CASE STUDY - Bute
Toxicity & Protein
Losing Enteropathy
"APRIL"
AQHA Filly
DOB 4/2/02
GastroPLUS™
and Pulmon-EZ™
Abstract
A weanling
AQHA filly suffered from protein-losing enteropathy due to Bute
(phenylbutazone) toxicosis. She had been administered the Bute
following an adverse reaction to her routine vaccinations. She was treated by
several different veterinarians, and hospitalized two times. She
underwent various different treatments including plasma transfusions, hetestarch
transfusions, antibiotics (Naxcel, penicillin, and SMZ's), and pink bismuth. She
suffered from chronic diarrhea, dehydration, anorexia, severe colic episodes,
weight loss, high fevers and intermittent facial swelling. In addition to these
she also suffered from chronic upper respiratory disease. After 5 months of
illness, numerous vet bills, and various treatment regimens, a new veterinarian
was introduced to the case. After numerous diagnostic tests, the diagnosis was
protein-losing enteropathy. This filly began treatment with GastroPLUS™ and
Pulmon-EZ™. After 5 days treatment with GastroPLUS™,
this filly finally had a normal day and her progress continued from that point
on. 5 weeks later, Pulmon-EZ™ was added to the treatment regime for the
respiratory illness she had suffered from for months. Within 24 hours after
beginning Pulmon-EZ™, her cough and snotty nose cleared up. She continued
treatment with Pulmon-EZ™ for approximately 10 days. Treatment with a total of 4
bottles of GastroPLUS™ were used intermittently over a period of 7 months and
completed by September
24, 2003. As
of
March 14, 2004,
she still healthy and has begun ground training.
Case Study:
GastroPLUS™
and Pulmon-EZ™
On September 5,
2002, April, a weanling 5-month-old AQHA show filly was vaccinated with 4 ways,
flu/rhino, rabies, and West Nile Virus (WNV). The filly had been vaccinated at
birth, 3, and 4 months of age for all of the above except WNV, without any
adverse reactions. This was her first and only WNV vaccine. The day following
the vaccinations the filly's head, vaccination area, chest and legs were
significantly swollen. She had developed edema from her chest to along her
ventral line. She was unable to walk without pain, was off her feed, stopped
drinking, and had diarrhea. The treating veterinarian recommended 1 gm Bute
2x per day. On September
7, 2002, while
administering the Bute via
paste form, the ring slipped and an overdose of 6-7 grams was administered. The
filly developed diarrhea and stopped eating and drinking. Pedialyte, salt water
and Red Cell were given by the owner to avoid dehydration and help stimulate
her. On September 9,
2002,
the veterinarian examined the filly and in his opinion she was not dehydrated,
but prescribed probios paste to help stop the diarrhea. GastroGuard was also
prescribed but declined due to the high cost.
September
12, 2002, April was examined by another veterinarian who diagnosed "Bute
toxicity" and referred her to an equine hospital where she was placed in ICU.
Blood work determined that she was losing proteins rapidly, they were at 3.4.
(Normal is 5.2-7.9 g/dL). The WBC was also low. A small ulceration was detected
in the intestine but with no signs of perforation. She was treated with IV
fluids, 2-3 liters plasma and also hetastarch transfusions, antibiotic therapy
with Naxcel, and pink bismuth for the diarrhea. Hetestarch is a commonly used
colloid. It is produced by chemical modification of the starch amylopectin,
through hydrolysis and hydroxyethyl substitution, and is a modified branched
chain glucose polymer. April was given only a 20% chance of survival.
Between September 15 and September 22, 2002 Aprils
condition was up and down. The edema continued on her legs, chest and neck
areas. Euthanasia was mentioned at one point. By September
23, 2002
she was eating and drinking well on her own. Protein was up to 4.0, and sodium
up to 137 (normal is 136-142 mEq/L). The following day September
24, 2002,
the filly had begun to develop pneumonia. Her protein dropped to 3.6 and her WBC
also dropped. More plasma and hetastarch transfusions were administered and
antibiotics were increased. By September
27, 2002, her
blood work was normal and the following day she was released to go home.
By 6 P.M.
on Aprils first day home, she became uncomfortable, bloated and gassy. Owner
administered Banamine and whisky and hand walking was done with some
improvement, but by 5 A.M.
she began thrashing and threw herself down, and was taken back to the ICU. IV's
were again administered, and numerous diagnostic tests were run. Her temperature
was 104 F and her proteins and WBC were way down. Surgery was contemplated, but
due to her extreme weakness was decided against. If she continued to worsen,
euthanasia was again to be considered. She received another plasma transfusion,
continued to improve and was discharged on October
5, 2002.
