The Use of a PEG/Ascorbate Booster Following Standard Bowel Preparation Improves Visualization for Capsule Endoscopy in a Randomized, Controlled Study

Abstract

Background

Background/Aims: The increasing use of capsule endoscopy (CE) to examine the gastrointestinal tract highlights the need to establish intestinal preparations that ensure optimal visualization while maximizing patient adherence. Thus, we assessed whether bowel preparation involving dietary restriction and a booster regimen produces adequate CE visualization in a real-world clinical setting.

Methods

We conducted a randomized, double-blind, prospective study of CE procedures at 2 tertiary-care centers. Patients were allocated to 3 groups: group 1 followed a clear liquid diet and fasting-based bowel preparation for the exploration (n = 55); group 2 followed the same procedure as group 1 and then ingested 1 L of a polyethylene glycol (PEG)/ascorbic acid booster solution when the capsule reached the small intestine (n = 55); and group 3 followed the same procedure but ingesting only 0.5 L of the booster solution (n = 56). The quality of visualization and the average gastric, orocecal and small-bowel transit times were evaluated.

Results

A total of 166 patients participated in the study. Significantly higher quality of visualization (Park score) was obtained in group 3 (2.28 ± 0.59) than in group 1 (1.84 ± 0.54, P < .001), while there were no significant differences in the average gastric (range: 36.58-48.32 min, P = .277), orocecal (range: 322.58-289.45 min, P = .072), and small-bowel transit time (range: 280.71-249.95 min, P = .286) between the 3 groups.

Conclusions

Following a clear liquid diet and fasting-based bowel preparation for CE exploration, administering a booster solution of PEG/ascorbic acid after the capsule had reached the small intestine improves mucosal visualization and cleansing without affecting capsule transit times.

INTRODUCTION

Capsule endoscopy (CE) is a procedure that is now often used to study conditions affecting the small intestine, offering certain benefits over conventional endoscopy examination.¹ CE still requires cleansing of the digestive tract for optimal visualization, and while active bowel preparation for CE may achieve this,² these regimens are often not well tolerated by patients and produce adverse events (e.g., dizziness, vomiting, etc.).³ Indeed, such protocols may ultimately be associated with poor patient adherence and even abandonment, potentially provoking poorer visualization and failure of the exploration, or non-attendance. Thus, the optimal patient preparation for CE remains unclear, highlighting the need to establish an efficient, standardized, and user-friendly preparative protocol.

There is evidence that bowel preparation with purgative agents prior to CE improves small-bowel mucosal visualization when compared to a preparation simply involving a clear liquid diet and overnight fasting. These improvements are generally achieved without affecting the CE completion rate, the capsule’s gastric transit time (GTT), or its small-intestine transit time (SITT). A large body of evidence supports the use of polyethylene glycol (PEG) 4-8 and, in particular, the combined use of PEG with other agents such as simethicone or ascorbic acid.^1,9-14 Of these, there is evidence that combining PEG with ascorbic acid is better tolerated by patients, producing fewer adverse events and hence, better patient adherence.¹¹ However, to date, no large, multicenter, randomized-controlled trials have been carried out to validate the use of these protocols or evaluate the ideal dose/volume of PEG or the most appropriate timing of bowel preparation before CE. Indeed, not all studies found benefits when using such active bowel preparations in terms of visualization quality and diagnostic performance.^15-18 Hence, more efforts are clearly necessary to establish a standard preparative protocol for CE.

Significantly, in many studies, patients are also required to ingest a booster during the exploration in order to propel the capsule through the small-bowel to reach the colon, and to ensure its rapid recovery. As such, we speculated that the use of a PEG booster after capsule ingestion, in conjunction with a clear liquid diet preparation the day prior to the procedure and a 10 h overnight fast, may be sufficient to produce optimal CE visibility of the small-bowel mucosa. Should this be the case, it might provide an alternative to the pre-ingestion PEG cleansing protocol, combining the comfort of a less stringent preparation with the visual quality of the latter. Accordingly, the main aim of this study was to evaluate the quality of mucosal visualization and cleansing when a booster solution of PEG plus ascorbic acid was administered after ingestion of the capsule, and following a clear liquid diet and overnight fasting bowel preparation for CE the day prior to the examination, in a real-world clinical setting.

