Erythromycin therapy did not resolve postoperative ileus in patients who underwent abdominal surgery in the prospective, randomized clinical trials conducted. Cisapride is a serotonin agonist that facilitates acetylcholine release from the intrinsic plexus. At least 9 randomized clinical trials - have been performed on patients treated with cisapride for postoperative ileus after undergoing various surgical procedures.
However, comparison of these studies is difficult because various end points were used, patients underwent different surgical procedures, and the doses, durations, and routes were variable. In 4 studies, - there was a statistically significant reduction in postoperative ileus. Although these results are encouraging, just as many studies , , reported no statistically significant effects.
The questions regarding the effectiveness of cisapride will remain as it has been removed from the market for deleterious side effects. Ceruletide is a synthetic peptide that may enhance gastrointestinal motility by acting as a cholecystokinin antagonist.
Further investigation is needed before clinical use can be recommended. Octreotide is an analogue of somatostatin that is known to inhibit the secretion of many gastrointestinal hormones. Cullen et al showed that octreotide therapy shortens the duration of ileus in the small intestine and colon of dogs. However, clinical studies are needed to prove its efficacy in humans. Gum chewing may be a simple but effective treatment for postoperative ileus.
Asao et al conducted a randomized, prospective, controlled study on gum chewing as a method to stimulate bowel motility after laparoscopic colectomy for colorectal cancer. The patients chewed gum 3 times a day starting postoperative day 1 until oral intake. The passage of first flatus was on average 1. The first defecation also was significantly earlier in the gum-chewing patients postoperative day 3. However, the length of hospital stay was not significantly different between the 2 groups The authors hypothesize that the aid in recovery from postoperative ileus achieved by gum chewing may be related to the effects of sham feeding.
Sham feeding causes vagal cholinergic stimulation of the gastrointestinal tract and elicits the release of gastrin, pancreatic polypeptide, and neurotensin, all of which affect gastrointestinal motility. Lobo et al wanted to determine the effect of water and salt balance on the recovery of gastrointestinal transit in patients undergoing colonic resection for colon cancer. The primary end points of the study included solid- and liquid-phase gastric emptying as measured by isotope radionuclide scintigraph on the fourth postoperative day, with first flatus and bowel movement serving as secondary end points.
The results demonstrated significantly longer solid and liquid gastric emptying for the standard group vs the restricted fluid group solid: vs 72 minutes; liquid: vs 73 minutes. Patients receiving restricted fluids passed first flatus 1 day earlier, had the first bowel movement 2. The authors concluded that a positive salt and water balance significant enough to add 3 kg of body weight after colonic resection delays gastrointestinal transit and prolongs hospital stay.
Of all the treatments available Table 2 , which is best? The best treatment currently available is a multimodal regimen. Basse et al examined a multimodal rehabilitation regimen for the treatment of postoperative ileus consisting of continuous epidural analgesia, early oral nutrition and mobilization, and cisapride and laxative treatment with magnesia.
Using this regimen, the authors observed normalization of gastrointestinal transit time within 48 hours of colonic resection compared with matched controls. Gastrointestinal transit time was assessed by an indium In pentetate scintigraphic method. The relative contribution of each modality is unknown. This particular approach is less than ideal, given that cisapride is no longer available. Also, ambulation has not been shown to improve postoperative bowel motility, although it is beneficial to patients for other reasons.
Another study supporting the multimodal approach was conducted on patients undergoing segmental colectomy. The authors used a regimen that included thoracic epidural anesthesia for 48 hours, omission of a nasogastric tube, 1 L of fluid orally on the day of surgery, mobilization within 8 hours of surgery, use of milk of magnesia, and an alteration in the incision curved or transverse to minimize pain and pulmonary dysfunction.
