Chronic vomiting and diarrhea in cats: it's really not hairballs or worms (Proceedings)

1) Overview

a) Most chronic vomiting and chronic diarrhea in cats originate in the small bowel

b) Many small bowel diseases are segmental

c) Endoscopic biopsies are a very poor way to diagnose most cases

     i) Location: stomach + 1-2 cm of duodenum OR colon

     ii) Sample Size: about 1 mm piece of tissue; not full thickness

d) Chronic small bowel disease is manifested as chronic vomiting, chronic diarrhea, or both.

2) Typical history

a) "My cat has vomited all of its life. The vomiting was occasional for months to years. Then it became 1-2 times per month. Now it is daily. Otherwise, he/she feels good and eats good."

     i) Think small bowel, not stomach.

b) "My cat has had soft stools ("not diarrhea") all of its life. The soft stool was occasional for months to years. Then it became 1-2 times per month. Now it is daily. Otherwise, he/she feels good and eats good."

c) Alternative: "has been losing weight" " has a tremendous appetite."

d) The diarrhea is typically small bowel diarrhea.

e) Small Bowel Diarrhea vs. Large Bowel Diarrhea

3) Cobalamin/Folate

a) They are not synthesized in the cat.

b) Folate: absorbed in the upper small bowel.

c) Cobalamin: absorbed in the lower small bowel.

d) If their levels are low, it tells you what part of the bowel is diseased.

     i) Low folate: rare in the cat.

     ii) Low cobalamin: common in the cat.

     iii) Most chronic small bowel disease occurs in the jejunum and ileum.

          (1) This explains why endoscopic biopsies fail to be diagnostic.

e) Recovery from chronic small bowel disease requires successful treatment.

     i) Cobalamin/B12 injections.

f) Diagnosed with fasted blood sample: IDEXX and Texas A&M GI Laboratory.

g) Treatment for low serum cobalamin

     i) 100-250 mcg/cat SC q7d for 6 weeks followed by 100-250 mcg q14d for 6 weeks (3 injections), and another injection (100-250 mcg) 4 weeks later.

     ii) Using the 1000 mcg/ml concentration, this is a very tiny dose (0.1-0.25 ml). I give 1 ml (1000 mcg) per dose because it is not toxic and often stimulates the appetite at this dose.

h) Treatment for low serum folate

     i) Rarely, if ever, needed.

     ii) 5 mg q24h PO. (1 mg tablets available)

4) Symptomatic Therapy for Chronic Vomiting

a) Diet

     i) i/d (Hill's)

     ii) OM (Purina)

     iii) Low Residue (Iams)

b) Medications

     i) Suppressing vomiting is not curative.

     ii) Cerenia – approved for up to 5 days of use.

     iii) Hairball remedies/food.

     iv) My preference: none unless the owner is insistent.

5) Symptomatic Therapy for Chronic Diarrhea

a) Diet

     i) i/d (Hill's)

     ii) DM/OM (Purina)

     iii) Low Residue (Iams)

b) Anti-diarrheals

     i) Diphenoxylate: ½ tablet q12h PO

          (1) Caution about overdosing due to small size of tablet.

          (2) Occasional bizarre behavior (hallucinations?)

          (3) A controlled substance; drug log entry required.

     ii) Loperamide: ¼ tablet (0.5 mg) q12h PO

          (1) Liquid has mint taste; objectionable to most cats

6) Lifestyle Causes

a) Hairballs

     i) Cats groom; cats swallow hair; it must be eliminated by vomiting or in the stool.

     ii) Vomiting hairballs is normal for cats if it occurs occasionally.

     iii) If it is frequent, it may be a sign of a motility disorder (IBD, LSA).

b) Grass

     i) Many cats love the taste of grass.

     ii) They eat it because they like it; not to "purge' themselves.

     iii) Grass causes gastritis resulting in vomiting.

7) Infectious Causes

a) Risk assessment is essential when pursuing this option.

     i) Multicat household or facility invites contagion

          (1) Catteries, shelters, and rescuers are high risk.

b) History should reveal that multiple cats in the same household are affected.

c) More likely in cats less than 1 year old.

d) Fecal Floatation

     i) Coccidia: found with careful observation.

     ii) Giardia: often poor sensitivity and specificity.

     iii) Ascarids rarely cause chronic diarrhea or vomiting.

     iv) Hookworms are rare in cats.

     v) Tapeworms are virtually non-pathogenic (except for the gross-out factor).

e) ELISA Giardia Test

     i) Much better sensitivity and specificity than fecal flotation.

     ii) Not as good as PCR.

     iii) Since the diagnostic workup should include other organisms, a Giardia test is usually obtained as part of a more comprehensive PCR profile.

     iv) Infectious PCR Profile

          (1) An expensive profile but the most sensitive and specific tests we have.

