The etiopathogenesis of idiopathic megacolon is still incompletely understood. Several reviews have emphasized the importance of considering an extensive list of differential diagnoses (e. g., neuromuscular, mechanical, inflammatory, metabolic and endocrine, pharmacologic, environmental, and behavioral causes) for the obstipated cat (Box Differential Diagnosis of Constipation in the Cat). A review of published cases suggests that 96% of cases of obstipation are accounted for by idiopathic megacolon (62%), pelvic canal stenosis (23%), nerve injury (6%), or Manx sacral spinal cord deformity (5%). A smaller number of cases are accounted for by complications of colopexy (1%) and colonic neoplasia (1%); colonic hypo- or aganglionosis was suspected, but not proved, in another 2% of cases. Inflammatory, pharmacologic, and environmental and behavioral causes were not cited as predisposing factors in any of the original case reports. Endocrine factors (e. g., obesity, hypothyroidism) were cited in several cases, but were not necessarily impugned as part of the pathogenesis of megacolon. It is important to consider an extensive list of differential diagnoses in an individual animal, but it should be kept in mind that most cases are idiopathic, orthopedic, or neurologic in origin. Behavioral (e. g., stress) or environmental (e. g., competition for the litter box) factors, or both, may play an important role in the development of this lesion, but they have not been very well characterized in retrospective or prospective studies.
Differential Diagnosis of Constipation in the Cat
Colonic smooth muscle: idiopathic megacolon, aging
Spinal cord disease: lumbosacral disease, cauda equine syndrome, sacral spinal cord deformities (Manx cat)
Hypogastric or pelvic nerve disorders: traumatic injury, malignancy, dysautonomia
Submucosal or myenteric plexus neuropathy: dysautonomia, aging
Intraluminal: foreign material (bones, plant material, hair), neoplasia, rectal diverticula, perineal hernia, anorectal strictures
Extraluminal: pelvic fractures, neoplasia
Perianal fistula, proctitis, anal sac abscess, anorectal foreign bodies, perianal bite wounds
Metabolic and Endocrine
Metabolic: dehydration, hypokalemia, hypercalcemia Endocrine: hypothyroidism, obesity, nutritional secondary hyperparathyroidism
Opioid agonists, cholinergic antagonists, diuretics, barium sulfate, phenothiazines
Environmental and Behavioral
Soiled litter box, inactivity, hospitalization, change in environment
Megacolon develops through two pathologic mechanisms: (1) dilation and (2) hypertrophy. Dilated megacolon is the end stage of colonic dysfunction in idiopathic cases. Cats affected with idiopathic dilated megacolon have permanent loss of colonic structure and function. Medical therapy may be attempted in such cases, but most affected cats eventually require colectomy. Hypertrophic megacolon, on the other hand, develops as a consequence of obstructive lesions (e. g., malunion of pelvic fractures, tumors, foreign bodies).
Hypertrophic megacolon may be reversible with early pelvic osteotomy, or it may progress to irreversible dilated megacolon if appropriate therapy is not instituted.
Constipation and obstipation are earlier manifestations of the same problem. Constipation is defined as infrequent or difficult evacuation of feces but does not necessarily imply a permanent loss of function. Many cats suffer from one or two episodes of constipation without further progression. Intractible constipation that has become refractory to cure or control is referred to as obstipation. The term obstipation implies a permanent loss of function. A cat is assumed to be obstipated only after several consecutive treatment failures. Recurring episodes of constipation or obstipation may culminate in the syndrome of megacolon.
The pathogenesis of idiopathic dilated megacolon appears to involve functional disturbances in colonic smooth muscle. In vitro isometric stress measurements have been performed on colonic smooth muscle obtained from cats suffering from idiopathic dilated megacolon. Megacolonic smooth muscle develops less isometric stress in response to neurotransmitter (acetylcholine, substance P, cholecystokinin), membrane depolarization (potassium chloride), or electrical field stimulation, when compared with healthy controls. Differences have been observed in longitudinal and circular smooth muscle from the descending and ascending colon. No significant abnormalities of smooth muscle cells or of myenteric neurons were observed on histologic evaluation. These studies initially suggested that the disorder of feline idiopathic megacolon is a generalized dysfunction of colonic smooth muscle and that treatments aimed at stimulating colonic smooth muscle contraction might improve colonic motility. More recent studies suggest that the lesion may begin in the descending colon and progress to involve the ascending colon over time.
