Pathophysiology and management of opioid-induced constipation: European expert consensus statement

Abstract

Background: Opioid-induced bowel dysfunction is a complication of opioid therapy, in which constipation is the most common and problematic symptom. However, it is frequently under-recognised and thus effective management is often not instituted despite a number of treatment options.

Objective: The central objective of this study is to provide a summary of the pathophysiology and clinical evaluation of opioid-induced constipation and to provide a pragmatic management algorithm for day-to-day clinical practice.

Methods: This summary and the treatment algorithm is based on the opinion of a European expert panel evaluating current evidence in the literature.

Results: The pathophysiology of opioid-induced constipation is multi-faceted. The key aspect of managing opioid-induced constipation is early recognition. Specific management includes increasing fluid intake, exercise and standard laxatives as well as addressing exacerbating factors. The Bowel Function Index is a useful way of objectively evaluating severity of opioid-induced constipation and monitoring response. Second-line treatments can be considered in those with recalcitrant symptoms, which include gut-restricted or peripherally acting mu-opioid receptor antagonists. However, a combination of interventions may be needed.

Conclusion: Opioid-induced constipation is a common, yet under-recognised and undertreated, complication of opioid therapy. We provide a pragmatic step-wise approach to opioid-induced constipation, which should simplify management for clinicians.

Keywords: Opioid-induced constipation; bowel dysfunction; gastro-intestinal motility; gastroenterology; management algorithm.

Figures

Figure 1.

A schematic summary of the effects of opioids on the gastro-intestinal (GI) tract. Opioid receptors are distributed throughout the GI tract. *The function of other GI sphincters can also be influenced opioids such as the lower oesophageal sphincter and pylorus.

Figure 2.

A highly schematic summary of the basic neural mechanisms leading to opioid-induced bowel dysfunction including constipation. Opioids bind to receptors expressed in the enteric nervous system. The overall result is a neuronal-mediated blockade of secretomotor gastro-intestinal (GI) function causing opioid-induced constipation (OIC). cAMP: cyclic adenosine monophosphate; OpR: opioid receptor.

Figure 3.

The Bowel Function Index. OIC: opioid-induced constipation.

Figure 4.

A suggested pragmatic stepwise management suggestion for the management of opioid-induced constipation (OIC) in clinical practice. Treatment goals are to establish regular bowel function, improve quality of life and avoid complications, such as haemorrhoids, rectal prolapse and faecal impaction. Regular clinical re-evaluation should be undertaken, and the Bowel Function Index (BFI) can also be used as a useful adjunct. *The length of the test treatment depends on the specific peripherally-acting µ-opioid receptor antagonist (PAMORA) or opioid antagonist. For instance, a two-week trial with naloxegol or a single test dose with subcutaneous methylnaltrexone may be appropriate. Following these pragmatic suggestions is dependent on cost, available expertise/technology and local practice circumstances.