MATERIALS AND METHODS

Patients and Study Design

This is a randomized, double-blind, prospective study on patients aged between 16 and 92 with various clinical indications that required CE. The patients who participated in this study were recruited between January 2017 and April 2018. All patients on whom videocapsule endoscopy was carried out at the Manoph and iCUF tertiary-care centers (2 affiliated healthcare centers) provided their informed consent were initially included in the study. Each of the patients was randomly assigned to one of 3 groups by MMS through a double-bind randomization prior to the examination. The clinician performing the intervention remained blind to this assignation and was responsible for the capsule’s real-time visualization throughout the intervention and for establishing the time at which the booster solution was administered. The patients in group 1 followed a commonly used bowel preparation prior to the exploration (n = 55), which involved 3 days without iron supplement intake and with light meals, adhering to a clear liquid diet from the afternoon of the day prior to the examination, and fasting for 10 h before the procedure was performed. The patients in group 2 followed the same bowel preparation prior to the examination as that followed by patients in group 1, but they also ingested a 1 L booster solution of PEG/ascorbic acid (prepared in water: Moviprep®: Supplementary File) when the capsule had reached the small intestine, as verified through real-time visualization by the clinician performing the intervention (n = 55). Finally, the patients in group 3 followed the same procedure as those in group 2, except they ingested a smaller volume of the booster solution, 0.5 L (n = 56). Patients who did not comply with the prescribed preparation or on whom a different capsule model from those established were used were excluded from the study.

All the patients recruited to this study provided their informed consent (or that of their legal guardians) prior to participating in this study, which was carried out in accordance with the guidelines laid down in the Helsinki declaration and with the approval of the 2 hospital’s local ethical committee.

Procedures and Study Design

CE examinations were carried out either using the PillCam(r) SB3 capsule endoscopy system (Given Imaging, Yokneam, Israel) or the MiroCam® Capsule endoscopy system (Intromedic, Seoul, Korea).

In the absence of a more universally accepted standard, small-intestine cleanliness/quality of visualization was assessed blindly, in accordance with a scale devised previously.¹⁹ In this scale, referred to as the Park score, the cleansing score is considered on a scale of 0 to 3, where 3 is better, and 0 is worse. To obtain this score, representative images from the small-bowel were selected in series at 5 min intervals, and the 2 parameters were evaluated in each of the images: the proportion of the mucosa visualized (visualization sub-score); and the degree of obscuration by bubbles, debris, bile, or other material (obscuration sub-score). Each of these parameters was scored on a similar three-point scale, with the visualized mucosa scored as: >75% = 3, 50-75% = 2, 25-50% = 1, <25% = 0. Similarly, the degree of obscuration was scored as: <5% = 3, 5-25% = 2, 25-50% = 1, >50% = 0. The mean score for each of these parameters was obtained by dividing the sum of all the images scored by the total number of images analyzed, and finally, the average of the 2 parameters was calculated as the overall Park cleansing score. In addition, the GTT, orocecal transit time (OTT), and SITT were measured and compared.

Outcomes

The primary end-point used in this study was the quality of visualization of the mucosal surface, measured as the Park score obtained as indicated above.¹⁹ In addition, the secondary end-points analyzed were the average GTT, OTT, and SITT.

Statistical Analysis

Statistical analyses were carried out using the SPSS statistical analysis package (IBM Corp., Armonk, NY, USA). The data are expressed as the mean ± standard deviation (SD) and compared using a one-way analysis of variance with a Bonferroni’s post hoc multiple comparison test. The significance level was set at 5%, and thus, a P value < .05 was considered significant.

RESULTS

This study was conducted between January 20017 and April 2018. A total of 166 patients fulfilling the inclusion criteria were enrolled in the study, 102 females (61.4%) and 64 males (38.6%), aged between 16 and 92 years (mean, 54.7 ± 19.2). The patients were assigned randomly to one of 3 study groups that differed in terms of the preparative protocol used for CE (see “Materials and methods” section): 55 were allocated to group 1, 55 to group 2, and 56 to group 3 (Table 1). Two subjects in group 2 were excluded as they refused to ingest the booster, leading to a final total of 53 subjects in that group. CE examinations were carried out using either the PillCam(r) SB3 (n = 113, 68.1%: Given Imaging, Yokneam, Israel) or the MiroCam® (n = 53, 31.9%: Intromedic, Seoul, Korea) CE system (Table 1).

Table 1.

