Motility Disorders

Vol. 19, No. 6 June 1997

Continuing Education Article

V N E W ! C O N T I N U I N G E D U C AT I O N S E R I E S

Refereed Peer Review

FOCAL POINT ★Disorders of gastrointestinal motility are a common cause of gastroenterologic disease in dogs and cats.

KEY FACTS ■ Motility disorders can be mechanical or functional in origin. ■ Examples of functional motility disorders of the esophagus include idiopathic megaesophagus, dysautonomia, hiatal hernia, esophagitis, and gastroesophageal reflux. ■ The following are functional motility disorders of the stomach: infection, inflammation, postgastric dilatation–volvulus, ulcer, and idiopathic disease. ■ Functional motility disorders of the intestine include infection, inflammation, postoperative ileus, and idiopathic and inflammatory bowel disease. ■ Examples of functional motility disorders of the colon are feline idiopathic megacolon and inflammatory bowel disease.

Successfully complete the quizzes at the end of each CE article in this series, and receive a certificate indicating completion of a course of study in Gastrointestinal Prokinetic Therapy. This is the fifth of five articles.

Diagnosis and Management of Gastrointestinal Motility Disorders in Dogs and Cats University of Pennsylvania

Oregon State University

Robert J. Washabau, VMD, PhD

Jean A. Hall, DVM, PhD

T

he first four articles in this five-part series on gastrointestinal prokinetic therapy discussed dopaminergic antagonist drugs, motilin-like drugs, serotonergic drugs, and acetylcholinesterase inhibitors or parasympathetic potentiating drugs, respectively. This article considers the diagnosis and management of esophageal, gastric, small intestinal, and colonic motility disorders.

ESOPHAGEAL MOTILITY DISORDERS Mechanical Obstruction Anatomic lesions of the esophagus (e.g., tumor, foreign body, stricture, vascular ring anomaly, fistula, and gastroesophageal intussusception) impede esophageal peristalsis because of mechanical obstruction. Diagnosis of mechanical obstruction of the esophagus is usually straightforward and involves the use of survey and contrast radiography, endoscopy, and occasionally ultrasonography. Mechanical obstruction should be treated as a primary disorder, which might require chemotherapy, surgical resection, endoscopic or surgical removal of foreign bodies, endoscopic or surgical reduction of intussusception, or balloon dilation or bougienage (Figure 1). Functional Obstruction Cricopharyngeal Achalasia Cricopharyngeal achalasia, a disorder of the cricopharyngeal sphincter, is

Small Animal

The Compendium June 1997

ESOPHAGEAL MOTILITY DISORDER

Functional disorders

Mechanical disorders

Tumor

Foreign body

1. Chemotherapy 2. Surgical resection

Stricture

Endoscopic or surgical removal

Vascular ring anomaly

Hiatal hernia

Balloon dilation or bougienage

Key Finding Therapy

Esophagitis

Surgical correction

Gastroesophageal reflux

1. Low-fat diet 2. Chemical diffusion barrier (e.g., sucralfate) 3. H2 receptor antagonist (e.g., cimetidine or ranitidine) 4. Prokinetic therapy (e.g., cisapride or metoclopramide) 5. Surgical correction— refractory hiatal hernia

Idiopathic megaesophagus

1. Elevated oral feedings 2. Gastrostomy tube feedings 3. Antibiotics (pneumonia)

Figure 1—Management of esophageal motility disorders.

characterized by cricopharyngeal hypertension and inadequate relaxation during swallowing. Affected puppies develop progressive dysphagia, and regurgitation is observed shortly after weaning. Patients make repeated, nonproductive attempts to swallow that culminate in regurgitation of undigested food. Coughing develops as a consequence of food aspiration; pulmonary crackles may be detected in patients with aspiration pneumonia. Diagnosis of cricopharyngeal achalasia is technically difficult and requires videofluoroscopy and esophageal manometry. Because of the inability to evaluate the rapid, complex series of events that occurs during swallowing, survey and static barium-contrast radiographs are not useful in diagnosing the disorder. The videofluoroscopic finding of multiple, nonproductive attempts at swallowing barium liquid or paste only suggests a diagnosis of cricopharyngeal achalasia. Definitive diagnosis requires the manometric demonstration of elevated basal pressures and inadequate relaxation during swallowing.1,2 If manometry is unavailable and the diagnosis

is questionable, electromyography of the oropharyngeal musculature should be performed to exclude the possibility of a more proximal oropharyngeal motility disorder. Cricopharyngeal achalasia is best treated by cricopharyngeal myotomy. Most patients experience immediate relief after surgery.3 Effective medical management of the disorder has not been reported.

Idiopathic Megaesophagus Congenital megaesophagus in puppies is usually diagnosed by a history of regurgitation, weight loss, and/or coughing associated with aspiration pneumonia as well as by the radiographic finding of generalized esophageal dilation. An increased incidence has been reported in Irish setters, Great Danes, German shepherds, Labrador retrievers, Chinese shar-peis, and Newfoundlands; heritability has been demonstrated in miniature schnauzers and wirehaired fox terriers. Although the pathogenesis of the congenital form is not

