Short Bowel Syndrome

Short bowel syndrome (SBS) has been described in people for over 30 years. Despite being a well-recognized syndrome for decades, however, we do not yet have a universally accepted definition [1]. Occurring after major intestinal resection, the key features of SBS in people are generally acknowledged to include dehydration (caused by diarrhea), malabsorption, and subsequent malnutrition severe enough to cause morbidity and put the patient at risk for death. The best definitions of SBS generally describe the constellation of signs caused by resection of excessive amounts of intestine (i.e., dehydration, malabsorption) or their consequences, rather than the amount of intestine resected. For example, one definition of human SBS is based on intestinal failure following resection being so severe that the patient needs parenteral nutrition for more than 1 to 3 months post-surgery [1].

Trying to define SBS based on how much bowel has been resected creates problems. Even though most surgeons agree that having less than 25% of the expected intestinal length left is almost always associated with SBS in people, one must also consider what portion of the bowel was resected (i.e., jejunum, ileum, colon), the functionality of the remaining bowel, and the body condition of the patient. For example, if one resects 65% of a person's intestines but leaves the ileum and colon intact, there is much less chance of SBS than if the ileum and colon were resected [2]. Furthermore, it has been stated that removal of the ileocolic valve is associated with a poorer prognosis; however, this seems to be based on a study in puppies [3] and may not be true for people. In fact, although most papers describe how much intestine was removed, it would probably be more important to know how many centimeters of intestine remain in the patient, and which segments of bowel were left.

SBS in Veterinary Medicine

Defining SBS in veterinary medicine has principally consisted of taking the criteria used in people and applying them to dogs and cats. Part of the reason for this is that, while SBS is generally well recognized in people, only a handful of cases are reported in the veterinary literature [4,6]. This paucity of reports is probably because veterinary patients with such a guarded-to-poor prognosis and requiring intense therapy (total parenteral nutrition) for long periods of time are typically euthanatized instead of treated. Therefore, much of the discussion of SBS in dogs and cats must draw on experimental work done in dogs and rats, as well as on clinical reports in people. Obviously substantial species differences may exist, and one must be cautious about extrapolating from human beings to dogs and cats. For example, people are usually expected to develop SBS if more than 75% of the intestines are resected, but dogs have been reported to tolerate 80% to 85% resection and function well postoperatively [3,5,7,8]. Therefore, SBS in veterinary medicine should probably be defined by the inability of the patient to compensate adequately after massive intestinal resection as seen by the need for protracted nutritional/pharmacologic therapy to keep the patient alive until intestinal adaptation occurs.

Intestinal Adaptation

Adaptation refers to the functional and structural changes that occur in the intestines as they attempt to increase fluid and nutrient absorption to pre-resection levels. The primary goal of therapy of the patient with SBS is generally to maintain the patient until sufficient intestinal adaptation can occur so that parenteral nutrition may cease.

Shortly after massive intestinal resection, the remaining intestines begin to adapt by increasing in length and diameter. Hypertrophy and hyperplasia occur of all layers of the remaining intestines [1], with epithelial hyperplasia in the intestinal crypts beginning within two to three days. Hyperplasia of the intestinal epithelium is one of the most important events [2]. The mechanisms for this adaptation are probably multifactorial and may include secretions from the remaining gastrointestinal tract (e.g., pancreatic) and various hormones, growth factors, and cytokines. However, the presence of enteral nutrition may in fact be the most important factor required for adaptation to occur. Studies in dogs [9] showed that enteral nutrition is associated with intestinal adaptation, whereas dogs feed strictly parenterally showed no evidence of intestinal adaptation. The composition of the enteral nutrition may be similarly critical. It is believed that complex nutrients are more trophic to the intestinal mucosa than are simple nutrients, and long-chain unsaturated fats may be the most important nutrients in this regard.

As intestinal adaptation takes place, usually some degree of dilatation of the diameter of the bowel lumen occurs [9], which in turn, results in some degree of stasis of luminal contents [10]. Changes can also occur in intestinal myoelectrical activity that slow the velocity of duodenal and jejunal motor activity [11]. Whereas these changes are designed to aid in digestion and absorption of nutrients by prolonging the exposure of the intestinal mucosa to the nutrients, they also have some potential disadvantages. A dilated small intestine with slowed motility can promote bacterial overgrowth. Administering drugs designed to increase transit time (e.g., opioids such as loperamide) can make this situation even worse. In some patients, poor gut motility coupled with bacterial overgrowth can lead to bacterial translocation from the intestines to the blood, mesenteric lymph nodes, and spleen [1].