History Constipation, obstipation, and megacolon mav in observed in cats ol any age, sex, or breed; however, most cases are observed in middle-aged (mean: 5.8 vears) male cats (70% male, 30% female) of domestic shorthair (DSH) (46%), domestic longhair (15%), or Siamese (12%) breeding. Affected cats are usually presented for reduced, absent, or painful defecation for a period of time ranging from days to weeks or months. Some cats are observed making multiple, unproductive attempts to defecate in the litter box, whereas other cats may sit in the litter box for prolonged periods of time without assuming a defecation posture. Dry, hardened feces are observed inside and outside of the litter box. Occasionally, chronically constipated cats have intermittent episodes of hematochezia or diarrhea due to the mucosal irritant effect of fecal concretions. This may give the pet owner the erroneous impression that diarrhea is the primary problem. Prolonged inability to defecate may result in other systemic signs, including anorexia, lethargy, weight loss, and vomiting.
Colonic impaction is a consistent physical examination finding in affected cats. Other findings will depend upon the severity and pathogenesis of constipation. Dehydration, weight loss, debilitation, abdominal pain, and mild to moderate mesenteric lymphadenopathy may be observed in cats with severe idiopathic megacolon. Colonic impaction may be so severe in such cases as to render it difficult to differentiate impaction from colonic, mesenteric, or other abdominal neoplasia. Cats with constipation due to dysautonomia may have other signs of autonomic nervous system failure, such as urinary and fecal incontinence, regurgitation due to megaesophagus, mydriasis, decreased lacrimation, prolapse of the nictitating membrane, and bradycardia. Digital rectal examination should be carefully performed with sedation or anesthesia in all cats. Pelvic fracture malunion may be detected on rectal examination in cats with pelvic trauma. Rectal examination might also identify other unusual causes of constipation, such as foreign bodies, rectal diverticula, stricture, inflammation, or neoplasia. Chronic tenesmus may be associated with perineal herniation in some cases. A complete neurologic examination, with special emphasis on caudal spinal cord function, should be performed to identify neurologic causes of constipation (e. g., spinal cord injury, pelvic nerve trauma, Manx sacral spinal cord deformity).
Diagnosis of Constipation
Although most cases of obstipation and megacolon are unlikely to have significant changes in laboratory data (e. g., complete blood count, serum chemistry, urinalysis), these tests should nonetheless be performed in all cats presented for constipation. Metabolic causes of constipation, such as dehydration, hypokalemia, and hypercalcemia may be detected in some cases. Basal serum T4 concentration and other thyroid function tests should also be considered in cats with recurrent constipation and other signs consistent with hypothyroidism. Although hypothyroidism was documented in only one case of obstipation and megacolon, obstipation is a frequent clinical sign in kittens affected with congenital or juvenile-onset hypothyroidism. Constipation could also theoretically develop after successful treatment of feline hyperthyroidism.
Abdominal radiography should be performed in all constipated cats to characterize the severity of colonic impaction and to identify predisposing factors such as intraluminal radioopaque foreign material (e. g., bone chips), intraluminal or extraluminal mass lesions, pelvic fractures, and spinal cord abnormalities. The radiographic findings of colonic impaction cannot be used to distinguish between constipation, obstipation, and megacolon in idiopathic cases. First or second episodes of constipation in some cats may be severe and generalized but may still resolve with appropriate treatment.
