Introduction
Cross-sectional imaging is sensitive and specific for diagnosing and staging small bowel Crohn’s disease (CD). Magnetic resonance enterography (MRE) has the advantage of not exposing patients to ionising radiation [
1]. It relies upon the combination of good small bowel distension and multi-parametric sequences to accurately identify disease and phenotype as either predominantly inflammatory or fibrostenotic [
2,
3]. Diagnostic accuracy pivots on the quality of luminal distension; poor distension can both conceal or mimic disease, leading to misdiagnosis. Distension is influenced by the type and volume of oral preparation agent ingested and a variety of protocols are used clinically [
4‐
7]. A recent literature review by the European Society of Gastrointestinal and Abdominal Radiology (ESGAR) found no evidence for the superiority of one oral preparation over another and made no specific recommendation on either the optimal agent nor ingested volume [
8].
Whilst MRE is generally well tolerated, compared to small bowel ultrasound (SBU), it is more burdensome and causes symptoms, such that SBU is usually preferred by patients [
9]. Gastrointestinal effects related to the oral preparation agent are most commonly cited by patients as the least acceptable characteristic of MRE [
9].
The existing literature investigating oral preparation agents has largely focused on a small number of healthy individuals at single centres [
5,
10‐
15]. Findings may not generalise to the (often) symptomatic patients undergoing MRE. Indeed, surprisingly, few studies have investigated oral contrast agents in patients [
16‐
17].
We conducted a prospective multi-centre study comparing the diagnostic accuracy of MRE with SBU in Crohn’s disease [Diagnostic accuracy of magnetic resonance enterography and small bowel ultrasound for the extent and activity of newly diagnosed and relapsed Crohn's disease (METRIC): a multicentre trial [
1,
18]. The study afforded the pragmatic opportunity to prospectively compare two commonly used MRE oral contrast agents, mannitol and polyethylene glycol (PEG) exactly as they are employed in clinical practice and was a pre-specified secondary outcome [
18,
19]. Specifically, the aims of the current study were to compare (1) distension quality and (2) patient symptoms, according to the agent ingested. We also investigated the influence of ingested volume on image distention quality and patients’ symptoms.
Discussion
We conducted a large multi-centre, prospective diagnostic accuracy trial investigating the sensitivity of MRE and SBU (METRIC trial) [
1]. This afforded the opportunity to prospectively assess the quality of bowel distension achieved in representative clinical practice by two of the most commonly used MRE distention agents, and to compare symptoms following ingestion. The results may also translate to other luminal investigations requiring luminal distension such as CT enterography and hydrosonography.
To date, the majority of previous literature pertaining to oral contrast agents has reported healthy volunteers who are unlikely to represent patients commonly undergoing MRE [5, 10–15], or limited to retrospective studies of small numbers at single centres [
21,
24,
25]. In this regard, our work adds to the current literature.
We found that, overall, there were no major differences in distention quality between either mannitol-based preparations or PEG. However, we did find some evidence that whilst jejunal distension remains challenging, it is more commonly good or excellent quality with mannitol (40%) compared to PEG (14%). This is potentially an important observation given difficulties with jejunal distention during MRE (as opposed to MR enteroclysis) and the potential impact on diagnostic accuracy. Importantly, the two groups were generally well-matched in terms of presentation (new diagnosis versus relapse), presence of stenosis, and history of prior surgical resection, which increases our confidence that our findings are real and not secondary to unequal disease phenotypes across cohorts. Although the colon is not the primary target for MRE, it is interesting to note superior transverse colonic distension with mannitol.
We also found ingesting more than 1 L of mannitol did not confer any beneficial effect. This concurs with Ajaj et al who reported that in a study of 10 volunteers, 1000, 1200, and 1500 mL of mannitol all gave similar quality distension [
5]. Overall, our data suggest there is no need for patients to ingest more than 1 L of oral contrast. Perhaps surprisingly, we did not find any difference in the immediate or delayed symptoms experienced by patients, regardless of the volume of contrast. There was perhaps a trend for greater diarrhoea in those drinking more contrast, but this was not statistically significant perhaps due to underpowering.
We also found mannitol and PEG were similarly tolerable, although patients ingesting PEG reported that fullness was significantly less tolerable immediately after MRE compared to those ingesting mannitol. We note that the proportion of patients ingesting 1 L or more was lower in the PEG cohort than in the mannitol cohort. Whilst the exact reasons for this observation are uncertain, it is possible the greater feelings of fullness in the PEG group led to reduced overall intake.
Of note, abdominal pain and diarrhoea increased over the 2 days after MRE compared to immediately afterwards. This is perhaps unsurprising as it takes time for contrast to traverse through the gut and concurs with a recent study in which oral contrast was rated the most unpleasant component of MRE; 18% of patients take longer than 1 day to recover [
9]. Patients should be warned of this prior to MRE.
