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Original Article Bowel preparation for small bowel capsule endoscopy: standard regimen with 2 L polyethylene glycol versus 1 L polyethylene glycol plus ascorbate
Riccardo Caccia1orcid, Alessandro Rimondi1orcid, Luca Elli1,2,orcid, Matilde Topa1orcid, Flaminia Cavallaro2orcid, Carmine Gentile1orcid, Lucia Scaramella2orcid, Nicoletta Nandi1orcid, Reena Sidhu3,4orcid, Pinhas Eidler1orcid, Maurizio Vecchi1,2orcid, Gian Eugenio Tontini1,2orcid

DOI: https://doi.org/10.5946/ce.2024.097
Published online: January 2, 2025

1Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy

2Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy

3Academic Unit of Gastroenterology, Sheffield Teaching Hospitals, Sheffield, UK

4Division of Clinical Medicine, School of Medicine and Population Health, University of Sheffield, Sheffield, UK

Correspondence: Luca Elli Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy E-mail: luca.elli@policlinico.mi.it
• Received: April 22, 2024   • Revised: August 1, 2024   • Accepted: August 3, 2024

© 2025 Korean Society of Gastrointestinal Endoscopy

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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  • Background/Aims
    Optimization of bowel preparation for small bowel capsule endoscopy (SBCE) is debated. Guidelines recommend 2 L of iso-osmolar polyethylene glycol (PEG) to improve SBCE visibility. We compared the efficacy of the standard 2 L PEG solution with a 1 L PEG plus ascorbate (PEG-ASC) preparation, which has already been established for large-bowel preparation.
  • Methods
    Between October 2020 and February 2022, patients undergoing SBCE were assigned to receive 2 L PEG or 1 L PEG-ASC bowel preparation on an even- or odd-day basis. Bowel cleanliness was evaluated using the small bowel mucosal visibility scoring system (SBMVSS).
  • Results
    Following propensity score matching using a random forest method, two comparable populations of patients treated with 2 L PEG (n=74, male 41%, 53±17 years) and 1 L PEG-ASC (n=74, male 42%, 55±21 years) were obtained from the original cohort of 221 consecutive SBCE patients. Our results showed a trend towards more frequent adequate mucosal visibility with 1 L PEG-ASC compared to 2 L PEG (small bowel mucosal visibility ≥2 in all three small bowel tertiles, p=0.07), as per the SBMVSS score. No significant differences were observed in the diagnostic yield (p=1.00), visibility score=9 (p=0.85), SBCE completeness (p=0.33), or adequate mucosal visibility in each tertile (p=0.61, p=0.74, and p=0.70 for the first, second, and third tertiles, respectively).
  • Conclusions
    Our study suggests the non-inferiority of the 1 L PEG-ASC solution over the standard 2 L PEG for SBCE preparation.
  • Keywords: Bowel preparation; Capsule endoscopy; Small bowel
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.
Statistics
Median, interquartile range and range are provided for non-normally distributed variables, while the mean±standard deviation (SD) is given for normally distributed variables. The two-tailed Student t-test for unpaired samples was used to compare continuous categorical variables such as gastric transit time with small bowel transit time, while the two-tailed Fisher exact test was used to compare DY, completion rate, and the rate of SBCEs with small bowel mucosal visibility scored ≥2 in all three small bowel tertiles. Due to the retrospective nature of this study, to better compare the outcomes in the two cohorts, we considered propensity score matching to determine whether statistically significant differences were noted in the analyses between the two populations. All statistical analyses were performed using R Studio (R: A language and environment for statistical computing; R Foundation for Statistical Computing).
Ethics
Given the nature of the present observational study, no sample size calculation was performed and all patients provided informed consent before undergoing SBCE. This study was approved by the local independent ethics committee (protocol number 137-2021) and conducted in accordance with the World Medical Association Declaration of Helsinki adopted in 1964, incorporating all later amendments.
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.
ce-2024-097f1.jpg
Table 1.
Comparison of 1 L PEG-ASC and standard 2 L PEG solution for small bowel preparation
1 L PEG-ASC (n=74) 2 L PEG (n=74) p-value
Age (yr) 53±16.9 55±21.1 0.36
Male 30 (40.5) 31 (41.9) 1.00
Diagnostic yield 49 (66.2) 48 (64.9) 1.00
Total visibility score=9 18 (24.3) 20 (27.0) 0.85
SBCE complete 71 (95.9) 67 (90.5) 0.33
SB1 SBMVSS 2.743±0.55 2.743±0.64 0.61
SB2 SBMVSS 2.514±0.58 2.465±0.81 0.74
SB3 SBMVSS 2.123±0.71 2.014±0.85 0.70
Visibility ≥2 in all segments 62 (83.8) 52 (70.2) 0.07
Gastric transit time 00:22:30 (00:12:00–00:55:00) 00:21:00 (00:09:15–00:47:00) 0.61
Small bowel transit time 04:31:00 (03:33:00–05:35:00) 04:59:00 (03:56:00–06:22:30) 0.10

Values are presented as mean±standard deviation, number (%), or median (interquartile range).

