The Efficacy of Peripheral Opioid Antagonists in Opioid-Induced Constipation and Postoperative Ileus

Abstract

Opioid-induced constipation has a negative impact on quality of life for patients with chronic pain and can affect more than a third of patients. A related but separate entity is postoperative ileus, which is an abnormal pattern of gastrointestinal motility after surgery. Nonselective μ-opioid receptor antagonists reverse constipation and opioid-induced ileus but cross the blood-brain barrier and may reverse analgesia. Peripherally acting μ-opioid receptor antagonists target the μ-opioid receptor without reversing analgesia. Three such agents are US Food and Drug Administration approved. We reviewed the literature for randomized controlled trials that studied the efficacy of alvimopan, methylnaltrexone, and naloxegol in treating either opioid-induced constipation or postoperative ileus. Peripherally acting μ-opioid receptor antagonists may be effective in treating both opioid-induced bowel dysfunction and postoperative ileus, but definitive conclusions are not possible because of study inconsistency and the relatively low quality of evidence. Comparisons of agents are difficult because of heterogeneous end points and no head-to-head studies.

Influence of reversal with sugammadex or neostigmine on postoperative bowel movement following robotic thyroidectomy: a retrospective study

“…Factors commonly associated to postoperative gastrointestinal tract dysfunction include surgical stress response, bowel dysfunction secondary to operative trauma, and opioid analgesics [4]. Moreover, postorthopedic, bowel, or pelvic surgeries are prone to cause intestinal pseudo-obstruction [12,13].…”

“…Although many clinical studies have been performed to decrease postoperative bowel dysfunction, it still remains a major concern [2]. Factors affecting postoperative bowel dysfunction are surgical stress response [3], secondary bowel dysfunction from operative trauma [4], and opioid analgesics [5]. However, an easily overlooked factor potentially affecting postoperative bowel function is the use of reversal agents of neuromuscular (NM) blockade during surgery.…”

Enhanced recovery after rectal surgery: what we have learned so far

“…Multiple RCTs and meta-analyses have demonstrated that early feeding stimulates recovery of bowel function [23,96] ; this is particularly true in younger patients operated on by subspecialist colorectal surgeons using laparoscopic techniques [97,98] .…”

“…Therefore, the use of peripheral opioid antagonists may reduce the risk of postoperative ileus [97] . Although this has been incorporated into the American ERAS guidelines [23] , some Authors suggest prudence as definitive evidence is not yet available [98] . A recent phase 2 study from Scotland confirmed that oxycodone and naloxone reduces time to first bowel motion when compared to oxycodone only within an ERAS protocol in laparoscopic colorectal surgery, but the authors admit that a proper RCT is still needed [99] .…”

Evaluation of the Effect of Oral Pyridostigmine on the Ileus after Abdominal Surgery: A Blinded Randomized Clinical Trial

“…Postoperative ileus (POI) is one of the most important and common complications experienced after abdominal surgeries and it costs 1.5 billion US $ a year in the United States [ 1 , 2 ]. Generally, POI is known as a disorder of the gastrointestinal tract after abdominal surgery and it is capable of affecting the entire digestive system whose time incidence for each section of this system is different [ 3 , 4 , 5 ]. After surgery, the movements of the small intestine start sooner than the rest of the digestive tract.…”