Optimal Bowel Preparation for Video Capsule Endoscopy

During video capsule endoscopy (VCE), several factors, such as air bubbles, food material in the small bowel, and delayed gastric and small bowel transit time, influence diagnostic yield, small bowel visualization quality, and cecal completion rate. Therefore, bowel preparation before VCE is as essential as bowel preparation before colonoscopy. To date, there have been many comparative studies, consensus, and guidelines regarding different kinds of bowel cleansing agents in bowel preparation for small bowel VCE. Presently, polyethylene glycol- (PEG-) based regimens are given primary recommendation. Sodium picosulphate-based regimens are secondarily recommended, as their cleansing efficacy is less than that of PEG-based regimens. Sodium phosphate as well as complementary simethicone and prokinetics use are considered. In this paper, we reviewed previous studies regarding bowel preparation for small bowel VCE and suggested optimal bowel preparation of VCE.


Introduction
Video capsule endoscopy (VCE) is useful in investigating small bowel as well as esophagus, stomach, and colon. Bowel preparation for small bowel VCE is recommended to improve small bowel visualization quality (SBVQ), diagnostic yield (DY), and cecal completion rate (CR). Particularly in the distal small bowel, DY of VCE can be limited due to reduced SBVQ-associated with residual material or dark colored bile. According to a 2009 meta-analysis of 12 studies [1], purgative bowel cleansing prior to VCE improves the SBVQ and increases the DY but does not alter the VCE CR. However, the gastric transit time (GTT) and small bowel transit time (SBTT) of VCE were not affected by purgatives.
We performed online search for VCE bowel preparationrelated clinical studies, comparative research, randomized controlled trials (RCTs), meta-analyses, and guidelines published from January 2002 to June 2015. Literature review was conducted using Key MeSH terms of "capsule endoscopy" and "bowel preparation." We also reviewed bowel preparation guidelines for VCE of small bowel based on 2009 European Society of Gastrointestinal Endoscopy (ESGE) guidelines [2], 2013 ESGE guidelines [3], and 2013 Korean guidelines [4] by the Korean Gut Image Study Group, part of the Korean Society of Gastrointestinal Endoscopy. The level of scientific evidence for recommendation was based on study design; for example, the evidence of randomized trial was considered high, observation study was low, and any other type of evidence was very low. The validity of the recommendation was divided into categories of "strong" or "weak" (Table 1) [5]. In this paper, we introduced previous studies on bowel preparation for VCE and suggested optimal preparation methods.

Polyethylene Glycol.
Polyethylene glycol-(PEG-) based regimens are first-line recommendation (Grade A) [3]. The majority of the evidence of bowel preparation prior to small bowel VCE is PEG-based regimens. The 2009 ESGE guidelines recommended purgative bowel preparations in order to enhance small bowel DY by VCE without affecting the CR (category of evidence, 2a; grade of recommendation, B) [2]. Low quality Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality Any estimate of effect is very uncertain.
Strength of a recommendation Strong Most or all individuals will be best served by the recommended course of action.

Weak
Not all individuals will be best served by the recommended course of action. There is a need to consider more carefully than usual individual patient's circumstances, preferences, and values. According to the Korean Gut Image Study Group guidelines [4], bowel preparation with PEG solution enhances DY and SBVQ, without effect on cecal CR (strong recommendation, moderate quality evidence). Table 2 shows many studies regarding bowel preparation with comparison of PEG versus clear liquid or fasting for small bowel VCE, including prospective randomized controlled trials [6][7][8][9][10][11][12][13], a prospective blinded nonrandomized trial [14], and a retrospective study [15]. Most studies were performed by comparing SBVQ, DY, and cecal CR between 2 L PEG solution and clear diet or fasting groups. Four-liter PEG solution was used in a few studies [10,14]. In addition, ingestion of a small amount of PEG (500 mL) beginning 30 minutes after swallowing the capsule significantly improves SBVQ and cecal CR, although DY was not affected [8]. Another study regarding a small amount (500 mL) of PEG solution over 2 hours, beginning 30 minutes after swallowing the capsule, showed increased SBVQ without any difference in cecal CR [12]. Since PEG is completely transparent, a view through PEG was considered better than a view through natural intestinal fluid. However, negative result regarding SBVQ with 2 L PEG was reported in one retrospective study [15].
Two-liter PEG solution bowel preparation is similar to that of 4 liters of PEG in DY, SBVQ, and CR of VCE (weak recommendation, moderate quality evidence). Two studies by Kantianis et al. [16] and Park et al. [11] indicated no significant difference between 2 L and 4 L PEG in regard to small bowel cleansing and CR. Therefore, 2 L PEG should be recommended as preparation for VCE, administered on the day prior to the procedure, as the most commonly used preparation method [17]. In colonoscopy, bowel preparation status is classified as excellent, good, fair, poor, or inadequate. Clinically, most gastroenterologists considered excellent and good bowel preparation status as optimal bowel preparation. However, there was no consensus of optimal bowel preparation for VCE, as each study with PEG suggested various definitions for bowel preparation quality (Table 3). A recent study considered excellent or good preparation (>75% small bowel visualization) as adequate bowel preparation [13]. Therefore, standardized definition of optimal bowel preparation for VCE is necessary.
To date, there has been no consensus regarding optimal timing of bowel preparation for VCE. To evaluate optimal timing of VCE bowel preparation, a single-center randomized controlled trial was conducted by Black et al. [18]. However, there was no significant difference between the quality and timing (day before VCE versus 4 hours prior to VCE) of small bowel preparation. Intestinal lavage administered one day prior was similar to same-day preparation with regard to overall preparation quality, SBTT, frequency of identified mucosal abnormalities, general DY, and CR. One of the issues for bowel preparation of VCE is that the distal segment of the small intestine should be improved. The main limitation of this study is that the number of patients ( = 34) is not sufficient for generalizing to actual practice. Therefore, multicenter large randomized controlled trial is required to clarify optimal timing of bowel preparation for VCE.
According to the 2012 consensus guidelines for bowel preparation [19], purgative is absolutely contraindicated in patients with gastrointestinal obstruction, ileus, ulcer, perforation, or inflammatory bowel diseases. In addition, it is also contraindicated in patients with decreased consciousness, swallowing disorders, and hypersensitivity to oral bowelcleansing agents and in patients having an ileostomy. Therefore, optimal bowel preparation should be made considering individual patient risk factors.

