Managing patients with parvoviral enteritis (Proceedings)

Puppies and young dogs - parvovirus enteritis

Disease caused by parvovirus in dogs (destruction of intestinal crypt epithelium, lymphocyte depletion, neutropenia) is generally more severe than that caused by coronavirus (destruction of intestinal villi). Coronavirus enteritis is often characterized by mild and self-limiting clinical signs. Intestinal mucosal injury due to parvovirus is more extensive, involving both crypt and villous epithelium. A combination of secretory and malabsorptive diarrhea results. Sepsis occurs commonly in dogs with parvovirus due to absorption of preformed bacterial toxins and intact bacteria across the damaged intestinal epithelium. Bacteremia is more likely to occur in severely leukopenic animals. Sepsis occurs infrequently in dogs with coronavirus enteritis.

Treatment of acute infectious diarrhea in dogs (e.g., parvovirus enteritis)

Fluid therapy

Fluid replacement is one of the most important treatments for patients suffering from vomiting and diarrhea. Rate and route varies with each patient, but patients with hemorrhagic gastroenteropathy are often dehydrated at presentation and strong consideration must be given to intravenous fluid therapy. Restoration of an effective circulating blood volume is of primary importance in the management of hypovolemic and septic shock. Subcutaneous fluid administration provides slow, unreliable volume replacement, may induce hypothermia, and occasionally results in the formation of subcutaneous abscesses.

Initially, a buffered crystalloid solution such as lactated Ringer's or Normosol-R should be given, followed by fluids with glucose added (lactated Ringer's or Normosol-R with 5% dextrose) when dehydration becomes less severe (5-6%). Both lactated Ringer's and Normosol-R are mildly alkalinizing and may be beneficial in patients with metabolic acidosis, especially in animals with severe diarrhea. The buffer sources in Normosol-R are acetate and gluconate. An advantage of acetate and gluconate is that they do not require hepatic metabolism and they do not contribute to lactate levels.

The calculation of fluid requirements should be the sum total of: 1)daily maintenance requirements, 2)deficits due to dehydration, and 3)continued (contemporary) losses (vomiting and diarrhea). Generally, the average adult dog requires a maintenance volume of approximately 30 ml/lb body weight per day. Estimation of dehydration is at best crude, but is derived from an accurate history, physical examination, and laboratory data. Once calculated only 75-80% of this volume is replaced the first twenty-four hours with the remainder given the second day.

If the animal is in critical condition, a "shock dose" of fluids is often given the first hour and is roughly up to 40 ml/lb (in the first one to two hours).

Antibiotic therapy

Most cases of simple vomiting and diarrhea do not warrant any antibiotic therapy. However, patients with hemorrhagic gastroenteropathies should be given antibiotics because the severe intestinal mucosal inflammatory changes which occur allow the normal intestinal microflora to invade the intestinal mucosa and lead to septicemia. Antibiotics are specifically given to eliminate microflora invading the mucosa, to eliminate microflora causing septicemia, and to eliminate pathogens that have invaded.

Bacteria invading the mucosa to produce bacteremia are members of the normal intestinal microflora. Antibiotic treatment is directed against both groups of bacteria, the aerobes (especially Escherichia coli) and anaerobes (especially Bacteroides and Clostridium of bowel origin). The important source of the bacteremia is the anaerobes (outnumber the aerobes in the colon by 1,000 to 1). Penicillin is the most effective antibiotic against anaerobes invading from the colon.

If patients with hemorrhagic gastroenteropathy are only mildly ill, and have an adequate number of white blood cells, penicillins are a good initial choice. Amoxicillin (10 mg/lb IM or SC every 12 hours) or ampicillin provide adequate coverage. Cephalosporins also provide good coverage for both aerobic and anaerobic bacteria (10 mg/lb IV every 8 hours). Antibiotics should not be administered subcutaneously in dehydrated animals because the rate of absorption will be delayed.. Aminoglycosides can cause acute renal tubular necrosis. Maintenance of normal blood volume is essential when using aminoglycoside antibiotics.

Antiviral therapy - oseltamivir (tamiflu, roche laboratories) for parvovirus enteritis

Tamiflu is an antiviral drug used most commonly in humans with Influenza A and B. Tamiflu is a neuraminidase inhibitor. NA is an enzyme that is necessary for viral replication and penetration through mucus and respiratory secretions. In people, it prevents the secondary bacterial complications that occur with influenza (such as pneumococcal pneumonia) and also decreases viral replication resulting in a milder course of disease. We think it does the same thing in parvovirus, preventing the penetration of the virus into the gut and the resultant bacterial effects such as endotoxemia and shock, which are leading causes of death in parvovirus enteritis patients.

