Burden of opioid-associated gastrointestinal side effects from clinical and economic perspectives: A systematic literature review

Kim Boswell, MD; Winghan Jacqueline Kwong, PharmD, PhD; Shane Kavanagh, MSc

doi:10.5055/jom.2010.0025

Authors

Kim Boswell, MD
Winghan Jacqueline Kwong, PharmD, PhD
Shane Kavanagh, MSc

DOI:

https://doi.org/10.5055/jom.2010.0025

Keywords:

opioid, analgesic, side effect, burden, economic, quality of life, cost

Abstract

Opioid analgesia is the mainstay of treatment for moderate to severe acute and chronic pain and is highly effective in relieving pain but can be limited by side effects, the most common of which affect the gastrointestinal (GI) and central nervous systems. A growing body of evidence demonstrates that opioid-associated GI side effects constitute an important health problem with significant humanistic and economic consequences that warrant consideration by healthcare professionals and administrators in optimizing patients’ pain management. This article documents the frequency of opioid-associated GI side effects and describes its clinical and economic burdens based on a systematic review of the medical literature between 1966 and 2008.

Author Biographies

Kim Boswell, MD

Xcenda, Palm Harbor, Florida.

Winghan Jacqueline Kwong, PharmD, PhD

Worldwide Health Economics and Pricing, Johnson & Johnson Pharmaceutical Services, LLC, Raritan, New Jersey.

Shane Kavanagh, MSc

Worldwide Health Economics & Pricing, Johnson & Johnson Pharmaceutical Services, Beerse, Belgium.

References

Holzer P: Treatment of opioid-associated gut dysfunction. Expert Opin Investig Drugs. 2007; 16: 181-194.

Mehandale SR, Yuan CS: Opioid-induced gastrointestinal dysfunction. Dig Dis. 2006; 24: 105-112.

Vella-Brincat J, Macleod AD: Adverse effects of opioids on the central nervous systems of palliative care patients. J Pain Palliat Care Pharmacother. 2007; 21: 15-25.

Thomas J: Opioid-associated bowel dysfunction. J Pain Symptom Manage. 2008; 35: 103-113.

Bell T, Leslie J, Annunziata K, et al.: Opioid-associated constipation compromises pain management and impacts patient quality of life. Abstract. 2007. Available at http//aapm.confex.com/aapm/2007am/techprogram/P2092.HTM. Accessed January 4, 2009.

Thomas JR, Cooney GA, Slatkin NE: Palliative care and pain: New strategies for managing opioid bowel dysfunction. J Palliat Med. 2008; 11(Suppl 1): S1-S19.

Aparasu R, McCoy K: Opioid-associated emesis among hospitalized nonsurgical patients: Effect on pain and quality of life. J Pain Symptom Manage. 1999; 18: 280-288.

Swegle JM, Logemann C: Management of common opioid-associated adverse effects. Ann Fam Physician. 2006; 74: 1347-1354.

Oderda GM, Evans S, Lloyd J, et al.: Cost of opioid-related adverse drug events in surgical patients. J Pain Symptom Manage. 2003; 25: 276-283.

Stannard C, Johnson M: Chronic pain management: Can we do better? An interview-based survey in primary care. Curr Med Res Opin. 2003; 19: 703-706.

Palos GR: Opioids and cancer survivors: Issues in side-effect management. Oncol Nurs Forum. 2008; 35(Suppl): 13-19.

Cepeda MS, Farrar JT, Baumgarten M, et al.: Side effects of opioids during short-term administration: Effect of age, gender, and race. Clin Pharm Ther. 2003; 74: 102-112.

McNicol E, Horowicz-Mehler N, Fisk RA, et al.: Management of opioid side effects in cancer-related and chronic noncancer pain: A systematic review. J Pain. 2003; 4: 234-256.

McNicol E, Boyce DB, Schumann R, et al.: Mu-opioid antagonists for opioid-associated bowel dysfunction. Cochrane Database Syst Rev. 2008; 2: CD006332.

Fallon MT: Constipation in cancer patients: Prevalence, pathogenesis and cost-related issues. Eur J Pain. 1999; 3(Suppl A): 3-7.

Senagore AJ: Pathogenesis and clinical and economic consequences of postoperative ileus. Am J Health Syst Pharm. 2007; 64(Suppl 13): S3-S7.

Bell T, Panchal S, Miaskowski C, et al.: The prevalence, severity, and impact of opioid-associated bowel dysfunction: Results of a US and European patient survey (PROBE 1). Pain Med. 2009; 10: 35-42.

Brown J, Klapow J, Doleys D, et al.: Disease-specific and generic health outcomes: A model for the evaluation of long-term intrathecal opioid therapy in noncancer low back pain patients. Clin J Pain. 1999; 15: 122-131.