PEG-ASC, polyethylene glycol plus ascorbate; SBCE, small bowel capsule endoscopy; SB1, small bowel tertile 1; SB2, small bowel tertile 2; SB3, small bowel tertile 3; SBMVSS, small bowel mucosal visibility scoring system.

Table 2.
Comparison of DY between 1 L PEG-ASC and standard 2 L PEG solution for small bowel preparation based on SBCE indication
Indication Procedure (n=221) DY positive/total (%)
 p-valuea)
1 L PEG-ASC 2 L PEG
SSBB occult 64 (29.0) 13/20 (65.0) 24/44 (54.5) 0.59
SSBB overt 53 (24.0) 6/9 (66.7) 32/44 (72.7) 0.70
Crohn’s disease 25 (11.3) 10/13 (76.9) 6/12 (50.0) 0.23
Celiac disease 48 (21.7) 11/20 (55.0) 20/28 (71.4) 0.36
Symptoms 6 (2.7) 2/3 (66.7) 1/3 (33.3) 1.00
Neoplasia 14 (6.3) 5/6 (83.3) 5/8 (62.5) 0.58

Values are presented as number (%) unless otherwise stated. All enrolled patients were included in the analysis apart from those with unconventional indications (n=11).

DY, diagnostic yield; PEG-ASC, polyethylene glycol plus ascorbate; SSBB, suspected small bowel bleeding.

a)DY% 1 L PEG-ASC vs. DY% 2 L PEG.

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      Graphical abstract

      Bowel preparation for small bowel capsule endoscopy: standard regimen with 2 L polyethylene glycol versus 1 L polyethylene glycol plus ascorbate
      1 L PEG-ASC (n=74) 2 L PEG (n=74) p-value
      Age (yr) 53±16.9 55±21.1 0.36
      Male 30 (40.5) 31 (41.9) 1.00
      Diagnostic yield 49 (66.2) 48 (64.9) 1.00
      Total visibility score=9 18 (24.3) 20 (27.0) 0.85
      SBCE complete 71 (95.9) 67 (90.5) 0.33
      SB1 SBMVSS 2.743±0.55 2.743±0.64 0.61
      SB2 SBMVSS 2.514±0.58 2.465±0.81 0.74
      SB3 SBMVSS 2.123±0.71 2.014±0.85 0.70
      Visibility ≥2 in all segments 62 (83.8) 52 (70.2) 0.07
      Gastric transit time 00:22:30 (00:12:00–00:55:00) 00:21:00 (00:09:15–00:47:00) 0.61
      Small bowel transit time 04:31:00 (03:33:00–05:35:00) 04:59:00 (03:56:00–06:22:30) 0.10
      Indication Procedure (n=221) DY positive/total (%)
      		 p-valuea)
      1 L PEG-ASC 2 L PEG
      SSBB occult 64 (29.0) 13/20 (65.0) 24/44 (54.5) 0.59
      SSBB overt 53 (24.0) 6/9 (66.7) 32/44 (72.7) 0.70
      Crohn’s disease 25 (11.3) 10/13 (76.9) 6/12 (50.0) 0.23
      Celiac disease 48 (21.7) 11/20 (55.0) 20/28 (71.4) 0.36
      Symptoms 6 (2.7) 2/3 (66.7) 1/3 (33.3) 1.00
      Neoplasia 14 (6.3) 5/6 (83.3) 5/8 (62.5) 0.58
      Table 1. Comparison of 1 L PEG-ASC and standard 2 L PEG solution for small bowel preparation

      Values are presented as mean±standard deviation, number (%), or median (interquartile range).

      PEG-ASC, polyethylene glycol plus ascorbate; SBCE, small bowel capsule endoscopy; SB1, small bowel tertile 1; SB2, small bowel tertile 2; SB3, small bowel tertile 3; SBMVSS, small bowel mucosal visibility scoring system.

      Table 2. Comparison of DY between 1 L PEG-ASC and standard 2 L PEG solution for small bowel preparation based on SBCE indication

      Values are presented as number (%) unless otherwise stated. All enrolled patients were included in the analysis apart from those with unconventional indications (n=11).

      DY, diagnostic yield; PEG-ASC, polyethylene glycol plus ascorbate; SSBB, suspected small bowel bleeding.

      DY% 1 L PEG-ASC vs. DY% 2 L PEG.

      Table 1.

      Table 2.

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