          (2) Tritrichomonas, Cryptosporidium, Giardia, Salmonella, Clostridium perfringens, Toxoplasma, feline panleukopenia virus, feline coronavirus.

          (3) Especially indicated for multicat situations: shelters, catteries, rescuers.

f) Therapy

     i) Panacur + Albon

          (1) Giardia + coccidia

          (2) A good initial treatment pending or in lieu of laboratory tests.

          (3) I use DM diet with them.

     ii) Cryptosporidium

          (1) Supposed to be self-limiting.

          (2) Azithromycin: 7-15 mg/kg q12h PO X 5-7 (or 14) days.

          (3) Tylocin: 11 mg/kg q12h PO for 28 days.

     iii) Tritrichomonas

          (1) Self-limiting in 5-24 months.

          (2) Ronidazole: 30 mg/kg q12h PO for 14 days.

          (3) Potentially neurotoxic

               (a) Usually reversible after the drug is stopped.

g) Non-Infectious Causes

     i) Differential list

          (1) Food intolerance

          (2) Inflammatory bowel disease

          (3) Neoplasia without mass formation

               (a) Small cell lymphoma

               (b) Lymphoblastic lymphoma

               (c) Note: Mast cell tumor, adenocarcinoma, small cell lymphoma, and lymphoblastic lymphoma can cause chronic small bowel signs, but a mass forms resulting in rapid weight loss and vomiting (partial to full obstruction). The mass is found by palpation, ultrasound, or surgery.

     ii) Typical history

          (1) Chronic vomiting and/or small bowel diarrhea (or both)

          (2) Was infrequent for months to years

          (3) Frequency became 1-2 times per month.

          (4) Now 5+ times per week.

          (5) If vomiting only, the cat is often otherwise healthy.

               (a) It is usually diagnosed as hairballs and treated accordingly.

          (6) If diarrhea only, weight loss has started recently (small bowel diarrhea).

               (a) The cat is otherwise normal.

               (b) The cat possibly has a history of vomiting or polyphagia.

     iii) Diagnostics

          (1) When the clinical picture is presented to me I recommend

               (a) Small intestinal ultrasound.

                    (i) If the walls are thick (0.28 cm or more), I recommend a full-thickness biopsy of the small bowel via laparotomy.

               (b) Possible exception: food trial first, but 6+ weeks are lost so you must consider the consequences of that.

          (2) Objections to this approach

               (a) Cannot do ultrasound.

          (3) What an ultrasound study does:

               (a) Allow you to document small bowel thickening.

               (b) Allows the owner to see it.

               (c) Makes a laparotomy much easier to sell.

               (d) The laparotomy and biopsies get a diagnosis leading to specific treatment.

               (e) Pays for the ultrasound machine.

          (4) Why palpation fails to get a diagnosis

               (a) Mild to moderate small bowel thickening is not palpable.

               (b) Heavy cats are hard to palpate.

               (c) Segmental disease occurs.

          (5) Small bowel biopsy technique

               (a) You need a full-thickness sample.

               (b) Cut out a wedge beginning on the antemesenteric side of the bowel.

               (c) Alternate: 6 Fr biopsy punch (better sample per my pathologist)

               (d) Trim away excess mucosa so you suture muscle and serosa to muscle and serosa.

               (e) Use simple interrupted through-and-through sutures of 4-0 PDS placed 1 mm apart.

               (f) When the bowel is closed, test with a saline injection.

               (g) Consider biopsy of the mesenteric lymph node if it is enlarged.

     iv) Miscellaneous observations and comments

          (1) On ultrasound, the wall thickness is not half the diameter of the bowel loop due to the luminal contents.

               (a) Measure from the outside of the wall (serosa) to the near edge of the lumen.

          (2) Enlargement of the mesenteric lymph node is not diagnostic or prognostic.

               (a) A biopsy of the LN will not substitute for a full-thickness biopsy of the small bowel. Sometimes the LN will be reactive and the bowel wall neoplastic.

               (b) Biopsy of the LN rarely adds to the diagnosis.

               (c) Biopsy of the LN is an optional procedure.

               (d) It is a friable organ; close it with mattress sutures.

               (e) Do not cut the mesenteric artery. Take a superficial biopsy.

          (3) Small masses may accompany thickened loops and be very hard to find with palpation or ultrasound.

          (4) Take more than one biopsy as the disease is segmental. Often, some samples will be normal and some abnormal.

          (5) Ropey bowel loops

               (a) May be due to severe IBD or due to lymphoma.

               (b) May dehisce easily when biopsied.

               (c) Usually have a bad prognosis.

               (d) Small bowel aspiration

                    (i) Isolate the desired site(s).