Ninety-five of patients evaluated defecated in 48 to 72 hours. Paralytic postoperative ileus continues to be a significant clinical problem. The etiology of this process can best be described as multifactorial. These factors act simultaneously or at various times during the development of postoperative ileus. The mechanisms involved in paralytic postoperative ileus include inhibitory sympathetic input; release of hormones, neurotransmitters, and other mediators; an inflammatory reaction; and the effects of analgesics.
Experimental studies continue to elucidate the roles and mechanisms of action of all of these factors. Numerous methods have been used in an attempt to alleviate postoperative ileus in the clinical setting, without much success. At this time, it is best to recommend an approach that will decrease factors contributing to paralytic postoperative ileus. This approach would include limiting the administration of narcotics and using alternative analgesics such as nonsteroidal anti-inflammatory drugs and placing a thoracic epidural with local anesthetics when possible.
Selective use of nasogastric decompression and the correction of electrolyte imbalances are also important in the multimodal approach to the treatment of paralytic postoperative ileus. Ongoing research can have a positive impact in areas such as selective opioid antagonist, laparoscopic surgery, and the manipulation of local factors, neurotransmitters, and stress hormones. Clinicians look forward to the day when paralytic postoperative ileus is an entity of the past.
Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy Continue. Table 1. View Large Download. Dig Dis Sci. Holte KKehlet H Postoperative ileus: a preventable event.
Br J Surg. Ann Surg. Neely JCatchpole B Ileus: the restoration of alimentary tract motility by pharmacological means.
J Physiol Lond. Dubois AHenry DKopin I Plasma catecholamines and postoperative gastric emptying and small intestinal propulsion in the rat.
Sargrada AFargeas MJBueno L Involvement of alpha-1 and alpha-2 adrenoreceptors in the postlaparotomy intestinal motor disturbances in the rat. Am J Physiol. J Surg Res. A model to investigate postoperative ileus with strain gauge transducers in awake rats. Szurszewski JH A migrating electric complex of the canine small intestine. Code CFSchlegel J The gastrointestinal interdigestive housekeeper: motor correlate of the interdigestive myoelectric complex of the dog.
Daniel EEed. Sarna SK Cyclic motor activity; migrating motor complex: Woodward's Postgastrectomy Syndromes. Fujimiya MInui A Peptidergic regulation of gastrointestinal motility in rodents. Am J Dig Dis. Kenwenter J The vagal control of duodenal and ileal motility and blood flow.
Acta Physiol Scand. Nilsson FJung B Gastric evacuation and small propulsion after laparotomy. Acta Chir Scand. Br J Pharmacol. Deloof SCroix DTramu G The role of vasoactive intestinal polypeptide in the inhibition of antral and pyloric electrical activity in rabbits.
J Auton Nerv Syst. Holzer PLippe IT Inhibition of gastrointestinal transit due to surgical trauma or peritoneal irritation is reduced in capsaicin-treated rats.
J Gastrointest Surg. Eur J Pharmacol. Kehlet HHolte K Review of postoperative ileus. Am J Surg. Jpn J Pharmacol. Proc Soc Exp Biol Med. Can J Gastroenterol. Ann N Y Acad Sci. J Gastrointest Motil. Regul Pept. Biphasic changes in hypothalamo-pituitary-adrenal function during the early recovery period of major abdominal surgery.
J Clin Invest. Clin Endocrinol Oxf. Pulsatile activation of the hypothalamic-pituitary-adrenal axis during major surgery. Edwards AVJones CT Secretion of corticotropin-releasing factor from the adrenal during splanchnic nerve stimulation in conscious calves.
J Physiol. Prostanoid production via COX-2 as a causative mechanism of rodent postoperative ileus. Eur J Anaesthesiol Suppl. Rashid MUBateman DN Effects of intravenous atropine on gastric emptying, paracetamol absorption, salivary flow and heart rate in young and elderly volunteers.