Brown R, Zuelsdorff S, Fleming M: Adverse effects and cognitive function among primary care patients taking opioids in chronic nonmalignant pain. J Opioid Manage. 2006; 2: 137-146.

Dolin SJ, Cashman JN: Tolerability of acute postoperative pain management: Nausea, vomiting, sedation, pruritus, and urinary retention. Evidence from published data. Br J Anaesth. 2005; 95: 584-591.

Kalso E, Edwards JE, Moore A, et al.: Opioids in chronic non-cancer pain: Systematic review of efficacy and safety. Pain. 2004; 112: 372-380.

Kosinski MR, Schein J, Vallow S, et al.: An observational study of health-related quality of life and pain outcomes in chronic low back pain patients treated with fentanyl transdermal system. Curr Med Res Opin. 2005; 21: 649-662.

Moore A, McQuay H: Prevalence of opioid adverse events in chronic non-malignant pain: Systematic review of randomised trials of oral opioids. Arthritis Res Ther. 2005; 7: R1046-R1051.

Remy C, Marret E, Bonnet F: Effects of acetaminophen on morphine side-effects and consumption after major surgery: Meta-analysis of randomized controlled trials. Br J Anaesth. 2005; 94: 505-513.

Sjogren P, Thomsen AB, Olsen AK: Impaired neuropsychological performance in chronic nonmalignant pain patients receiving long-term oral opioid therapy. Pain Manage. 2000; 19: 100-108.

Davis KL, Candrilli S, Iyer S: Impact of constipation on resource utilization and costs in non-metastatic cancer patients on opioid therapy. Poster presented at American Academy of Pain Management, New Orleans, LA, February 7-10, 2007. [Abstract citation to be substituted.]

Eisenberg E, McNicol ED, Carr DB: Opioids for neuropathic pain. Cochrane Database Syst Rev. 2006; Issue 3. Art. No:CD006146: 1-37. DOI:10.1002/14651858.CD006146.

Glare P, Walsh D, Sheehan D: The adverse effects of morphine: A prospective survey of common symptoms during repeated dosing for chronic cancer pain. Am J Hosp Palliat Care. 2006; 23: 229-235.

Hudcova J, McNicol E, Quah C, et al.: Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database Syst Rev. 2006; Issue 4. Art. No:CD003348: 1-67. DOI:10.1002/14651858.CD003348.pub2.

Oderda GM, Said Q, Evans RS, et al.: Opioid-related adverse drug events in surgical hospitalizations: Impact on costs and length of stay. Ann Pharmacother. 2007; 41: 400-406.

Werawatganon T, Charuluxanun S: Patient controlled intravenous opioid analgesia versus continuous epidural analgesia for pain after intra-abdominal surgery. Cochrane Database Syst Rev. 2005; Issue 1. Art. No:CD004088: 1-19. DOI:10.1002/14651858.CD004088.pub2.

Cook SF, Lanza L, Zhou X, et al.: Gastrointestinal side effects in chronic opioid users: Results from a population-based survey. Aliment Pharmacol Ther. 2008; 27: 1224-1232.

Carroll NV, Miederhoff P, Cox FM, et al.: Postoperative nausea and vomiting after discharge from outpatient surgery centers. Anesth Analg. 1995; 80: 903-909.

Campora E, Merline M, Pace M, et al.: The incidence of narcotic-induced emesis. J Pain Symptom Manage. 1991; 6: 428-430.

Bennett M, Cresswell H: Factors influencing constipation in advanced cancer patients: A prospective study of opioid dose, dantron dose and physical functioning. Palliat Med. 2003; 17: 418-422.

Robinson CB, Fritch M, Hullett L, et al.: Development of a protocol to prevent opioid-associated constipation in patients with cancer: A research utilization project. Clin J Oncol Nurs. 2000; 4: 79-84.

Pappagallo M: Incidence, prevalence, and management of opioid bowel dysfunction. Am J Surg. 2001; 182(5A Suppl): 11S-18S.

McMillan S: Presence and severity of constipation in hospice patients with advanced cancer. Am J Hosp Palliat Care. 2002; 19: 426-430.

Staats PS, Markowitz J, Schein J: Incidence of constipation associated with long-acting opioid therapy: A comparative study. South Med J. 2004; 97: 129-134.

Hartung DM, Middleton L, Haxby DG, et al.: Rates of adverse events of long-acting opioids in a state Medicaid program. Ann Pharmacother. 2007; 41: 921-928.

Bell T, Milanova T, Grove G, et al.: OBD symptoms impair quality of life and daily activities, regardless of frequency and duration of opioid treatment: Results of a US patient survey (PROBE survey). Abstract. J Pain. 2007; 8(4 Suppl 1): S71.