Another problem that can be caused by an altered gut anatomy plus bacterial flora changes is d-lactic acidosis. When nutrients are malabsorbed in the small bowel, substantially increased amounts of carbohydrates may enter the colon. Colonic metabolism of these carbohydrates can result in acidification of the colon with subsequent overgrowth of bacteria that tolerate acidic environments, such as Lactobacilli. If overgrowth of Lactobacilli occurs, overproduction and subsequent absorption of d-lactate may follow as well [12]. The resulting acidosis can be so severe as to make patients weak and encephalopathic.

In people, intestinal adaptation may require months to years of support (i.e., parenteral nutrition to maintain the patient plus enteral nutrition to stimulate adaptation) before the intestines regain sufficient function and can maintain the patient without parenteral support [1]. No obvious, recognized relationship exists between the residual intestine length and the time required for adaptation. In general, about 75% of people with SBS ultimately adapt and are able to stop parenteral nutrition. In general, children seem to have more potential than adults to have successful intestinal adaptation, but this depends on many factors [1].

Treatment

The most important aspect of treating SBS is trying to avoid massive resection in the first place. For example, when faced with a condition that seems to require massive intestinal resection, it may be better to leave questionable tissue instead of resecting it, even though a second operation will be required 1 to 3 days later to assess the viability of tissue left the first time. The risks involved with performing a second surgery may be less than the risks occurring if SBS develops.

If SBS occurs or seems highly likely to develop, then aggressive medical management is the first step. The first phase of therapy consists of stabilizing the patient; this generally requires up to 4 weeks in affected people [13]. Administration of intravenous fluids is generally required to maintain hydration as well as normal electrolyte and acid-base status. Oral rehydration solutions have been reported to be beneficial in some human patients [14], but they have not replaced IV administration. Nutrition is best started sooner rather than later. If one anticipates SBS, then parenteral nutrition can begin two to three days after surgery. Partial parenteral nutrition is easier than total parenteral nutrition, but if long-term therapy is needed, and it usually is, then total parenteral nutrition may be preferable [13].

The second phase of therapy consists of promoting intestinal adaptation by gradually increasing the amount of nutrients entering the intestines. Enteral nutrition should usually begin shortly after starting parenteral nutrition (during the first phase of therapy). Various studies have looked at the addition of glutamine and various other nutrients, hormones (e.g., growth hormone [15]), and/or enzymes (e.g., pancreatic enzymes [16]) to the enteral diet, but none has been shown to help unequivocally [13,14]. Use of hydrolyzed diets has not been shown to be beneficial in human infants with SBS [17]. People with SBS are generally expected to malabsorb 30% to 50% of ingested nutrients; therefore, these patients are often fed 50% more than their calculated caloric requirement [10]. Owing to the intestines' reduced ability to absorb water and nutrients, it is important to start administering relatively small amounts of more dilute enteral diets and gradually increase the volume, lest severe diarrhea occur with subsequent dehydration [18]. Therefore, a constant-rate infusion of enteral diet as opposed to bolus feeding is usually preferred. In people with SBS, the presence or absence of a colon affects the choice of diet [19]. For example, patients with colons can obtain energy from bacterial fermentation of carbohydrates within the colon. Whether the same occurs in dogs is unknown.

Initiating enteral nutrition is typically associated with severe diarrhea. Therefore, antidiarrheals (e.g., loperamide) have typically been used [13]. In people, loperamide has seemed more effective than other opioids [10]. However, the decreased intestinal absorption that characterizes SBS often means that higher than normal doses may be required. In some cases, IV administration is necessary. Occasionally, a combination of loperamide and another opioid (e.g., codeine) is necessary.

