The European Society of Gastrointestinal Endoscopy (ESGE) recommends a modified diet and administration of purgative agents, such as 2 L of polyethylene glycol (PEG), prior to small bowel capsule endoscopy (SBCE) to improve visibility.1 Systematic reviews and randomized controlled trials have shown that small bowel visibility can be improved by using purgative agents.2-6 However, the practice of prescribing laxatives before SBCE remains a topic of debate because of their limited impact on capsule diagnostic yield (DY) and completion rates, coupled with challenges in patient tolerability and adherence.7-14 Notably, 15% of SBCE referral centers opt not to prescribe purgatives, and a significant majority (85%) struggle to meet the ESGE’s minimum standards for adequate or good small bowel preparation (i.e., ≥95%).15,16 In clinical settings, suboptimal small bowel preparation frequently leads to diagnostic delays, increased costs, and inconvenience, necessitating repeated SBCE procedures.

The use of 1 L of polyethylene glycol plus ascorbate (PEG-ASC) in large-bowel preparation has demonstrated enhanced patient adherence and tolerability.17,18 Moreover, we found initial evidence for the use of PEG-ASC in capsule endoscopy.19-21 Our study is the first to describe the promising impact of this small bowel preparation on the corresponding SBCE DY in a large series of patients receiving SBCE for a variety of clinical indications, not limited to suspected small bowel bleeding. Accordingly, we designed this study to assess the efficacy of 1 L PEG-ASC in comparison with the standard 2 L of iso-osmolar PEG solution for SBCE in a real-life setting.

Consecutive patients referred for SBCE (any indication) between October 2020 and February 2022 at our academic center in Milan, Italy were retrospectively included in a real-life clinical scenario. The exclusion criteria included the inability to provide informed consent, use of cleansing products or diet regimens different from those recommended, and prior SBCE examination during the same period. During the study period, two laxative solutions were assigned based on local clinical protocol: a standard solution of 2 L of iso-osmolar polyethylene glycol (PEG 4000 solution plus simethicone and electrolytes; SELG-ESSE, Promefarm) or a very low volume solution with hyperosmolar 1 L PEG plus ascorbate (NEER1006; PLENVU, Norgine). Both preparations were used and presented as valid alternatives during the study period. However, the type of bowel preparation suggested to each patient was determined by the prescription day, with SBCEs prescribed on even days advised to preferably perform 1 L PEG-ASC, while those on odd days were advised to drink 2 L PEG. In the absence of an established gold standard for SBCE preparation, this practice was intended not to induce a preference in patients towards one or the other commercially available bowel preparations, thereby ensuring transparency and equity.

All patients received detailed written instructions on how to take the laxative solution the evening before, starting at 19:00 to 20:00, and 80 mg of liquid simethicone 30 to 60 minutes before the SBCE. Additionally, all patients were provided with written instructions regarding adherence to a low-residue diet, including avoiding fruits, legumes, vegetables, or iron supplements the day before and consuming a light dinner based on a clear liquid diet the day before. SBCE examinations were performed using PillCam SB3 or PillCam Crohn’s capsules (for suspected or established Crohn’s disease only) and read by expert capsule readers (with over 10 years of experience, reading more than 50 capsules per year; LE, GET, FC) who were blinded to the small bowel preparation assignment.

Endoscopic findings were classified based on their clinical significance in relation to the indications for the procedure. In cases of suspected small bowel bleeding, we used the classification proposed by Saurin et al.22 (P0, low probability; P1, intermediate probability; or P2, high probability), considering positive SBCE cases with at least one relevant endoscopic finding (i.e., P2 lesions).

In cases where complicated celiac disease was suspected, a SBCE was deemed positive if scalloping, mosaic patterns, or ulcers were observed. For Crohn’s disease, a positive SBCE result was identified based on the presence of inflammatory lesions, including ulcers and strictures. When a neoplasm was suspected, the indicators included masses, bulges, and ulcerated lesions.23-27

As per our local protocol, SBCE visibility was quantitatively scored using the small bowel mucosal visibility scoring system (SBMVSS) for each small bowel tertile.27 This system involves assigning a score of 0 to 3 points to each small bowel tertile based on the relative amount of videorecording during which any residue affects the correct visualization of at least 50% of the mucosal surface.27 The total score was the sum of each tertile’s score. Therefore, adequate SBCE visibility was defined as a score ≥2 in each tertile and a total score ≥6. However, visibility was considered adequate if relevant findings could be identified, even if the visibility score was less than 6. Inadequate SBCE visibility necessitated repeat examinations.