PROGRESSIVE DYSPHAGIA ■ ELEVATED BASAL PRESSURES ■ REGURGITATION

The Compendium June 1997

completely understood, recent studies suggest a defect in vagal afferent innervation to the esophagus.4–6 Treatment consists of dietary management and supportive care for aspiration pneumonia. Some patients exhibit improvement or resolution of clinical signs with maturation. Congenital idiopathic megaesophagus has also been reported in several cats.7,8 Megaesophagus may have been secondary to pyloric dysfunction in one group of cats.8 Acquired megaesophagus is a common cause of regurgitation in adult dogs. Like the congenital form, the disorder is characterized by ineffective esophageal peristalsis and esophageal dilation. Acquired megaesophagus may develop as a consequence of an underlying disease process (e.g., myasthenia gravis, myositis or myopathy, esophagitis, adrenocortical insufficiency, lead poisoning, distemper, brain stem disease, or dysautonomia).9 In most cases, there is no known cause and the condition is referred to as idiopathic megaesophagus. The morbidity and mortality of the disorder are unacceptably high. Many patients eventually succumb to the effects of chronic malnutrition and repeated episodes of aspiration pneumonia. The minimal diagnostic investigation of acquired megaesophagus should include complete blood count, serum chemistry analysis, urinalysis, serology for nicotinic acetylcholine receptor antibodies, serum antinuclear antibody titer, survey thoracic radiographs, and esophageal videofluoroscopy. Additional tests that might be considered are fecal examination for Spirocerca lupi ova, serum lead concentration, thyroid function assays, esophageal endoscopy, and electrophysiologic evaluation (nerve conduction velocity and electromyography). The additional medical investigation depends on the individual case presentation.9,10 The pathogenesis of idiopathic megaesophagus is not completely understood. The disorder has been compared with esophageal achalasia in humans. Achalasia is a failure of relaxation of the gastroesophageal sphincter with secondary dilation of the esophageal body. A similar disorder has not been rigorously documented in dogs.11 Recent studies suggest several important differences between canine idiopathic megaesophagus and human achalasia. In dogs with idiopathic megaesophagus, (1) the response of the cricopharyngeal sphincter and gastroesophageal sphincter to swallowing is intact and normal, (2) balloon distention in the proximal esophageal body induces minimal increases in cricopharyngeal sphincter pressure, and (3) balloon distention of the distal esophageal body induces minimal relaxation of the gastroesophageal sphincter. The diminished motor

Small Animal

response of the cricopharyngeal and gastroesophageal sphincters to intraluminal stimuli suggests a defect in the afferent neural pathway,12 like the disturbance that has been characterized in congenital canine megaesophagus.5,6 Because the gastroesophageal sphincter is normotensive and relaxes appropriately with swallowing in dogs affected with idiopathic megaesophagus, gastroesophageal sphincter myotomy cannot be recommended in treating this disorder. Instead, current therapeutic recommendations include elevated feedings, treatment for reflux esophagitis in cases in which it can be demonstrated, and antibiotic therapy for documented aspiration pneumonia (Figure 1). Affected animals should be fed a high-calorie diet, in small, frequent feedings, from an elevated or upright position to take advantage of gravity drainage through a nonperistaltic esophagus. Dietary consistency should be formulated to produce the fewest clinical signs. Some patients handle liquid diets well; others do better with solids. Patients that cannot maintain adequate nutritional balance with oral intake should be fed by temporary or permanent tube gastrostomy. Gastrostomy tubes can be placed surgically or percutaneously with endoscopic guidance. Esophagitis, if present, should be treated with oral sucralfate suspensions (0.5 to 1.0 g three times daily) and gastric acid secretory inhibitors (e.g., oral or intravenous cimetidine at 5 to 10 mg/kg three to four times daily; oral or intravenous ranitidine at 1.0 to 2.0 mg/kg two to three times daily; or oral omeprazole at 0.7 mg/kg once daily). Pulmonary infections should be identified by culture and sensitivity, and an appropriate antibiotic should be selected for the offending organisms. This may be accomplished by transtracheal wash or by bronchoalveolar lavage at the time of endoscopy. It has been suggested that cisapride, a 5-HT4 serotonergic agonist, might improve esophageal peristalsis in dogs with idiopathic megaesophagus. This would not seem to be a rational clinical application of the drug because a smooth muscle prokinetic agent would not be expected to have much effect on striated muscle function. Indeed, the prokinetic effect of cisapride in the esophagus of humans or cats is confined to the lower esophageal body at the transition zone from striated muscle to smooth muscle. Cisapride has no effect on upper esophageal peristalsis in these species. Furthermore, 5-hydroxytryptamine (serotonin) stimulates contraction of the smooth muscle of the canine gastroesophageal sphincter but does not affect the striated muscle of the canine esophageal body.13 Cisapride thus cannot be recommended in treating idiopathic megaesophagus in dogs.14,15 A cisapride-induced increase in

DIETARY MANAGEMENT ■ THYROID FUNCTION ASSAYS ■ REFLUX ESOPHAGITIS

Small Animal

The Compendium June 1997

gastroesophageal sphincter pressure could diminish esophageal clearance and worsen clinical signs in dogs with idiopathic megaesophagus. A preliminary report suggests that cisapride actually decreases esophageal transit rate in normal dogs.16 There are no other clinically useful drugs for improving esophageal peristalsis in dogs with acquired idiopathic megaesophagus. Bethanechol chloride, a cholinomimetic drug, reportedly increased esophageal contraction amplitude in dogs with idiopathic megaesophagus but did not affect the frequency of motor response to swallowing.17

Dysautonomia Dysautonomia is a generalized autonomic neuropathy originally reported (as the Key-Gaskell syndrome) in cats in the United Kingdom. The condition has now been reported in dogs and cats from Western Europe and the United States. The clinical signs reflect generalized autonomic dysfunction; megaesophagus, esophageal hypomotility, and regurgitation are consistent findings.18 Pathologically, degenerative lesions are found in autonomic ganglia, intermediate gray columns of the spinal cord, and some sympathetic axons. Despite an intensive search for genetic, toxic, nutritional, and infectious causative agents, a definitive cause has not been established. The most frequently reported clinical signs are depression, anorexia, constipation, and regurgitation or vomiting. Fecal and urinary incontinence are reported less commonly. Physical examination findings that are consistent with dysautonomia include dry mucous membranes, pupillary dilation, prolapsed nictitating membranes, reduced or absent pupillary light reflex, bradycardia, and areflexic anus. Paresis and conscious proprioceptive deficits have been reported in a few patients.18 In most cases, a clinical diagnosis is based on the history and physical examination findings. Additional findings that are consistent with the diagnosis include esophageal dilation and hypomotility on survey and barium-contrast radiographs, delayed gastric emptying on barium-contrast radiographs, reduced tear production in Schirmer’s tear tests, atropine-insensitive bradycardia, and bladder and colonic distention on survey radiographs. There are few diagnostic differentials to consider in a cat with the myriad of manifestations characteristic of this syndrome. Early in the course of the illness, however, other diagnostic differentials to consider are colonic or intestinal obstruction, other causes of megaesophagus, and feline lower urinary tract disease. Although supportive care (e.g., artificial tears, elevat-

ed feedings, expressing the urinary bladder, and antibiotics) is the basis of therapy for this disorder, some cats reportedly demonstrate improvement with parasympathomimetic drugs (e.g., bethanechol or metoclopramide). Gastrostomy tube feeding or total parenteral nutrition may sustain some patients until they regain neurologic function. In general, dysautonomia is associated with a guarded to poor prognosis for long-term survival in dogs and cats. Although 20% to 40% of affected cats are likely to recover, recovery may take 2 to 12 months. Complete recovery is uncommon; many cats are left with residual impairment (e.g., intermittent regurgitation, dilated pupils, and fecal or urinary incontinence).