Descriptive Analysis of the Patient Cohort

Characteristic	Total (N = 166)
Age mean years ± SD (range)	54.7 ± 19.2 (16-92)
Gender, n (%)
Female	102 (61%)
Male	64 (39%)
Group according to preparative protocol, n (%)
Group 1	55 (33%)
Group 2	55 (33%)
Group 3	56 (34%)
Type of capsule endoscopy system, n (%)
PillCam	113 (68%)
MiroCam	53 (32%)
Indication
Ferropenic anemia	55
Suspected inflammatory bowel disease	45
Obscure bleeding	38
Reassessment of inflammatory bowel disease	27
Rendu–Osler–Weber syndrome	1

Group 1, clear liquid diet and fasting-based preparation; group 2, clear liquid diet and fasting-based preparation + 1 L of polyethylene glycol/ascorbic acid booster; group 3, clear liquid diet and fasting-based preparation + 0.5 L of polyethylene glycol/ascorbic acid booster.

When visualization in the 3 groups was compared, significant differences were evident in the total Park cleansing score (F = 2.582, P < .001: Table 2). Indeed, this overall difference in the total cleansing score was reflected by a significant difference in each of the sub-scores that make up this score, the visualization (F = 11.104, P < .001) and the obscuration score (F = 5.464, P = .005). Pairwise multiple comparisons with a Bonferroni Post hoc test revealed that there was a significant difference in these 3 variables between group 1 and group 3, with significantly lower scores for the 2 individual parameters and for the total Park scores in group 1 than in group 3 (P < .01: Table 3). By contrast, no significant differences in the GTT, OTT, and SITT were detected between the 3 groups (Table 2).

Table 2.

Effect of the Small-Bowel Preparation Protocols on Transit Time and Mucosa Visualization for CE

	Group 1		Group 2		Group 3		F	P
Mean	SD	Mean	SD	Mean	SD
Visualization sub-score	1.92	0.54	2.18	0.56	2.43	0.61	11 104	<.001
Obscuration sub-score	1.79	0.55	2.04	0.55	2.13	0.56	5464	.005
Total Park score	1.84	0.54	2.07	0.54	2.28	0.59	8290	<.001
GTT	36.58	36.16	41.13	35.57	48.32	43.97	1294	.277
OTT	322.58	100.68	268.16	115.23	289.45	151.36	2671	.072
SITT	280.71	94.70	250.33	113.91	249.95	137.43	1260	.286

SD, standard deviation; GTT, gastric transit time; OTT, orocecal transit time; SITT, small-intestine transit time.

Table 3.

Multiple Comparisons Among the Groups for Bowel Preparation in Capsule Endoscopy

	GTT		OTT		SITT		Visualization Sub-score		Obscuration Sub-score		Total Park Score
Multiple Comparison	Mean Difference	P*	Mean Difference	P	Mean Difference	P*	Mean Difference	P*	Mean Difference	P*	Mean Difference	P*
G1 vs. G2	−4.545	1.000	54.418	.069	30.382	.523	−0.25745	.060	−0.24873	.060	−0.22109	.118
G1 vs.G3	−11.740	.339	33.135	.488	30.763	.502	−0.51341 *	<.001	−0.33617 *	.005	−0.43136 *	<.001
G2 vs. G3	−7.194	.990	−21.283	1.000	0.381	1.000	−0.25595	.060	−0.08744	1.000	−0.21027	.147

G1, clear liquid diet and fasting-based preparation; G2, clear liquid diet and fasting-based preparation + 1 L of polyethylene glycol/ascorbic acid booster; G3, clear liquid diet and fasting-based preparation + 0.5 L of polyethylene glycol/ascorbic acid booster;

GTT, gastric transit time; OTT, orocecal transit time; SITT, small-intestine transit time.*The mean difference is significant at P ≤ .05 level.

DISCUSSION

In this study, we set out to determine the efficacy of using a basic clear liquid diet and fasting, in conjunction with the intake of a PEG/ascorbic acid-based booster, as a suitable preparation for CE explorations in a real-world situation. The data obtained demonstrate that better visualization of the intestinal mucosa can be achieved in this manner, with no detriment to the capsule’s intestinal transit. Indeed, ingestion of a reduced volume of the booster solution was sufficient to achieve these effects. Accordingly, we propose that this approach should be explored in greater depth as a more convenient yet effective preparation for CE explorations in order to maximize their success while reducing patient non-compliance and abandonment.