There are no published studies comparing mannitol and PEG in MRE but a recently published randomised controlled trial did compare the two preparations in 70 patients undergoing CT enterography at a single centre. Each patient underwent 2 L of PEG bowel preparation prior to ingesting either 1.5 L of mannitol or PEG solution. The study reported no significant differences in the quality of luminal distension between the agents but stated that patients undergoing mannitol preparation reported nausea as more tolerable, the taste as more acceptable, and were more willing to ingest again compared to patients undergoing PEG preparation. [
26]
Our study has limitations. We investigated the impact of mannitol and PEG-based oral preparations alone, as these were the two agents utilised at centres recruiting to the main diagnostic accuracy trial. The number of patients undergoing PEG-based oral preparation was smaller, and as a result, we were unable to incorporate the PEG cohort into the assessment of the impact of ingested oral volume on either luminal distension or patient experience. Furthermore, whilst we had a good proportion of delayed patient experience questionnaires returned in the PEG cohort, this was much reduced in the mannitol cohort, which impairs comparison for delayed symptoms. This may in part reflect the different tenacity of individual recruitment sites when encouraging patients to return questionnaires but risks some bias. Whilst we compare the main agents of the oral preparation, we acknowledge that some mannitol preparations utilised additives such as LBG or Carobel in small quantities and we have not assessed the specific contribution of these additives. Both readers for the qualitative assessment of luminal distension work at one centre which employed a mannitol-based preparation. This may introduce some bias related to their prior experience. For practical reasons, other centres did not provide readers for this substudy although that would have been optimal. Agreement between readers was generally good, although less so for the terminal ileum in particular. Reassuringly though, both readers were consistent in the relative grading of distension quality between the two preparations for all segments so any disagreement in absolute levels of distension did not impact our main conclusion. Whilst the main trial evaluated the diagnostic accuracy of MRE (and SBU), this substudy was underpowered to draw conclusions on whether the differing quality of luminal distension affected the overall diagnostic accuracy. This would be a useful topic for further research. However, it is reassuring that although distension quality was judged as excellent in slightly over 50% of terminal ileal segments, the results on the main trial showed MRE has a high sensitivity for terminal ileal Crohn’s disease, suggesting accurate diagnosis does not always require optimal distension. Anecdotally, the segmental small bowel distension will alter throughout the MRI acquisition (as the study typically takes 30–45 min to acquire); it would be of interest to review whether this change in segmental distension is different for differing luminal preparation agents; this was felt to be outside the remit of this study.
Patients who reported at least one symptom as “not tolerable” generally completed the day 2 questionnaire, whereas those less affected completed fewer. This may introduce spectrum bias, with a greater proportion returning this questionnaire more likely to experience less tolerable symptoms. Ours was a convenience sample based on data return, which could induce bias. Reassuringly, we found no major difference between PEG and mannitol cohorts regarding disease phenotype or baseline symptom level. Although to our knowledge, ours is the largest prospective patient study on this topic to date, we did not perform a prior power calculation and so some of our comparisons are likely unpowered, for example, the effects of agent volume on distension and symptoms.
In summary, mannitol-based solutions and PEG generally achieve comparable distension quality and side effect profiles, although jejunal distension is more frequently of better quality with mannitol. Distension quality is not improved by ingestion of more than 1 L, although doing so does not adversely influence patent tolerability.
Declarations
List of METRIC study investigators
Rachel Baldwin-Cleland, Richard Beable, Margaret Betts, Stuart Bloom, Helen Bungay, Peter J Hamlin, Ailsa L Hart, Antony, Ilan Jacobs, Sara McCartney, Anne Miles, Charles D Murray, Richard C Pollok, Shonit Punwani, Manuel Rodriguez-Justo, Zainib Shabir, Simon Travis, Alastair Windsor, Peter Wylie, Jade Dyer, Pranitha Veeramalla, Sue Tebbs, Steve Hibbert, Richard Ellis, Fergus Thursby-Pelham, Nicola Gibbons, Claire Ward, Anthony O'Connor, Hannah Lambie, Nigel Scott, Roger Lapham, Doris Quartey, Deborah Scrimshaw, Simona Fourie, Niall Power, Phillip Lung, Ian Johnston, Mani Naghibi, Morgan Moorghen, Adriana Martinez, Christopher Alexakis, Anisur Rahman, Jonny Vlahos, Anita Wale, Teresita Beeston, Wivijin Piga, Joey Clemente, Farooq Rahman, Simona de Caro, Shameer Mehta, Roser Vega, Roman Jastrub, Hameed Rafiee, Mairead Tennent, Caron Innes, Craig Mowat, Gillian Duncan, Rebecca Greenhalgh, Rachel Hyland, Hannah Lambie, Evgenia Mainta, James Pilcher, Andrew Plumb, François Porté, Harbir Sidhu, Florian Tomini, and Steve Morris
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