This Guideline is an official statement of the European Society of Gastrointestinal
Endoscopy (ESGE). It provides practical advice on the different aspects of bowel preparation
for colonoscopy. The Grading of Recommendations Assessment, Development, and Evaluation
(GRADE) system was adopted to define the strength of recommendations and the quality
of evidence.
Abbreviations
ADR:
adenoma detection rate
CI:
confidence interval
ESGE:
European Society of Gastrointestinal Endoscopy
GI:
gastrointestinal
GRADE:
Grading of Recommendations Assessment, Development, and Evaluation
HR:
hazard ratio
IBD:
inflammatory bowel disease
LGIB:
lower gastrointestinal bleeding
MCSP:
magnesium citrate plus sodium picosulfate
OSP:
oral sodium phosphate
OSS:
oral sulfate solution
OR:
odds ratio
PEG:
polyethylene glycol
RCT:
randomized controlled trial
RR:
relative risk
Introduction
Inadequate bowel preparation has a detrimental effect on all aspects of the colonoscopy
procedure and, especially, on its accuracy. It has been associated with significantly
lower rates of detection of adenomas and advanced adenomas in two recent meta-analyses
[1]
[2]. A subsequent prospective observational study with repeat colonoscopy performed
by a blinded endoscopist revealed a threefold higher miss rate for adenomas ≥ 5 mm
in size when bowel cleansing was inadequate [3]. Inadequate bowel preparation is also one of the most unfavorable predictors for
cecal intubation failure [4]
[5]
[6] and unsatisfactory patient experience [7]. In addition it results in shorter colonoscopy surveillance intervals [8]
[9], longer hospital stays, and increased healthcare costs [10]
[11] and may render screening colonoscopy cost-ineffective [12]. For these reasons, a ≥ 90 % minimum standard for adequate bowel preparation (assessed
using validated scales) has been recently recommended by the Quality Committee of
the European Society of Gastrointestinal Endoscopy (ESGE) [13].
Since the publication of the ESGE Guideline on bowel preparation in 2013 [14], additional evidence has been published on the efficacy and safety of different
aspects of bowel preparation, including diet, timing, and type of laxative, as well
as patient information and specific scenarios. The main aim of this update is to incorporate
such new evidence into the clinical recommendations to be adopted in routine and specific
scenarios.
Methods
The Guideline Committee chairs worked with subgroup leaders (C.H., J.E, J.-M.D., C.S.,
F.R.) to identify pertinent systematic search terms that included “colon,” “rectum,”
“bowel preparation,” “diet,” “laxative,” “colonoscopy,” and “endoscopy.” Searches
were performed (at least) on Medline (via PubMed) and the Cochrane Central Register
of Controlled Trials from after 2013 (date of the previous ESGE guideline [14]) up to December 2018. Evidence tables were generated for each key question (Appendix 1s, online-only Supplementary Material), summarizing the level of evidence from the
available studies. For important outcomes, articles were individually assessed using
the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system
to grade the evidence levels and recommendation strengths (see Appendix 2s) [15]. The role of bowel preparation as a metric of the quality of colonoscopy was excluded
as this had already been addressed in the ESGE Quality Improvement Initiative [13]. The evidence tables are presented in Appendix 3s.
The subgroups developed draft proposals that were presented to the entire group for
general discussion during a meeting held in January 2019 in Munich. Further details
on the development methodology of ESGE guidelines have been reported elsewhere [16]. In March 2019, a draft prepared by the task force leaders was sent to all group
members. After the agreement of all group members had been obtained, the manuscript
was sent for further comments to the ESGE national societies and individual members.
After this it was submitted to the journal Endoscopy for publication.
This Guideline was issued in 2019 and will be considered for update in 2024. Any interim
updates will be noted on the ESGE website: http://www.esge.com/esge-guidelines.html.
Diet, and patient information
Diet, and patient information
ESGE recommends a low fiber diet on the day preceding colonoscopy.
Strong recommendation, moderate quality evidence.