Several studies have assessed the effectiveness of different bowel preparations for CE explorations. For some years, there has been evidence that bowel preparation using PEG solutions improves image quality in CE as opposed to protocols that simply involve reduced iron intake, a clear liquid diet, and a limited period of fasting.^18,20 Indeed, it was proposed that PEG solutions in conjunction with oral simethicone or ascorbic acid may represent the preparation of choice for CE,^6,10 the latter apparently better tolerated by patients and producing less adverse effects (e.g., vomiting).⁸ While different meta-analyses concluded that the intake of 2L of PEG 12 h prior to capsule ingestion improves the visibility of the small-bowel mucosa without disturbing the completion rate, the influence of such preparation on diagnostic yield remains unclear.^2,10,14 However, bowel preparation with 2 L PEG prior to ingestion of the capsule may be poorly tolerated by many patients, possibly leading to a lack of compliance with the preparative protocol. Compliance with the preparation for CE procedures is an important issue. It is clearly related to successful visualization of the gastrointestinal tract and the completion or postponement of such explorations.²¹ These are 2 factors that directly affect the diagnostic capacity of these tests and their ability to ensure rapid clinical responses, both of which are fundamental to the cost-effective treatment of gastrointestinal diseases and to produce enhanced patient satisfaction.

The use of the “Park” scoring system¹⁹ served to demonstrate the quality of visualization that can be achieved in CE explorations following different patient preparation protocols. Nevertheless, a consensus regarding the most appropriate intestinal preparation for CE is still lacking.^5,13,21,22 The use of booster solutions in CE explorations was originally devised as a method to ensure transit and recovery of the capsule during the examination. However, here we assessed whether administering a booster solution of PEG plus ascorbic acid after ingestion of the capsule by patients might complement a clear liquid diet and fasting-based bowel preparation and enhance CE visualization. Indeed, in a real-world cohort of patients, the quality of small-intestine visualization was significantly better in patients who were administered the booster of a PEG/ascorbic acid solution once the capsule had been seen to have reached the small intestine, in addition to a clear liquid diet and fasting-based small-bowel preparation. In fact, the scores obtained for the 2 parameters that make up the overall Park cleansing score and the overall cleansing score itself were similar to those obtained using a stringent protocol involving the ingestion of 1 liter of the PEG/Ascorbic solution in a similar population (article under review).

We believe that the approach tested here is likely to be more comfortable for the patient and thus, it is likely to enhance patient compliance and the success rate of these procedures. Although we did not assess the tolerability of the protocols used here or the degree of patient satisfaction between the 3 groups, the protocol used is less aggressive. It involves smaller volumes than other preparative regimens involving the use of PEG/Ascorbic acid. In fact, the most significant improvements were achieved when a smaller volume of the PEG/ascorbic acid booster was administered. Importantly, transit times were not significantly affected by the different preparative protocols, indicating that this protocol is unlikely to compromise the battery life of the capsule, nor will it accelerate transit to the extent that it might possibly reduce to the accuracy of the exploration. It is possible that the use of a PEG/ascorbic acid preparation may favor erosion in the small-bowel. However, when we evaluated the small-bowel erosion in the patients studied here there was no clear difference between the individuals that received either the clear liquid diet and fasting-based preparation alone or in conjunction with the PEG/ascorbic acid booster. As such, the erosion detected is more likely to be due to a prior pathological process rather than to the preparation used.

One limitation of this study is that we did not include other possible preparative regimens, such as a 2 liter PEG ingestion prior to capsule ingestion plus the post-ingestion PEG booster. Likewise, we did not compare the booster solution used with other similar solutions, such as a PEG/simethicone solution. Nevertheless, the administration of a PEG/Ascorbic acid booster solution after ingestion of the capsule in patients who had simply followed a clear liquid diet and fasting-based bowel preparation for CE improved the quality of mucosal visualization to levels achieved previously with more stringent protocols (data not shown).^10,11 In addition, the protocol followed improves visualization and aids the recovery of the capsule, the principal motivation for employing booster solutions, and an effect that is not achieved with the stringent protocols used previously.

In summary, a bowel preparation with low iron intake, a clear liquid diet the day prior to examination, and 10 h fasting, in combination with the administration of 0.5 l of a PEG/Ascorbic acid booster solution after capsule ingestion, appears to be a suitable preparation to achieve adequate cleanliness and good quality visualization of the small intestine through CE. Such a preparative regimen does not alter the transit time of the capsule, yet it potentially provides a user-friendly alternative to the more stringent cleansing protocols involving PEG ingestion on the day prior to the CE procedure. It is notable that the benefits we observed were evident in everyday clinical practice; nevertheless, further studies will be necessary to confirm these results and to optimize the protocol.

Funding Statement

The authors declared that this study has received no financial support.