The standard high-volume PEG-based preparation is safe and effective, but even in clinical studies a significant proportion of patients is unable to take all the prescribed dose(19) with detrimental effect on its efficacy. RCTs and meta-analyses have shown a comparable efficacy of different low-volume preparations compared to high-volume PEG(9,10,13–15), and the use of these preparations is now recommended in both the European(16) and North American(17) guidelines. However, most RCTs did not compare clinically relevant outcomes such as ADR. This comparison is short of the newer LV preparations such as 2L PEG plus citrate and 1L PEG plus ascorbate. While the former was compared to high-volume PEG at least in terms of efficacy and tolerability(14), the latter has been compared only with other low-volume preparations(20–22). Moreover, real-life data are conflicting: a recent prospective observational study has shown better cleansing results and higher ADR and AADR with 4L PEG compared to lower volume preparations(23).
In our real-life setting, only a slight majority of patients (52%) preferred the LV preparation over the standard HV. This may be partially explained by the order in which the two preparations were listed in the instructions handed to the patients (HV preparation listed first). However, among the patients with IBD, frequently reluctant to perform bowel preparation, the use of the LV preparation was much more frequent than the HV one (75.2%). Women also used more frequently the LV preparation, while we did not find any age-related difference. Even if stated equally effective in the instructions given, it is possible that the patients perceived more effective a high-volume preparation and leaned towards that choice, especially for “strong” indications such as positive FBT. Interestingly, 52% of patients with colonoscopy planned in the afternoon chose the HV preparation. This may suggest that the possibility to reduce the volume of PEG was not felt so compelling once given the possibility to split its assumption.
Overall, 87.9% of our patients achieved adequate preparation. This result is in line or superior to the results reported in the literature(24,25), even if slightly inferior to the 90% target proposed by the European Society of Gastrointestinal Endoscopy (ESGE) in 2019(26). We confirmed that the low-volume PEG plus bisacodyl preparation is equally effective than HV in all the colonic segments (while some studies have shown worse performances of low-volume preparations in the right colon(27)) and irrespective of the intake schedule. In particular, the split LV preparation was as effective as the split HV preparation, confirming the results achieved in a recent meta-analysis(28).
Our real-life setting results confirm the importance of bowel preparation in terms of relevant outcomes such as complete colonoscopy rate, PDR and ADR, while we did not find differences in terms of AADR, SDR and cancer detection. Advanced adenomas and cancers are usually bigger lesions, easier to find even in a not well-prepared colon(6), while the SDR result can be explained by their low prevalence in our population.
Quite surprisingly, despite similar efficacy, the use of the HV preparation was related to higher PDR (OR 1.37), ADR (OR 1.38) and AADR (OR 1.72) compared to the LV preparation. To remove confounding factors due to the absence of randomization, we adjusted the OR considering three main characteristics related to the prevalence of colorectal lesions (age, sex and indication). Even after this adjustment, the HV preparation showed better results, with a statistically significant difference for PDR (adjusted OR 1.30, p = 0.0254) and differences very close to significance for ADR (adjusted OR 1.28, p = 0.0519) and AADR (adjusted OR 1.54, p = 0.0519). Despite better cleansing results with the split-dose as compared to the day-before regimen (93.7% vs. 82.8%, p < 0.0001), we did not find any correlation with clinical outcomes in both the HV and LV group. LV split-dose was inferior to either HV day-before or split-dose.
LV preparations(10,14) and in particular 2L PEG plus bisacodyl(9) were found to be better tolerated as compared to high-volume PEG in previous RCTs. On the contrary, we have observed more self-reported gastrointestinal symptoms such as nausea, vomiting and abdominal pain in the LV group. This result can be explained by the real-life observational design of our study, rather than reflecting an intrinsic lower tolerability of the LV preparation. Nonetheless, these GI symptoms affected neither the patients’ adherence nor tolerability. In fact, the LV preparation was judged as tolerable as the HV preparation according to the VAS scale, and it was more frequently taken completely. The use of a split-dose regimen increased the reported tolerability of both the HV (higher VAS score) and the LV (less frequent symptoms) preparations, as previously shown in RCTs and meta-analyses(29,30).
Our study has several limitations. Firstly, the single-center observational design implies the risk of sub-optimal reproducibility. However, the large sample size and the prospective nature of this study support our results. Secondly, as compared to RCTs, the real-life patients-determined allocation among different study groups could result in an unbalanced distribution of risk factors. Notably, the baseline characteristics of the two study groups (HV, LV) were mostly comparable and the few relevant differences (mainly sex and indication for colonoscopy) were adjusted when comparing the endoscopic performance measures between the groups. Thirdly, it is important to acknowledge that the application of the day-before schedule is no longer recommended by the 2019 ESGE guidelines because of its inferior efficacy when compared to split-dose, as confirmed by our results. Due to the extension of the metropolitan area served by our center, however, we decided to maintain the possibility to choose a day before regimen. In fact, living far from the endoscopic centers has been demonstrated to be a significant limitation for adherence to split dose regimen, especially for early morning scheduled colonoscopy(31). On the other hand, additional strengths of our study consist in the blindness of the endoscopists to the type of preparation taken and the use of a well-validated bowel preparation scale.