On October
22, 2002, April began swelling around her jowls, cheeks and chin. Hot packs
would reduce the swelling and the veterinarian suspected that her teeth were
bothering her and placed her on SMZ antibiotics. She developed a fever of 102 F,
her diarrhea resumed, and she became gassy again. She had tremors and chills,
was blanketed with 2 blankets and put under heat lamps. Banamine and whisky were
again administered. Her swelling and fever continued and the treating
veterinarian thought she may have a tooth abscess and wanted her to continue
antibiotics. Another veterinarian felt she was too young for teething problems
and felt she had developed the flu, he recommended penicillin. The swelling,
low-grade fevers, diarrhea and gassy spells were intermittent through the month
of November. By December, the fevers had subsided, but the chronic swelling of
her face, cheeks, throat and jowls, and the soft stool continued through
December and into the middle of January 2003.
January 9,
2003, when April tried to exercise herself, she developed a cough and snotty
nose.
January 19,
2003, the fillies snotty nose worsened and she began to have the chills again. A
new veterinarian was called in. He suggested the following tests: Glucose
absorption test to test for juvenile diabetes; malabsorption tests; anti-nuclear
work up; CBC, and an intestinal biopsy (not feasible due to cost). He also
wanted to test proteins and Albumin levels. The above tests were performed and
the diagnosis was Protein Losing Enteropathy. He recommended ulcer medication,
and in 4-6 months re-run CBC and ANA tests.
On January 26,
2003, Aprils' owner ordered GastroPLUS™ for the treatment of gastric ulcers.
On February
4, 2003, her snotty nose was still present and she began treatment with Naxcel
12cc 2x per day, to aggressively combat the respiratory infection.
February 5,
2003, April began treatment with GastroPLUS™, at 45cc oral 2x per
day. That evening before the initial dosing, the filly's symptoms were still the
same, snotty nose and chin swollen. The following morning no swelling
was present, and she was dosed again. But by evening her jowl and chin
were swollen again. After dosing with GastroPLUS™ in the evening, the swelling
was down within 2 hours.
February 6,
2003, her swelling episodes were reduced and after dosing with GastroPLUS™ the
swelling would be eliminated. On February 8, 2003, AM, her head was completely
swollen. After dosing with GastroPLUS™ the swelling was down within an
hour. That evening she was found down, suffering from chills and tremors,
swelling was back and she was not eating. Again she was dosed with GastroPLUS™
and by 9 P.M. she no longer had the chills, and her swelling was gone. She had
some swelling around her chin and jowls and again after dosing with GastroPLUS™
the swelling was gone.
February 9,
2003, was the last day of treatment with the antibiotic Naxcel.
February 10,
2003, her fifth day on GastroPLUS™, was her first completely normal day. The
following day she finally had normal stool for the first time since Sept.
6, 2002.
While April
was responding favorably to the GastroPLUS™, and showing signs of recovering,
she still had a way to go. When the dosages of the GastroPLUS™ were reduced from
45cc powder to 30cc powder on February
13, 2003, she
began to show some slight swelling again, and also began a golf ball size lump
in her throat. Her respiratory illness continued to be a problem in spite of the
Naxcel she had received for 6 days. Even though she still had the snotty nose,
by February 15, 2003, she was very bright and beginning to show an
attitude. April started getting some exercise and turn out time. April was
improving very well, and had more normal days than not, with her energy level
increasing. Swelling was infrequent now, but the snotty nose would keep
reappearing.
By February 27,
2003 she appeared normal, attitude was good, swelling diminished, stools normal,
but she had started to develop a cough. It worsened and her snotty nose
continued.
On March 15,
2003, Pulmon-EZ™, another nitric oxide delivering product was added to her treatment regime. Pulmon-EZ™ uses nitric oxide
precursors to support lung function and to help combat chronic respiratory
disease. April had not been able to shake this respiratory illness that began on
January 9, 2003,
even though she had been on Naxcel and penicillin several times over the
previous months.
April began
Pulmon-EZ™ in addition to GastroPLUS™ on March 15,
2003,
and her respiratory illness, snotty nose and chronic coughing ceased by the next
day.
April remained
on Pulmon-EZ™ for less than 2 weeks, as
her symptoms were
relieved immediately. She remained on GastroPLUS™ and was gradually weaned off
of that product. First by lowering the dosages, then decreasing the frequency of
doses. By May 18,
2003, she was dosed with GastroPLUS™ every other day and then only twice a week.
She has not had any GastroPLUS™ since September 24, 2003. Every so often she
will have a little swelling in her jowls, or some softer stool. Overall April is
now in very good health. With everything the owner has been through she found
that in addition to successfully treating her internally with GastroPLUS™ and
Pulmon-EZ™, that her feeding has also been a factor in Aprils condition. Coarse
hay is not well tolerated, so only fine stem hay is fed to April. April and all
the others at this facility owned by Vicki Spina- Maraugha are very well cared
for, and follow a strict de-worming and vaccination program.
