GI hemorrhage (Proceedings)

Causes and Specific Therapy - Hemorrhage in the gastrointestinal tract may have a number of different pathogenetic mechanisms. Specific therapy for gastrointestinal hemorrhage will depend upon the etiopathogenesis as well as the site of hemorrhage.

Nasal Disease. Causes of epistaxis include systemic processes (quantitative and qualitative platelet disorders, coagulation factor abnormalities, polycythemia, and hypertension) and local processes (neoplasia, foreign bodies, inflammation, infection, and trauma). Disorders of epistaxis are not true disorders of gastrointestinal hemorrhage; instead, affected animals manifest G.I. hemorrhage as a result of swallowing blood emanating from the nasal cavity.

Oropharyngeal Disease. Diseases of the oral and pharyngeal cavities most frequently associated with hemorrhage include severe periodontal disease, foreign bodies, trauma, and neoplasia. The diagnosis and treatment of these disorders are usually straightforward.

Esophageal Disease. Esophageal foreign bodies should be removed promptly. Prolonged retention increases the likelihood of esophageal mucosal damage, ulceration, and perforation. Endoscopic retrieval should be the initial approach, but some foreign bodies may require surgical removal. Followup treatment in severe cases may include gastrostomy tube feedings, oral sucralfate suspensions (0.5-1.0 grams PO TID), and broad spectrum antiobiotics. Esophageal neoplasia are usually malignant and well-advanced at the time of diagnosis. Chemotherapy, radiation therapy, and surgical resection are the only treatment options. The prognosis is very poor for cure or palliation. Esophagitis is an acute or chronic inflammatory disorder of the esophageal mucosa that may also involve the underlying submucosa and muscularis. Regurgitation is the most important sign in cats and dogs with esophagitis. However, severely affected animals may also manifest excessive salivation, dysphagia, painful swallowing and frank hematemesis.

Gastric Disease. Gastric ulcer is the most important cause of gastric hemorrhage. Most cases of gastric ulcer are associated with drug administration (NSAIDs, corticosteroids), systemic and metabolic disease (e.g. uremia, liver failure, hypoadrenocorticism), and toxicity. The pathogenesis of ulcer in these cases likely involves acid/peptic injury as well as disruption of the gastric mucosal barrier. Although occasional ulcers result from large increases in acid secretion (e.g. gastrinoma and mastocytosis), and acid and peptic activity is critical to the formation of ulcers, ulcers generally develop only when mucosal defense is also perturbed. Thus, drugs, systemic and metabolic disease, and toxicity must somehow interfere with the defense mechanisms of the gastric mucosal barrier. The defense mechanisms contributing to the mucosal barrier include mucosal bicarbonate and mucus secretion, epithelial cell renewal and restitution, mucosal hydrophobicity, mucosal blood flow, and mucosal prostaglandins. Disruption of one or more of these components permits acid and pepsin back diffusion into the mucosa and submucosa. Treatment of gastric ulcer includes specific (e.g. treatment of kidney failure or hypoadrenocorticism) and non-specific therapy.

Small Intestinal Disease. The diagnostic evaluation, causes and specific therapy of small intestinal hemorrhage are similar to those associated with gastric hemorrhage.

Large Intestinal Disease. Idiopathic colitis or inflammatory bowel disease is an important cause of lower gastrointestinal hemorrhage in many parts of the United States. It may occur as a distinct entity or in conjunction with inflammation of the small intestine. There are likely many inciting causes of inflammatory bowel disease, including infection, toxicity, immunologic reactions to foreign substances, and neoplasia.

Gastrointestinal Ischemia. Except for intussusception and gastric dilatation/volvulus syndrome, ischemic events are uncommon causes of gastrointestinal hemorrhage. Mesenteric volvulus, mesenteric thrombosis/infarction, and mesenteric avulsion are all associated with a poor prognosis.

Systemic Disease. Gastrointestinal hemorrhage may be associated with a number of systemic diseases, including: liver disease, acute pancreatitis, systemic hypertension, mastocytosis, septicemia and DIC, neoplasia and DIC, hypoadrenocorticism, Rocky Mountain spotted fever, and Ehrlichiosis. All of these entities should be considered in the initial medical investigation of gastrointestinal hemorrhage. Recognizing and treating the underlying primary disease will usually resolve the gastrointestinal hemorrhage.

Coagulation Disorders. Gastrointestinal hemorrhage may occur as a consequence of platelet deficiency (thrombocytopenia), platelet defects (thrombocytopathia, myeloma), coagulation factor deficiency (genetic disorders, liver disease, anticoagulant rodenticide toxicity), or mixed coagulation disorders (DIC).