A total of 221 consecutive SBCE examinations collected prospectively were retrospectively analyzed. Of these, 147 patients received the 2 L PEG bowel preparation, while 74 patients received the 1 L PEG-ASC solution. Indications included suspected occult (64 patients) or overt (53 patients) small bowel bleeding, celiac disease (48 patients), Crohn’s disease (25 patients), neoplasia (14 patients), others (11 patients), and symptoms (6 patients). In the initial crude data analysis, a statistically significant difference in patient age was observed between the two populations (p=0.002). Following propensity score matching using the random forest method, we successfully obtained a comparable population, with 74 2 L PEG-treated patients matched to the original cohort of 1 L PEG-ASC patients, resulting in mean ages of 55 years (SD, 21.1) and 53 years (SD, 16.9). The sex distribution in both cohorts was similar, with 30 men out of 74 in the 1 L PEG-ASC group and 31 men out of 74 in the 2 L PEG group.

No significant differences were observed in terms of DY (p=1.00), procedure completion (p=0.33), visibility score=9 (p=0.85), overall visibility in the small bowel tertiles (p=0.61, p=0.74, and p=0.70 for the first, second, and third tertiles, respectively), gastric transit time (p=0.61), and small bowel transit time (p=0.10). DY in both groups was approximately 65%.

There was a trend towards a statistically significant difference in the proportion of SBCE examinations scoring at least 2 in all tertiles between the two cohorts. Specifically, the 1 L PEG-ASC population achieved this result in 62 of 74 procedures, whereas the 2 L PEG group achieved this result in 52 of 74 procedures (p=0.07). The results are summarized in Table 1.

The DY was not influenced by the indication for SBCE (details are reported in Table 2).

International guidelines strongly advocate the use of laxatives before SBCE, with the 2 L PEG regimen being the most widely adopted.1 The low-volume 1 L PEG-ASC regimen has previously demonstrated effectiveness as an alternative to high-volume preparations before colonoscopy and might therefore represent a new standard for preparation in patients receiving SBCE.28 This study aimed to compare these two small bowel preparations for SBCE and assess their impact on quality indicators and SBCE performance.

Our study showed that there were no significant differences in small bowel visibility between the two cohorts of consecutive patients who underwent either 2 L PEG or 1 L PEG-ASC bowel preparations following propensity score matching. Specifically, the type of intestinal preparation did not influence total mucosal visibility or visibility in each tertile. The gastric and small bowel transit times were similar between the two cohorts. The DY was not significantly different between the two groups, aligning with or exceeding the values reported in the literature.23,29,30 These findings substantiate the evidence favoring the notion that the specific type of small bowel preparation has a negligible impact on the DY.7-14 Notably, visibility scores of ≥2 in all segments exhibited a trend towards a statistically significant difference (p=0.07) in favor of patients administered the 1 L PEG-ASC preparation.

The limitations of our study include its retrospective nature without formal randomization of patients to 2 L PEG or 1 L PEG-ASC, incomplete clinical data (e.g., body mass index and comorbidities), and the absence of patient feedback on preparation palatability, tolerability, compliance, and adverse events, along with their quantification. Additionally, the study did not assess the impact of split preparation, that is, dividing the purgative solution between the evening before and morning of the procedure, a method proven to be effective for colonoscopy in a single randomized controlled trial.31 This issue should be the subject of future research. Although the study was monocentric and involved only three experts evaluating intestinal visibility, this setup may be considered a limitation in terms of reproducibility or strength by avoiding potential bias.

In conclusion, our findings indicate that the 1 L PEG-ASC bowel preparation is comparable to 2 L PEG in terms of visibility. Prospective studies and/or randomized controlled trials could explore patient perspectives on tolerability and palatability as well as the impact of split preparation.