Ileus

Ileus, also known as adynamic ileus, paralytic ileus, postoperative ileus, or intestinal dysmotility is a transient and usually reversible intestinal obstruction caused by delayed intestinal motility. Intestinal contents fail to progress aborally because of ineffective intestinal propulsion in the absence of mechanical occlusion of the lumen. Ileus is clinically manifested by abdominal distension, lack of bowel sounds, delayed passage of ingesta, and accumulation of gas and fluid in the bowel that may lead to nausea and vomiting. The exact pathophysiologic basis of ileus is unknown but is likely multifactorial with three major interrelated mechanisms -- neurogenic, inflammatory, and pharmacologic - leading to its development [1]. It is among the most significant side effects of abdominal surgery in humans and horses, accounting for increased morbidity and prolonged hospitalization. The condition is less well understood in small animals. Whether it is less prevalent or whether the clinical signs are less severe than in other species is unclear.

Etiology

Ileus may be caused by a wide variety of intraabdominal, extra-abdominal, and systemic conditions, in addition to a host of chemical and pharmacologic agents (Table 36-1). Peritoneal inflammation, caused by infection, bile leakage, pancreatic enzymes, or surgery, can induce ileus in small animals. Systemic derangements owing to sepsis and electrolyte imbalances are also associated with ileus. In addition, ileus can be pharmacologically initiated via the administration of opioids, anticholinergic drugs, and the phenothiazine tranquilizers. Reported extra-abdominal causes may include systemic toxicity, uremia, spinal cord trauma, shock, and prolonged anesthesia [2]. Extra-abdominal thoracic lesions such as pneumonia, myocardial infarction, congestive heart failure, or rib fractures are reported causes of ileus in humans, but these remain undocumented in the dog and cat. Abrasion of the intestinal serosal surfaces with dry surgical sponges creates an ileus model in dogs that is used to study the human disease [3]. Postoperative ileus is inherent to any intra-abdominal surgical procedure, but its severity and duration appear less with laparoscopic procedures [1].

Neurohormonal Mechanisms of Ileus

Parasympathetic (cholinergic) stimulation increases intestinal motility and secretion, whereas sympathetic (adrenergic) stimulation results in reduced motility and an increase in sphincter tone. Postoperative ileus may occur secondary to sympathetic hyperactivity and parasympathetic hypoactivity. Evidence of increased circulating levels of epinephrine and norepinephrine following abdominal surgery supports this theory. Stimulation of the sympathetic nervous system inhibits the interdigestive motor complexes that ordinarily propel the bowel contents aborally. Release of norepinephrine also appears to inhibit release of excitatory neurotransmitters such as acetylcholine, thereby allowing the inhibitory neurons to dominate [2]. The protective effect of alpha and beta sympathetic nerve blockers, splanchnic nerve division, or spinal anesthesia against the development of postoperative ileus in dogs and cats further supports this concept [3].

The dog normally undergoes a period of reduced myoelectric activity after exploratory laparotomy. Studies in dogs have shown that normal small intestinal myoelectric activity usually resumes by 12 hours postoperatively, whereas gastric paresis persists for approximately 24 hours. Colonic motility is most affected; normal status does not return until approximately 48 hours after laparotomy [4]. Myoelectric slow waves still exist in the outer longitudinal muscles with ileus but do not initiate action potentials and associated contractile activity within the circular muscle layers. This electromechanical dissociation appears to result from a tonic discharge of inhibitory neurons and an absence of spike waves. Because the presence of ingesta may stimulate parasympathetic tone and resultant contractile activity, surgeons have noted that patients receiving enteral alimentation in the immediate postoperative period experience less postoperative ileus than do patients who are made to fast [1].

Humoral intestinal peptides may also contribute to the pathophysiology of postoperative ileus. The hormone vasopressin disrupts jejunal motility and occurs in high levels in plasma following laparotomy, whereas the prokinetic hormones motilin and neurotensin stimulate small-intestinal activity and are suppressed for 24 hours following laparotomy [4]. Return of motilin to normal levels corresponds with return of motility. Release of endogenous opiates has also been proposed as a cause of ileus. Although naloxone does not relieve postoperative ileus in dogs, fedotozine, a k-opioid agonist does restore intestinal motility in rats [5].