Ancillary studies may be indicated in some cases. Extraluminal mass lesions may be further evaluated by abdominal uhrasonography and guided biopsy, whereas intraluminal mass lesions are best evaluated by endoscopy. Colonoscopy mav also be used to evaluate the colon and anorecuim for suspected inflammatory lesions, strictures, sacculations, and diverticula. Barium enema contrast radiography may be used if colonoscopy is not possible. Both colonoscopy and barium enema contrast radiography will require general anesthesia and evacuation of impacted feces. Cerebrospinal fluid analysis, CT or MRI, and electrophysiologic studies should be considered in animals with evidence of neurologic impairment. Finally, colonic biopsy or anorectal manometry will be necessary to diagnose suspected cases of aganglionic megacolon.
Treatment of Constipation
The specific therapeutic plan will depend upon the severity of constipation and the underlying cause (Table Drug Index — Constipation). Medical therapy may not be necessary with first episodes of constipation. First episodes are often transient and resolve without therapy. Mild to moderate or recurrent episodes of constipation, on the other hand, usually require some medical intervention. These cases may be managed, often on an outpatient basis, with dietary modification, water enemas, oral or suppository laxatives, colonic prokinetic agents, or a combination of these therapies. Severe cases of constipation usually require brief periods of hospitalization to correct metabolic abnormalities and to evacuate impacted feces using water enemas, manual extraction of retained feces, or both. Follow-up therapy in such cases is directed at correcting predisposing factors and preventing recurrence. Subtotal colectomy will become necessary in cats suffering from obstipation or idiopathic dilated megacolon. These cats, by definition, are unresponsive to medical therapy. Although pelvic osteotomy is described for cats with pelvic canal stenosis, subtotal colectomy is an effective treatment and is considered the standard of surgical care.
Drug Index — Constipation
|Drug Classification And Example
|Dioctyl sodium sulfosuccinate (Colace, Mead Johnson)
||1-2 pediatric suppositories
||1-2 pediatric suppositories
|Bisacodyl (Dulcolox; Boehringer Ingelheim)
||1-2 pediatric suppositories
|Warm tap water
||5-10 mL / kg
|Warm isotonic saline
||5-10 mL / kg
|Dioctyl sodium sulfosuccinate (Colace, Mead Johnson)
||5-10 mL / cat
|Dioctyl sodium sulfosuccinate (Disposaject, PittmanMoore)
||250 mg (12 ml) given pre rectum
||5-10 mL / cat
|Lactulose (Cephulac. Merrell Dow; Duphalac, Reid Rowell)
||5-10 mL / cat
|Psyllium (Metamucil, Searle)
||1-4 tsp mixed with food, every 24 or 12 hours
||1-4 tsp mixed with food, every 24 hours
|Coarse wheat bran
||1-4 tblsp mixed with food, every 24 hours
|Dioctyl sodium sulfosuccinate (Colace, Mead Johnson)
||50 mg orally, every 24 hours
|Dioctyl calcium sulfosuccinate (Surfax, Hoechst)
||50 mg orally, every 24 or 12 hours as needed
||10-25 ml orally, every 24 hours
|Petrolatum (Laxatone, Evsco)
||1-5 ml orally, every 24 hours
|Lactulose (Cephulac, Merrell Dow, Duphalac, Reid Rowell)
||0.5 ml / kg orally, every 12 to 8 hours as needed
|Bisacodyl (Dulcolax, Boehringer Ingelheim)
||5 mg orally, every 24 hours
|Cisapride (compounding pharmacies)
||0.1-1.0 mg / kg orally every 12 to 8 hours
|Tegaserod (Zelnorm, Novartis) – dogs
||0.05-0.10 mg / kg orally, twice a day
|Ranitidine (Zantac, Claxo SmithKline)
||1.0-2.0 mg / kg orally, every 12 to 8 hours
|Nizatidine (Axid, Eli Lilly)
||2.5-5.0 mg / kg orally, every 24 hours
Removal of Impacted Feces
Removal of impacted feces may be accomplished through the use of rectal suppositories, enemas, or manual extraction.
