David C. Twedt, DVM, DACVIM
Vomiting is a common clinical sign in small animals. Although vomiting is a protective mechanism developed to remove ingested noxious substances, it is also associated with many disease conditions. A few of those diseases include disorders of the gastrointestinal system, other abdominal conditions, systemic or metabolic disease, and drug toxicity. Severe vomiting can result in serious consequences, such as volume depletion, acid-base and electrolyte disturbances, esophagitis, aspiration pneumonia, and malnutrition. Following is an overview of the pathophysiology, potential causes, antiemetic therapy, and a logical clinical approach to the chronic vomiting canine patient.
Components of Vomiting
Vomiting is a reflex act that is initiated by stimulation of the conceptualized "vomiting or emetic center" located in the medulla oblongata of the brain. Activation of the vomiting center occurs either through a humoral pathway, initiated via bloodborne substances, or by activation through various neural pathways leading to the vomiting center.
Neural stimulation of the vomiting center arises through either vagal afferent, sympathetic, vestibular, or cerebrocortical pathways. Activation of peripheral receptors (via inflammation, distention or stretching) found throughout the body can stimulate these neural pathways. Disease of the gastrointestinal tract, other abdominal organs, or peritoneum can directly stimulate vomiting through vagal afferent pathways. The vomiting center is also stimulated by activation of the chemoreceptor trigger zone (CRTZ) located in the area postrema. In this area the blood-brain barrier is limited, which allows the CRTZ to be exposed to chemical stimuli found in the circulation. Vestibular stimulation in the dog passes through the CRTZ before activating the vomiting center.
Antiemetics are drugs used to control nausea and vomiting. Antiemetic drugs should be administered because they aid in controlling nausea and vomiting, make the patient more comfortable, and may actually return the dog to an earlier state of positive nutrition. Antiemetics are also indicated in cases of serious fluid and electrolyte loss with dehydration or when there is fear of aspiration pneumonia. Antiemetics should not be given if the patient has a GI obstruction (as it may mask signs and delay a diagnosis) for which surgery is indicated.
Antiemetic drugs can be classified as working centrally (in the CNS), peripherally (predominately vagal input), or a combination of the two.
Metoclopramide is a central antiemetic. At low doses it inhibits dopamine (D2) receptors and at higher doses inhibits serotonin (5HT3) receptors in the CRTZ. Cats are reported to have few CNS dopamine receptors and consequently metoclopramide may be a poor antiemetic choice. It also has effects on GI motility, albeit a poor prokinetic agent.
Serotonin antagonists work both centrally and peripherally by blocking 5HT3 receptors found on vagal afferent nerves, in the CRTZ, and vomiting center. Common drugs used include ondansetron and dolasetron. Another serotonin antagonist sometimes used in cats is mirtazapine.
Maropitant is a neurokinin 1 antagonist (NK1) that blocks receptors found in the emetic center, CRTZ, and in peripheral afferent nerves. Maropitant is a good broad-spectrum antiemetic approved for use in dog and cat. Our experience finds it very effective in preventing vomiting and nausea associated with chemotherapy, in management of parvovirus, pancreatitis, and many other causes of vomiting. Recent published studies in our lab found maropitant to have a significant effect in also blocking visceral pain in a dog model of ovarian ligament stretch.
Clinical Approach to the Vomiting Patient
When dealing with the vomiting patient, there are four key aspects to determine in the history: 1) Is the patient actually vomiting? 2) A detailed vomiting record, 3) A drug and diet history, and 4) Other signs associated with the vomiting.
The history should confirm that the patient is truly vomiting and that the signs described are not associated with gagging, coughing, dysphagia, or regurgitation, all of which may be confused with vomiting by the client. In some cases, the distinction may be challenging to differentiate based on history alone.
The history should then focus on the actual vomiting episodes. There are 5 important things one must obtain in the history: 1) the duration, 2) the frequency, 3) character of the vomit, 4) association with eating or drinking and 5) prior treatments that may have been given.
A dietary history, including the type of diet or a recent diet change, is equally important because vomiting can be associated with an adverse reaction to food. Vomiting in the immediate postprandial period may suggest a food reaction. Vomiting undigested or a partially digested meal, especially when the vomiting occurs more than 6 to 8 hours following eating (a point at which the stomach should normally be empty), suggests a gastric outflow obstruction or a primary gastric hypomotility disorder. Gastric outflow obstructions occur because of foreign bodies, mucosal hypertrophy, tumors, or polyps. Vomiting of bile-tinged fluid, especially in the early morning, often results from enterogastric reflux syndrome. The presence of blood in the vomitus, either as fresh "bright red" blood or digested blood that has a "coffee grounds" appearance, indicates gastrointestinal erosion or ulceration. Hematemesis with metabolic-related ulcers, such as is seen with hypoadrenocorticism or uremia, drug-induced ulceration, gastritis, or gastric neoplasia, are possible causes.