Non-Specific Therapy

Specific therapy is designed to treat the primary underlying disease, but it will not sufficiently address all problems associated with acute gastrointestinal hemorrhage. Non-specific therapy should also address: a) ongoing bleeding; b) anemia, hypoproteinemia, and thrombocytopenia; c) fluid and acid/base disturbances; d) ulcer; e) bacterial translocation; and f) gastrointestinal perforation.

Ongoing bleeding

Vitamin K - Vitamin K1 (AquaMephyton-10 mg/ml; Mephyton-5 mg tablets) should be administered if there is any suspicion of anticoagulant rodenticide toxicity, intestinal lipid malabsorption (e.g. lymphangitis), or liver disease. Doses should not exceed 5 mg/kg BID.

Surgery - Surgical removal of an ulcer is indicated if the animal is at risk for exsanguination, as determined by serial evaluations of hematocrit and cardiovascular status.

Anemia/Hypoproteinemia/Thrombocytopenia

Packed red blood cells - The most important indication for the transfusion of packed red blood cells is the acute or chronic anemia patient with normal serum protein and coagulation parameters. Whole blood transfusions may be not be needed if plasma proteins and plasma volume are otherwise normal. Doses of packed red blood cells should not exceed 5-10 ml/kg, and the animal should be monitored for circulatory overload. Packed cells should be re-constituted in 0.9% saline and filtered through a 20µ micropore filter to avoid dissemination of microemboli. Cross matching prior to transfusion is recommended. Immediate transfusion reactions may be manifest as fever, shivering, urticaria, hyperemia, vomiting, and/or diarrhea; delayed transfusion reactions (usually immunologic) may occur 2-21 days after transfusion of packed red blood cells.

Fresh plasma or fresh frozen plasma - Fresh or fresh frozen plasma contains clotting factors and oncotically active plasma proteins (mostly albumin). Therefore, fresh or fresh frozen plasma should be used to treat animals with coagulopathy (e.g. hemophilia, anticoagulant rodenticide toxicity, liver disease, and DIC) and hypoproteinemic disorders. Doses of 10-20 ml/kg are transfused as needed at a rate not exceeding 4-5 ml/min. Animals should be monitored for hyperproteinemia and hypervolemia following transfusion. Immediate allergic reactions may be manifest as facial edema, pruritus, urticaria, dyspnea, vomiting, and diarrhea.

Whole blood - Fresh whole blood transfusions will replace the cellular and plasma components of whole blood, as well as the immunoglobulins and clotting factors. Whole blood transfusions should be considered in animals with anemia, hemorrhagic shock, thrombocytopenia, thrombocytopathia, or combined hemostatic disorders. Initial doses should not exceed 10-20 ml/kg with a transfusion rate of 4-5 ml/min. Higher transfusion rates (5-10 ml/min) can be used if the patient is actively hemorrhaging.

Colloids - Hetastarch (Hespan 6% in 0.9% NaCl) and dextrans (Dextran-70 6% w/v in 0.9% NaCl) may be used to elevated oncotic pressure in hypoalbuminemic patients if plasma is not readily available. Dose rates should not exceed 20 ml/kg/24 hours.

Fluid, Electrolyte, and Acid/Base Disturbances

Severe gastrointestinal hemorrhage will likely result in serious fluid, electrolyte, and acid/base disturbances. The goal of fluid therapy is to restore the volume and composition of body fluids to normal and, once this is acheived, to maintain external fluid and electrolyte balance so that input by treatment matches fluid losses. Electrolyte solutions can be divided into replacement and maintenance solutions. Replacement solutions provide 130 to 147 mkEq/L of sodium, similar to values in the extracellular fluid. Maintenance electrolyte solutions provide 40 to 77 mEq/L of sodium, about one-half or less of values in the extracellular fluid. Replacement fluids that are available include lactated Ringers, Ringers, normal saline (0.9% NaCl), and Normosol R solutions; maintenance solutions include 2.5% dextrose in 0.45% NaCl, 2.5% dextrose in half-strength lactated Ringers solution, Normosol M, and Normosol M in 5% dextrose. Supplementation of replacement fluids may be required to correct acid/base imbalance and potassium deficits, particularly in animals suffering from vomiting and/or diarrhea. Animals suffering from severe blood loss and hypovolemic shock require immediate rapid intravenous fluid treatment to restore intravascular volume and tissue perfusion. In the absence of cardiopulmonary disease, intravenous fluids can be safely administered to dogs and cats at 90 ml/kg/hr. Animals with mild volume depletion can be treated with lower fluid rates (10-20 ml/kg/hr, as needed).

Ulcer Management

It may be difficult, if not impossible, to determine the pathogenesis of gastric ulcer in an individual animal. Most cases will likely result from the combined effects of acid injury and disruption of the gastric mucosal barrier. Therefore, acid suppression and stimulation of the gastric mucosal defense mechanisms are the cornerstones of treatment.