Br J Clin Pharmacol. Br J Anaesth. Eur J Anaesthesiol. Steinbrook RA Epidural anesthesia and gastrointestinal motility. Anesth Analg. Holte KKehlet H Epidural anesthesia and analgesia-effects on surgical stress responses and implications for postoperative nutrition. Clin Nutr. Acta Anaesthesiol Scand. Epidural analgesia in colonic surgery: results of a randomized prospective study. Riwar ASchar BGrotzinger U Effect of continuous postoperative analgesia with peridural bupivacaine on intestinal motility following colorectal resection [in German].
Helv Chir Acta. Effects of perioperative analgesic technique on rate of recovery after colon surgery. Asantila REklund PRosenberg PH Continuous epidural infusion of bupivacaine and morphine for postoperative analgesia after hysterectomy. Bisgaard CMouridsen PDahl JB Continuous lumbar epidural bupivacaine plus morphine versus epidural morphine after major abdominal surgery. Treatment options for an ileus include waiting for the ileus to resolve, making dietary changes, or adjusting medication use.
Sometimes, surgery is necessary. The treatment will depend on the severity of the ileus and its underlying cause. Surgery-related ileus often heals within a few days of surgery, and paralytic ileus usually resolves once a person makes changes to their medication.
However, individuals may require a stay in the hospital until the issue resolves fully. Some bowel material can pass through the intestine, but not all of it.
A doctor may recommend that people with this issue follow a low-fiber diet to make it easier to pass stool. This involves cutting down on whole-grain foods, raw vegetables, and nuts. A paralytic ileus that is caused by medication can often be treated by taking another medicine, such as metoclopramide Reglan , to stimulate the movement of the intestines.
Another option is to discontinue use of the medication that is causing the ileus. It is not always advisable to stop antidepressants and some other medications suddenly.
If medication or dietary changes do not resolve the ileus, or if the blockage is severe, then a person may need surgery. Surgical procedures involve removing the blockage, or repairing or removing the damaged portion of the intestine. Older adults or people with colon cancer may not be suitable candidates for extensive surgery. Instead, they may be fitted with a stent tube to keep the intestine open and allow bowel materials to pass through more easily. In some cases, a person may need to have their entire intestine removed.
In this case, the surgeon will perform an ostomy. They will create an opening in the abdomen, called a stoma, allowing stool to pass from the intestine into a pouch. An undiagnosed and untreated ileus can cause severe and potentially life-threatening complications, such as:. Necrosis is tissue death. Necrosis occurs when blood cannot reach the intestine. The intestinal tissue dies and becomes weakened. A weak intestinal wall is prone to tearing, which causes bowel contents to leak out.
Bowel contents are full of bacteria. When they leak into the abdominal cavity, they cause a serious infection called peritonitis. Bacterial peritonitis can lead to sepsis, a widespread infection that can be fatal. It has not been studied for use beyond 4 months, and it should be discontinued if opioids are discontinued.
Methylnaltrexone is pregnancy category B. Methylnaltrexone should be used during pregnancy only if clearly needed. Methylnaltrexone is excreted in the milk of lactating rats; whether it is excreted in human milk is not known. Caution is advised if methylnaltrexone is administered to a breastfeeding woman.
Methylnaltrexone has not been studied in pediatric patients, end-stage renal disease ESRD , or severe hepatic impairment. Adverse reactions associated with methylnaltrexone include abdominal cramping, diarrhea, dizziness, flatulence, nausea, and soft stool.
Methylnaltrexone is a weak inhibitor of CYP 2D6 in vitro; in vivo, however, it has not affected the metabolism of the CYP2D6 substrate dextromethorphan.
The potential for drug interactions with agents that are actively secreted by the kidney has not been studied in humans. Methylnaltrexone is contraindicated in known or suspected mechanical bowel obstruction. Rare cases of GI perforation have been reported in patients with advanced illness.