                    (ii) Insert a 22 ga. needle through the bowel wall at an acute angle.

                    (iii) Vigorously "vacuum" the opposite mucosa to recover "snot."

                    (iv) Advantages

                         1. Multiple locations in little time.

                         2. No dehiscence.

                    (v) Disadvantages

                         1. Not a full-thickness biopsy.

                         2. This is not usually significant for ropey bowel loops.

          (6) Loss of layering of the bowel wall

               (a) There is a strong correlation with neoplasia.

               (b) But, many cats with lymphoma have normal layering.

          (7) Anesthesia and Surgery on Geriatric Cats

               (a) Pre-Anesthetic Workup

                    (i) Good physical examination

                    (ii) Chemistry panel with electrolytes (and TT4)

                    (iii) PCV (or CBC)

                    (iv) Careful cardiac auscultation

                    (v) Single-lead ECG with Biolog (DVM Solutions; 1-866-373-9627)

               (b) Anesthetic Induction

                    (i) Isoflurane (or sevoflurane) by face mask

                         1. In my practice we do this 5-10 times per day

                         2. Problems with face mask induction are due to

                              a. Wrong size mask (Jorgensen; 5.5" diameter

                              b. Improper restraint

                              c. Lack of cleanliness

               (c) Medications

                    (i) Pre-op

                         1. Buprenorphine: 0.2 mg/kg IM or SC

                         2. Antibiotics: Baytril + ampicillin injectables

                         3. Fluids: IV or SC

                    (ii) Intra-op

                         1. Atropine PRN for bradycardia (HR <90 bpm)

                    (iii) Post-op

                         1. Acepromazine for rough recovery

                              a. Dilute 1:10; 1 mg/kg concentration

                              b. Give 0.05 mg/# IM or SC

                         2. Buprenorphine

                              a. 0.2 mg/kg q12h PO X 5-7

                         3. Alternative analgesic

                              a. Metacam

                                   i. SC injection pre-op with SC or IV fluids

                                   ii. Oral: Half the canine dose; give q24h

                              b. Tramadol

                                   i. 12.5 mg/cat q12h PO (50 mg tabs)

               (d) Surgical Monitoring

                    (i) Parameters

                         1. Respiration rate *

                         2. Heart rate *

                         3. Temperature *

                         4. ECG tracing

                         5. Blood pressure

                         6. Pulse Ox

                         7. End Tidal CO2

                    (ii) Equipment

                         1. VetGard (DVM Solutions; 1-866-373-9627)

               (e) Temperature Control during Surgery

                    (i) Warm IV fluids

                    (ii) Hot Dog (Augustine BioMedical; 1-952-465-3500)

                    (iii) ChillBusterVet (ThermoGear, Inc.; 1-503-697-1900) ***

               (f) Body Wall Closure

                    (i) Needs to be secure and fast

                    (ii) Muscle

                         1. 2-0 PDS

                         2. Simple interrupted pattern about 1-1.5 cm apart

                         3. Continuous pattern from end to middle and middle to end.

                    (iii) Subcutaneous tissue

                         1. 4-0 PDS in continuous pattern

                    (iv) Skin

                         1. 4-0 Braunamid/Polymid

                         2. Ford interlocking pattern.

               (g) Recovery

                    (i) Very rapid due to the anesthetic protocol used.

                    (ii) Wrap in warm bath towel

                    (iii) Beanies and Chillbuster for warmth

                    (iv) Heating pad below the cage rack PRN

                    (v) Watch brachycephalic cats for airway obstruction during recovery.

               (h) Post-op Protocol

                    (i) Continue IV fluids for 24 hours post-op and keep the cat NPO.

                    (ii) Then, offer food and keep the cat another night.

                    (iii) If the cat eats and does not spike a fever, it goes home on the second post-op day (after two nights in the hospital).

          (8) Important factors that determine whether or not an owner will treat a chronic disease on a long-term basis? (Ref: AVMA, 2007)

     v) Therapy

          (1) General prognoses

               (a) Good: food reaction, inflammatory bowel disease, small cell lymphoma, mast cell tumor.

               (b) Bad: lymphoblastic lymphoma, adenocarcinoma.

          (2) Food reaction

               (a) There is a technical difference in food allergy vs. food intolerance, but it is not clinically feasible to make the distinction. This distinction is skirted by using the term 'food reaction.'

               (b) As a rule, anti-inflammatories are not effective or may be effective for only a few days to weeks.

               (c) Food trials based on novel protein diets (rabbit, duck, venison) or hydrolyzed protein diets (z/d by Hill's).

               (d) The food trial should go 6 weeks before deeming it to be a failure.

          (3) Inflammatory bowel disease

               (a) Diet: novel protein, hydrolyzed, or high fiber may help some cats.