Diet restriction, either a clear liquid diet or a low residue diet, has traditionally
been recommended before colonoscopy but adherence is low. In a real-life prospective
study (789 patients), the proportion of patients actually following a low residue
diet for 2 days before colonoscopy was 44.2 % and a high residue diet was independently
associated with inadequate bowel preparation [17]. In trials, adherence to a low residue diet was 90.4 % (874 of 967 patients randomized
to a low residue diet) [18]
[19]
[20]
[21]
[22]
[23]. Two meta-analyses [24]
[25] have compared a low residue diet vs. a clear liquid diet on the day before colonoscopy,
with the same laxative in both arms. In the included trials, a diet was usually considered
to be low residue when the total fiber intake was < 10 g/day. Most of the randomized
controlled trials (RCTs) used the terms low residue/low fiber interchangeably and
few of them specified the amount of fiber in their regimen. Examples of foods allowed
in a low residue diet included some fresh peeled and pitted fruits and cooked vegetables
(e. g., apples, carrots), cheese, meat, fish, and white bread, while wholegrain bread,
muesli, brown rice were not allowed together with some fruits and vegetables (e. g.,
orange, mushroom). Some trials used prepackaged low fiber or fiber-free food while
in others instructions were given to the participants on preparation of their food.
The first meta-analysis (9 RCTs, 1686 participants) found that, compared with a clear
liquid diet, a low residue diet was associated with a higher willingness to repeat
bowel preparation (odds ratio [OR] 1.86, 95 % confidence interval [CI] 1.34 – 2.59;
P < 0.01) and better tolerability (OR 1.92, 95 %CI 1.36 – 2.70; P < 0.01) [24]. No differences between groups were found in terms of adequate bowel preparation
(OR 1.21, 95 %CI 0.64 – 2.28; P = 0.58) or adverse effects (OR 0.88, 95 %CI 0.58 – 1.35; P = 0.57).
The most recent meta-analysis (12 RCTs, 3674 participants) grouped patients taking
a low residue diet (8 RCTs) or a regular diet (4 RCTs) and compared them to patients
taking a clear liquid diet [25]. The low residue diet was provided until breakfast (n = 1), lunch (n = 3), or dinner
(n = 4), depending on study protocol. Compared with a clear liquid diet, the low residue/regular
diet was associated with higher willingness to repeat the procedure (relative risk
[RR] 1.08, 95 %CI 1.01 – 1.16), better tolerability (RR 1.04, 95 %CI 1.01 – 1.08),
and more frequent consumption of a targeted amount of the bowel laxative (RR 1.04,
95 %CI 1.01 – 1.08). No differences between groups were found in terms of adequate
bowel preparation for the whole meta-analysis (RR 1.00, 95 %CI 0.97 – 1.04) as well
as for subgroup analyses of high quality trials (5 RCTs, 1649 patients), split/morning
preparations (5 RCTs, 1431 patients), or single-dose preparation (4 RCTs, 1528 patients).
No differences between groups were found in terms of adenoma detection rate (ADR)
(3 RCTs, 1228 participants) or adverse events except for more hunger in the clear
liquid diet arm (RR 1.93, 95 %CI 1.13 – 3.3).
A third meta-analysis (7 RCTs, 1590 participants) had similar inclusion criteria except
that it did not restrict inclusion to studies with an identical purgative in both
arms [26]. Compared with a clear liquid diet, a low residue diet was associated with higher
willingness to repeat the procedure (RR 1.17, 95 %CI 1.09 – 1.26) and better tolerance
(RR 1.06, 95 %CI 1.02 – 1.11). No differences between groups were found in terms of
adequate bowel preparation (RR 1.01, 95 %CI 0.91 – 1.13), adverse events, and compliance
with diet (RR 0.97, 95 %CI 0.87 – 1.08).
A further four recent RCTs have also shown that patient satisfaction, ease of preparation,
and
willingness to repeat an identical preparation were higher with a low residue diet
vs. a clear liquid diet in all trials that analyzed those outcomes (3, 2, and 1 RCTs,
respectively); and the proportions of patients with adequate bowel preparation (3
RCTs) were similar or higher with a low residue diet vs. a clear liquid diet (Table 1s, Appendix 3s, online-only Supplementary Material) [18]
[19]
[27]
[28]. Recently, a possible additional effect of multiple-day vs. single-day low residue
diet among participants receiving a split-dose bowel preparation has been excluded
in a randomized trial [29].