Esophagitis Esophagitis is an acute or chronic inflammatory disorder of the esophageal mucosa that may involve the underlying submucosa and muscularis. Regurgitation is the most important sign in cats and dogs with esophagitis. Severely affected patients may manifest excessive salivation, dysphagia, and painful swallowing (odynophagia) with severe inflammation of the esophagus. Esophagitis most often results from chronic gastritis with persistent vomiting or, less frequently, from reflux of gastric juice during anesthetic episodes. Esophagitis is more likely to develop after repeated episodes of gastric reflux than after a single, long episode of acid exposure.19 Esophageal endoscopy is the preferred method of diagnosing esophagitis. After predisposing conditions are corrected, therapy for the disorder is based on drugs that form diffusion barriers (oral sucralfate at 0.5 to 1.0 g three times daily) and H2-receptor antagonists (e.g., oral or intravenous cimetidine at 5 to 10 mg/kg three to four times daily). Oral cisapride (0.1 to 0.5 mg/kg two to three times daily) or metoclopramide (0.2 to 0.5 mg/kg three times daily) can be administered to increase gastroesophageal sphincter tone and reduce reflux (Figure 1). Hiatal Hernia Hiatal hernias may occur as congenital or acquired lesions. Congenital hiatal hernias have been reported in Chinese shar-peis, English bulldogs, and chow chows and apparently result from incomplete closure of the diaphragmatic hiatus during embryologic development.20 Clinical signs include regurgitation, vomiting, and dyspnea. Clinical signs result from mechanical obstruction or the deleterious effects of gastric and intestinal juice (e.g., hydrogen ions, pepsins, and bile salts) on esophageal mucosa. A clinical diagnosis may be made if a gas-filled, soft tissue opacity is radiograph-

ESOPHAGEAL PERISTALSIS ■ DEPRESSION ■ CHRONIC GASTRITIS

Small Animal

The Compendium June 1997

ically evident in the caudodorsal thorax. Affected patients often fail to respond to medical treatment and subsequently require surgery (e.g., crural apposition, gastropexy, and possibly esophagopexy).20 Although the pathogenesis of acquired hiatal hernia is not completely understood, recent reports suggest that hiatal hernia is likely to occur secondary to increased intraabdominal pressure with chronic vomiting disorders.21 Regurgitation is the most important clinical sign observed in cats and dogs with acquired hiatal hernia.20,22 Patients with acquired hiatal hernia usually respond to acid neutralization therapy (e.g., H2-receptor antagonists and/or application of diffusion barriers) and occasionally require restorative surgery22 (Figure 1).

Gastroesophageal Reflux Gastroesophageal reflux has been poorly documented in veterinary species but is more common than was previously believed. Reflux is a disorder of the gastroesophageal sphincter that permits retrograde movement of gastrointestinal fluids or ingesta into the esophagus. Chronic vomiting, disorders of gastric emptying, hiatal hernia, and anesthesia-induced decreases in gastroesophageal sphincter pressure are the major causes of gastroesophageal reflux in dogs and cats. The normal esophagus rapidly clears acid by secondary peristalsis; remaining acid is neutralized by swallowed saliva.23 Anesthetic drugs can decrease gastroesophageal sphincter pressure,24 reduce peristalsis, and decrease salivation. The frequency of reflux, the length of contact time, and the composition of the refluxed material (gastric acid, pepsin, trypsin, bile salts, and duodenal bicarbonate) determine the severity of the esophagitis. Gastric acid alone produces mild esophagitis; combinations of acid and pepsin or trypsin, bicarbonate, and bile salts produce severe esophagitis.25 The risk of reflux esophagitis is greater with multiple episodes of acid exposure than with a single, long episode.19 The clinical signs of gastroesophageal reflux are similar to those of esophagitis. In severe cases, patients may exhibit regurgitation, salivation, odynophagia, extension of the head and neck during swallowing, and total avoidance of food. In milder cases, patients may have occasional episodes of regurgitation in the early morning. Such cases probably result from transient relaxation of the gastroesophageal sphincter during sleep.26 The history may suggest a diagnosis of gastroesophageal reflux. Survey thoracic radiographs are often normal. Videofluoroscopy may demonstrate intermittent gastroesophageal reflux, but this finding may also be observed in normal animals without esophagitis.27 Endoscopy is currently the best means of documenting mucosal inflammation in the distal esophagus, which is

consistent with reflux esophagitis. Definitive diagnosis requires determinations of gastroesophageal sphincter pressure and 24-hour intraluminal pH measurement; these techniques are available only in major referral centers. Because dietary fat delays gastric emptying and reduces gastroesophageal sphincter pressure, patients should be fed fat-restricted diets. Owners should avoid late-night feedings, which tend to reduce gastroesophageal sphincter pressure during sleep. In addition to nutritional considerations, rational medical therapy for this disorder includes drugs that form diffusion barriers (e.g., sucralfate), gastric acid secretory inhibitors (e.g., cimetidine, ranitidine, or omeprazole), and prokinetic agents (e.g., cisapride or metoclopramide). Drugs that form diffusion barriers may be the most important medical therapy in patients with gastroesophageal reflux. Oral sucralfate (0.5 to 1.0 g three times daily) protects against mucosal damage from gastroesophageal reflux and promotes healing of existing esophagitis. 28 Dogs with refractory cases of gastroesophageal reflux should be medicated with acid secretory inhibitors and/or prokinetic agents. The H2-histamine receptor antagonists (e.g., oral or intravenous cimetidine at 5 to 10 mg/kg three to four times daily and ranitidine at 1.0 to 2.0 mg/kg two to three times daily) inhibit gastric acid secretion and reduce the amount of acid reflux. Omeprazole (0.7 mg/kg once daily), an H+,K+-ATPase inhibitor, could also be used to inhibit gastric acid secretion. Oral cisapride (0.1 to 1.0 mg/kg two to three times daily) and metoclopramide (0.2 to 0.5 mg/kg three to four times daily) are useful in treating gastroesophageal reflux because they promote gastric emptying and increase gastroesophageal sphincter pressure (Figure 1 and Table I).