Clinical experience in shelter settings dating back several years showed potentially significant benefit when Tamiflu was used early along with basic supportive care (fluids, antibiotics, oral rehydration products). Pups that did not respond to basic care alone (no Tamiflu) often either died or were euthanized. When the human antiviral drug Tamiflu was added to the therapeutic regimen, survival rate improved. It is believed that there is truly very good potential for Tamiflu to become an accepted and recommended part of our treatment guidelines for severe parvoviral enteritis.

Early use of Tamiflu in parvo puppies may shorten hospitalization time. In a situation where one or more puppies from a litter are infected, it may be possible to prevent some of the puppies from getting ill by giving Tamiflu to the entire litter.

Recommended dose schedule: 1 mg/lb PO bid for 5 days. It is available as a liquid (12 mg/ml when reconstituted). It is also available in 75 mg capsules, but in most cases we will be using the liquid.

To better insure that a vomiting patient will keep the Tamiflu down, I recommend administering it 30 minutes after a chlorpromazine injection (for antiemetic effect). Patients that are on metoclopramide CRI for control of emesis may also be able to keep the drug down without need for readministration.

Glucose

It is not uncommon for hemorrhagic gastroenteropathy patients to be hypoglycemic at or shortly after the time of presentation. Glucose is required in adequate levels for normal white blood cell migration and phagocytosis and for treatment and prevention of hypoglycemia occurring with septic or endotoxic shock. A bolus of glucose (1 to 2 gms/10 lb, or approximately 1 ml 50% dextrose per 4 lb), is given slowly IV at the start of therapy and then added to the fluids as a 5% solution as dehydration nears resolution. A bolus of 25% dextrose is preferred over a 50% concentration because the latter is quite hypertonic and may induce vomiting.

Antiemetics

The most effective antiemetic drugs for viral enteritis patients are maropitant (Cerenia), chlorpromazine, or the prokinetic drug metoclopramide. Ondansetron and dolasetron are also very effective. See notes titled Pharmacologic Control of Vomiting elsewhere in this proceedings for details. Use of anticholinergic drugs (e.g., aminopentamide [Centrine], atropine) must be avoided.

Corticosteroids

Pharmacologic doses of glucocorticoids have been shown to have antishock effects in all forms of shock, especially septic. There is still no definitive evidence, however, to show that these agents improve overall survival. Beneficial effects include improved tissue perfusion, decreased leukocyte margination and perivascular leukocyte degeneration, and reduced absorption of endotoxins. It seems advisable at this time that corticosteroids should be administered as early as possible in a septic shock state. Dexamethasone sodium phosphate is administered at 1 to 2 mg/lb IV after an initial bolus of IV fluids is delivered. It may be necessary to repeat the dose at 8 to 12 hour intervals for 2 to 3 total treatments (decision based on patient response).

Potassium

Hypokalemia is a frequent occurrence in patients with anorexia, vomiting and diarrhea. Significant potassium losses also occur through the kidneys. As a result, potassium supplementation is a very important part of therapy for animals with hemorrhagic gastroenteropathies.

Early potassium supplementation is extremely important for successful management of dogs with severe parvovirus enteritis. Supplementation should be instituted before hypokalemia is detected because serum potassium concentration represents only a small fraction of total body potassium stores. Most patients receive 20 to 30 mEq per liter of fluids administered. Some dogs require supplementation at 40 mEq per liter.

Flunixin meglumine

Flunixin meglumine is a potent nonsteroidal antiinflammatory, analgesic agent that has antidiarrheal and antipyretic effects. It is believed to act by reducing the excessive production of prostaglandin synthetase. With regard to diarrhea, flunixin meglumine acts at the intestinal cellular level to decrease fluid production, gut fluid secretion, and mucus secretion. Flunixin meglumine also helps to reverse the severe intestinal inflammatory changes that occur with viral and bacterial enteritis, and is circulatory supportive in an endotoxic shock state. Effectiveness is improved if administered along with fluids, antibiotics, and corticosteroids. Flunixin is dosed at 0.5 mg/lb IV in dogs. Antiprostaglandin drugs such as flunixin meglumine have some potentially deleterious side effects. The most common appears to be GI ulceration and hemorrhage. Flunixin meglumine should not be administered more than once in a patient that has received corticosteroids.