Three RCTs assessed the effect of different liquids for bowel preparation with polyethylene
glycol (PEG) [30]
[31]
[32]. One of these used dilution of PEG powder in Coca Cola Zero instead of water [30], and in another orange juice was kept in the mouth for a few seconds just before
drinking the bowel preparation solution [32]. Various parameters were improved, including palatability of the bowel preparation
(in both RCTs), speed of bowel preparation intake, bowel cleanliness, willingness
to repeat the same preparation, and adverse events (mainly nausea) (in one RCT each).
The third RCT found that the addition of 1 L of pineapple juice after bowel preparation
intake had little effect (better proximal colon cleanliness but not in the whole colon)
[31]. Polyp and adenoma detection rates were not modified by these interventions.
Gum chewing was tested in three RCTs that used different protocols of gum chewing
[33]
[34]
[35]. One of them used a purgative rarely employed for bowel preparation and reported
below-standard cecal intubation rates [33]. The other two RCTs reported higher patient satisfaction and willingness to repeat
the same bowel preparation, more complete and faster bowel preparation intake, and
less abdominal discomfort (one RCT each) but no improvement in bowel cleansing [34]
[35].
ESGE recommends the use of enhanced instructions for bowel preparation.
Strong recommendation, moderate quality evidence.
A meta-analysis (8 RCTs, 3795 patients) found that, compared with patients receiving
regular instructions before colonoscopy, those who received enhanced instructions
had better bowel cleanliness (OR 2.35, 95 %CI 1.65 – 3.35; P < 0.001), a higher cecal intubation rate (OR 2.77, 95 %CI 1.73 – 4.42; P < 0.001) and more willingness to repeat the preparation (OR 1.91, 95 %CI 1.20 – 3.04;
P = 0.006), but a similar polyp detection rate [36]. Enhanced instructions consisted of visual aids, a social media app, telephone or
short message service (SMS), and smartphone applications. Improvements were observed
with 2 L as well as 4 L PEG and with split-dose as well as single-dose regimens, and
with a delay between enhanced instructions and colonoscopy of 1 week or less as well
as with a delay of more than 1 week. Adverse events were similar in both groups.
These data were confirmed in three more recent RCTs that used a phone call, a series
of SMSs or a video as enhanced instructions for bowel preparation: compared to regular
instructions, these improved bowel cleansing and ADR (three RCTs), and cecal intubation
rate, and patient satisfaction (one RCT each) [37]
[38]
[39] (Table 2s). Interestingly, in the study that used SMSs, each patient received a total of 15
nonpersonalized messages and 89 % of them reported that they would use SMS guidance
again for their next colonoscopy. Finally, an RCT (283 patients) that used different
types of bowel preparation found that sending a video before colonoscopy improved
bowel cleanliness with low volume bowel preparations (2 L PEG glycol/ascorbate or
sodium picosulfate/magnesium citrate) but not with 4 L PEG [40].
Adjunctive drugs
ESGE does not suggest the routine use of prokinetic agents for bowel preparation.
Weak recommendation, low quality evidence.
RCTs that compared identical bowel preparation regimens with vs. without prokinetics
are summarized in Table 3s.
The effect of 24 – 96 µg lubiprostone, a chloride channel-2 activator increasing intestinal
secretion and transit, has been assessed in three RCTs; all of them used single-dose
bowel preparation [41]
[42]
[43]. The three RCTs reported better bowel cleansing with lubiprostone but the difference
was significant in only one study [41]; this was the largest study and the only one to use low dose (2 L) PEG. These results
need to be confirmed by other studies using split regimens.
Itopride (200 mg) improved bowel cleanliness in an RCT that used split-dose bowel
preparation, with similar ADRs and adverse event rates between groups [44]. Finally, mosapride, a drug that is not as widely available as other prokinetics,
has been tested in two RCTs with a single-dose bowel preparation; bowel cleansing
was better in one study, in the left colon only [45].
Prokinetics have also been used in attempts to reduce the dose of purgative but the
data do not allow conclusions to be drawn [46]
[47].
ESGE suggests adding oral simethicone to bowel preparation.