GASTRIC MOTILITY DISORDERS Mechanical Obstruction Anatomic lesions of the pylorus and adjacent duodenal segment (e.g., infiltrative pyloric neoplasia, chronic hypertrophic pyloric gastropathy, chronic hypertrophic gastritis, eosinophilic gastritis, gastric foreign bodies, antral polyps, hepatic or pancreatic abscesses, and intraabdominal neoplasia) impede gastric emptying because of mechanical obstruction.29,30 Diagnosis of mechanical obstruction is usually straightforward and involves survey and contrast radiography, ultrasonography, and/or gastroscopy. Mechanical obstruction should be treated as a primary disorder (e.g., with endoscopic polypectomy, surgical pylorectomy, and gastroduodenostomy) (Figure 2). Surgical removal of the foreign object or the affected area is the preferred therapy.29 Gastrointestinal prokinetic agents are contraindi-

CRURAL APPOSITION ■ ACQUIRED HIATAL HERNIA ■ CHRONIC VOMITING

The Compendium June 1997

Small Animal

TABLE I Mechanisms, Sites of Activity, and Indications for Gastrointestinal Prokinetic Agents Agent

Mechanism of Action

Sites of Activity

Indications

Metoclopramide

D2 dopaminergic antagonist α2-adrenergic antagonist β2-adrenergic antagonist 5-HT4 serotonergic agonist 5-HT3 serotonergic antagonist

LES, stomach, intestine, CRTZ Stomach Stomach LES, stomach, intestine Stomach, intestine

Vomiting disorders, gastroesophageal reflux, delayed gastric emptying, postoperative ileus, intestinal pseudoobstruction

Domperidone

D2 dopaminergic antagonist α2-adrenergic antagonist β2-adrenergic antagonist

Stomach, CRTZ Stomach Stomach

Vomiting disorders

Cisapride

5-HT4 serotonergic agonist 5-HT1 serotonergic antagonist 5-HT3 serotonergic antagonist 5-HT2 serotonergic agonist Nonserotonergic mechanism

LES, stomach, intestine Stomach, intestine, emetic center Stomach, intestine, CRTZ Colon Canine antrum

Gastroesophageal reflux, delayed gastric emptying, postoperative ileus, intestinal pseudoobstruction, constipation, chemotherapy-induced emesis

Erythromycin

Motilin agonist (in cats) 5-HT3 serotonergic agonist (in dogs)

Stomach, intestine Stomach, intestine

Delayed gastric emptying (liquids more than solids)

Ranitidine

Acetylcholinesterase inhibitor Possibly M3 muscarinic agonist

Stomach, intestine, colon Stomach

Delayed gastric emptying, intestinal pseudo-obstruction, constipation

Nizatidine

Acetylcholinesterase inhibitor Possibly M3 muscarinic agonist

Stomach, intestine, colon Stomach

Delayed gastric emptying, intestinal pseudo-obstruction, constipation

CRTZ = chemoreceptor trigger zone; 5-HT = 5-hydroxytryptamine; LES = lower esophageal sphincter.

cated in treating patients with mechanical obstruction.

Functional Obstruction Functional disorders of gastric emptying (referred to as delayed gastric emptying or gastroparesis) result from abnormalities in myenteric neuronal or gastric smooth muscle function or from abnormalities in antropyloroduodenal coordination. Delayed gastric emptying is now recognized as an important cause of upper gastrointestinal tract signs (e.g., anorexia and vomiting).31 Delayed gastric emptying has been reported in animals recovering from gastric dilatation–volvulus,32 infectious and inflammatory gastric diseases,33 experimental gastric ulcer,34 and radiation gastritis.35

Delayed gastric emptying has also been associated with several secondary conditions, including electrolyte disturbances, metabolic disorders, concurrent drug usage (anticholinergics, β-adrenergic agonists, and opiates), acute stress, and acute abdominal inflammation.33 Gastric emptying disorders are usually diagnosed after mechanical obstruction has been ruled out. A gastric motility disorder should be considered when there is a history of chronic vomiting. Vomiting of undigested to partially digested food usually occurs more than 10 hours after a meal, at a time when the stomach should be empty. Other signs of a gastric motility disorder include gastric distention, nausea, anorexia, belching, polydipsia, pica, and weight loss.

FREQUENCY OF REFLUX ■ VIDEOFLUOROSCOPY ■ FAT-RESTRICTED DIETS

Small Animal

The Compendium June 1997

GASTRIC MOTILITY DISORDER

Functional obstruction (delayed gastric emptying)

Mechanical obstruction

Polyp

Tumor

Polypectomy

1. Chemotherapy 2. Partial gastrectomy

Foreign body

1. Endoscopic removal 2. Surgical removal

Inflammation

Antiinflammatory drugs (e.g., prednisone)

Resolution

Key Finding Therapy

Infection

Idiopathic

Antibiotics

Low-fat/lowprotein diet: neutral pH, low osmolality, liquid consistency

No improvement

Prokinetic therapy: 1. Cisapride 2. Erythromycin 3. Ranitidine or nizatidine

Figure 2—Management of gastric motility disorders.