Treatment of pronounced hypoproteinemia

Hypoproteinemia often develops rapidly in animals with severe diarrhea and small intestinal injury. Replacement of lost proteins by administration of fresh-frozen plasma may prove beneficial, especially when the total protein level drops below 3.5 g/dl. A plasma transfusion serves to both help in restoration of plasma oncotic pressure and to provide a source of immunoglobulins. Administration of fresh-frozen plasma from regularly immunized donor animals is a means of providing antibodies against circulating parvovirus. This is an effective means of neutralizing the virus in clinical patients. Use of fresh-frozen plasma may help reduce mortality in severely ill parvovirus enteritis patients.

A dose of 3 to 5 ml/lb of plasma is usually administered. This volume can be administered up to 2 times per 24 hours. An in-line filter is used to remove particulate material during plasma infusion. Plasma should be administered slowly for the first 10 to 30 minutes to monitor for signs of adverse reaction.

Intestinal parasite control

In addition to providing primary care for the sequelae of viral enteritis, it is important that any concurrent intestinal parasite problems be controlled as well. Intestinal parasitism, especially in puppies, can add significantly to the debilitation that viral or bacterial enteritis can cause. Fecal samples should be evaluated as early as possible for evidence of parasites (zinc sulfate with centrifugation). This should include using a Giardia antigen test to help improve diagnostic sensitivity for Giardia.

Anthelmintic drugs most commonly used include pyrantel pamoate (roundworms, hookworms) or fenbendazole (roundworms, hookworms, whipworms, and Giardia) at 22 mg/lb once daily for 3 to 5 consecutive days. For animals that are vomiting I prefer to use fenbendazole since it requires only one dose per day and has such a broad spectrum of activity (including Giardia).

Reflux esophagitis

Significant reflux esophagitis probably occurs in animals with persistent vomiting much more commonly than we recognize. Dogs with parvovirus enteritis that are debilitated and recumbent are especially at risk. Vomited fluid that is retained in the esophagus is not cleared adequately in weak and recumbent animals. As a result, the esophageal mucosa is bathed with gastric acid and activated enzymes that will cause mucosal injury. Because significant discomfort can result from esophagitis it is important that it be recognized and treated in a timely manner.

Treatment of esophagitis in animals with persistent vomiting includes use of an injectable histamine H2-receptor antagonist (e.g., ranitidine, famotidine), and a cytoprotective drug in suspension form (sucralfate). Metoclopramide is also beneficial because of its promotility (gastric emptying) effect and because it increases lower esophageal sphincter tone. H2-receptor antagonists are used to decrease gastric acid production, thereby decreasing acid volume available for reflux. H2-blockers also reduce the volume of gastric juice that is produced. I most often use famotidine at a dose of 0.25 mg/lb IV every 12 hours, if I am concerned about esophagitis being present.

Pain management for patients with parvovirus enteritis

Dogs with parvovirus enteritis, or any other cause of severe viral enteritis, can experience significant abdominal pain. Causes of pain include diffuse intestinal injury, cramping, and reflux esophagitis (described above).

Butorphanol will help provide relief in patients with mild pain and it also has some level of antiemetic activity. Buprenorphine is useful in patients with mild to moderate pain. Transdermal Fentanyl (Fentanyl patch) or injectable morphine (0.1-0.5 mg/lb every 6 hours SC or IM) or hydromorphone (0.05-0.2 mg/lb every 6 hours SC or IM) can be used in parvovirus enteritis patients that are experiencing moderate to severe abdominal pain. Notable changes in patient behavior that can be indicative of good pain relief often include more frequent assumption of a position of relief or comfort (less curling up, more laying out in a more extended or "sprawling" form), more effective antiemetic drug effects, and an earlier return of appetite. Butorphanol should not be given in conjunction with other opioids, including fentanyl, morphine, or hydromorphone, since it is a partial antagonist. It must be noted that both human and animal patients that receive the benefit of effective analgesia often have lower morbidity and mortality.

The antiemetic drug maropitant (Cerenia) also provides visceral analgesic effect and this adjunctive weffect, when given in conjunction with opioids to control pain, effect makes it a very versatile drug for use in management of patients with severe viral enteritis that experience both vomiting and abdominal pain.

When a fentanyl patch is placed on a patient that is already in significant pain, morphine or hydromorphone are administered every 6 hours for 24-36 hours, so that the patient receives adequate analgesia while awaiting achievement of effective blood levels of fentanyl from the patch.

Summary

Successful management of dogs with severe parvovirus enteritis requires a multifaceted treatment approach, a hospital staff that is dedicated to high detail patient care, and a committed pet owner. The success rate is very high when all of these factors are present.