Weak recommendation, moderate quality evidence.
A meta-analysis published in 2011 (7 RCTs, 714 patients) concluded that the amount
of bubbles was less frequently unacceptable in patients who had received oral simethicone
vs. those who had not, but no difference in colon cleanliness was found and the diagnostic
yield was not reported [48].
Since then, four RCTs (see Table 4s) have compared identical bowel preparation regimens with vs. without oral simethicone;
they found that oral simethicone decreases the amount of bubbles (four RCTs), improves
bowel cleanliness (three RCTs), and also the ADR (two RCTs). Adverse events were analyzed
in only three RCTs; two found that they were less frequent with vs. without simethicone.
A meta-analysis assessed these four RCTs (1536 patients); in a subgroup analysis it
found that oral simethicone increases the ADR (OR 1.23, 95 %CI 1.04 – 1.47, P = 0.02) [49]. Of note, the doses of simethicone used in these four RCTs were higher than those
used in previous RCTs (400 – 1200 mg vs. < 400 mg in 6 of 7 RCTs included in the 2011
meta-analysis) [48]. No other antifoaming agent has been recently studied for colonoscopy.
Another meta-analysis is difficult to interpret as it included studies using different
purgatives in the arm with vs. without simethicone [50].
Various professional societies, including ESGE, as well as endoscope manufacturers,
have warned against the use of simethicone through the auxiliary water channel during
endoscopy [51]
[52]. If it is used during endoscopy, simethicone should be injected via the biopsy rather
than the auxiliary water channel of the endoscope, at the lowest effective concentration.
Simethicone residues could contribute to the formation of biofilms and the biopsy
channel is brushed during reprocessing while the auxiliary water channel is not.
ESGE recommends against the routine use of enemas for bowel preparation.
Strong recommendation, moderate quality evidence.
An RCT found that adding an enema to standard bowel preparation did not improve bowel
cleansing and decreased the acceptability of bowel preparation [53]. Another RCT found that a 5-day regimen of oral nutritional supplements plus enema
did not provide adequate bowel cleansing [54].
Timing
ESGE recommends split-dose bowel preparation for elective colonoscopy.
Strong recommendation, high quality evidence.
A meta-analysis (47 RCTs, 13 478 patients) found that split-dose regimens, regardless
of the type and dose of the cleansing agent, provided excellent/good colon cleansing
more frequently than day-before bowel preparation (OR 2.51, 95 %CI 1.86 – 3.39). This
result was confirmed in subanalyses restricted to PEG (OR 2.60, 95 %CI 1.46 – 4.63),
sodium phosphate (OR 9.34, 95 %CI 2.12 – 41.11), and picosulfate (OR 3.54, 95 %CI
1.95 – 6.45). Moreover, split dosing was associated with a higher proportion of patients
willing to repeat the preparation (OR 1.90, 95 %CI 1.05 – 3.46) [55].
Seven subsequent RCTs comparing identical cleansing agents (sodium picosulfate, three
studies [56]
[57]
[58]; high volume PEG, two studies [59]
[60]; low volume PEG, two studies [61]
[62]) further confirmed the superiority of split dosing over a day-before regimen in
terms of colon cleansing [56]
[57]
[58]
[59]
[60]
[61]
[62] and patient tolerability [59]
[60]
[61] (Table 5s).
Concerning the detection of neoplastic lesions, the abovementioned meta-analysis [55] included two small trials that reported on this outcome, and no difference was found.
Two further RCTs were specifically designed and adequately powered to compare split-dose
vs. single-dose regimens regarding the detection of neoplastic lesions. In one RCT
that included 690 patients undergoing screening colonoscopy after positive fecal immunochemical
testing, split-dose vs. day-before bowel preparation with 2 L PEG/ascorbate resulted
in a higher detection rate of adenomas (primary study endpoint; 53.0 % vs. 40.9 %;
RR 1.22, 95 %CI 1.03 – 1.46; number needed to treat [NNT] = 9) and of advanced adenomas
(26.4 % vs. 20.0 %; RR 1.35, 95 %CI 1.06 – 1.73; NNT = 16) [62]. The other RCT compared split-dose 2 L PEG/ascorbate vs. a day-before regimen of
sodium picosulfate/magnesium citrate; the split regimen was associated with a trend
towards a higher polyp detection rate (primary endpoint; 51.5 % vs. 44.0 %, P = 0.14), and a significantly higher detection rate of right-sided polyps (28.0 %
vs. 16.6 %, P = 0.007) and adenomas (21.0 % vs. 11.9 %, P = 0.015) [63]. Moreover, large observational studies confirmed that split dosing led to higher
polyp and/or adenoma detection rates compared with single-dose regimens [64]
[65]
[66].