Protein
losing enteropathy is a disease affecting the gastro intestinal system resulting
in protein loss when the epithelial cell barrier is lost due to mucosal
ulceration, or when interstitial edema disrupts the tight junctions between
epithelial cells. Protein-losing enteropathy has most commonly been associated
with mucosal absorptive defects such as granulomatous enteritis, eosinophilic
gastroenteritis, gastrointestinal neoplasia (lymphosarcoma, and squamous cell
carcinoma), intestinal parasitism, acute salmonellosis, congestive heart failure
and NSAID toxicity. Aprils' Protein-losing enteropathy is thought to have been
caused from NSAID toxicity, the Bute
overdose she received when the plastic ring slipped on the paste Bute
she had been administered. Bute was
prescribed to try and relieve the pain and swelling caused by the reaction to
her vaccines. According to research, severe intestinal protein loss from mucosal
ulceration resulting from NSAID toxicity is caused from high doses of
phenylbutazone (Bute) or other NSAIDs given over a period of several days.
Experimentally, hypoproteinemia has developed in horses even when a standard
dosage of NSAIDs has been administered. The implication is that stress and
dehydration increases the susceptibility of the horse to the adverse affects of
NSAIDs. April was already experiencing diarrhea, and was quite possibly
dehydrated before the Bute was administered.
Experimentally induced Bute
toxicosis in ponies produces ulcerations in the mucosa of the tongue, gingiva,
hard palate, stomach, small intestine and the colon. Gastric ulceration induced
by NSAIDs involves increased gastric mucosal permeability to hydrogen ions,
inhibition of mucus synthesis, and decreased gastric mucosal blood flow.
There
is growing evidence in humans that NSAID toxicity (example: ibuprofen) increases
permeability of the small and large intestinal mucosa by damaging the
intercellular junctions. Bacterial invasion of the submucosa after damage to the
mucosal barrier appears to be important in the pathogenesis of the ulcerative
lesions.
Phenylbutazone (Bute)
toxicity has been thought to be a cause of protein-losing enteropathy
attributable to extensive ulceration of the right dorsal colon. Gross
examination has revealed severe diffuse ulceration and congestion of the tunica
muscuilaris. Fibrinonecrotic debris partially covers the ulcerated mucosa.
Microscopic examination reveals a mixed population of inflammatory cells and
fibroblast proliferation. It is postulated (a set of criteria for judging
whether a given bacterium is the cause of a given disease) that small ulcers
form initially and are then invaded by colonic bacteria. Mucosal regeneration is
impaired and a chronic active disease results.
Clinical
signs usually associated with protein-losing enteropathy include: lethargy,
exercise intolerance, weight loss, diarrhea, intermittent colic and dependent
edema. The edema is secondary to low plasma oncotic pressure caused by
hypoalbuminemia. Anorexia, depression and weight loss are the most common
clinical signs when gastric sguamous cell carcinoma is present. Acute colic and
clinical signs of endotoxemia sometimes occurs in protein-losing enteropathy
caused by NSAID toxicity or severe intestinal parasitism.
Laboratory
findings: Hypoalbuminemia with decreased, increased or normal plasma globulin
concentrations characterizes the plasma protein changes in protein-losing
enteropathy. Because hyperglobulinemia occurs in many different gastrointestinal
diseases, total plasma protein concentrations are often normal. Quantitation of
protein fractions is an important laboratory evaluation when protein-losing
enteropathy is suspected. With horses suffering from granulomatous enteritis,
early intestinal protein loss involves relatively greater quantities of albumin
than globulins, whereas all protein fractions may be lost in the later stages of
disease.
Recommended
treatments for protein-losing enteropathy involve managing the primary disease
and/or treatment of hypoproteinemia. Plasma transfusions are necessary when
total protein concentration decreases below 4g/dL. It must be realized that
continued protein losses tend to decrease the efficacy of the plasma
transfusion. NSAID therapy should be discontinued if hypoproteinemia or signs of
gastrointestinal disease are noted. For NSAID toxicity, broad-spectrum
antimicrobial drugs can help. Cimetadine (Tagamet) and other histaminergic
receptor antagonists allow the body's own healing process of the gastric ulcers, but do not treat
protein-losing enteropathy. It is advisable for horses receiving Cimetidine to
be monitored for kidney and liver functions. In rare cases in humans receiving
this drug, decreased white blood cell or platelet counts were also reported.
