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Postoperative Ileus Medication

  • Author: Burt Cagir, MD, FACS; Chief Editor: Julian Katz, MD  more...
 
Updated: Dec 28, 2015
 

Medication Summary

Thoracic epidural administration has been shown to be beneficial, both with open and with endoscopic colorectal surgery.[32] Epidural blockade with local anesthetics improves postoperative ileus by blockage of inhibitory reflexes and efferent sympathetics. Studies have shown that combinations of thoracic epidurals containing bupivacaine alone or in combination with opioids improve postoperative ileus.[33, 34] Continuous intravenous administration of lidocaine during and after abdominal surgery may decrease the duration of postoperative ileus.[35]

In a randomized study, systemic infusion of lidocaine is compared with placebo infusions in postoperative patients. Patients in the lidocaine group appear to have earlier return of flatus, bowel function, and discharge to home. Although only 11 patients were used in the each arm, systemic lidocaine lessened the postoperative pain sensation. Therefore, it is recommended that further studies are warranted to evaluate systemic lidocaine infusion in postoperative patients.[36]

Peripherally selective opioid antagonists are an option for the treatment of postoperative ileus.[37] Methylnaltrexone (Relistor) and alvimopan (Entereg) are approved by the Food and Drug Administration. These agents inhibit peripheral mu-opioid receptors, which abolishes the adverse gastrointestinal effects of opioids; however, because these agents do not cross the blood-brain barrier, they do not impair the analgesic effects of opioids.[38]

Methylnaltrexone is indicated for opioid-induced constipation in patients with advanced illness receiving palliative care, when response to laxatives has not been sufficient. In a study of 14 healthy volunteers evaluating the use of morphine plus oral methylnaltrexone in increasing doses, methylnaltrexone significantly reduced morphine-induced delay in oral-cecal transit.[39] Another study reported subcutaneous methylnaltrexone is effective in inducing laxation in patients receiving palliative care who have opioid-induced constipation and in whom conventional laxatives have failed.[40] However, because methylnaltrexone has only recently been approved by the US Food and Drug Administration (FDA), more rigorous trials are needed.

Another phase III multicenter, double-blind, placebo-controlled study revealed that methylnaltrexone at 12-mg and 24-mg doses did not reduce the duration of postoperative ileus.[41] Although the utility of intravenous methylnaltrexone was not demonstrated, it was well tolerated by postcolectomy patients.[41]

Alvimopan is indicated to help prevent postoperative ileus following bowel resection. It has a longer duration of action than methylnaltrexone. Using data from four phase 3 bowel trials and one phase 4 radical cystemectomy trial, investigators evaluating the economic impact of postoperative adminstration of alvimopan (accounting for varying definitions of postoperative ileus) found that the addition of this agent to existing treatment strategies for those undergoing abdominal procedures resulted in overal hospital savings.[42]

Taguchi et al examined 78 postoperative patients randomized to receive either placebo or alvimopan.[43] Fifteen patients underwent partial colectomy, 36 were status post simple hysterectomy, and the remaining 27 underwent radical hysterectomy. All of the patients were on patient-controlled analgesia pumps using either meperidine or morphine. Compared with patients on placebo, patients on alvimopan had their first bowel movement 2 days earlier, resumed a solid diet 1.3 days earlier, and returned home 1.4 days earlier. Other recent trials have been completed, including a meta-analysis comparing alvimopan with placebo[44] and a study that found alvimopan to accelerate gastrointestinal tract recovery after bowel resection, regardless of age, gender, race, or concomitant medication.[45]

Use of prokinetic agents has shown mixed results. Randomized trials have shown some benefit of the colon-stimulating laxative bisacodyl for the treatment of ileus.[46, 47] Erythromycin, a motilin receptor agonist, has been used for postoperative gastric paresis but has not been shown to be beneficial for ileus.[48] Metoclopramide (Reglan), a dopaminergic antagonist, has antiemetic and prokinetic activities, but data have shown that the drug may actually worsen ileus. In a randomized controlled study on 210 patients undergoing major abdominal surgery, Wattchow et al reported that perioperative low dose celecoxib markedly reduced the development of paralytic ileus compared to diclofenac.[49] The effect was independent of narcotic use and was not associated with any increase in postoperative complications.

A review of meta-analyses and randomized controlled trials on drugs used for post-operative ileus was reported by Yeh et al.[50] The investigators identified three meta-analyses (2 on gum-chewing and 1 on alvimopan) and 18 clinical trials. Only gum chewing and alvimopan were effective in preventing ileus but due to safety concerns and costs with alvimopan, gum chewing may be preferred as first-line therapy. Gum chewing has also been used in women recovering from cesearian section with good effect when compared to standard of care in a randomized study conducted.[51]

In summary, ileus remains a significant health problem in North America. Successful therapy involves multimodality treatment such as minimally invasive/less traumatic surgery, opiate-sparing pain management, and fast tract recovery protocols.