ESGE recommends, for patients undergoing afternoon colonoscopy, a same-day bowel preparation
as an acceptable alternative to split dosing.
Strong recommendation, high quality evidence.
Two meta-analyses (11 and 14 RCTs) compared split-dose with same-day bowel preparation
and showed similar results regarding the quality of bowel preparation, patient willingness
to repeat it, and the overall tolerability [67]
[68], albeit patients taking the same-day regimen reported less bloating (OR 0.68, 95 %CI
0.40 – 0.94) [67] and better sleep quality (OR 0.44, 95 %CI 0.24 – 0.82) [68]. The ADR was similar for the two regimens [67]. It is noteworthy that most patients included in these studies were scheduled in
afternoon colonoscopy slots.
Three RCTs compared same-day vs. split regimens for morning colonoscopy only, using
an identical PEG bowel preparation [69]
[70]
[71]. The same-day regimen was associated with a significantly lower quality of bowel
preparation in one study [69], whereas the other two studies reported similar efficacy in bowel cleansing but
lower patient tolerability and compliance [70]
[71], and lower willingness to repeat the same preparation in the future [70]. Overall, these data favor split-dose over same-day regimens for morning colonoscopy
(Table 6s).
ESGE recommends to start the last dose of bowel preparation within 5 hours of colonoscopy,
and to complete it at least 2 hours before the beginning of the procedure.
Strong recommendation, moderate quality evidence.
Observational studies have shown an inverse correlation between the degree of mucosal
cleanliness and the interval between the last dose of bowel preparation and the start
of colonoscopy [72]
[73]; an interval of 3 – 5 hours resulted in the best preparation quality scores throughout
the colon [73]. A meta-regression analysis of 29 RCTs comparing split vs. day-before regimens showed
that the clinical gain of the split-dose regimen was highest within 3 hours from last
dose intake, progressively decreased after 4 to 5 hours, and became statistically
not significant at 5 hours [74].
Some clinicians, mainly anesthesiologists, are concerned about the risk of pulmonary
aspiration of residual gastric fluid when a second dose of bowel preparation is given
close to the time of endoscopy.
However, a systematic review, including 28 RCTs, 2 controlled trials, and 10 observational
studies (22 936 patients) did not show any association between shorter “nothing per
mouth” intervals prior to colonoscopy and pulmonary aspiration risk [75].
In addition, several endoscopic studies demonstrated that the residual gastric volumes
in patients who had a split-dose regimen were similar to [76]
[77]
[78]
[79] or even lower [80] than those obtained by more prolonged fasting after a day-before regimen. This supports
the notion that bowel preparation regimens should be regulated in the same way as
clear liquids. Thus, it is reasonable and safe to recommend 2 hours as the minimum
interval between the intake of last dose of preparation and the colonoscopy, in line
with the American Society of Anesthesiologists’ recommendation for clear liquids (e. g.,
water, fruit juice without pulp, carbonated beverages, clear tea, and black coffee)
before elective procedures requiring sedation/analgesia or anesthesia [81].
Laxatives
ESGE recommends the use of high volume or low volume PEG-based regimens as well as
that of non-PEG-based agents that have been clinically validated for routine bowel
preparation. In patients at risk for hydroelectrolyte disturbances, the choice of
laxative should be individualized.
Strong recommendation, moderate quality evidence.
Data on the efficacy and safety of laxatives formally validated in a clinical setting
are provided in [Table 1].