The physical examination may be normal or reveal findings associated with the underlying cause. There may be increased bowel sounds with abdominal auscultation or nonspecific pain on abdominal palpation. Laboratory findings depend on the underlying cause. Dogs with persistent vomiting may exhibit dehydration, electrolyte abnormalities, or acid–base imbalances. Hypokalemia is the most common electrolyte abnormality. Paradoxic aciduria is observed in some dogs when vomiting occurs secondary to pyloric outflow obstruction. Methods that are available for evaluating gastric emptying include oral administration of radioisotopes coupled with external scanning, serial sampling of gastric contents by intubation, ultrasonography, computed tomography, electrophysiology, and manometry. Radiographic techniques are the most definitive means that are generally available to practitioners for diagnosing gastric motility disorders. Liquid barium sulfate can be used to detect gross

abnormalities of gastric emptying in routine upper gastrointestinal radiographic studies. However, such studies provide inadequate information for assessing emptying of the typical heterogeneous meal because solids and liquids empty differently, as do large and small particles, and lipids and carbohydrate solutions. Barium mixed with food is believed to be better than liquid barium for testing distal gastric motor function. Small radiopaque particles mixed with food are also used to assess gastric emptying. If available, radioisotopic methods are the most tolerable and clinically accurate means of evaluating gastric emptying. Because surgical procedures are often unsuccessful, dietary management and gastric prokinetic agents are used to treat patients with delayed gastric emptying disorders (Figure 2). Dietary management is based on the knowledge that liquids are emptied from the stomach more rapidly than solids, carbohydrates are emptied more rapidly than proteins, and proteins are emptied more rapidly than lipids. A low-fat, low-protein diet of

GASTRIC EMPTYING ■ ELECTROLYTE DISTURBANCES ■ PARADOXIC ACIDURIA

The Compendium June 1997

liquid or semiliquid consistency thus should be fed at frequent intervals to facilitate gastric emptying. Diets should be selected for low acidity and low osmolality and should be fed at warm temperatures (22˚ to 38˚C [72˚ to 100˚F]). Gastric prokinetic agents should be considered in patients that fail to respond to dietary management alone. The 5-HT4 serotonergic agonists (e.g., cisapride and metoclopramide), motilin-like drugs (e.g., erythromycin), and acetylcholinesterase inhibitors (e.g., ranitidine and nizatidine) have been used to treat delayed gastric emptying (Figure 2 and Table I). We currently recommend cisapride as the initial gastric prokinetic agent. Doses of cisapride from 0.05 to 0.20 mg/kg enhance gastric emptying in dogs with normal emptying.14,36 However, doses of 0.5 to 1.0 mg/kg are required to enhance gastric emptying in dogs with delayed gastric emptying induced by α2-adrenergic agonists, dopamine, disopyramide, or antral tachygastria.14,15 Cisapride accelerates gastric emptying in dogs by stimulating pyloric and duodenal motor activity, by enhancing antropyloroduodenal coordination, and by increasing the mean propagation distance of duodenal contractions.36 In this regard, cisapride is apparently superior to metoclopramide and domperidone in stimulating gastric emptying.15,36,37 If oral cisapride (0.1 to 1.0 mg/kg two to three times daily) fails to improve gastric emptying, we recommend the use of oral erythromycin (0.5 to 1.0 mg/kg three times daily) or one of the acetylcholinesterase inhibitors (e.g., oral ranitidine at 1.0 to 2.0 mg/kg twice daily or nizatidine at 2.5 to 5.0 mg/kg once daily) in place of cisapride.10,38,39

SMALL INTESTINAL MOTILITY DISORDERS Mechanical Obstruction Mechanical obstruction of the small intestine may be associated with foreign body ingestion, neoplasia, strictures, hematomas, or intussusceptions.40 Acute obstruction of the intestine is characterized by distention, increased intraluminal pressure, and increased motor activity in the segment of bowel proximal to the occlusion. Distention of the bowel proximal to the obstruction results from fluid and gas accumulation. Intestinal secretion is stimulated, absorption of fluid is decreased, and aerophagia causes gas accumulation. As the small bowel distends, neuromuscular activity increases.41 Distally, the bowel becomes quiescent; nearly all motor activity ceases.42,43 The increased motor activity of the proximal segment tends to subside with chronic obstruction. The diagnosis of obstruction can be confirmed via radiography. Mechanical obstruction of the small intestine should be treated as a primary disorder (e.g., by enterectomy, foreign body removal, or reduction of in-

Small Animal

tussusception) (Figure 3). Gastrointestinal prokinetic agents are contraindicated in treating patients with these disorders.

Functional Obstruction Functional disorders of small intestinal transit (intestinal pseudo-obstruction) have been associated with parvoviral enteritis, postoperative ileus, nematode infestation, intestinal sclerosis, and radiation enteritis.40,44,45 The clinical signs vary depending on the cause, the location in the small intestine, and the duration. Chronic diarrhea and weight loss are common. Vomiting is common with more proximal obstructions. Overgrowth of small intestinal bacteria, a common complication of disordered motility, contributes to the pathophysiology and clinical signs. The medical investigation should be directed at identifying the underlying cause. In some cases, a primary entity may not be obvious. Gastrointestinal prokinetic therapy should be used to promote intestinal transit in such cases (Figure 3). 5-HT4 serotonergic agonists (e.g., cisapride or metoclopramide) and motilin-like drugs (e.g., erythromycin) have been recommended in the therapy of patients with these disorders.15,37,38 In the treatment of small intestinal motility disorders, the 5-HT4 serotonergic agonists apparently have distinct advantages over other gastrointestinal prokinetic agents. Cisapride, for example, stimulates jejunal spike burst migration,46 jejunal propulsive motility,47 and antropyloroduodenal coordination48 after intestinal lipid infusion in dogs. Cisapride thus apparently has a rational place in the treatment of patients with postoperative ileus and intestinal pseudo-obstruction. Welldesigned clinical trials are required to determine the effectiveness of cisapride compared with that of other prokinetic agents in treating patients with these disorders. Inflammatory Bowel Disease Inflammatory bowel disease is a common disorder of dogs and cats. The disorder may involve several anatomic sites (e.g., the stomach, small intestine, and colon). Clinical signs associated with inflammatory bowel disease include vomiting, diarrhea, weight loss, tenesmus, urgent defecation, hematochezia, and excessive mucus in feces. The diarrhea of inflammatory bowel disease is associated with excessive secretion and malabsorption. Inflammation disrupts the tight junctions between epithelial cells, which reduces absorption and promotes loss of nutrients, electrolytes, and water. Inflammatory mediators may also stimulate abnormal motor activity. Inflammation produced by 95% ethanol–20% acetic acid perfusion in the canine ileum,