Electrolyte imbalances have been associated with experimental ileus in dogs. A significant reduction in intestinal propulsion is associated with decreases in serum sodium and chloride values. Potassium deficits may play a more profound role than the sympathetic nervous system in the development of ileus. Hypokalemia may negatively effect the exchange of cellular potassium for plasma hydrogen ions when acidosis is present and greatly reduce smooth muscle contractility [6].

Progression of Ileus

Ileus may affect the entire gastrointestinal tract or may be localized to one area. Obstruction in any one segment of the intestine may secondarily affect the rest of the intestinal tract via an intestinointestinal reflex whereby distention of bowel in one area inhibits motility in other areas. Therefore, segmental ileus can ultimately become diffuse. With prolonged ileus, pathophysiologic changes are similar to those seen in simple mechanical obstruction. Although there is no physical barrier to the passage of ingesta, the bowel becomes functionally obstructed owing to lack of effective intestinal motility. The lumen of the adynamic segment fills with swallowed air, gas from bacterial fermentation, ingested fluids, and secretions from the stomach, pancreas, intestine, and biliary tract. During ileus, these fluids are not resorbed and additional fluids are secreted from the distended gut wall. The net loss of circulating intravascular fluid results in dehydration and ensuing hypovolemic shock [3].

Unresolved ileus perpetuates a vicious cycle, whereby distention promotes further ileus, which leads to greater distention. Prolonged ileus may also result in diffuse intestinal damage as a result of lymphatic and venous obstruction. Mucosal arteriovenous shunting, hypoxia, ischemia, and necrosis may all result. Early ischemia of the bowel wall initially results in hypermotility and spasms; complete cessation of motility occurs as the bowel-wall ischemia progresses toward necrosis. Similar to simple mechanical obstruction, bacterial overgrowth occurs, and endotoxins may be produced in larger quantities than normal. In severe cases of long-standing ileus, transmural migration of bacteria and endotoxins may result in signs consistent with septic shock.

Pain-Induced Ileus

Animals that have post-laparotomy ileus characteristically do not show severe abdominal pain, although those that develop ileus secondary to septic peritonitis show abdominal splinting and clinical signs associated with abdominal pain. The mechanism of ileus secondary to peritonitis is a direct result of noxious stimuli of the abdominal viscera and parietal peritoneum. Visceral pain impulses stimulate sympathetic splanchnic nerves, which traverse the splenic ganglion and sympathetic chain to increase sympathetic tone. The inflammatory response must involve multiple nerve endings and be acute in order to create visceral abdominal pain (colic). This adrenergic stimulation of receptors in the gut wall is thought to inhibit intestinal motility.

Nerve endings of pain fibers are located in the submucosa of the bowel wall. Therefore, any process that causes fluid or gaseous distention, intestinal obstruction, forceful contraction, hypersegmentation, or traction (adhesions) may produce pain. Inflammation, whether it be secondary to peritonitis or due to tissue ischemia produces abdominal pain by creating a local intestinal inflammatory response, which leads to the subsequent release of cytokines (TNF, IL-1, IL-6, IL-8) [7]. Nerve endings are also plentiful in the parietal peritoneum, and these are sensitive to the massive inflammatory response. This is why the splenic rigid abdominal posture and resistance to palpation are seen in most cases of ileus secondary to generalized peritonitis [8].

Drug-Induced Ileus

Postoperative pain can cause bowel stasis, abdominal distention, discomfort, and vomiting. Analgesic intervention may alleviate these signs but may also have the potential to exacerbate ileus. Perioperative administration of drugs that inhibit intestinal motility may potentiate the severity of ileus in the postoperative period. In dogs, opioids such as morphine or hydromorphone act as gastrointestinal µ2 receptor agonists. They cause stasis by decreasing longitudinal muscle propulsive motility and increasing segmental contractions. Other opiates such as loperamide decrease pancreatic and biliary secretions and have antisecretory effects on the bowel that contribute to their antidiarrheal properties [1]. The effect on motility of other opioids such as butorphanol or pentazocine at recommended analgesic doses appears less inhibitory in dogs [9].