Table 1
Summary data on efficacy and safety of validated laxatives for routine bowel preparation.
|
Agent
|
Efficacy (split/same-day regimen)
|
Safety
|
|
High volume polyethylene glycol (PEG)
|
Noninferior or superior to low volume PEG or non-PEG regimens
|
Not recommended in:
|
|
Low volume PEG plus adjuvants
|
|
|
Noninferior to high volume PEG and non-PEG regimens
|
Not recommended in patients with:
-
Severe renal insufficiency (creatinine clearance < 30 mL/min);
-
Congestive heart failure (NYHA III or IV);
-
Phenylketonuria; or
-
Glucose-6-phosphate dehydrogenase deficiency.
|
|
|
Noninferior to high volume PEG or 2 L PEG + ascorbate
|
Not recommended in patients with:
-
Severe renal insufficiency (creatinine clearance < 30 mL/min):
-
Congestive heart failure (NYHA III or IV)
-
Unstable angina; or
-
Acute myocardial infarction.
No long-term data available.
Limited post-marketing data available.
|
|
|
Noninferior to 2 L PEG + ascorbate, oral sulfate solution (OSS), and magnesium citrate
plus picosulphate (MCSP).
No comparison with high volume PEG.
|
Not recommended in patients with:
-
Severe renal insufficiency (creatinine clearance < 30 mL /min);
-
Congestive heart failure (NYHA III or IV);
-
Phenylketonuria; or
-
Glucose-6-phosphate dehydrogenase deficiency.
Adequate hydration must be maintained.
Limited post-marketing data available.
|
|
|
Noninferior to high volume PEG or 2 L PEG + ascorbate
|
Occasional reports of ischemic colitis with high dose bisacodyl.
Not recommended in:
|
|
Magnesium citrate plus picosulphate (MCSP)
|
Noninferior to high volume PEG or 2 L PEG + ascorbate
|
Not recommended in patients with:
Not recommended in patients at risk for:
-
Hypermagnesemia; or
-
Rhabdomyolysis.
|
|
Trisulfate (magnesium sulfate, sodium sulfate, and potassium sulfate), also called
oral sulfate solution (OSS)
|
Noninferior to high volume PEG, 2 L PEG ascorbate
Superior to MCSP in a single RCT
|
Not recommended in patients with:
|
NYHA, New York Heart Association; RCT, randomized controlled trial.
High volume PEG
Efficacy
In a recent meta-analysis, split-dose high volume (≥3 L) appeared to be superior to
split-dose low volume PEG (6 studies; 1305 patients; OR 1.89, 95 %CI 1.01 – 3.46)
[82]. This confirmed a previous meta-analysis [83] showing the superiority of split-dose high volume PEG vs. other alternatives (9
studies; 2477 patients; OR 3.46, 95 %CI 2.45 – 4.89) including low volume PEG with
different adjuvants and sodium phosphate, regardless of the adoption of the split
regimen. After the meta-analyses were published, several trials compared high volume
PEG vs. low volume PEG or non-PEG split regimens as detailed in each of the sections
below. Overall, such trials showed an equivalence or superiority of the high volume
vs. low volume PEG or non-PEG regimens in terms of efficacy, while confirming the
worse tolerability of the high volume PEG regimens.
Safety
High volume osmotically balanced solutions containing PEG and electrolytes are intended
to impair the intestinal absorption of water and sodium. This is achieved by maintaining
isosmosis of the bowel lumen content. Studies have not demonstrated significant alterations
in vital or biochemical parameters (e. g., sodium, potassium, chloride, bicarbonates)
linked to these formulations. This accounts for the high safety and few contraindications
associated with these products, which are also considered safe in the setting of renal
failure, pre-existing electrolyte imbalance, or in those who cannot tolerate sodium
loads (e. g., patients with cirrhosis) [84]
[85].
Low volume PEG plus adjuvants
Efficacy
1 2 L PEG plus ascorbate ([Table 1], Table 7s)
In order to reduce the volume of PEG solutions, with the aim of improving tolerability,
a formulation of 2 L PEG with the adjunct of osmotically active ascorbic acid has
been introduced. One meta-analysis [86], including 11 RCTs comparing 2 L PEG plus ascorbate vs. 4-L PEG preparations for
elective colonoscopies, has shown a noninferior efficacy for bowel cleansing (OR 1.08,
95 %CI 0.98 – 1.28) but a significantly better compliance for 2 L PEG plus ascorbate
(OR 2.23, 95 %CI 1.67 – 2.98), with reduced nausea and vomiting. Initial reports questioned
the ability of the product to provide a satisfactory cleansing in the right colon
[87], but more recent RCTs have reported a similar efficacy of colon cleansing also in
this clinically important segment [88]
[89]
[90]
[91].