A number of pediatric rectal suppositories are available for the management of mild constipation. These include dioctyl sodium sulfosuccinate (emollient laxative), glycerin (lubricant laxative), and bisacodyl (stimulant laxative). The use of rectal suppositories requires a compliant pet and pet owner. Suppositories can be used alone or in conjunction with oral laxative therapy.
Mild to moderate or recurrent episodes of constipation may require administration of enemas, manual extraction of impacted feces, or both. Several types of enema solutions may be administered, such as warm tap water (5 to 10 mL / kg), warm isotonic saline (5 to 10 mL / kg), dioctyl sodium sulfosuccinate (5 to 10 mL / cat), mineral oil (5 to 10 mL / cat), or lactulose (5 to 10 mL / cat). Enema solutions should be administered slowly with a well-lubricated 10 to 12F rubber catheter or feeding tube. Enemas containing sodium phosphate are contraindicated in cats because of their propensity for inducing severe hypernatremia, hyperphos-phatemia, and hypocalcemia in this species.
Cases unresponsive to enemas may require manual extraction of impacted feces. Cats should be adequately rchydrated and then anesthetized with an endotracheal tube in place to prevent aspiration should colonic manipulation induce vomiting. Water or saline is infused into the colon while the fecal mass is manually reduced by abdominal palpation. Sponge forceps may also be introduced rectally (with caution) to break down the fecal mass. It may be advisable to evacuate the fecal mass over a period of several days to reduce the risks of prolonged anesthesia and perforation of a devitalized colon. If this approach fails, colotomy may be necessary to remove the fecal mass. Laxative or prokinetic therapy (or both) may then be instituted once the fecal mass has been removed.
Laxatives promote evacuation of the bowel through stimulation of fluid and electrolyte transport or increases in propulsive motility. They are classified as bulk-forming, emollient, lubricant, hyperosmotic, or stimulant laxatives according to their mechanism of action. Hundreds of products are available for the treatment of constipation. Table Drug Index — Constipation summarizes those products that have been used with some success in cats.
Most of the available bulk-forming laxatives are dietary fiber supplements of poorly digestible polysaccharides and celluloses derived principally from cereal grains, wheat bran, and psyllium. Some constipated cats will respond to supplementation of the diet with one of these products, but many require adjunctive therapy (e. g., other types of laxatives or colonic prokinetic agents). Dietary fiber is preferable because it is well tolerated, more effective, and more physiologic than other laxatives. Fiber is classified as a bulk-forming laxative, although it has many other properties. The beneficial effects of fiber in constipation include increased fecal water content, decreaseo intestinal transit time, and increased frequency of defecation. Fiber supplemented diets are available commercially, or the pet owner may wish to add psyllium (1 to 4 teaspoon per meal), wheat bran (1 to 2 tablespoon per meal), or pumpkin (1 to 4 tablespoon per meal) to canned cat food. Cats should be well hydrated before commencing fiber supplementation to maximize the therapeutic effect. Fiber supplementation is most beneficial in mildly constipated cats, prior to the development of obstipation and megacolon. In obstipated and megacolon cats, fiber may in fact be detrimental. Low-residue diets may be more beneficial in obstipated and megacolonic cats.
Emollient laxatives are anionic detergents that increase the miscibility of water and lipid in digesta, thereby enhancing lipid absorption and impairing water absorption. Dioctyl sodium sulfosuccinate and dioctyl calcium sulfosuccinate are examples of emollient laxatives available in oral and enema form. Anecdotal experience suggests that dioctyl sodium sulfosuccinate therapy may be most useful in animals with acute but not chronic constipation. As with bulk-forming laxatives, animals should be well hydrated before emollient laxatives are administered. It should be noted that clincial efficacy has not been definitively established for the emollient laxatives. Dioctyl sodium sulfosuccinate, for example, inhibits water absorption in isolated colonic segments in vitro, but it may be impossible to achieve tissue concentrations great enough to inhibit colonic water absorption in vivo. Dioctyl sodium sulfosuccinate at a dose of 30 mg / kg / day had no effect on fecal consistency in beagle dogs. Further studies are required to determine the clinical efficacy and therapeutic role of dioctyl sodium sulfosuccinate in the management of the constipated cat.