Gastric hypersecretion is commonly seen after massive intestinal resection [10,20] and seems to contribute substantially to the diarrhea. Therefore, inhibition of gastric secretion with H-2 receptor antagonists (e.g., famotidine) or proton pump inhibitors (e.g., omeprazole) is often necessary as well. Peptic ulcer disease and gastroesophageal reflux are recognized complications of SBS in people, ostensibly due, at least in part, to the gastric hypersecretion [10]. Rarely, somatostatin analogs (e.g., octreotide [10]) or other drugs (e.g., clonidine[21]) are required to control intestinal hypersecretion in people with SBS.

Bacterial overgrowth, for reasons stated earlier (intestinal dilatation, loss of ileocolic valve, altered motility), is a concern in human patients with SBS. In addition, pharmacologic suppression of gastric acid secretion necessary to minimize problems caused by gastric hypersecretion may help enable such overgrowth. The term "small bowel bacterial overgrowth" is controversial in dogs and cats, and the criteria used to diagnose small bowel bacterial overgrowth in people are not clearly appropriate for dogs and cats [22,23]. Nonetheless, dogs can have antibiotic-responsive enteropathies apparently caused, at least in part, by excessive numbers of bacteria in the small intestines [23,24].

Bacterial overgrowth is usually suspected either when there is failure to respond to apparently appropriate therapy, or when unexpected weight loss occurs in a previously stable patient. Antibiotic therapy is often utilized in these patients. One cannot hope to eliminate all bacteria from the remaining small intestines; rather, one seeks to decrease the number of bacteria so that they no longer cause disease. Tetracycline, tylosin powder, metronidazole plus enrofloxacin, and cephalosporins are examples of therapy that have been used for this problem in veterinary medicine [25]. One must often experiment to see which antibiotic(s) will be most effective in a particular patient. Periodic rotation of antibiotics is sometimes practiced in people in an effort to prevent selection of resistant bacteria inhabiting the dilated section of intestine. Restriction of carbohydrates, use of probiotics (with or without concurrent prebiotics [26]), periodic small bowel irrigation with balanced hypertonic electrolyte solution [27], and surgery (to reduce the lumen of the bowel [1]) have also been used to try to reduce bacterial overgrowth in affected people.

In people, the goal of therapy is eventually to wean the patient from parenteral nutrition (i.e., adequate intestinal adaptation occurs) and be able to maintain the patient on enteral nutrition. When this happens, one must consider whether supplementation of micronutrients (e.g., zinc, magnesium, cobalamin, fat-soluble vitamins) will be required. Some patients do not respond adequately to medical management alone.

Cases of SBS reported in Veterinary Medicine

To date, seven cases of canine SBS have been reported in the veterinary literature. The first case was a 12-month-old German shorthaired pointer that had an intussusception [5]. It was reported to have 1.5 meter of small bowel remaining and was euthanatized within eight weeks of surgery. The second case was an 8-year-old dog that had surgery 15 months prior to admission. It was euthanatized approximately six weeks after admission and had 66 cm of small and large intestines remaining [4]. Next there was a series of four dogs [6]. Three of these dogs (i.e., a 4-year-old pointer, a 4-month-old German shepherd, and an 8-year-old German shepherd) died within three months of surgery. One of these three dogs (i.e., the 4-year-old pointer) did well initially and declined only after it refused to eat the prescribed diet. It had received total parenteral nutrition promptly after surgery. The dog that did well was lost to follow up after 27 months. The last report is of a 10-year-old Doberman pinscher that had approximately 80% of its intestines, including the ileocolic valve resected. It did well and was primarily treated with enteral nutrition [28].

Surgical Therapy of SBS

Surgery is considered in humans with SBS when it appears that medical/nutritional management will be inadequate. Intestinal transplantation seems to hold the most promise. It is unreported in clinical veterinary medicine but has been performed experimentally in dogs []. Surgical therapy of SBS has principally aimed at decreasing the diameter and/or increasing the length of the remaining intestines. Various techniques are reported in human SBS patients (e.g., intestinal tapering and plication, antiperistaltic segments, creation of intestinal valves, longitudinal lengthening, serial transverse enteroplasty, colonic interposition), and specific indications exist for each surgery [1]. For example, patients with a short, dilated bowel are candidates for serial transverse enteroplasty, whereas those with a dilated bowel that is sufficiently long might be managed by simple tapering enteroplasty. Because we have minimal experience with these techniques in clinical veterinary medicine, it appears that such surgeries should be reserved for those patients in which aggressive medical/nutritional management has failed or appears likely to fail.