Four additional trials published after the abovementioned meta-analysis have compared
2 L PEG plus ascorbate vs. 4 L PEG [60]
[89]
[92]
[93]. One of these included only afternoon colonoscopies [92] and demonstrated a trend for the 4 L PEG to provide better colon cleansing than
2 L PEG plus ascorbate (both administered in a same-day regimen), but no difference
was noticed in overall cleansing adequacy and patient satisfaction (despite higher
bloating in the PEG plus ascorbate regimen). In the other three published RCTs [60]
[89]
[93] comparing split-dose 2 L PEG plus ascorbate with split-dose 4 L PEG, successful
cleansing was very high (between 92.1 % [60] and 97.5 % [89]) and not different between the two products (two studies also demonstrated similarly
high ADRs [89]
[93]); moreover, differently from previous studies, no difference was demonstrated in
the adequacy of right colon cleansing. As previously demonstrated, 2 L PEG plus ascorbate
solutions were associated with higher tolerability and willingness to repeat the regimen.
Four RCTs have compared 2 L PEG plus ascorbate vs. magnesium citrate plus sodium picosulfate
(MCSP) [94]
[95]
[96]
[97]. The most recent of these [95], with both preparations in split-dose regimens, demonstrated similarly high overall
cleansing success (93.5 % vs. 93.8 %, P = 0.72; including successful cleansing of the right colon), polyp detection rates,
and ADRs, along with a higher rate of adverse events (mainly nausea) in the PEG plus
ascorbate group and a higher willingness to repeat the regimen in the MCSP group (83.4 %
vs. 92.1, P = 0.001). Another RCT involving 973 patients [96] and comparing 2 L PEG plus ascorbate vs. MCSP and vs. 4 L PEG found no difference
in bowel cleansing between products, provided they were used in split-dose regimens,
but MCSP (OR = 8.39 [95 %CI 5.74 – 12.27]) and 2 L PEG ascorbate (OR = 1.69 [95 %CI
1.21 – 2.35]) were better tolerated than 4 L PEG.
After the abovementioned meta-analysis had been published, two RCTs compared 2 L PEG
plus ascorbate vs. oral sodium phosphate (OSP) [98]
[99]. In one [98], the two products were equivalent in cleansing efficacy, but PEG plus ascorbate
was associated with less vomiting and more complaining about the volume and inability
to complete the regimen. In the other RCT [99], in contrast, 2 L PEG plus ascorbate was associated with higher efficacy of bowel
cleansing (93.4 % vs. 22.8 %, P < 0.001; also in the right colon), significantly higher willingness to repeat bowel
preparation (88.4 % vs. 78.1 %, P < 0.001), and fewer electrolyte disturbances; however in this last trial PEG plus
ascorbate was administered in split-dose fashion, while OSP was administered as a
day-before bowel preparation.
2 2 L PEG plus citrate ([Table 1])
More recently, a new formulation of 2 L PEG plus citrate and simethicone has become
available. When this solution has been compared (in RCTs) with 4 L PEG, there was
no difference in adequate bowel cleansing (73.6 % vs. 72.3 %, 95 %CI difference −7.5
to 10.1), safety, and compliance, but gastrointestinal tolerability was better for
the low volume solution (25.4 % vs. 37.0 %, P < 0.01) and acceptability was higher (93.9 % vs. 82.2 %, P < 0.001) [100]. Moreover, when compared with 2 L PEG plus ascorbate, bowel cleansing (78.3 % vs.
74.3 %, P = 0.37), safety (including electrolyte measurement), acceptability (81.4 % vs. 80.8 %,
P = 0.74), compliance, and willingness to repeat the same preparation were equivalent
[101]. In both studies, the rates of adequate colon preparation were higher for all the
products when administered according to the split-dose modality. Adenoma and polyp
detection rates were not evaluated.
