blood concentrations of d- and l-lactate in healthy rabbits. J Small Anim Pract 2014;55:451456.

  • 8. Kamphues J, Carstensen D, Schroeder D, et al. Effects of increasing calcium and vitamin D supply on calcium metabolism of rabbits. J Anim Physiol Anim Nutr (Berl) 1986;56:191208.

    • Search Google Scholar
    • Export Citation
  • 9. Di Girolamo N, Toth G, Selleri P. Prognostic value of rectal temperature at hospital admission in client-owned rabbits. J Am Vet Med Assoc 2016;248:288297.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10. Schuhmann B, Cope I. Medical treatment of 145 cases of gastric dilatation in rabbits. Vet Rec 2014;175:484.

  • 11. Graham JE, Orcutt CJ, Casale SA. Liver lobe torsion in rabbits: 16 cases (2007 to 2012). J Exot Pet Med 2014;23:258265.

  • 12. Harcourt-Brown FM, Harcourt-Brown SF. Clinical value of blood glucose measurement in pet rabbits. Vet Rec 2012;170:674.

  • 13. Holowaychuk MK, Hansen BD, DeFrancesco TC, et al. Ionized hypocalcemia in critically ill dogs. J Vet Intern Med 2009;23:509513.

  • 14. Holowaychuk MK. Hypocalcemia of critical illness in dogs and cats. Vet Clin North Am Small Anim Pract 2013;43:12991317.

  • 15. Hupfeld C. Lactate concentration in blood of healthy and ill rabbits. Tierarztl Prax Ausg K Klientiere Heimtiere 2009;37:244249.

  • 16. Watson MK. Therapeutic review: simethicone. J Exot Pet Med 2014;23:415417.

  • 17. da Silva KG, de Andrade C, Sotomaior CS. Influence of simethicone and fasting on the quality of abdominal ultrasonography in New Zealand White rabbits. Acta Vet Scand 2017;59:48.

    • Crossref
    • Search Google Scholar
    • Export Citation

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