               (b) Immune suppressants

                    (i) Corticosteroids: prednisolone 10 mg q12h PO for 10 days then reduce.

                    (ii) Cyclosporine (Atopica): 25 mg q24h PO for 15-30 days then 25 mg q48h PO. May change to prednisone for long-term control.

                    (iii) Megestrol: 5 mg q24h PO for 7 days then 5 mg q48h for 14 days then change to prednisone.

                    (iv) Chlorambucil: 0.1 mg/kg q24h PO or 6-8 mg/m2 q24h PO. The tablets should never be split, so must cats take 2 mg q24h PO to q3d PO days depending upon the weight of the cat.

                    (v) Lomustine (CCNU): 10 mg capsule for cats 5-15 pounds q28d PO. Monitor for leukopenia.

               (c) Others

                    (i) Cobalamin injections for hypocobalaminemia.

                    (ii) Prebiotics and/or probiotics.

                    (iii) Omega-3 fatty acids.

                    (iv) Metronidazole + prednisone/prednisolone.

          (4) Small cell lymphoma

               (a) Prednisolone/prednisone: 2 mg/kg q12h PO fo r7-10 days then reduce slowly to 5-10 mg/cat q24h PO. Least expensive approach with fewest side effects. If given alone for several weeks, the response to other chemo protocols may be reduced significantly.

               (b) Modified Wisconsin protocol: 15 treatments in 24 weeks using Modified CHOP) (L-asparaginase, vincristine, cyclophosphamide, chlorambucil, doxorubicin, prednisone); first remission rate 68%; median survival time 225 days. See The Feline Patient editions 2, 3, or 4 for specific protocol. The protocol of choice for most veterinary oncologists.

                    (i) Chlorambucil + prednisone

                         1. Chlorambucil: 0.1 mg/kg q24h PO or 6-8 mg/m2 q24h PO. The tablets should never be split, so must cats take 2 mg q24h PO to q3d PO days depending upon the weight of

                         2. the cat. Prednisone/prednisolone: 1-2 mg/kg q24h PO.

               (c) Lomustine + prednisone

                    (i) In generally, not considered a first-line chemotherapy agent.

                    (ii) Lomustine: (CCNU): 10 mg capsule for cats 5-15 pounds q28d PO. Monitor for leukopenia. See Norsworthy study below.

                    (iii) Prednisone/prednisolone: 1 mg/kg q24h PO.

                    (iv) Protocol:

                         1. Visit 1: CBC + lomustine; dispense prednisone.

                         2. Visit 2: CBC 2 weeks later.

                         3. Visit 3: lomustine 4 weeks after first dose.

                         4. Visit 4: CBC 2 weeks later.

                         5. Repeat #3 and #4 for a total of 6 (or more) doses.

                    (v) Monitor for leukopenia. If it occurs, discontinue lomustine until WBC is in the normal range but continue prednisone. Recheck WBC q14 days. In Norsworthy study it occurred 40% of the time, but all cats were eventually able to get 6 doses or more.

                    (vi) Usual protocol is to give 6 doses over 5 months. Some cats require up to 9 doses to achieve remission.

                    (vii) Cost: $196.06/bottle of 20 capsules (3/2010).

                    (viii) The capsule becomes very sticky when moist

                         1. Use a Pill Popper if needed for clean administration.

                         2. Syringe 2-3 ml of water orally to prevent the capsule from sticking to the esophageal wall and causing an esophageal stricture.

                    (ix) Norsworthy Study (Data collected March 2010)

                         1. 20 cats with history of chronic vomiting or diarrhea, ultrasound confirmed thickening of small bowel wall, laparotomy, full-thickness biopsies of small bowel, and HP diagnosis of small cell lymphoma.

                         2. 11 (53%) went into remission.

                         3. Remission group

                              a. Average survival time: 582 days (19.4 months); range 6-45 months.

                              b. 3 still alive when data collected: 18, 32, and 45 months.

                              c. Quality of life excellent during and after treatment.

References

Crystal MA. Chemotherapy for Lymphoma. Feline Patient, 4th ed., 2006:692-696. Ames, IA; Blackwell.

Kleinschmidt S, Harder J, Nolte I, et. al. Chronic inflammatory and non-inflammatory diseases of the gastrointestinal tract in cats: diagnostic advantages of full-thickness intestinal and extraintestinal biopsies. J Fel Med Surg. 2010;12:97-103.

Zwingenberger, AL, Marks SL, Baker TW, Moore PF. Ultrasonographic Evaluation of the Muscularis Propria in Cats with Diffuse Small Intestinal Lymphoma or Inflammatory Bowel Disease. J Vet Intern Med. 2010;24:289-292.