LOW ACIDITY ■ CISAPRIDE ■ ACETYLCHOLINESTERASE INHIBITORS

Small Animal

The Compendium June 1997

INTESTINAL MOTILITY DISORDER

Functional obstruction (pseudo-obstruction)

Mechanical obstruction

Tumor

Intussusception

1. Chemotherapy 2. Partial gastrectomy

Surgical reduction

Foreign body

Inflammation

Surgical removal

Antiinflammatory drugs (e.g., prednisone)

Resolution

Key Finding Therapy

Infection

Idiopathic

Low-fat diet, antibiotics

Antibiotics

No improvement

Prokinetic therapy: cisapride or metoclopramide

Figure 3—Management of intestinal motility disorders.

for example, significantly increases the frequency of giant migrating contractions and decreases the frequency of migrating motor complexes.49 In this canine model, diarrhea, urgent defecation, hematochezia, and apparent abdominal discomfort are related to the increased frequency of giant migrating contractions.49 Inhibition of giant migrating contractions by specific antagonists during inflammation thus may minimize clinical signs and may alter the course of the disease. Platelet-activating factor (PAF) is believed to be one of the inflammatory cytokines that mediates the increased frequency of giant migrating contractions.50 The PAF antagonist BN 50727 inhibits the contractile response to PAF in the experimentally inflamed canine ileum.50 Motor abnormalities (i.e., giant migrating contractions) thus may be the major cause of clinical signs in experimental inflammatory bowel disease. It remains to be determined whether the same motor abnormalities and inflammatory cytokines are involved in spontaneous canine inflammatory bowel disease.

COLONIC MOTILITY DISORDERS Feline Idiopathic Megacolon Colonic dilatation results in disruption of the coordinated motility patterns of the distal colon and rectum that permit receptive relaxation for fecal storage as well as the giant migrating contractions associated with the defecation reflex. This eventually leads to constipation, obstipation, and idiopathic megacolon. Many cats present with chronic histories of tenesmus and inability to pass feces. Diagnosis is usually based on a history of obstipation (dyschezia, depression, anorexia, and vomiting) and abdominal palpation (colonic impaction). Radiography is often necessary to rule out obstructive causes. Several researchers have emphasized the importance of considering an extensive list of diagnostic differentials (e.g., neuromuscular, mechanical, inflammatory, metabolic–endocrine, pharmacologic, environmental, and behavioral causes) for an obstipated cat. A recent review, however, suggests that 96% of cases of obstipation

INCREASED INTRALUMINAL PRESSURE ■ INTESTINAL TRANSIT ■ DIARRHEA

Small Animal

The Compendium June 1997

Resolution Mild constipation

Dietary fiber

Recurrence

Moderate or recurrent constipation

Enemas and/or manual extraction of feces

Dietary fiber, lactulose, cisapride

Dioctyl sodium sulfosuccinate or petrolatum and/or cisapride

Resolution Dietary fiber, lactulose, bisacodyl

Recurrence

< 6 mo

Pelvic osteotomy or colectomy

> 6 mo

Colectomy

Hypertrophy

Obstipation or megacolon Dilation

Colectomy

Key Finding Therapy Time period Figure 4—Management of feline idiopathic megacolon. (From Washabau RJ, Hasler AH: Constipation, obstipation, and megacolon, in August JR [ed]: Consultations in Feline Internal Medicine. Philadelphia, WB Saunders Co, 1996, p 108. Modified with permission.)

are accounted for by idiopathic megacolon (62%), pelvic canal stenosis (23%), nerve injury (6%), or Manx sacral spinal cord deformity (5%).51 Fewer cases are accounted for by complications of colopexy (1%) and colonic neoplasia (1%). In another 2% of cases, colonic hypoganglionosis or aganglionosis was suspected but not proven. Inflammatory, pharmacologic, and environmental– behavioral causes were not cited as predisposing factors in any of the original case reports. Endocrine factors (obesity in five cases and hypothyroidism in one case) were cited but were not necessarily implicated as part of the pathogenesis of megacolon. Although it is important to consider an extensive list of diagnostic differentials in an individual animal, most cases are idiopathic, orthopedic, or neurologic in origin.51 The pathogenesis of idiopathic megacolon has been variably attributed to a primary neurogenic or degenerative neuromuscular disorder. Although few cases (11%) evidently result from neurologic disease, most

cases (more than 60%) have no evidence of neurologic disease.51 These idiopathic cases may involve disturbances of colonic smooth muscle. Recent studies suggest that colonic smooth muscle function is impaired in cats with idiopathic megacolon.52 In vitro isometric stress measurements were performed on colonic smooth muscle segments obtained from cats with idiopathic dilated megacolon. Compared with that of healthy controls, megacolonic smooth muscle developed less isometric stress in response to neurotransmitters (acetylcholine, substance P, and cholecystokinin), membrane depolarization (potassium chloride), and electrical field stimulation. These differences were observed in longitudinal and circular smooth muscle from the ascending and descending colon. No significant abnormalities of smooth muscle cells or myenteric neurons were observed on histologic evaluation. These studies suggest that feline idiopathic megacolon is a generalized dysfunction of colonic