Sodium Picosulfate.
Recently, various types of bowel preparation such as PEG, PEG plus ascorbic acid, sodium picosulfate, and phosphate (NaP) are available. There has been no published evidence to support the use of sodium picosulfate; however, it is used in some units. Anecdotal evidence suggests that it is not as effective as PEG [3].

Sodium Phosphate (NaP).
NaP is not recommended for bowel cleansing due to the potential for renal damage and other adverse effects (Grade B) [3]. However, the use of NaP is possible in patients for whom PEG or sodium picosulfate is ineffective or not tolerated (Grade D). According to a previous study conducted using NaP, SBVQ of NaP group is better than overnight fasting (35% versus 4%) [20]. However, recent meta-analysis of NaP-based regimens revealed no significant difference from fasting alone (OR = 1.32, 95% CI = 0.52-2.96, < 0.0001) [21]. Therefore, NaP should not be used in general.

Simethicone
Preparing the small bowel with simethicone has been reported to increase SBVQ by reducing intraluminal air bubbles [22,23]. Table 4 demonstrates several studies regarding bowel preparation with simethicone for small bowel VCE [13,[22][23][24][25][26]. Systemic review and meta-analysis of RCTs of simethicone revealed that supplemental use of simethicone prior to VCE enhances SBVQ, especially for patients without purgative, but does not affect the cecal CR [27]. It decreases air bubbles in the colonic lumen but does not improve bowel preparation. Additionally, its effect on DY remains controversial. Bowel preparation by fasting or administration of PEG solution combined with simethicone enhances SBVQ, but it does not affect CR for VCE (strong recommendation, moderate quality evidence) [4].

Prokinetics
Prokinetics can be used for shortening of the GTT and may improve cecal CR. To date, various prokinetics including erythromycin [28][29][30], mosapride [31], metoclopramide [32][33][34], and lubiprostone [35,36] have been investigated for bowel preparation of VCE. Table 5 exhibits previous studies regarding bowel preparation with various prokinetics for small bowel VCE. Previously, the battery time of VCE was 8 hours and approximate 20% do not reach the colon due to limited recording time [34]. Currently, the battery time of VCE is about 12 hours; therefore the effect of prokinetics on the CR could be minimal. Lubiprostone, a selective activator of type 2 chloride channels in the apical membrane of the GI epithelium, as a propulsive agent was investigated for decreasing the SBTT by VCE. However, there were opposite results regarding the GTT and SBTT in two studies [35,36]. Lubiprostone neither decreased the GTT and SBTT nor improved SBVQ for VCE in one double-blind placebo-controlled study [35], while it decreased the SBTT by VCE in another exploratory randomized, double-blind, controlled study [36]. Bowel preparation with prokinetics does not enhance the SBVQ, DY, or CR of VCE. Therefore, it is not generally recommended (weak recommendation, moderate quality evidence) [4].

Miscellaneous
Recently, there have been new studies using substances such as coffee enema or magnesium citrate. Coffee enema is known to induce dilation of bile ducts and excretion of bile through the colon wall. During VCE, excreted bile is one of the causes of poor bowel preparation. Coffee enema for preparation for small bowel VCE was investigated by a pilot study ( = 34) [37]. Comparison of coffee enema plus 2 L PEG versus 2 L PEG demonstrated greater efficacy of bowel preparations in the mid-to-distal segments of the small bowel in patients who received coffee enema plus 2 L PEG than in those who received PEG only. In one magnesium citrate trial of bowel preparation for VCE [38], there was no significant difference between the group that received the preparation (34 g magnesium) and the control group.

Conclusion
Bowel preparation is generally recommended for small bowel VCE. Currently, a combination of 2 L PEG and simethicone appears to be the optimal bowel preparation before VCE. After reviewing current articles regarding bowel preparation for VCE, we suggest using purgatives such as PEG as first line and sodium picosulfate as second line with antifoaming agent. However, sodium phosphate should not be used except for the patients whom PEG or sodium picosulfate is not effective and intolerable. However, prokinetics (erythromycin, metoclopramide, or lubiprostone) are not generally recommended. For each of these agents, including purgative (PEG, sodium picosulfate, and sodium phosphate), consensus is needed regarding optimal timing of bowel preparation. Therefore, best bowel preparation is determined considering individual patient status.