A complete physical examination may provide important information. A rectal examination provides characteristics of colonic mucosa and feces. Melena suggests upper gastrointestinal bleeding, and the presence of foreign material in the feces helps support a foreign-body diagnosis. Patients with colitis or severely obstipated animals often vomit.
The history, physical examination, and basic laboratory findings should direct the clinician to a diagnosis or to the next step in the workup. Because most cases of acute vomiting are associated with "garbage gut" and few to no diagnostics are required, a response to symptomatic therapy confirms the diagnosis. In severe cases or in patients with chronic vomiting, laboratory diagnostics are indicated and should include a minimum database (complete blood cell count, biochemical profile, and urinalysis), fecal examination, and abdominal radiographs. This basic evaluation is essential to excluding all nongastrointestinal causes of vomiting. If no abnormalities are identified, then chronic vomiting patients should next be classified as having mild disease with minimal debilitation. Those patients with a considerable vomiting history should be classified as having serious or a debilitating condition. Animals with mild disease are generally treated symptomatically first. If they fail to respond to symptomatic therapy, then they require an in-depth diagnostic workup. Patients having significant or serious disease require an in-depth diagnostic workup, with emphasis on the gastrointestinal tract, including contrast studies, ultrasound examination.
Animals with mild signs and minimal debilitation should first undergo dietary manipulation with food trials and treatment for gastrointestinal parasites. These therapeutic trials are very appropriate in this classification of cases. Adverse reactions to food consist either of food allergies or food intolerances. Intolerances refer to direct reactions to a particular substance in the diet, such as a preservative or dye. An allergy is a specific immunologic reaction mediated against a protein antigen. Both can result in variable inflammatory gastric mucosal changes and vomiting. Dietary food intolerances are probably the most common cause of chronic intermittent vomiting. Most animals appear healthy and vomit intermittently, primarily food, shortly after eating. Removal of the causal agent often results in prompt improvement. Food allergies result from reaction to a specific protein antigen, usually the major antigen in the diet. Animals suspected of having food-related reactions should be placed on a hypoallergenic diet for a minimum 2-week trial as GI-related signs tend to respond within several weeks. No universal ideal diet exists, so various dietary trials may be required. If the patient is diet-responsive, then the response supports the diagnosis. There is evidence that many dogs having GI disease or IBD respond to hydrolyzed diets. Response rates as high as 50% are reported. It may actually not be what is in the hydrolyzed diets but rather what is not there as these tend to be free of "other stuff.'
Parasites must always be considered when dealing with chronic vomiting in animals that show little debilitation. Giardia sp., ascarids, and whipworms are diagnosed by using proper fecal examination techniques. Giardia need not only cause diarrhea but can cause nausea, and bilious vomiting. Physaloptera spp. infection in dogs is uncommon but may be underestimated due to the difficulty of diagnosis. Prevalence rates in the United States range from 1% to 25%. The worm burden needs not be large to cause clinical signs; in fact, it is not unusual to find only one or two worms causing significant clinical signs, including chronic intermittent vomiting. The adults produce few eggs and, because the eggs are larvated, they may not float during routine fecal flotation. Diagnosis is most frequently made during endoscopy simply by viewing the parasite in the stomach or proximal duodenum. When symptomatic therapy is indicated in a chronic vomiting case, anthelmintic trial therapy can rule out parasites as a cause. The author usually prescribes fenbendazole at 50 mg/kg daily for 3 to 5 days.
Another cause of chronic vomiting in the older patient is Helicobacter. The role of Helicobacter in gastric disease is uncertain because the bacteria are found in most normal dogs and cats. Some however have both Helicobacter sp. infection and concurrent gastritis. In these cases I will treat accordingly and many will improve. Current recommendations for treatment include combinations of metronidazole and amoxicillin with an acid-blocking drug given for 2 to 3 weeks. Other antibiotic combinations, such as clarithromycin (7.5 mg/kg/day) and amoxicillin, have also been used and some without acid blockage. If presented with a chronic vomiting patient with minimal clinical signs that has failed to resolve with diet and fenbendazole, I will consider a trial course of Helicobacter therapy before in-depth diagnostic testing especially if owner finances are somewhat limiting.
