What Medications Are Effective in Preventing and Relieving Constipation in the Setting of Opioid Use?

Evaluation

Considerable variability exists in the meaning of the word constipation to patients and health care practitioners. One consideration is stool frequency, which normally varies from once per week to several times per day. Other symptoms include straining with bowel movements, passage of small, hard stools, or a sense that the bowel has not completely evacuated. To better characterize constipation, consensus groups have made attempts to create a standard definition. The Rome IV criteria help to better define functional constipation and take into account bowel movement frequency with associated discomfort. The Bowel Function Index is a reliable and valid measure that evaluates the impact and severity of opioid-induced constipation among patient populations with and without cancer. When considering opioid-induced constipation, any recent change in bowel habits reported by the patient warrants further inquiry.

Taking an adequate history and performing a physical examination are essential first steps in evaluating a patient with constipation, including opioid-induced constipation. The history should detail frequency and consistency of stools (both current and baseline before opioid use); whether or not evacuation was satisfactory; associated factors such as nausea, vomiting, and obstipation; history of laxative use; activity level; diet; blood in the stool; prescription and over-the-counter medications; comorbid conditions; and any other related symptoms, such as pain with defecation. Clinicians should also consider and mitigate other contributors to opioid-induced constipation whenever possible (e.g., discontinuation of other constipating medications) ( Table 18.3 ).

Physical examination should focus on abdominal distension, presence or absence of bowel sounds, evaluation for masses, tenderness to palpation, and, when indicated, rectal examination for fecal impaction, perianal fissures, and ulcerations. The rectum may be empty if hard or impacted stool is higher up in the bowel. In addition, patients presenting with impaction may pass loose stool or develop fecal seepage and stool incontinence that may be mistaken for normal bowel movements (often referred to as overflow fecal incontinence). Constipation may be the first sign of spinal cord compression, and patients who are at risk should undergo a complete neurological assessment, including evaluation for saddle anesthesia and rectal tone. Some patients may benefit from blood work to detect contributing metabolic abnormalities, radiological imaging such as abdominal radiography, computed tomography scans, and spinal magnetic resonance imaging, depending on the clinical presentation of symptoms of constipation and goals of care.

Prevention

The goal of laxative therapy is to achieve comfortable defecation based on a frequency determined in collaboration with the patient, with most patients benefiting from one nonforced bowel movement every 1 to 2 days. Tolerance does not develop to constipating effects of opioids, therefore prophylactic treatment with stool softeners and laxatives is considered the standard of care for as long as opioids are prescribed. Other preventive measures such as increasing fluid intake and dietary soluble fiber, scheduled toileting, and regular physical activity should be incorporated when feasible but may not be possible or appropriate in persons with advanced illness.

Pharmacological Treatment

No studies have been reported indicating superiority of one conventional laxative versus another in the management of opioid-induced constipation. Current recommendations are largely based on a few studies including a small number of randomized controlled trials and observational studies. Selection of laxatives depends on the nature of the stools, causes of constipation, and acceptability to the patient, as well as the cost and availability of the agent. Treatment must be individualized because each agent has considerable side effects that can limit tolerability. Rectal interventions may be uncomfortable and embarrassing for a patient, therefore oral therapies are usually considered first-line treatment. Expert opinion supports prevention as the cornerstone of the management of opioid-induced constipation, which starts with a scheduled osmotic agent or stimulant. An escalation of laxatives is recommended every 2 days if constipation persists, using a stepwise approach as depicted in Fig. 18.1 . Current evidence does not identify a linear relationship between opioid dose and amount of laxative required; however, as opioid doses are increased, additional laxatives are usually necessary to manage opioid-induced constipation. The following is a description of commonly used classes of medications for management of opioid-induced constipation (see also Table 18.4 ).