Use caution in patients with known or suspected lesions of the GI tract. The average wholesale price for a single 0. Alvimopan formerly known as ADL is a quaternary mu-opioid receptor antagonist with a pharmacologic profile that differs from that of methylnaltrexone, particularly in binding affinity.
Alvimopan was approved in May for accelerating the time to upper-GI and lower-GI recovery following partial large-bowel or small-bowel resection with primary anastomoses.
Through competitive binding to the GI mu receptor, alvimopan antagonizes the peripheral effects of opioids on GI motility and secretion without reversing the central analgesic effects of the opioid. The drug is highly selective for the mu-opioid receptor; it also has an active metabolite that has less affinity for the mu-opioid receptor than the parent compound does. Alvimopan is an amide hydrolysis compound that is exclusively a product of intestinal-flora metabolism.
No significant accumulation was noted after twice-daily dosing, and high-fat meals decreased the extent and rate of absorption. Approval of alvimopan was based on the results of five four in the U. All five trials had these design features in common: Patients were randomized to receive alvimopan oral capsules or placebo; the initial dose was given preoperatively, with subsequent doses administered twice daily from postoperative day 1 until postoperative day 7 or hospital discharge; and patients taking chronic opioids before surgery and those scheduled to have laparoscopic surgery or epidural anesthesia were excluded.
In all studies, the primary efficacy endpoint was time to recovery of both upper and lower GI-tract motility following surgery. Secondary efficacy endpoints included the following measurements of length of hospitalization: discharge order written , the time from the end of surgery to the time the hospital discharge order was written; and ready , the time from the end of surgery to the time the patient was ready for hospital discharge based solely on the recovery of GI function, as determined by the surgeon.
In all five studies, treatment with alvimopan significantly accelerated the time to recovery of GI function versus placebo by Patients randomized to alvimopan were discharged 13 to 21 hours sooner than those in the placebo group, and use of alvimopan did not reverse opioid analgesia.
Alvimopan is dosed as a mg tablet administered 30 minutes to 5 hours prior to surgery followed by 12 mg twice daily for up to 7 days, for a maximum of 15 doses. Coadministration of alvimopan does not appear to alter the pharmacokinetics of morphine or alvimopan's metabolite, morphineglucuronide, when morphine is administered IV; dosage adjustments, therefore, are not necessary.
Alvimopan is classified as pregnancy category B. Alvimopan is contraindicated in patients who have been receiving therapeutic doses of opioids for more than 7 consecutive days. Program is required to purchase the drug. Hospitals that perform bowel resection are eligible and must acknowledge that educational materials are distributed to health care professionals responsible for ordering, dispensing, or administering alvimopan; systems, order sets, protocols, or other measures are in place to limit use to 15 doses; the hospital will not dispense alvimopan for outpatient use; and the hospital will not transfer a patient taking alvimopan to a nonregistered hospital.
Pharmacists play an integral role in the management and monitoring of patients with POI. Their contributions are not only clinical, but also economic in nature. It is the pharmacist's responsibility to ensure optimum pharmaceutical care at the most reasonable cost. In monitoring the patient at risk for POI, it is necessary to review medication regimens to ensure that patients are not taking medications that may exacerbate POI.
If it is discovered that a patient is currently on such a regimen, the pharmacist should ensure that all preventive measures are being utilized. All patients receiving narcotics for pain control should be on a bowel regimen, which should be initiated as soon as possible. An effective bowel regimen should include a stimulant laxative and a stool softener. These agents may include senna, bisacodyl, and docusate sodium. FDA approval of methylnaltrexone and alvimopan has prompted formulary committees to evaluate these agents for inclusion in the health care system.
Alvimopan may be restricted to 15 doses, as per the package insert. A number of drugs have been used to treat POI. Methylnaltrexone and alvimopan are promising new agents that could become an important component of perioperative care for the treatment of POI after bowel resection and, potentially, other major abdominal surgeries. These therapies may also reduce the economic burden of POI on health systems. Postoperative ileus.
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