Tofil, N.M., Benner, K.W., Faro, S.J., & Winkler, M.K. (2006). The use of enteral naloxone to treat opioid-induced constipation in a pediatric intensive care unit. Pediatric Critical Care Medicine, 7, 252–254.

To describe the effects of enteral naloxone for the treatment opioid-induced constipation.

Patients in the treatment group received opioids and enteral naloxone for suspected opioid-induced constipation. Patients in the control group received opioids and were randomly chosen from patients receiving opioids during the study period.

• The study reported on a sample of 46 pediatric patients (23 in the treatment group and 23 in the member-matched control group).
• Mean patient age was 6.4 years (range 5 months to 18 years) in the treatment group and 6.1 years (range 4 months to 17 years) in the control group.
• The sample comprised 14 boys (61%) in the treatment group and 14 boys (61%) in the control group.
• The morphine equivalent was 86 mg per day (SD = 83, range 9–197) in the treatment group and 20 mg per day (SD = 17, range 1.3–59) in the control group.
• Mean length of stay in the pediatric intensive care unit was 15 days (SD = 8, range 7–43) in the treatment group and 10 days (SD = 7, range 3–31) in the control group.
• Mean length of stay in the pediatric intensive care unit five days before enteral naloxone initiation ranged from 0 to 13 days.

Pediatric intensive care unit of a children’s hospital in Alabama

This was a retrospective study conducted from January 2003 to February 2004.

• Daily stool output and opiate usage
• Nutrition
• Adjuvant laxative use
• Side effects

• In the treatment group, mean stool output before enteral naloxone was 0.14 (SD = 0.38) stools per day. After initiation, mean stool output was 1.6 (SD = 1.14) stools per day (p < 0.001).
• In the control group, mean stool output was 0.53 (SD = 1.21) stools per day.
• Eighteen patients in the treatment group (78%) received other bowel agents in addition to enteral naloxone (13 Miralax^®, 7 bisacodyl, 4 glycerin suppositories, and 1 milk-and-molasses enema).
• Eight patients in the control group (35%) received other bowel agents (4 Miralax, 4 bisacodyl, 1 glycerin suppository, and 1 milk-and-molasses enema).
• A significant inverse relationship existed between opioid dose and increase in stool output after naloxone initiation (r² = 0.17; p < 0.05).
• Two patients experienced withdrawal symptoms. One was caused by medication error.

Enteral naloxone may be effective for increasing stool output in opioid-induced constipation but carries risk of withdrawal symptoms. Additional study is needed.

• The study was retrospective.
• The study was not able to control several variables that could be confounders (e.g., dose, duration, and type of opioids; use of additional bowel stimulants; amount of nutrition).
• Other patients may have had unrecognized mild withdrawal symptoms.
• Stool size or weight would have been a more objective outcome measure, but was not available.
• A significant difference existed in morphine equivalent per day between the treatment and control groups (p = 0.01).