The use of analgesics is particularly important with regard to intestinal motility in cats. The combination of ketamine (5 mg/kg) and midazolam (0.1 mg/kg) decreases gastrointestinal motility. Intramuscular acepromazine at 0.1 mg/kg combined with buprenorphine 0.01 mg/kg or medetomidine (50 µg/kg) does not affect orocecal transit time when used for short periods; however, oral buprenorphine used over several days may slow transit time [10]. Transdermal fentanyl patches do not seem to slow motility in dogs or cats. Anesthetic regime also will affect the incidence of postoperative ileus. In human medicine, the use of short-acting induction agents such as propofol, rapidly cleared inhalants such as sevoflurane, and minimally inhibitory opiates such as fentanyl is a preferred regime in the prevention of postoperative ileus [9].

Clinical Signs

Clinical signs associated with ileus in dogs and cats are often obscure. Small-animal clinicians rarely auscultate the abdomens of their patients so reduction in intestinal sounds and borborygmi may be inconsistent findings. Gross abdominal distention may be present, and evidence of fluid and gas distention of the small intestine may be noted on radiographs or ultrasonography. Distended loops of bowel also may be present on abdominal palpation. Loops of bowel distended by ileus are generally not as large, turgid, or painful as those distended by simple mechanical or strangulation obstruction. In long-standing cases of ileus, feces may be minimal or absent. In the absence of peritonitis, pain is not usually associated with ileus unless intestinal distention becomes severe. Gastric reflux on intubation is a hallmark of intestinal ileus in horses and humans, but its significance in small animals appears minimal [2].

Treatment

Ileus that is uncomplicated and not associated with organic obstruction often resolves spontaneously without aggressive treatment. Early postoperative feeding is recommended to stimulate gastrointestinal motility and speed intestinal wound healing in patients recovering from gastrointestinal surgery. Failure of ileus to resolve spontaneously indicates that mechanical obstruction, strangulation obstruction, or septic peritonitis may be present. Abdominocentesis may be indicated to differentiate simple ileus from more severe strangulation obstruction.

Successful treatment of ileus involves the correction of concurrent electrolyte imbalances, elimination of underlying abdominal disease (including decompression of the distended bowel when possible), and possibly, promotilility drug therapy. Dehydration and serum electrolyte and acid-base status imbalances should be corrected. Serum potassium concentration is particularly important, because the concurrent movement of potassium from the extracellular to the intracellular space may result in hyperkalemia or hypokalemia. In the case of hypokalemia, supplementation with intravenous potassium is indicated. Bicarbonate supplementation may also be indicated to correct metabolic acidosis.

Because most cases of paralytic ileus in dogs and cats resolve spontaneously, the presence of continued, unaccounted for intestinal distention should warn the clinician of a residual problem that warrants exploratory laparotomy. Any areas of devitalized bowel must be removed at surgery. Gas and fluids should be removed from remaining distended loops of bowel, using a 22-gauge needle and continuous-suction apparatus. An indwelling nasogastric tube may also be placed, to decompress the stomach in the postoperative period. Continuous or intermittent suction can be applied to these tubes to facilitate continued gastric and intestinal decompression in the postoperative period.

Pharmacologic Therapy

Administration of drugs to stimulate intestinal motility and counteract the effects of ileus has not been consistently successful. Sympathetic blockade, parasympathetic stimulation, or both have been advocated. The anticholinesterase drug neostigmine does increase propulsive motility of the colon, although it decreases propulsive motility of the jejunum and delays gastric emptying. Pain may also occur secondary to intestinal spasm. In addition, neostigmine may increase the risk of anastomotic dehiscence and, therefore, is not recommended [3].