OBSTIPATION ■ ENDOCRINE FACTORS ■ IDIOPATHIC MEGACOLON

Small Animal

smooth muscle and that treatments aimed at stimulating colonic smooth muscle contraction might improve colonic motility.52 Traditional therapy for constipation and idiopathic megacolon has been aimed at improving fecal hydration and bulk (Figure 4). Cat owners thus are advised to encourage water consumption and to increase the fiber content of the diet with bulk laxatives (e.g., psyllium). Warm-water enemas can be given intermittently as needed. Thereafter, patients may be treated with emollient laxatives (e.g., dioctyl sodium sulfosuccinate), stimulant laxatives (e.g., bisacodyl), lubricant laxatives (e.g., mineral oil or petrolatum), saline laxatives (e.g., magnesium citrate), hyperosmotic agents (e.g., lactulose), or motility agents.51 Hyperosmotic agents that contain sodium phosphate are contraindicated in cats because these agents tend to induce severe hypernatremia, hyperphosphatemia, and hypocalcemia in this species.53 In several species, cisapride enhances colonic propulsive motility via activation of colonic smooth muscle 5HT2a receptors.14,15 Although in vitro studies demonstrate that cisapride stimulates feline colonic smooth muscle contraction,54 it has not yet been proven that cisapride stimulates feline colonic propulsive motility in vivo. Current anecdotal reports suggest that cisapride is effective in stimulating colonic propulsive motility in cats with mild to moderate idiopathic constipation; cats with longstanding obstipation and megacolon are not likely to demonstrate much improvement with cisapride therapy. The recommended dosage of oral cisapride for cats with mild to moderate idiopathic constipation has been 0.1 to 0.5 mg/kg two to three times daily. Higher doses (0.5 to 1.0 mg/kg) may be necessary in cats with moderate to severe constipation. No significant side effects have yet been observed or reported in cats medicated with oral cisapride at dosages of 0.1 to 1.0 mg/kg two to three times daily. Colectomy should be considered in cats that are refractory to medical therapy (Figure 4). Cats have a generally favorable prognosis for recovery after colectomy. Mild to moderate diarrhea occasionally persists for weeks to months after surgery; constipation may recur in some cats.

Inflammatory Bowel Disease Experimental canine colitis is associated with an increased incidence of giant migrating contractions that is highly correlated with the clinical signs of tenesmus, diarrhea, hematochezia, and excessive mucus in feces.55,56 These findings are similar to those reported in experimental canine ileitis49,50 and suggest that the diarrhea produced in inflammatory bowel disease may be largely

The Compendium June 1997

attributable to the numerous giant migrating contractions that emerge during acute inflammation. Therapy and resolution of disease may be facilitated by characterizing the mechanisms that are involved in the regulation of this abnormal motor pattern.

About the Authors Dr. Washabau is affiliated with the Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Dr. Hall is affiliated with the college of Veterinary Medicine, Oregon State University, Corvallis, Oregon. Drs. Washabau and Hall are Diplomates of the American College of Veterinary Internal Medicine.

REFERENCES 1. Rosin ER: Quantitation of the pharyngoesophageal sphincter in the dog. Am J Vet Res 47:660–662, 1986. 2. Lang IM, Dantas RO, Cook IJ, et al: Videoradiographic, manometric, and electromyographic analysis of canine upper esophageal sphincter. Am J Physiol 260:G911–G919, 1991. 3. Goring RL, Kagan KG: Cricopharyngeal achalasia in the dog: Radiographic evaluation and surgical management. Compend Contin Educ Pract Vet 4(5):438–444, 1982. 4. Tan BJK, Diamant N: Assessment of the neural defect in a dog with idiopathic megaesophagus. Dig Dis Sci 32:76–85, 1987. 5. Holland CT, Satchell PM, Farrow BRH: Vagal afferent dysfunction in naturally occurring canine esophageal motility disorder. Dig Dis Sci 39:2090–2098, 1994. 6. Holland CT, Satchell PM, Farow BRH: Vagal esophagomotor nerve function and esophageal motor performance in dogs with congenital idiopathic megaesophagus. Am J Vet Res 57:906–911, 1996. 7. Hoenig M, Mahaffey MB, Parnell PG, et al: Megaesophagus in two cats. JAVMA 196:763–765, 1990. 8. Pearson H, Gaskell CJ, Gibbs C, et al: Pyloric and esophageal dysfunction in the cat. J Small Anim Pract 15:487– 501, 1974. 9. Washabau RJ: Swallowing disorders, in Simpson JW, Hall EJ (eds): Manual of Canine and Feline Gastroenterology. Cheltenham, England, British Small Animal Veterinary Association, 1996, pp 67–89. 10. Washabau RJ, Hall JA: Gastrointestinal motility disorders of dogs and cats. Eur J Comp Gastroenterol 2:9–19, 1997. 11. Diamant N, Szczepanski M, Mui H: Manometric characteristics of idiopathic megaesophagus in the dog: An unsuitable model for achalasia in man. Gastroenterology 65:216–223, 1973. 12. Washabau RJ, Gaynor A: Pathogenesis of canine megaesophagus: Neuropathy. Proc ACVIM:581–582, 1996. 13. Cohen ML, Susemichel AD, Bloomquist W, et al: 5-HT4 receptors in rat but not guinea pig, rabbit or dog esophageal muscle. Gen Pharmacol 25:1143–1148, 1994. 14. Washabau RJ, Hall JA: Clinical pharmacology of cisapride. JAVMA 207:1285–1288, 1995. 15. Washabau RJ, Hall JA: Gastrointestinal prokinetic therapy:

The Compendium June 1997

16. 17.

18. 19. 20. 21. 22. 23. 24.

25. 26.

27. 28. 29. 30. 31.

32. 33. 34. 35. 36.