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Opioid Antagonist, Selective

Class Summary

Selective opioid antagonists are indicated to prevent postoperative ileus.

Alvimopan (Entereg)

 

Peripherally acting mu-opioid receptor antagonist. Binds mu-opioid receptors in gut, thereby selectively inhibiting negative opioid effects on GI function and motility. Indicated for postoperative ileus following bowel resection with primary anastomosis. Five clinical studies with enrollment >2500 patients demonstrated accelerated recovery time of upper and lower tract GI function with alvimopan compared with placebo. Decrease of hospital days also observed in the alvimopan group compared with placebo.

Only available to hospitals after they complete a registration process designed to maintain the benefits associated with short-term use and prevent long-term, outpatient use (Entereg Access Support and Education [EASE] program).

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Contributor Information and Disclosures
Author

Burt Cagir, MD, FACS Clinical Professor of Surgery, The Commonwealth Medical College; Attending Surgeon, Assistant Program Director, Robert Packer Hospital; Attending Surgeon, Corning Hospital

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, American Medical Association, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Julian Katz, MD Clinical Professor of Medicine, Drexel University College of Medicine

Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law, Medicine & Ethics, American Trauma Society, Association of American Medical Colleges, Physicians for Social Responsibility

Disclosure: Nothing to disclose.

Acknowledgements

Avram M Cooperman, MD Professor of Surgery and Radiation Oncology, Cabrini Medical Center

Disclosure: Nothing to disclose.

Sandeep Mukherjee, MB, BCh, MPH, FRCPC Associate Professor, Department of Internal Medicine, Section of Gastroenterology and Hepatology, University of Nebraska Medical Center; Consulting Staff, Section of Gastroenterology and Hepatology, Veteran Affairs Medical Center

Sandeep Mukherjee, MB, BCh, MPH, FRCPC is a member of the following medical societies: Royal College of Physicians and Surgeons of Canada

Disclosure: Merck Honoraria Speaking and teaching; Ikaria Pharmaceuticals Honoraria Board membership

Ese Otah, MD, FACS Consulting Surgeon, Center For General and Laparoscopic Surgery, PA; Consulting Staff, St Luke's Sugar Land Hospital, Memorial Hermann Southwest Hospital, Memorial Hermann Sugar Land Hospital

Ese Otah, MD, FACS is a member of the following medical societies: American College of Surgeons and Association of Women Surgeons

Disclosure: Nothing to disclose.

Kenneth E Otah, MD, MSc, FACC Consulting Staff, Methodist and Memorial Hermann Hospital Systems, Total Heart Cardiovascular Consultants, LLC

Kenneth E Otah, MD, MSc, FACC is a member of the following medical societies: American College of Cardiology, American College of Physicians, and Association of Black Cardiologists

Disclosure: Nothing to disclose.

Oluwagbenga Serrano, MD Consulting Staff, Lake Havasu Gastroenterology, PC

Disclosure: Nothing to disclose.

John A Walker, MD Consulting Staff, Gastroenterology Consultants PC; Consulting Staff, Department of Gastroenterology, Rogue Valley Medical Center, Providence-Medford Medical Center, Surgery Center of Southern Oregon and Ashland Community Hospital

John A Walker, MD is a member of the following medical societies: American Society for Gastrointestinal Endoscopy

Disclosure: Nothing to disclose.

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Postoperative ileus after an open cholecystectomy.
Ogilvie pseudo-obstruction in a septic elderly patient. Note the massive dilatation of the colon, especially the right colon and cecum.
Mechanical bowel obstruction due to a left colon carcinoma. Note the paucity of bowel gas throughout the colon.
Contrast study, in the same patient as in Media File 3, showing the classic "apple-core" lesion of colon carcinoma.
Table. Characteristics of Ileus, Pseudo-obstruction, and Mechanical Obstruction
  Ileus Pseudo-obstruction Mechanical Obstruction (Simple)
Symptoms Mild abdominal pain, bloating, nausea, vomiting, obstipation, constipation Crampy abdominal pain, constipation, obstipation, nausea, vomiting, anorexia Crampy abdominal pain, constipation, obstipation, nausea, vomiting, anorexia
Physical Examination Findings Silent abdomen, distention, tympanic Borborygmi, tympanic, peristaltic waves, hypoactive or hyperactive bowel sounds, distention, localized tenderness Borborygmi, peristaltic waves, high-pitched bowel sounds, rushes, distention, localized tenderness
Plain Radiographs Large and small bowel dilatation, diaphragm elevated Isolated large bowel dilatation, diaphragm elevated Bow-shaped loops in ladder pattern, paucity of colonic gas distal to lesion, diaphragm mildly elevated, air-fluid levels
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