Correspondence

Selective Postoperative Inhibition of Gastrointestinal Opioid Receptors

N Engl J Med 2002; 346:455February 7, 2002

Article

To the Editor:

In their article on prophylaxis against postoperative ileus with the use of ADL 8-2698, Taguchi et al. (Sept. 27 issue)1 refer to our report on intravenous methylnaltrexone, a peripheral opioid antagonist.2 We call attention to an error in their description of our study population. Our study did not involve patients with pain from cancer but, rather, subjects receiving methadone-maintenance therapy, who are exquisitely sensitive to the withdrawal of opioids. The outcome measures thus included the laxation response, oral–cecal transit times, and symptoms of central opioid withdrawal.

All subjects in our treatment group had immediate laxation, and none had symptoms of opioid withdrawal. We have reported similar results with oral methylnaltrexone, although evacuation was not immediate.3 The difference in the time to evacuation may have been related to the route of administration. Although ADL 8-2698 is clearly effective as prophylaxis against ileus, a parenterally administered opioid antagonist may be more useful for treatment, particularly in patients undergoing gastric suction. Unlike ADL 8-2698, methylnaltrexone is formulated and effective both orally and parenterally.

As Dr. Steinbrook suggests in the accompanying editorial,4 there may be other therapeutic roles for peripheral opioid antagonists. Nevertheless, their role in preventing postoperative emesis remains unclear. The multifactorial nature of postoperative emesis and the fact that opiates can both induce and prevent emesis complicate the issue. The results of our study of methylnaltrexone in dogs for the prevention of opioid-induced emesis were encouraging,5 but neither we nor other investigators6 have found that methylnaltrexone significantly reduces postoperative vomiting in humans. However, methylnaltrexone reduces both the undesirable subjective effects and the pruritus associated with opiate use.7

Jonathan Moss, M.D., Ph.D.
Chun-Su Yuan, M.D., Ph.D.
University of Chicago, Chicago, IL 60637
jm47@airway2.uchicago.edu

7 References

1. 1

   Taguchi A, Sharma N, Saleem RM, et al. Selective postoperative inhibition of gastrointestinal opioid receptors. N Engl J Med 2001;345:935-940
   Full Text | Web of Science | Medline

2. 2

   Yuan CS, Foss JF, O'Connor M, et al. Methylnaltrexone for reversal of constipation due to chronic methadone use: a randomized controlled trial. JAMA 2000;283:367-372
   CrossRef | Web of Science | Medline

3. 3

   Yuan CS, Foss JE. Oral methylnaltrexone for opioid-induced constipation. JAMA 2000;284:1383-1384
   CrossRef | Web of Science | Medline

4. 4

   Steinbrook RA. An opioid antagonist for postoperative ileus. N Engl J Med 2001;345:988-989
   Full Text | Web of Science | Medline

5. 5

   Foss JF, Yuan CS, Roizen MF, Goldberg LI. Prevention of apomorphine- or cisplatin-induced emesis in the dog by a combination of methylnaltrexone and morphine. Cancer Chemother Pharmacol 1998;42:287-291
   CrossRef | Web of Science | Medline

6. 6

   Moerman I, Franck P, Camu F. Evaluation of methylnaltrexone for the reduction of postoperative vomiting and nausea incidences. Acta Anaesthesiol Belg 1995;46:127-132
   Medline

7. 7

   Yuan CS, Foss JF, O'Connor M, Osinski J, Roizen MF, Moss J. Efficacy of orally administered methylnaltrexone in decreasing subjective effects after intravenous morphine. Drug Alcohol Depend 1998;52:161-165
   CrossRef | Web of Science | Medline

Author/Editor Response

The editorialist replies:

To the Editor: Nausea and vomiting remain all too common after surgery. I agree with Moss and Yuan that postoperative emesis is complex and probably multifactorial. Although numerous pharmacologic approaches to prophylaxis and treatment for emesis have been recommended,1-3 opioid antagonists are not among them. Taguchi et al. reported a substantial reduction in maximal nausea scores and an absence of vomiting with the 6-mg dose of ADL 8-2698. Additional studies are warranted to define the role of opioid antagonists in the prevention and management of postoperative nausea and vomiting.

Richard A. Steinbrook, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 02215

3 References

1. 1

   Watcha MF, White PF. Postoperative nausea and vomiting: its etiology, treatment, and prevention. Anesthesiology 1992;77:162-184
   CrossRef | Web of Science | Medline

2. 2

   ASHP therapeutic guidelines on the pharmacologic management of nausea and vomiting in adult and pediatric patients receiving chemotherapy or radiation therapy or undergoing surgery. Am J Health Syst Pharm 1999;56:729-764
   Web of Science | Medline

3. 3

   Scuderi PE, James RL, Harris L, Mims GR III. Multimodal antiemetic management prevents early postoperative vomiting after outpatient laparoscopy. Anesth Analg 2000;91:1408-1414
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Jonathan Moss, Joseph Foss. (2005) Pain Relief without Side Effects. ASA Refresher Courses in Anesthesiology 33:1, 175-186
   CrossRef