Mineral oil and white petrolatum are the two major lubricant laxatives available for the treatment of constipation. The lubricating properties of these agents impede colonic water absorption and permit greater ease of fecal passage. These effects are usually moderate, however, and, in general, lubricants are beneficial only in mild cases of constipation. Mineral oil use should probably be limited to rectal administration because of the risk of aspiration pneumonia with oral administration, especially in depressed or debilitated cats.
This group of laxatives consists of the poorly absorbed polysaccharides (e. g., lactose, lactulose), the magnesium salts (e. g., magnesium citrate, magnesium hydroxide, magnesium sulfate), and the polyethylene glycols. Lactose is not effective as a laxative agent in all cats. Lactulose is the most effective agent in this group. The organic acids produced from lactulose fermentation stimulate colonic fluid secretion and propulsive motility. Lactulose administered at a dose of 0.5 mL / kg body weight every 8 to 12 hours fairly consistently produces soft feces in the cat. Many cats with recurrent or chronic constipation have been well managed with this regimen of lactulose. The dose may have to be tapered in individual cases if flatulence and diarrhea become excessive. Magnesium salts are not currently recommended in the treatment of feline constipation and idiopathic megacolon. Some veterinarians have reported anecdotal successes with the polyethylene glycols.
The stimulant laxatives (bisacodyl, phenolphthalein, castor oil, cascara, senna) are a diverse group of agents that have been classified according to their ability to stimulate propulsive motility. Bisacodyl, for example, stimulates NO-mediated epithelial cell secretion and myenteric neuronal depolarization. Diarrhea results from the combined effect of increased mucosal secretion and colonic propulsion. Bisacodyl (at a dose of 5 mg orally, every 24 hours) is the most effective stimulant laxative in the cat. It may be given individually or in combination with fiber supplementation for long-term management of constipation. Daily administration of bisacodyl should probably be avoided, however, because of injury to myenteric neurons with chronic use.
Colonic Prokinetic Agents
Previous studies of feline colonic smooth muscle function have suggested that stimulation of colonic smooth muscle contraction might improve colonic motility in cats affected with idiopathic dilated megacolon. Unfortunately, many of the currently available gastrointestinal prokinetic agents have not proved useful in the therapy of feline constipation, either because of significant side effects (e. g., bethanechol) or because the prokinetic effect is limited to the proximal gastrointestinal tract (e. g., metoclopramide, domperidone, erythromycin). The 5-HT4 serotonergic agonists (e. g., cisapride, prucalopride, tegaserod, mosapride) appear to have the advantage of stimulating motility from the gastroesophageal sphincter to the descending colon with relatively few side effects. Cisapride, for example, increases gastroesophageal sphincter pressure, promotes gastric emptying, and enhances small intestinal and colonic propulsive motility. Cisapride enhances colonic propulsive motility through activation of colonic neuronal or smooth muscle 5-HT receptors in a number of animal species. In vitro studies have shown that cisapride stimulates feline colonic smooth muscle contraction, although it has not yet been conclusively shown that cisapride stimulates feline colonic propulsive motility in vivo. A large body of anecdotal experience suggests that cisapride is effective in stimulating colonic propulsive motility in cats affected with mild to moderate idiopathic constipation; cats with long-standing obstipation and megacolon are not likely to show much improvement with cisapride therapy. Cisapride was widely used in the management of canine and feline gastric emptying, intestinal transit, and colonic motility disorders throughout most of the 1990s. Cisapride was withdrawn from the American, Canadian, and certain Western European countries in July 2000 after reports of untoward cardiac side effects in human patients. Cisapride causes QT interval prolongation and slowing of cardiac repolarization via blockade of the rapid component of the delayed rectifier potassium channel (IKr). This effect may result in a fatal ventricular arrhythmia referred to as torsades de pointes. Similar effects have been characterized in canine cardiac Purkinje fibers, but in vivo effects have not yet been reported in dogs or cats. The withdrawal of cisapride has created a clear need for new gastrointestinal prokinetic agents, although cisapride continues to be available from compounding pharmacies throughout the United States. Two new prokinetic agents, tegaserod and prucalopride, are in differing stages of drug development and may prove useful in the therapy of gastrointestinal motility disorders of several animal species.