In-depth GI evaluation should be considered for the vomiting animal having significant or severe gastric or intestinal disease or in the patient that has failed to respond to adequate dietary, anthelmintic and Helicobacter therapy. Persistent vomiting, hematemesis, weight loss, and debilitation signify the need for further diagnostic evaluation. Diagnostic techniques for the stomach involve radiology, ultrasonography, endoscopy, surgery, or any combination. Radiology should be performed when a gastric lesion, foreign body, or outflow obstruction is suspected. In many cases I also investigate pancreatitis (PLI, ultrasound) and for typical or atypical hypoadrenocorticism (cortisol or ACTH stimulation).
Endoscopy offers the best means of examining the gastric mucosal surface and lumen and obtaining a gastric mucosal biopsy. When evaluating the vomiting patient, the author always obtains duodenal biopsies to rule out inflammatory bowel disease, performs gastric mucosal brush cytology for Helicobacter sp., and obtains a gastric mucosal biopsy sample to check a urea culture for Helicobacter sp.
If endoscopy is unavailable, then exploratory surgery and full-thickness biopsy may be indicated. The clinician should evaluate the entire abdomen, carefully noting the liver, pancreas, and small intestine. Full-thickness biopsy of the duodenum, jejunum, and ileum, in addition to the stomach, is always performed in patients with gastrointestinal signs.
Gastric disorders can be basically grouped into conditions of mucosal involvement, those causing gastric outflow obstruction, and gastric motility disorders. Inflammatory gastric mucosal disorders most commonly include lymphocytic-plasmacytic, eosinophilic, or granulomatous gastritis. These conditions are diagnosed by biopsy. Inflammatory gastric disease can occur in conjunction with inflammatory changes in bowel (IBD). Less common mucosal disorders include conditions causing gastric ulcerations, fungal disease, and neoplasia. GI lymphoma is common in cats usually with mucosal involvement.
Conditions that cause gastric outflow obstructions are most often associated with gastrointestinal foreign bodies or neoplasia. Antral-pyloric mucosal hypertrophy is an uncommon condition characterized by hypertrophy of the mucosa in the antral and pyloric regions of the stomach, which causes obstruction of gastric outflow. We tend to see this in older small-breed dogs. The syndrome is associated with chronic vomiting of food or gastric secretions, the diagnosis is made by identifying distinct mucosal folds in the antral region of the stomach and gastric retention on a barium contrast study. It is confirmed endoscopically finding large mucosal folds proximal to the pylorus. Therapy involves surgery (pyloric opening techniques) and generally has a good prognosis.
If inflammatory and obstructive gastric disorders have been eliminated, then gastric motility disorders should be considered. Most gastric motility disorders result in delayed gastric emptying, with gastric retention and vomiting. The vomiting may occur at any interval following a meal; however, the relationship to eating is important, as the normal stomach should be empty of a meal in approximately 6–8 hours (cats are usually faster). Vomiting of a meal more than 10 hours after eating is suggestive of abnormal gastric retention (obstructive or motility) as the primary disease or part of another disorder. Animals having hypomotility may respond to frequent small amounts of semi-liquid diets and gastric prokinetic agents, such as metoclopramide, cisapride, or erythromycin.
Bilious vomiting syndrome, or reflux gastritis, is a condition commonly observed in older dogs. It is generally associated with early morning vomiting of bile without food. The condition is thought to result from reflux of duodenal fluid into the gastric lumen, bile in the stomach, then gastric mucosal irritation and vomiting. Reflux may result from duodenal irritation (IBD or Giardia) or as a primary abnormal gastric motility disorder. Most dogs with this syndrome respond to a late bedtime meal. Food may buffer the bile or actually increase motility. If diet fails, then prokinetic agents with diet should be used. Prokinetic drugs include metoclopramide, cisapride, and erythromycin. Metoclopramide is a poor prokinetic and cisapride is the most potent. Erythromycin is a novel prokinetic that is effective. It binds to motilin receptors in the GI tract having a motilin-like effect (increasing GI motility). Pharmacologic dose (subantibiotic dose) of 0.5–1 mg/kg (usually in the evening) is used.
Vomiting is a common clinical sign in small animals and can result from many causes. Understanding the pathophysiology and potential etiologies, a logical clinical approach to the vomiting canine patient can be. The therapy is first directed at treating the inciting cause. Next, antiemetics may be given to control nausea and vomiting and in preventing further fluid and electrolyte loss. Often controlling the vomiting may return the dog to an earlier state of positive nutrition.