How Is Opiate-Induced Constipation in Children Treated?

Jessica Stovel, RPH

Disclosures

June 10, 2010

Question

How do you treat opioid-induced constipation in pediatric patients?

Response from Jessica Stovel, RPH
Pediatric Pharmacist, London Health Sciences Center, London, Ontario, Canada

Constipation is common in children -- the incidence ranges from 7%-30%.[1,2,3,4] While many factors may contribute to constipation (eg, limited physical activity, diet, hydration status), certain medications, such as opioids, can cause and/or worsen this condition.[5]

Opioids are used in the pediatric population for acute pain, such as fractures; postoperative pain; and chronic pain associated with cancer. Moreover, opioid-induced constipation may be worsened by pain-related factors (eg, immobility secondary to a fracture or bed restriction, reduced fluid and/or fiber intake postoperatively). Opioids decrease bowel motility and transit time of stool primarily because of their effect on opioid receptors in the gastrointestinal (GI) tract.[5] Opioids also cause decreased intestinal secretions and increased fluid absorption from the intestines, resulting in a drier, harder stool.[5,6]

Prevention is critical, as constipation can cause abdominal pain and cramping, nausea and vomiting, and decreased appetite.[5] Moreover, the longer the stool remains in the colon, the harder and larger it will get, and the more painful it will be to pass. The child is, therefore, likely to avoid having bowel movements for fear of painful defecation. This can result in a vicious cycle, leading to fecal impaction.[2] If no bowel movement has occurred in the past 7 days, the child should be referred to a physician because untreated impaction may lead to serious complications, such as megacolon and bowel obstruction or perforation.[5]

Nonpharmacologic approaches may help prevent opioid-induced constipation. Modifications to the child’s diet, such as increased intake of fluid and absorbable and nonabsorbable carbohydrates and/or fiber, have been shown to reduce constipation.[2,7] Exercise may also be helpful; however, recent evidence suggests that the benefits may not be as clear-cut as initially believed.[8] There is insufficient evidence to suggest that any of these measures alone will treat constipation.[8]

Mineral oil, a lubricant, has been used to treat constipation in children; however, due to the potential for aspiration and development of lipoid pneumonia, there are major safety concerns with its use.[2,3] Mineral oil is contraindicated in children younger than 12 months and in those with any risk factor for pulmonary aspiration.[1]

Stool softeners, such as docusate sodium, are well-tolerated, but a lack of data exists to support their efficacy in treating constipation.[9] Consequently, docusate should be used in combination with a stimulant laxative, such as bisacodyl or senna. Stimulant laxatives are often required to overcome opioid-induced constipation.[6]

Osmotic laxatives may be useful for managing opioid-induced constipation. While not indicated for use in the pediatric population, polyethylene glycol 3350 without electrolytes (PEG 3350) has been used to treat opioid-induced constipation[6] and can effectively prevent or treat this condition.[10] Another advantage is that it is tasteless.[5] Magnesium hydroxide (Milk of Magnesia) has been used successfully and safely on a long-term basis in children. While there are few data regarding its use for opioid-induced constipation specifically, it has been compared with PEG 3350 in children with functional constipation and found to have similar efficacy.[11,12] However, more children refuse treatment with magnesium hydroxide, probably because it is unpalatable.[8]Lactulose is usually not selected as a first-line agent for this type of constipation because it can cause flatulence, abdominal distention, and colic.[13]

Several popular herbal laxatives are used to treat constipation. In general, herbal agents (excluding senna) for treatment of opioid-induced constipation should be avoided in children due to a lack of efficacy and safety data. Interactions may also exist with other medications prescribed for the child.

Emerging evidence supports use in adults of agents that treat constipation by acting directly on the opioid receptors.[6] Methylnaltrexone bromide assists with restoration of bowel function in patients with late-stage, advanced illness who are receiving opioids continuously.[14] Methylnaltrexone is a peripherally restricted mu-receptor antagonist. It is believed to block opioid entrance into GI cells sufficiently enough to allow the intestines to function normally. Methylnaltrexone does not significantly decrease analgesic effects because it is not systemically absorbed and does not cross the blood-brain barrier.[5,14] Although it has been discussed as a potential drug on the horizon in some pediatric literature,[5] safety and efficacy have not been studied in the pediatric population.[14]

Like methylnaltrexone, alvimopan, a peripherally restricted mu-receptor antagonist, has been discussed as a potential drug for opioid-induced constipation in children.[4,5] At this time, alvimopan is not indicated for opioid-induced constipation and its safety and efficacy have not been established for pediatric patients.

Naloxone, a specific mu antagonist that exerts an effect similar to that of methylnaltrexone, has been investigated for treatment of opioid-induced constipation.[5] However, it readily crosses the blood-brain barrier and can cause reversal of opioid analgesia even at low systemic concentrations that are not effective for treating constipation.[5] Clinical studies have found that due to large interpatient variability, dose titration requires close patient monitoring.[5] Enteral naloxone use in a pediatric critical care population with opioid-induced constipation was found to improve stool output but caused opioid withdrawal symptoms in some patients.[6]

Further investigation of these newer agents in a pediatric population is required to establish efficacy, dosing guidelines, and safety. To date, methylnaltrexone shows the most promise.

While constipation resolves once the opioid is discontinued, first-line management is to prevent constipation by proactively recommending a standard laxative early in treatment. In conjunction with pharmacologic agents, clinicians should remember to recommend nonpharmacologic management. Clinicians are well-positioned to help preempt much discomfort and distress for the child and his or her family.

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