Comparing different doses of PEG 4000 for Managing Functional Constipation in Children

PEG is a mixture of non-absorbable and non-metabolizable polymers that bind water molecules through hydrogen bonds; this leads to an increase in water in the colonic content, which facilitates bowel movements (BM) and painless defecation (2,3). A Cochrane review of randomized clinical trials showed that PEG is superior to placebo, lactulose, milk of magnesia, and mineral oil in the management of childhood constipation (4), and thus, PEG presently is considered as the first-line treatment for maintenance therapy (5).

Polyethylene glycol 4000 (PEG 4000) is a non-toxic, hydrosoluble, high-molecular polymer, which is not absorbed in the gastrointestinal tract following oral administration. PEG 4000 acts as an osmotic agent that increases faecal water content. (8)

Studies done in the past have shown that PEG 4000 is safe for long-term therapy in children with chronic constipation in terms of biochemical parameters (9). With its suggested long-term use in pediatric patients with functional constipation, it is important to determine what would be the most apt dose for PEG 4000 in the long run

The suggested dose of PEG in children ranges from 0.2 to 0.8 g kg -1 day -1 (3). As, there is a paucity of data regarding the most effective dose of PEG, more dose-finding studies in children have been needed (6).

Keeping this limited knowledge about the dose-related effectiveness of PEG in mind, in 2014, Piotr Dziechciarz et. al., (7) from the Department of Paediatrics, Medical University of Warsaw, Poland undertook a study to evaluate the effectiveness and safety of 2 different PEG doses for the maintenance treatment of functional constipation in children.

Findings were published in the journal of Gastroenterology.

A randomized open-label trial from June 2013 through November 2013 at the Department of Paediatrics of the Medical University of Warsaw. The trial was initiated by the investigators and conducted independently of any commercial entities.

The study population consisted of children 1 to 18 years of age with functional constipation defined according to the Rome III criteria (9, 10) (i.e., defecation frequency of <3 times per week and 1 or more of the following criteria: faecal incontinence >1 episode per week, a large number of stools that clog the toilet, painful defecation, withholding behaviour, or abdominal or rectal faecal impaction on physical examination) for at least 2 months.

Those patients having a diagnosis of irritable bowel syndrome, mentalretardation, endocrine disease (eg, hypothyroidism), an organiccause of defecation disorders (eg, Hirschsprung disease, spinalanomalies, anorectal pathology, a history of gastrointestinalsurgery), functional nonretentivefaecal incontinence, or intake ofmedications influencing gastrointestinal motility, we excluded from the study.

After making the diagnosis of functional constipation and assessing for eligibility, and written informed consent to participate in the study was obtained. For children with faecal impaction, an enema (once per day, for a maximum of 3 days) was recommended. Eligible children were randomly allocated to receive PEG 4000 at a dose of either 0.7 g/kg (high-dose group) or 0.3 g/kg (low-dose group), for 6 weeks, in sachets to be dissolved in a fluid and consumed once daily. Outcome assessment was recorded by parents who noted each child's BM, any discomfort duringdefecation, and adverse effects of the treatment. During the study period, if <3 BM per week or >3 loose stools per day wereobserved, the dose of PEG was adjusted and/or an additional laxative was administered.

The primary outcome measure was treatment success, defined as 3 or more BM per week with no faecal soiling during the last week of the intervention.

The secondary outcome measures included the need for therapy adjustment (i.e., the number of patients in need for laxatives during treatment and/or a change of the starting dose throughout the study period).

Besides these, at week 6 interval, thefollowing additional outcome measures were assessed: the numberof stools per week, painful defecation, abdominal pain, and faecalincontinence. Parental satisfaction with the treatment was assessed during the final visit and all adverse events and their possible relation to the studyproduct consumption were evaluated.

Upon analysis, the following key facts emerged.

1. Of the 92 children who underwent randomization, 45 were assigned to the high-dose PEG group (0.7 g/kg) and 47 were assigned to the low-dose PEG group (0.3 g/kg).A total of 90 of 92 randomized children, with a mean age of 3.7 - 2.1 years, completed the study as one patient was lost in each group to follow-up.

2. In the analysis based on allocated treatment, treatment success was similar in both groups (relative risk 0.9, 95% confidence interval 0.78–1.03).

3. Compared with the high-dose PEG group, the low-dose PEG group had an increased need for therapy adjustment of borderline significance (relative risk 2.0, 95% confidence interval 1.0–4.2), an increased risk of painful defecation, a lower number of stools per week, and lower parental satisfaction.

4. Adverse events were similar in both groups.

Based on the results, the researchers made some important observations.

• The trial showed that both doses of PEG 4000 were equally effective in the treatment of children with functional constipation.

• At the same time The low-dose PEG group, however,showed a trend toward the dose adjustment and/or other laxatives,which could have contributed to the treatment success in that groupwhen compared with the high-dose PEG group.

• Moreover, the low-dose PEG group had an increased risk of painful defecation compared with the high-dose PEG group, a reduced number of stools per week, and lower parental satisfaction with the treatment.

• At the end of the intervention, the study groups did not significantly differ about the number of children with faecal incontinence episodes and the number of children with

abdominal pain.

These findings lie in contrast to the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition/European Society for Pediatric Gastroenterology, Hepatology, and Nutrition guidelines, where a starting PEG dose of 0.4 kg -1 day -1 is recommended and should be adjusted according to clinical response (6).

"The results of our study suggest that PEG at a dose of either 0.3 or0.7 g/kg administered for 6 weeks was equally effective and well-tolerated. No need for the dose adjustment in the majority of patients in the high-dose PEG group suggests that in clinicalpractice this dose can be considered as an appropriate initial dose,particularly in settings with limited resources for follow-up" the authors stated

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9. Bae SH. Long-term safety of PEG 4000 in children with chronic functional constipation: A biochemical perspective. Korean J Pediatr 2010; 53:741–744.