Antacids - The best antacids, e.g. aluminum hydroxide and magnesium hydroxide, react chemically with gastric acid to produce the conjugate chloride salt and water: Al(OH)3 + 3 HCl → AlCl3 + 3 H2O, and Mg(OH)2 + 2 HCl → MgCl2 + 2 H2O. Antacids are very effective in neutralizing gastric acid, but frequent administration is required because of ongoing acid secretion. Indeed, rebound acid hypersecretion may occur with some antacid formulations. The use of this classification of drugs should probably be limited to animals with mild gastritis and gastrointestinal hemorrhage.

Diffusion Barriers - Sucralfate is a cytoprotective drug composed of sulfated sucrose and polyaluminum hydroxide. In the acidic environment of the stomach, sucralfate is extensively cross-polymerized to form a viscous gel that binds to the necrotic tissue proteins in an ulcer. In addition to acting as a diffusion barrier, sucralfate may have additional beneficial effects, i.e. stimulation of prostaglandin production, adsorption of bile salts, and inactivation of gastric pepsins. Sucralfate is a very effective drug in the treatment of gastric ulcer, either alone or in combination with other gastric anti-secretory drugs (e.g. histamine H2 receptor antagonists, H+ ,K+ ATPase inhibitors). In vitro studies of sucralfate activation and histamine H2 receptor antagonist absorption have suggested that the two drugs should be administered independently, e.g. 30 minutes apart. It is still unclear whether this is true of the whole animal.

Histamine H 2 receptor antagonists - This group of drugs (cimetidine-Tagamet, SmithKline Beecham; ranitidine-Zantac, Glaxo; famotidine-Pepcid, MerckSharp & Dohme; nizatidine-Axid, EliLilly) inhibits gastric acid secretion by antagonizing the histamine H2 receptor on gastric parietal cells. All are very effective in the treatment of gastric ulcer disease in dogs and cats. There is no good evidence to suggest that one drug is more efficacious than any other member of the same drug classification. The histamine H2 receptor antagonists are remarkably safe and effective in treating gastric ulcer. Cimetidine and ranitidine bind to the hepatic cytochrome P-450 enzyme system and can interfere with the clearance of drugs (e.g. acetaminophen, theophylline, coumadin) metabolized by this route.

Acetylcholine M 1 receptor antagonists - Pirenzepine, a selective M1 cholinergic antagonist, selectively inhibits cholinergicially-mediated gastric acid secretion without significant effects on other muscarinic receptors (M2, M3) that mediate gastrointestinal, airway, and urinary bladder smooth muscle contraction. Pirenzepine is available in Canada and Europe, but not the United States.

H +,K + ATPase inhibitors - The substituted benzimidazoles (e.g. omeprazole, Prilosec-MerckSharp & Dohme), inhibit gastric acid secretion by irreversibly binding the proton transporting enzyme at the luminal surface of the parietal cell. Omeprazole inhibits gastric acid secretion in the dog for 24 hours following administration of a single dose (0.7 mg/kg PO). Omeprazole is as effective as cimetidine in healing mechanically-induced ulcers, but it is more effective than cimetidine in the treatment of aspirin-induced gastritis. Additional studies will be needed to determine the comparative efficacy of these drugs in the treatment of other gastric pathology.

Prostaglandin E 1 analogues - Endogenously produced prostaglandins promote gastric mucosal defense mechanisms by inhibiting parietal cell acid secretion, and by stimulating mucosal blood flow, bicarbonate secretion, mucus secretion, and epithelial cell renewal. Nonsteroidal antiinflammatory drugs (NSAIDs) inhibit this endogenous prostaglandin production and place animals at increased risk for gastritis, gastric erosion, and gastric ulcer. Synthetic analogues of prostaglandin E1 (misoprostol-Cytotec, Searle) diminish the pathology produced by aspirin and other NSAIDs. Thus, prophylaxis against gastric mucosal injury induced by NSAIDs is the primary indication for misoprostol usage.

Bacterial Translocation - Animals with mucosal disruption and severe gastrointestinal hemorrhage are at increased risk for intestinal bacterial translocation and sepsis. Parenteral, broad spectrum antibiotics (e.g. cephalosporins, aminoglycosides) should be used during episodes of acute gastrointestinal hemorrhage.

Gastrointestinal Perforation - Surgical removal of an ulcer is indicated if the animal is at risk for perforation (determined endoscopically) or if the animal has not responded to appropriate medical therapy that has been administered for at least 7-10 days. Exploratory laparotomy is clearly indicated if the patient develops abdominal pain and septic effusion.

References available upon request