Serotonergic drugs. Compend Contin Educ Pract Vet 19(4): 473–480, 1997. Mears EA, Jenkins C, Mays L, et al: The effect of metoclopramide and cisapride on esophageal motility in normal beagles. J Vet Intern Med 10:156, 1996. Diamant N, Szczepanski M, Mui H: Idiopathic megaesophagus in the dog: Reasons for spontaneous improvement and a possible method of medical therapy. Can Vet J 15:66–71, 1974. Sharp NJH: Feline dysautonomia. Semin Vet Med Surg 5:67–71, 1990. Cassidy Y, Geisinger KT, Kraus BB, et al: Continuous versus intermittent acid exposure in the production of esophagitis in a feline model. Dig Dis Sci 37:1206–1211, 1992. Callan MB, Washabau RJ, Saunders HM, et al: Congenital esophageal hiatal hernia in the Chinese shar-pei dog. J Vet Intern Med 7:210–215, 1993. Twedt DC: Diseases of the esophagus, in Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine, ed 4. Philadelphia, WB Saunders Co, 1995, pp 1124–1142. Prymak C, Saunders HM, Washabau RJ: Hiatal hernia repair by restoration and stabilization of normal anatomy. Vet Surg 18:386–391, 1989. Johnson SE, Zelner H, Sherding RG: Esophageal acid clearance test in healthy dogs. Can J Vet Res 53:244–247, 1989. Hall JA, Magne M, Twedt DC: Effect of acepromazine, diazepam, fentanyl-droperidol, and oxymorphone on gastroesophageal sphincter pressure in healthy dogs. Am J Vet Res 48:556–558, 1987. Evander A, Little AG, Riddell RH, et al: Composition of the refluxed material determines the degree of reflux esophagitis in the dog. Gastroenterology 93:280–286, 1987. Patrikios J, Martin CJ, Dent J: Relationship of transient lower esophageal sphincter relaxation to postprandial gastroesophageal reflux and belching in dogs. Gastroenterology 90:545–551, 1986. Watrous B, Suter PF: Normal swallowing in the dog: A cineradiographic study. Vet Radiol 20:99–109, 1979. Katz PO, Geisinger KR, Hassan M, et al: Acid-induced esophagitis in cats is prevented by sucralfate but not synthetic prostaglandin E. Dig Dis Sci 33:217–224, 1988. Gualtieri M, Monzeglio MG: Gastrointestinal polyps in small animals. Eur J Comp Gastroenterol 1:5–11, 1996. Matthiesen DT, Walter MC: Surgical treatment of chronic hypertrophic pyloric gastropathy in 45 dogs. JAAHA 22: 241–247, 1986. Burrows CF: Gastric disease, in Simpson JW, Hall EJ (eds): Manual of Canine and Feline Gastroenterology. Cheltenham, England, British Small Animal Veterinary Association, 1996, pp 90–113. Hall JA, Solie TN, Seim HB, et al: Gastric myoelectric and motor activity in dogs with gastric dilation–volvulus. Am J Physiol 265:G646–G653, 1993. Hall JA: Diagnosis and management of gastric motility disorders. Proc ACVIM:180–183, 1994. Fioramonti J, Bueno L: Gastrointestinal myoelectric activity disturbances in gastric ulcer disease in rats and dogs. Dig Dis Sci 25:575–580, 1980. DuBois A, Jacobus JP, Grissom MP, et al: Altered gastric emptying and prevention of radiation-induced vomiting in dogs. Gastroenterology 86:444–448, 1984. Orihata M, Sarna SK: Contractile mechanisms of action of gastroprokinetic agents: Cisapride, metoclopramide, and

Small Animal

domperidone. Am J Physiol 266:G665–G676, 1994. 37. Hall JA, Washabau RJ: Gastrointestinal prokinetic therapy: Dopaminergic antagonist drugs. Compend Contin Educ Pract Vet 19(2):214–221, 1997. 38. Hall JA, Washabau RJ: Gastrointestinal prokinetic therapy: Motilin-like drugs. Compend Contin Educ Pract Vet 19(3): 281–288, 1997. 39. Hall JA, Washabau RJ: Gastrointestinal prokinetic therapy: Acetylcholinesterase inhibitors. Compend Contin Educ Pract Vet 19(5):615–621, 1997. 40. Guilford WG, Strombeck DR: Intestinal obstruction, pseudo-obstruction, and foreign bodies, in Strombeck’s Small Animal Gastroenterology, ed 3. Davis, CA, Stonegate Publishing, 1996, pp 487–502. 41. Ellison GW: Intestinal obstruction, in Bojrab MJ (ed): Disease Mechanisms in Small Animal Surgery. Philadelphia, Lea & Febiger, 1993, pp 252–257. 42. Summers RW, Yanda R, Prihoda M, et al: Acute intestinal obstruction: An electromyographic study in dogs. Gastroenterology 85:1301–1306, 1983. 43. Prihoda M, Flatt A, Summers RW: Mechanisms of motility changes during acute intestinal obstruction in the dog. Am J Physiol 247:G37–G42, 1984. 44. Moore R, Carpenter J: Intestinal sclerosis with pseudoobstruction in three dogs. JAVMA 184:830–833, 1984. 45. Otterson MF, Sarna SK, Moulder JE: Effects of fractionated doses of ionizing radiation on small intestinal motor activity. Gastroenterology 95:1249–1257, 1988. 46. Summers RW, Flatt AJ: A comparative study of the effects of four motor-stimulating agents on canine jejunal spike bursts. Scand J Gastroenterol 23:1173–1181, 1988. 47. Schemann M, Ehrlein HJ: 5-hydroxytryptophan and cisapride stimulate propulsive jejunal motility and transit of chyme in dogs. Digestion 34:229–235, 1986. 48. Edelbroek M, Schuurkes JAJ, de Ridder WJE, et al: Effect of cisapride on myoelectrical and motor responses of antropyloroduodenal region during intraduodenal lipid and antral tachygastria in conscious dogs. Dig Dis Sci 40:901–911, 1995. 49. Jouët P, Sarna SK, Singaram C, et al: Immunocytes and abnormal gastrointestinal motor activity during ileitis in dogs. Am J Physiol 269:G913–G924, 1995. 50. Jouët P, Sarna SK: Platelet-activating factor stimulates giant migrating contractions during ileal inflammation. J Pharmacol Exp Ther 279:207–213, 1996. 51. Washabau RJ, Hasler AH: Constipation, obstipation, and megacolon, in August JR (ed): Consultations in Feline Internal Medicine. Philadelphia, WB Saunders Co, 1996, pp 104–113. 52. Washabau RJ, Stalis I: Alterations in colonic smooth muscle function in cats with idiopathic megacolon. Am J Vet Res 57:580–587, 1996. 53. Atkins CE, Tyler R, Greenlee P: Clinical, biochemical, acid–base, and electrolyte abnormalities in cats after hypertonic sodium phosphate enema administration. Am J Vet Res 46:980–986, 1985. 54. Washabau RJ, Sammarco J: Effects of cisapride on feline colonic smooth muscle function. Am J Vet Res 57:541–546, 1996. 55. Sethi AK, Sarna SK: Colonic motor activity in acute colitis in conscious dogs. Gastroenterology 100:954–962, 1991. 56. Sethi AK, Sarna SK: Colonic motor response to a meal in acute colitis. Gastroenterology 101:1537–1546, 1991.