Hardikar, W., Cranswick, N., & Heine, R.G. (2007). Macrogol 3350 plus electrolytes for chronic constipation in children: A single-centre, open-label study. Journal of Paediatrics and Child Health, 43, 527–531.

To evaluate the safety and efficacy of macrogol 3350 plus electrolytes in the treatment of chronic constipation in children.

All children received macrogol 3350 plus electrolytes for 12 weeks. Children aged 2 to 6 years received one sachet daily on days 1 and 2, one sachet twice daily on days 3 and 4, and one sachet three times daily on day 5. Children aged 7 to 11 years received one sachet twice daily on days 1 and 2, and two sachets twice daily on days 3, 4, and 5. After day 5 and until the end of the study, the dosage was titrated according to fecal form. The dose was increased by one sachet per day in the event of continued hard stools or no bowel movement, and decreased by one to two sachets per day in the event of loose stools or diarrhea.

The mean duration of treatment was 75.5 days, during which time the participants took an average of 1.3 sachets (6.9 g) of macrogol plus electrolytes per day.

• The study reported on a sample of 78 children with chronic constipation for greater than three months.
• Patients were aged 2 to 11 years, with a mean age of 4.9 years (SD = 2.6).
• The sample comprised 34 boys (44%).
• Patients were included in the study if they had chronic constipation defined as fewer than three complete bowel movements per week over the previous 14 days, in association with either straining or passage of hard stools in at least 25% of bowel movements. The existing constipation was either untreated or inadequately treated by laxatives.
• Patients were excluded if they were treated for fecal impaction with bowel washouts within the previous two months or if they had a past history of intestinal perforation or obstruction; Hirschsprung disease; paralytic ileus; toxic megacolon; severe inflammation of the intestinal tract; urinary tract infections; uncontrolled renal, hepatic, or cardiac diseases; endocrine disorders; or any other severe unstable coexisting disease within the previous 30 days.

Royal Children’s Hospital, Melbourne, Australia

This was an open-label, nonrandomized study.

• The primary outcome was number of spontaneous defecations per week.
• The secondary outcomes were fecal form, abdominal pain, rectal bleeding, pain on defecation, straining, soiling, amount of stool, stool withholding, and assessments of efficacy by the investigators and parents.
• Safety assessments included adverse events, laboratory tests (full blood examination; urea, electrolyte, and liver function tests) and changes in vital signs. Adverse events were monitored throughout the study; venous blood samples for laboratory safety were taken at visits 1, 3, and 5. 
• Compliance was rated on a four-point scale from very poor (less than 25% of prescribed dose taken) to very good (more than 75% of prescribed dose taken).

•  Sixty-five patients (80%) completed the study.
• The mean number of spontaneous defecations per week increased from 1.4 (SD = 0.55) at baseline to 6.8 (SD = 3.45) after 14 days and 7.1 (SD = 3.45) at 12 weeks (p < 0.001).
• Stool frequency remained unchanged from visit 2 until the final visit (ANOVA: F = 0.81, p = 0.518).
• Similar improvements were found in the secondary efficacy variables. A significant reduction in reported abdominal pain from 53 children (68%) at baseline to 3 (4%) at the final visit occurred (p < 0.0001). Similarly, 61 children (78%) had pain on defecation at baseline, compared with 7 (9%) at the final visit (p < 0.0001). Treatment was well tolerated.
• Of 318 adverse events, 262 (82%) were considered mild, and 241 (76%) were deemed unrelated to treatment.
• Only 3 children (4%) were withdrawn because of poor compliance. Mean duration of treatment was 75.5 days, during which time the participants took an average of 1.3 sachets (6.9 g) of macrogol plus electrolytes per day. Ratings of excellent compliance (higher than 75% intake of study medication) were reported for 86%, 81%, 76%, and 79% of participants at visits 2, 3, 4 and 5, respectively.

Longitudinal studies are needed to determine the long-term outcome of successful treatment of chronic constipation during childhood.

• The study did not mention which electrolytes were added and in what amount.
• This study design did not allow determination of a true treatment effect from spontaneous improvement.
• Open-label studies are subject to bias in assessments of efficacy, but the findings in this study are supported by results from several nonrandomized and randomized controlled studies of polyethylene glycol 3350–based preparations in children.
• Study results are not relevant to oncology.