Tegaserod is a potent partial nonbenzamide agonist at 5-HT4 receptors and a weak agonist at 5-HT1D receptors. Tegaserod has definite prokinetic effects in the canine colon, but it has not yet been studied in the feline colon. Intravenous doses of tegaserod (0.03 to 0.3 mg / kg) accelerate colonic transit in dogs during the first hour after intravenous administration. Tegaserod at doses of 3 to 6 mg / kg orally has also been shown to normalize intestinal transit in opioid-induced bowel dysfunction in dogs, and it may prove useful in other disorders of intestinal ileus or pseudo-obstruction. Gastric effects of tegaserod have not been reported in the dog, so this drug may not prove as useful as cisapride in the treatment of delayed gastric emptying disorders. In vitro studies suggest that tegaserod does not prolong the QT interval or delay cardiac repolarization as has been occasionally reported with cisapride. Tegaserod was marketed under the trade name of Zelnorm in the United States in September 2002 for the treatment of constipation-predominant IBS in women. As with many other drugs in companion animal medicine, tegaserod has not been licensed for the treatment of canine or feline gastrointestinal motility disorders.
Prucalopride is a potent 5-HT4 receptor agonist that stimulates giant migrating contractions and defecation in the dog and cat. Prucalopride also appears to stimulate gastric emptying in the dog. In lidamidine-induced delayed gastric emptying in dogs, prucalopride (0.01 to 0.16 mg / kg) dose-dependendy accelerates gastric emptying of dextrose solutions. Prucalopride has not yet been marketed in the United States or elsewhere.
Misoprostol is a prostaglandin E, analogue that reduces the incidence of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric injury. The main side effects of misoprostol therapy are abdominal discomfort, cramping, and diarrhea. Studies in dogs suggest that prostaglandins may initiate a giant migrating complex pattern and increase colonic propulsive activity. In vitro studies of misoprostol show that it stimulates feline and canine colonic smooth muscle contraction. Given its limited toxicity, misoprostol may be useful in cats (and dogs) with severe refractory constipation.
Ranitidine and nizatidine, classic histamine H2 receptor antagonists, may also stimulate canine and feline colonic motility. These drugs stimulate contraction apparently through inhibition of tissue acetylcholinesterase and accumulation of acetylcholine at the motor endplate. It is not yet clear how effective these drugs are in vivo, although both drugs stimulate feline colonic smooth muscle contraction in vitro. Cimetidine and famotidine, members of the same classification of drug, are without this effect.
Colectomy should be considered in cats that are refractory to medical therapy. Cats have a generally favorable prognosis for recovery after colectomy, although mild to moderate diarrhea may persist for weeks to months postoperatively in some cases. Although pathologic hypertrophy may be reversible with early pelvic osteotomy in some cases, subtotal colectomy is an effective treatment for this condition regardless of duration, and pelvic osteotomy is not required.
Prognosis of Constipation
Many cats have one or two episodes of constipation without further recurrence, although others may progress to complete colonic failure. Cats with mild to moderate constipation generally respond to conservative medical management (e. g., dietary modification, emollient or hyperosmotic laxatives, colonic prokinetic agents). Early use of colonic prokinetic agents (in addition to one or more laxative agents) is likely to prevent the progression of constipation to obstipation and dilated megacolon in these cats. Some cats may become refractory to these therapies, however, as they progress through moderate or recurrent constipation to obstipation and dilated megacolon. These cats eventually require colectomy. Cats have a generally favorable prognosis for recovery after colectomy, although mild to moderate diarrhea may persist for 4 to 6 weeks postoperatively in some cases.