To the best of our knowledge, this is the first prospective study to investigate the efficacy and safety of macrogol 4000 intake the night before colonoscopy, in addition to the PEG dose of 1500–2000 mL for colonoscopy preparation, in patients with chronic constipation. The results showed that bowel preparation was good in 92.5% of cases, indicating the effectiveness of this method. There were almost no adverse events, and it was well tolerated.
Polypectomy can prevent the onset of colorectal cancer. However, if bowel preparation is poor, polyps < 10 mm in size are particularly difficult to detect, and the ADR declines.4 One study found that compared with an ADR of > 20%, an ADR < 20% increased the risk of interval cancer by tenfold.19 Another study reported that a 1% improvement in the ADR led to a 3% reduction in the development of colorectal cancer and a 5% reduction in colorectal cancer deaths.20 Colonoscopy results from this study were extremely good, with an ADR of 60.0%, PDR of 75.0%, and median insertion time of 6.0 min, thus indicating that this method was also effective from the standpoint of colonoscopy.
Although one patient was unable to ingest 1500 mL of PEG, intake of macrogol 4000 did not cause any adverse events, such as abdominal pain or vomiting. Previous studies have reported the occurrence of abdominal pain, diarrhea, nausea, and other adverse events in 4.5–15.7% of patients who received macrogol 4000.16,21−22 However, this might be attributed to the continual intake of macrogol 400 for at least a week. In contrast, in our study, macrogol 400 was ingested only once on the night before colonoscopy. We observed that macrogol 400 was better tolerated than PEG. In addition, we found that even though macrogol 4000 has same composition as PEG, dissolving it in apple juice minimized the discomfort associated with its use.
In Japan, the dose of PEG is generally lower than that used in Western countries. Nevertheless, efforts to improve the effectiveness of colon cleansing and to reduce this dose are required. Conventionally, stimulant laxatives have been used in Japan, such as sodium picosulfate hydrate, senna, and bisacodyl. However, the use of these stimulants for colon cleansing has been reported to cause ischemic colitis and requires careful attention.23–24 Macrogol 4000 is a non-stimulant laxative that is unlikely to overstimulate the bowel and can thus be safely used for colon cleansing. Several previous reports have described the use of additional non-stimulant laxatives the previous night as adjuvant colon cleansers. In one randomized controlled trial, lubiprostone was shown to significantly improve the BBPS score (7.44 + 0.14 vs. 6.36 + 0.16, p < 0.0001) when compared with the placebo.25 Another study of mosapride as an adjuvant to bowel preparation with 2000 mL of PEG found that the addition of mosapride to 2000 mL of PEG resulted in significantly better bowel preparation in the left colon (78.2% vs. 65.6%, p < 0.05).26 When mosapride was used as an adjuvant for bowel preparation with 2000 mL or 1500 mL of PEG, the results for 1500 mL were not inferior to those obtained with 2000 mL, while the 1500 mL dose was better tolerated.27 These findings suggested that the use of mosapride may reduce the volume of PEG ingested. Yoshida et al. reported that the continuous intake of macrogol 4000 for 1 week prior to colonoscopy improved the rate of effective bowel preparation to 72.6%, in addition to the improvement in insertion time and discomfort during insertion; however, this was a retrospective study.21 In this study, we evaluated intake of macrogol 4000 only on the night before the colonoscopy procedure to ensure patient adherence. Hence, future comparative studies are required to investigate whether taking additional medication only on the night before the procedure is sufficient or whether it should be taken for approximately a week, taking into account both patient adherence and efficacy.
One of the major strengths of our study is that it was the first prospective study on the use of macrogol 4000 for colon bowel preparation. Our results not only support the findings of previous retrospective studies of its value, but we also observed almost no side effects. In addition, this study only included patients with constipation. We also evaluated the ease of macrogol 4000 intake by patients and confirmed the better tolerability of macrogol 4000 than PEG. These findings may help in reducing the dose of PEG by increasing the dose of macrogol 4000.
This study has several limitations. First, it was conducted at a single center. In addition, it was a single-arm, non-randomized trial. Therefore, comparative studies including patients who did not receive macrogol 4000 and those who used other additional bowel cleansing drugs are required to further investigate the efficacy of macrogol 4000. Second, the study included only Japanese patients, and the results may not be applicable to patients from other regions who have greater mean body weight than that of Japanese patients. Westerners and Asians have different physiques, and studies have also suggested that there may be racial differences in the efficacy of PEG28, suggesting that complex elements may have some effect.
When conducting colonoscopies, the choice of bowel cleansing agents is extremely important. The results of this study suggest that macrogol 4000 as an adjuvant bowel preparation may be used as a new alternative. However, it is too early to draw concrete conclusions and further studies with larger number of patients are required.