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ANESTHETIC PHARMACOLOGY

Peripherally Acting Mu-Opioid Receptor Antagonists and Postoperative Ileus: Mechanisms of Action and Clinical Applicability

Eugene R. Viscusi, MD^*, Tong J. Gan, MD, John B. Leslie, MD, MBA, Joseph F. Foss, MD, Mark D. Talon, CRNA^||, Wei Du, PhD^¶, and Gay Owens, PharmD^¶

From the *Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina; Department of Anesthesiology, Mayo Clinic College of Medicine, Rochester, Minnesota; Cleveland Clinic, Cleveland, Ohio; ||Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas; and ¶Adolor Corporation, Exton, Pennsylvania.

Address correspondence and reprint requests to Eugene R. Viscusi, MD, Department of Anesthesiology, Acute Pain Management Service, Thomas Jefferson University, 111 S. 11th St., Suite G-8490, Philadelphia, PA 19107. Address e-mail to eugene.viscusi{at}jefferson.edu.

Postoperative ileus (POI), a transient cessation of coordinated bowel function after surgery, is an important health care problem. The etiology of POI is multifactorial and related to both the surgical and anesthetic pathways chosen. Opioids used to manage surgical pain can exacerbate POI, delaying gastrointestinal (GI) recovery. Peripherally acting mu-opioid receptor (PAM-OR) antagonists are designed to mitigate the deleterious effects of opioids on GI motility. This new class is investigational for POI management with the goal of accelerating the recovery of upper and lower GI tract function after bowel resection. In this review, we summarize the mechanisms by which POI occurs and the role of opioids and opioid receptors in the enteric nervous system, discuss the mechanism of action of PAM-OR antagonists, and review clinical pharmacology and Phase II/III POI trial results of methylnaltrexone and alvimopan. Finally, the role of anesthesiologists in managing POI in the context of a multimodal approach is discussed.