Sympathetic nervous system blockade with phenothiazine derivatives such as chlorpromazine has been used to treat postoperative ileus in humans. This drug is a sympathetic alpha-blocker, which can potentiate shock. Therefore, animals should be well hydrated and their cardiovascular status stable before acetylpromazine or chlorpromazine is administered [1]. Sympathetic blockage with topical analgesics or opioids has been shown to counteract ileus in people, but is little used in dogs.

Metoclopramide is an anti-dopaminergic drug that appears to enhance coordination of gastroduodenal motor activity. Its gastrointestinal smooth muscle action is thought to result from antagonism of the inhibitory neurotransmitter dopamine; however, it now appears that metoclopramide acts to directly enhance gastrointestinal motility by augmenting release of acetylcholine, and perhaps by inhibiting serotonin release. Metoclopramide was shown to reverse decreased gastrointestinal myoelectric and contractile activity in surgically created adynamic ileus in dogs but its efficacy in humans is questionable [1,11]. Metoclopramide may decrease nausea and vomiting owing to its gastric effects rather than by correcting postoperative ileus.

Cisapride is a benzamide drug that stimulates gastrointestinal motility, most likely by facilitating acetylcholine release from myoenteric nerves. Unlike metoclopramide, cisapride possesses no antidopaminergic properties. In addition, it has no effect on gastrointestinal secretion. Experimentally it has been shown to increase lower esophageal sphincter tone, accelerate gastric emptying, and accelerate colonic transit. Experimental work in dogs indicates that cisapride increases the amplitude of intestinal peristaltic waves [12]. The drug was withdrawn from North American and Western European markets in 2000 owing to reported cardiac effects in people, but the drug is still available through compounding agencies in the United States. A new human prokinetic agent, tegaserod may prove useful in therapy of intestinal motility disorders of animals in the future. Tegaserod is a potent partial non benzamide agonist without the effect of prolonging cardiac QT intervals as does cisapride. Tegaserod at doses of 3 to 6 mg/kg has been shown to normalize intestinal transit time in opioid-induced bowel dysfunction in dogs [13].

Nonsteroidal anti-inflammatory drugs may reduce the incidence of ileus by reducing postoperative pain and inflammation. The Cox-2 inhibitors in particular are thought to reduce the risk and duration of postoperative ileus in people, in part owing to reduction in the need for opiates by as much as 30% [1]. This, of course, must be balanced with the increased tendency toward gastrointestinal bleeding and nephrotoxicity.

Opioid antagonists such as naloxone and alvimopan have been used in human medicine in an attempt to reduce postoperative ileus. Naloxone has been unsuccessful but alvimopan was shown to reduce the incidence of postoperative ileus if given before surgery [1].

Experimental work has demonstrated that electrical pacing can alter frequency and direction of propagation of the enteric myoelectric pacesetter in dogs. Potentially, antegrade pacing might be expected to enhance gastric or intestinal emptying or to play a positive role in disorders of intestinal atony or stasis. Although these studies are experimental, clinical use may be feasible in the future [3].

Summary

Motility of the intestinal tract depends on a highly integrated and coordinated response of the smooth muscle of the bowel wall. Motility of the small and large intestine is controlled by three basic mechanisms: myogenic, neural, and humoral. Present understanding of the control mechanisms and the physiologic and pathologic states that initiate ileus is not complete; however, it can be said that motor disorders usually affect the entire gastrointestinal tract. The disorders can be intrinsic to the gut wall itself, can be caused by an inflammatory process or myogenic dysfunction, or can result from inflammation of the bowel.

Surgical therapy is seldom indicated for the treatment of adynamic or postoperative ileus. Promotility agents, including metoclopramide, cisapride, and tegaserod may be useful in the supportive treatment of hypomotility disorders. Opiates prolong gastrointestinal transit time and may compound the problems seen with ileus. Opioid antagonists may show promise as potentiators of intestinal motility in the future. Laparoscopic procedures show promise of reducing the incidence and severity of postoperative ileus when compared with open laparotomy.