Polyethylene Glycols with or without Electrolytes for Constipation in Children: A Network Meta-Analysis

Abstract

Background: Polyethylene glycol-based laxatives are the mainstay for the management of constipation in children as they are effective, easy to use and well tolerated.1 They are available in formulations with and without electrolytes, with the latter developed to improve taste and patient acceptance.2 The objective of this systematic review and network meta-analysis (NMA) was to assess the relative effectiveness of polyethylene glycol with (PEG + E) or without electrolytes (PEG) in the management of constipation in children. Methods: Text word searches were conducted in MEDLINE, MEDLINE in Progress, EMBASE, Cochrane Database and Systematic Reviews databases covering inception to April 2015. Randomised controlled trials comparing oral polyethylene glycols with placebo or other laxative for the management of constipation in children, published in English, were included in the systematic review. The primary efficacy analysis was the mean number of bowel movements per week. Secondary endpoints related to safety, tolerability and compliance. Studies included in the analysis were grouped according towhether the polyethylene glycol investigated included electrolytes or not and then according to the comparator (placebo or active control). For all pairings where there was more than one study, a direct estimate of the difference in mean number of bowel movements per week was obtained using Bayesian random effects model. All available data were combined using an NMA with a Bayesian random effects model fitted to assess the relative effectiveness of PEG and PEG + E.2. Results: 15 studies (involving 1,384 patients) were included in the NMA. PEG and PEG+ E are both more effective than placebo, increasing the mean number of bowel movements per week by 2.2 (CrL: 0.4, 4.0) and 2.1 (CrL: 0.2, 4.0) respectively. Direct comparison of PEG+ E with PEG suggests no difference in efficacy-0.2 (CrL: -1.6, 1.5). Overall PEG and PEG+ E were well tolerated and generally better tolerated than other laxatives, lactulose, liquid paraffin and milk of magnesia. Head-to-head comparison indicated a better tolerability for PEG alone compared to PEG+ E in terms of a lower incidence of nausea. The addition of electrolytes may compromise constipation therapy due to issues associated with the salty taste and willingness to adhere to therapy. Head-to-head comparison of PEG and PEG+ E indicated that the taste of PEG was considered better than PEG +E (p<0.001), more patients had no difficulties with taking PEG than PEG+ E (p<0.001) and there was a trend towards improved compliance with PEG alone (p = 0.062). Conclusions: This NMA confirmed that PEG alone is equally effective to PEG+ E. There were no safety benefits associated with the addition of electrolytes. This NMA reaffirms the position that polyethylene glycols are the mainstay pharmacotherapy for the management of constipation in children and formulations without electrolytes should be considered first to optimise adherence and tolerability.