Sucralfate (Carafate) will also help promote the body's own healing process of the gastric ulcers, and
may increase production of prostaglandin E. Sucralfate is poorly absorbed, and
also binds to and partially prevents absorption of some drugs like ranitidine
and cimetidine, some oral antibiotics, phenytoin, and digoxin. Surgical
resection of the affected portion of the right dorsal colon for ulcerative
colitis has been recommended in some cases. The prognosis for horses with severe
NSAID toxicity and right dorsal ulcerative colitis is guarded whether or not
surgery is performed. Dietary management consisting of feeding pellets and
restricting roughage may benefit some horses suffering from protein-losing
enteropathy. Treatment of granulotamous enteritis with corticosteroids,
salicylazosulfapyridine, azathioprine, and isoniazid has been attempted without
success, and the prognosis for recovery is poor.
GastroPLUS™ was not only created to help increase
necessary mucus to line and coat the stomach and intestinal linings to allow
the body's own healing process. More importantly GastroPLUS™ helps provide crucial nitric oxide
formation. Studies have shown that insufficient amounts of nitric oxide will
allow the intestinal walls to become damaged, and to possibly perforate. These
same studies have also shown that by increasing nitric oxide that the intestinal
walls not only heal, but also become resistant to damage.
One study done at the
University of Calgary in 1995 states that with sufficient nitric oxide, they
were unable to damage the intestine. This same study also addressed the question
of possibly dosing with too much nitric oxide, and would it be harmful? This
study concluded that nitric oxide is necessary, and excessive amounts of nitric
oxide are not considered harmful, but instead are beneficial.
The researcher who
headed these studies was Paul Kubes Ph.D. Dr. Kubes was awarded the 1995
Gastroenterology Young Investigator Award from the American Gastroenterology
Association for this CCFC funded work. The
University
of Calgary and Assistant Professor Paul Kubes PhD also received new funding from
the CCFC to continue this work for 1996-1999 for the role of iNOS in models of
Inflammatory Bowel Disease.
Testimonial
from Vicki Spina-Maraugha, owner of April:
In August
2002, our filly April was given the West Nile Virus shot to comply with our 4-H
State show rules. Within hours of receiving the shot, she began to swell
throughout her head. By the next morning, her entire head was swollen, along
with her legs and the underline of her belly, plus a large lump in her chest.
Upon the next call to our vet, she was given a regimen of Bute, which
happened to be a toxic dose for a filly of this age (6 months). April was rushed
to the nearest equine ICU and given a 20/80 shot of survival, not in her favor.
After tons of medications, tests and an extraordinary amount of money were
expended, the vet suggested putting her down or placing her on Gastro Guard for
her ulcerated intestines, which happened to be $975 per month. I couldn't see
spending the money that I didn't have on a 20/80 shot, nor did I want to put her
down, so she was brought home. I used home remedies such as Pepto Bismol to coat
her stomach while I searched the Internet for solutions. I then found the web
site for GastroPlus, and began to email my story and shortcomings to its
owner. At that time, he suggested his product, GastroPLUS™, which was more cost
efficient and offered money back guarantee, so I couldn't really lose anything.
After 2 weeks on this product, April began to eat a whole portion of her feed
and finish it, along with improving in brightness and had limited swelling. I
used this product for approximately 7 months and now April is living a healthy,
normal life, with very few problems. With a corrected high fiber diet and an
occasional dose of GastroPLUS™ to keep her levels up, she is now being started
into training.
March 22,
2004
Vicki
Spina-Maraugha
Scenic View
Acres
Adah,
PA
References:
GastroPLUS™
and Pulmon-EZ™
Vicki
Spina-Maraugha "Aprils Daily Diary"
Susan Clark
Eades, DVM, PhD, Dipl ACVIM "Equine Medicine and Surgery" fifth edition
"Diseases Affecting Plasma Proteins"
William P.
Hay, DVM, Dipl ACVS and P.O. Eric Mueller, DVM, PhD, Dipl ACVS and Janice E.
Sojka, VMD, MS, Dipl ACVIM "Equine Medicine and Surgery" fifth edition "Diseases
of the Small Intestine"
Paul Kubes
PhD CCFC Journal-fall 1996- Epithelial Permeability in the Healthy and Inflamed
Intestine
Eleanor M.
Kellon, VMD "Equine Drugs and Vaccines"
K. Gary
Magdesian, DVM, Dipl ACVIM and ACVECC "Colloid Replacement in the ICU"
"Clinical Techniques in Equine Practice", Vol 2 (June) 2003 pp 130-137
|
GastroPLUS™
2 lb. Tub
(30 day supply) $169.90
|
Pulmon-EZ™
2 lb. Tub
(30 day supply) $169.90
|
|
1.JPG)
