Current therapies to shorten postoperative ileus
ABSTRACTPostoperative ileus delays hospital discharge, increases costs, and contributes to adverse outcomes. A variety of neural and chemical factors are involved. To shorten the duration of postoperative ileus, we may need to establish standard plans of care that favor earlier feeding, use of nasogastric tubes only on a selective basis, and prokinetic drugs as needed.
KEY POINTS
- Postoperative ileus can selectively affect the stomach, small intestine, or large intestine, each with different causes and clinical presentation and each managed differently.
- Laparoscopic surgery is associated with a shorter duration of postoperative ileus compared with open surgery.
- Epidural anesthesia reduces the need for opiate analgesia after surgery and thus shortens the duration of postoperative ileus.
- Drugs are being developed that block the effects of opiates on the gut while preserving their pain-relieving properties.
Sympathetic-parasympathetic imbalance
The sympathetic nervous system inhibits the small bowel; the parasympathetic nervous system stimulates it. Although vagal (parasympathetic) stimulation appears to have little actual impact on small-bowel activity, if sympathetic activity is blocked, contractility increases, indicating that tonic sympathetic inhibition normally predominates. The balance of these two competing influences determines the amount of acetylcholine released by excitatory nerve fibers in the myenteric plexi of the bowel.
These neural pathways can be manipulated clinically. Epidural catheters can block sympathetic output, thus allowing small-bowel function to return faster.
Vagus nerve activity appears to be more important in the stomach, where it promotes receptive relaxation of the fundus and contraction of the antrum, facilitating gastric emptying.10 After vagotomy, emptying of liquids may be normal or accelerated, but emptying of solids is impaired. This can occur after peptic ulcer surgery but is more likely after gastric resection for malignancy or after inadvertent vagal nerve injury during antireflux surgery.
The enteric nervous system is a complex, intrinsic network of neurons consisting of two distinct plexi within the bowel wall: the submucosal (Meissner) plexus, and the myenteric (Auerbach) plexus.11 The enteric nervous system in the small bowel is fundamentally different than the one in the colon in that the former contains gap junctions, allowing for coordinated electrical activity. Lacking these gap junctions, the colon depends more on input from the autonomic nervous system, perhaps explaining the longer recovery from postoperative ileus and the susceptibility to isolated colonic ileus due to a variety stressors and traumatic insults.12
Chemical mediators of bowel activity
A host of chemical mediators influence bowel motility. Perhaps the most important nonadrenergic inhibitor of gastrointestinal motility is nitric oxide.13 Animal studies have firmly established nitric oxide as an important factor in postoperative ileus, but its exact role in humans is not clear.14,15
Other mediators with possible roles include vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, and endogenous opioids.13 Lack of duodenal-derived motilin is thought to be one cause of delayed gastric emptying after pancreaticoduodenectomy.2
Inflammation
The inflammatory response after surgery has also been an attractive target of study of the factors promoting postoperative ileus. In rat studies, Kalff et al16 found that surgical manipulation of the bowel induced an inflammatory cellular infiltrate in the bowel wall and diminished the response of smooth muscle to cholinergic stimulation. Cyclooxygenase-2, the enzymatic precursor to prostaglandins, has also been shown to be induced in enteric neurons after laparotomy.17
Narcotic analgesics
One of the greatest hurdles in preventing postoperative ileus is the use of narcotic analgesics to treat postoperative pain. It is also one of the most important modifiable risk factors.
Opiates delay colonic transit in postoperative patients, an effect that can be reversed by the narcotic antagonist naloxone (Narcan).18 This inhibitory effect is mediated by peripheral mu-opioid receptors. In a study of patients undergoing colectomy, the more morphine given, the longer the time to the return of bowel sounds and flatus and the first bowel movement.19
These observations have led to a search for selective opiate antagonists that allow narcotics to continue relieving pain while counteracting their effect on bowel motility, a topic discussed later in this review.
Nonsteroidal anti-inflammatory drugs such as ketorolac (Toradol) are attractive alternatives to opiate analgesics, both for their anti-inflammatory effect and for their opiatesparing properties. However, they can cause bleeding, renal insufficiency, and gastritis, drawbacks that limit their applicability and duration of use.
DIAGNOSIS BY CLINICAL SUSPICION AND IMAGING
The diagnosis of postoperative ileus is driven by a combination of clinical suspicion and imaging tests.
Regardless of the segment of bowel involved, it is imperative to exclude an obstructive cause. The diagnosis of ileus is presumed once obstruction has been excluded.
Diagnosing gastroparesis
Postoperative gastroparesis is usually suspected by its symptoms of early satiety, nausea, vomiting, eructation, and gastroesophageal reflux. Abdominal distention is usually not a prominent sign, but a succussion splash may be detected, indicating retention of food and liquid in the stomach.
Plain radiographs may reveal a large gastric air bubble in the left upper quadrant but may underestimate the degree of gastric distention. Computed tomography (CT) may show a large, fluid-filled stomach, often containing high-density food debris.
The gold standard for diagnosis is gastric emptying scintigraphy after a radiolabelled solid meal. The patient consumes a meal of egg white labelled with technetium 99m sulfur colloid, and scanning is performed at specified intervals to measure the percent retention of the isotope. Retention of more than 10% at 4 hours is considered abnormal.1 Severity can be graded on the basis of percent retention after 4 hours.20
This test is rarely indicated in the acute postoperative setting, however, and patients should be treated presumptively to prevent aspiration once mechanical obstruction is excluded.
Diagnosing small-bowel ileus
Small-bowel ileus often presents like gastroparesis, except that it more often causes abdominal distention. Plain radiographs reveal air-fluid levels and dilated loops of bowel.
Small-bowel ileus must then be differentiated from small-bowel obstruction by clinical and radiographic features. The presence of crampy abdominal pain, bowel sounds, and some bowel function implies a degree of mechanical obstruction. Plain radiographs showing “step-ladder” air-fluid levels also suggest obstruction. CT is more definitive in diagnosing obstruction by the presence of distended and decompressed bowel loops and may also reveal a source of obstruction (eg, postoperative interloop abscess).
Diagnosing colonic ileus
Colonic ileus is also characterized by abdominal distention, sometimes marked. Although it is the colon that is primarily involved, upstream small-bowel dilatation can also be seen if the ileocecal valve is incompetent. The cecum often shows the greatest degree of dilatation on plain radiographs and is at the greatest risk of perforation. CT, contrast enema studies, and endoscopy help rule out mechanical obstruction due to volvulus or a mass lesion.
