| Background: Chronic constipation is a common functional gastrointestinal disorder, which the prevalence is very high and decreases the patients' quality of life. Nearly half of the patients are dissatisfied with the treatment because of lack of efficacy. Polyethylene glycol (PEG) is an emerging osmotic laxative. In the gastrointestinal tract, PEG can not be metabolized by colonic bacteria and absorbed, thus it obligates intraluminal water and exerts its substantial osmotic activity, leading to modification of stool consistency and increased faecal bulk. Some studies have indicated that PEG can increase the bowel movement frequency and improve the symptoms of chronic constipation. PEG was recommended for constipation as grade A by American College of Gastroenterology Chronic Constipation Task Force. At present, polyethylene glycol-based laxatives are increasingly being used widely in practice. But its exact effectiveness and safety for treatment of chronic constipation in adults are inconsistent, and a systematic review is needed to provide further data.Objectives: To evaluate the efficacy and safety of PEG for the treatment of chronic constipation in adults.Methods: Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders (IBD/FBD) Group methods in reviews were used to collect the randomized controlled trials. The following electronic databases were searched irrespective of language and publication status: IBD/FBD Group Specialized Register (March 6, 2007), Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 1, 2007), MEDLINE (1950～2007), EMBASE (1980～2007) and Chinese Biomedical Database (1978～2007). The references of papers related to PEG were tracked down for more trials. All randomized controlled trials comparing polyethylene glycol based osmotic laxatives with placebo, lactulose, psyllium or tegaserod for the treatment of chronic constipation in adults were included. Two authors independently assessed the methodological quality of studies and extracted data. Any disagreements between authors were resolved by discussion or the third author if needed. The following outcome measures were assessed: global improvement of symptoms, bowel movement frequency, stool consistency, improvement of ease of defecation, relief of symptoms related to constipation, gastrointestinal transit time, quality of life and the number and types of adverse events. Data were analyzed using Review Manager (RevMan 4.2.8). Dichotomous data were presented as relative risk (RR) and continuous outcomes as weighted mean difference (WMD), both with corresponding 95% confidence intervals (95% CI).Results: 17 randomized clinical trials involving 1472 patients met the inclusion criteria. Most included trials were of poor quality. In the 17 clinical trials, only 3 trials reported the methods of allocation concealment, 6 trials were double-masked and 3 trials were crossover designs. The sample size of the trial involving most patients is 186. Two different polyethylene glycols, PEG3350 and PEG4000 were studied. The controlled interventions were placebo, lactulose and psyllium. The pooled results indicated that: 1. PEG was superior to the controlled interventions in global improvement of symptoms (PEG3350 vs Placebo: RR=1.56, 95%CI 1.21～2.02; PEG4000 vs Placebo: RR=4.00, 95%CI 2.00～8.02; PEG vs Lactulose: RR=1.12, 95%CI 1.01～1.23; PEG vs Psyllium: RR=1.29, 95%CI 1.12～1.48). 2. PEG was superior to the controlled interventions in improving bowel movement frequency (PEG vs Placebo: WMD=2.39, 95%CI 1.87～2.90; PEG3350 vs Lactulose: WMD=2.80, 95%CI 1.24～4.36; PEG4000 vs Lactulose: WMD=0.12, 95%CI 0.00～0.24; PEG3350 vs Psyllium: WMD=2.77, 95%CI 1.70～3.84; PEG4000 vs Psyllium: WMD=1.09, 95%CI 0.45～1.73). 3. PEG was superior to the controlled intervention in improving stool consistency (PEG vs Placebo: RR=1.95, 95%CI 1.47～2.32; PEG vs Lactulose: RR=1.42, 95%CI 1.26～1.59; PEG vs Psyllium: RR=1.31, 95%CI 1.07～1.60). 4. PEG was superior to placebo and lactulose in improving straining at defaecation (PEG vs Placebo: RR=1.96, 95%CI 1.51～2.55; PEG vs Lactulose: RR=1.19, 95%CI 1.02～1.39), but PEG was not superior to psyllium (RR=1.06, 95%CI 0.92～1.23). 5. There were no significant differences between the PEG groups and the control groups in relieving abdominal pain (PEG3350 vs Placebo: RR=1.50, 95%CI 0.90～2.50; PEG4000 vs Lactulose: RR=1.09, 95%CI 0.97～1.35; PEG vs Psyllium: RR=1.26, 95%CI 0.94～1.70). 6. There were no significant differences between the PEG groups and the control groups in relieving abdominal bloating (PEG3350 vs Placebo: RR=1.61, 95%CI 0.96～2.72; PEG4000 vs Lactulose: RR=1.09, 95%CI 0.91～1.30; PEG vs Psyllium: RR=1.09, 95%CI 0.95～1.24).7. Only 1 trial reported that there was a trend to accelerate the gastrointestinal transit by PEG3350 but no significant difference between the PEG3350 group and the control group (WMD=0.13, 95%CI -0.05～0.31). 8. PEG resulted in more adverse events compared with placebo (RR=10.24, 95%CI 2.45～42.72), the common adverse events reported were diarrhea, abdominal pain, abdominal bloating and nausea. The symptoms were not serious and disappeared after discontinuation. There were no significant differences in adverse events between PEG and lactulose or psyllium (PEG vs Lactulose: RR=0.79, 95%CI 0.52～1.20; PEG vs Psyllium: RR=0.97, 95%CI 0.45～2.07).Conclusions: PEG can improve the global improvement of symptoms, increase the bowel movement frequency and soften the stools. PEG can relieve the patients' straining at defaecation compared with placebo or lactulose. But there are no statistically significant differences in relieving abdominal pain and abdominal bloating between PEG groups and control groups. Shortening the gastrointestinal transit time is not identified. PEG may result in mild to moderate gastrointestinal discomfort which would disappear after discontinuation. The above evidences show that PEG may be a safe and effective treatment for chronic constipation in adults. However, the evidence is not enough strong because of the low qualities of trials and publications bias. Multicenter, randomized, double-blind, controlled trials with high quality and large sample size are needed to further assess the effect.
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