Saunders W, Bowers B, Moss B, et al.: Recorded rate and economic burden associated with postoperative ileus. Poster Presented at American Society of Health-System Pharmacists Midyear Clinical Meeting, December 5-9, 2004, Orlando, Florida.

Salvador CG, Sikirica M, Evans E, et al.: Clinical and economic outcomes of patients with prolonged postoperative ileus undergoing hysterectomy and hemicolectomy at an academic medical institution. Poster presented at American Society of Hospital Pharmacists Midyear Clinical Meeting, December 5-9, 2004, Orlando, Florida.

Goettsch WG, Sukel M, van der Peet D: In-hospital use of opioids increases the rate of coded postoperative ileus. Pharmacoepi Drug Saf. 2007; 16: 668-674.

Delaney CP, Wolff BG, Viscusi ER, et al.: Alvimopan, for postoperative ileus following bowel resection: A pooled analysis of Phase III studies. Ann Surg. 2007; 245: 355-363.

Panchal SJ, Muller-Schwefe P, Wurzelmann JI: Opioid-induced bowel dysfunction: Prevalence, pathophysiology and burden. Int J Clin Pract. 2007; 61: 1181-1187.

Strassels SA, Chen C, Carr DB: Postoperative analgesia: Economics, resource use, and patient satisfaction in an urban teaching hospital. Anesth Analg. 2002; 94: 130-137.

Kovac AL: Management of postoperative nausea and vomiting in children. Paediatr Drugs. 2007; 9: 47-69.

Williams KS: Postoperative nausea and vomiting. Surg Clin North Am. 2005; 85: 1229-1241.

Leslie J, Bell T, Annunziata K, et al.: Opioid-associated constipation compromises pain management and impacts patient quality of life. Abstract. Anesthesiology. 2006; 105: A1490.

Cook SF, Bell T, Sweeney CT, et al.: Impact on quality of life of constipation-associated GI symptoms related to opioid-treatment in chronic pain patients: PAC-QOL results from the OPIOID Survey. Abstract. J Pain. 2007; 8(4 Suppl 1): S71.

Bell T, Annunziata K, Freedman D, et al.: Opioid-associated constipation increases healthcare resource use and impairs work productivity: Comparison with other patient groups with and without constipation. Abstract. J Pain. 2007; 8 (4 Suppl 1): S75.

Benyamin R, Trescot AM, Datta S, et al.: Opioid complications and side effects. Pain Phys. 2008; 11: S105-S120.

National Cancer Institute: Constipation, impaction, and bowel obstruction. CancerWeb Web site. Available at http://cancer.web.ncl.ac.uk/cancernet/303510.html. Accessed May 6, 2008.

Passik SD, Kirsh KI, Whitcomb L, et al.: Monitoring outcomes during long-term opioid therapy for noncancer pain: Results with the Pain Assessment and Documentation Tool. J Opioid Manage. 2005; 1: 257-266.

Kurz A, Sessler DI: Opioid-associated bowel dysfunction: Pathophysiology and potential new therapies. Drugs. 2003; 63: 649-671.

Ogilvy AJ, Smith G: The gastrointestinal tract after anaesthesia. Eur J Anaesthesiol. 1995; 12: 35-42.

Kwong WJ, Diels J, Kavanagh S: Costs of gastrointestinal events after outpatient opioid treatment for non-cancer pain; Ann Pharmacother. 2010; 44: xxxx. Published online, March 2, 2010 DOI 10.1345/aph.1M520.

Flynn TN, Guest JF: Cost of managing constipation among terminally ill cancer patients treated with transdermal fentanyl and 12 hour sustained-release morphine in Canada. J Med Econ. 1999; 2: 15-32.

Guest J, Munrol V, Cookson R: Comparison of the cost of managing constipation in cancer patients receiving oral morphine or transdermal fentanyl. Eur J Cancer. 1997; 33: 19.

Ahmedzai S, Brooks S: Transdermal fentanyl versus sustained-release oral morphine in cancer pain: Preference, efficacy, and quality of life. J Pain Symptom Manage. 1997; 13: 254-261.

Chou R, Fanciullo GJ, Fine PG, et al.; American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel: Clinical guidelines for the use of chronic opioids therapy in chronic non-cancer pain. J Pain. 2009; 10: 113-130.

Chou R, Ballantyne JC, Fanciullo GJ, et al.; American Pain Society-American Academy of Pain Medicine Opioids Guidelines Panel: Research gaps on use of opioids for chronic noncancer pain: Findings from a review of the evidence for an American Pain Society and American Academy of Pain Medicine clinical practice guideline. J Pain. 2009; 10: 147-159.