3 1 L PEG plus ascorbate ([Table 1])
A new 1 L PEG solution with a higher ascorbate concentration has been evaluated against
MCSP, oral sulfate solution (OSS), and 2 L PEG plus ascorbate in three RCTs. These
included patients aged between 18 and 85, with blinded central readers evaluating
primary endpoints using validated scales.
Compared with MCSP, with both products taken in a day-before fashion [102], 1 L PEG plus ascorbate demonstrated noninferior overall cleansing (62.0 % vs. 53.8 %;
P = 0.04) and high quality cleansing in the right colon (4.4 % vs. 1.2 %; P = 0.03) in the intention-to-treat analysis (and superiority in the per-protocol analysis),
along with noninferior polyp and adenoma detection rates. Tolerability and adherence
were high (but the latter was higher with MCSP), despite a higher rate of mild adverse
events in the 1 l PEG plus ascorbate group (17.0 % vs. 10.0 %; P = 0.03).
When compared with OSS in a split-dose schedule [103] 1 L PEG plus ascorbate was noninferior in terms of successful bowel cleansing (85.1 %
vs. 85.0 %; P = 0.53) and high quality cleansing of the right colon (35.9 % vs. 29.3 %; P = 0.06). No difference was demonstrated in polyp and adenoma detection rates, adherence,
overall tolerability and safety.
Finally, when 1 L PEG plus ascorbate in split-dose and same-day fashion was compared
with split-dose 2 L PEG plus ascorbate [104], noninferiority of 1 L PEG plus ascorbate in both regimens was established in the
intention-to-treat analysis. Furthermore, superiority was demonstrated in the per-protocol
analysis of overall success of split-dose 1 L PEG plus ascorbate (97.3 % vs. 92.2 %;
P = 0.01) and of high quality right colon cleansing for both split-dose and same-day
1 L PEG plus ascorbate regimens vs. 2 L PEG plus ascorbate. Polyp and adenoma detection
rates were also noninferior. Adherence, tolerability, and safety (including blood
and urinary values) were comparable between arms, despite a higher rate of vomiting
in the same-day regimen arm compared with the split-dose 2 L PEG ascorbate regimen
(6.3 % vs. 1.1 %, P = 0.002).
4 2 L PEG plus bisacodyl ([Table 1], Table 8s)
One meta-analysis [105] of 6 RCTs found that, compared with 4 L PEG, 2 L PEG plus bisacodyl (10 – 20 mg)
provided similar bowel cleansing with no difference in abdominal pain, but was associated
with less nausea, vomiting, and bloating.
After this meta-analysis was published, seven RCTs evaluated the addition of bisacodyl
to PEG [88]
[106]
[107]
[108]
[109]
[110]
[111] compared with 4 L PEG and 2 L PEG plus ascorbate. Two RCTs further evaluated whether
the addition of bisacodyl could lower the required volume of PEG plus ascorbate to
1 L [88]
[111], using 2 L PEG plus ascorbate as comparator. Three RCTs [106]
[107]
[109] evaluated the addition of bisacodyl to PEG plus citrate plus simethicone.
All these trials, except one [106], demonstrated no substantial difference in overall colon cleansing, but improved
tolerability only in RCTs using higher volumes of PEG as comparator. No difference
was demonstrated in head-to-head comparison of split-dose 2 L PEG plus ascorbate with
split-dose 2 L PEG plus bisacodyl [108]).
Safety
Solutions containing aspartame and ascorbate (such as 2 L and 1 L PEG plus ascorbate
solutions) are contraindicated in patients with phenylketonuria or glucose-6-phosphate
dehydrogenase deficiency [112]. These products are not recommended in patients with renal insufficiency and creatinine
clearance < 30 mL/min and in patients with New York Heart Association (NYHA) III or
IV congestive heart failure. A high rate of hypernatremia has been observed following
the administration of 1 L PEG plus ascorbate, primarily due to the sodium content
of the product. For this reason, additional clear liquids are recommended. Hyponatremia
cases have been described with 2 L PEG ascorbate; this prompted caution in patients
at risk of electrolyte disturbances.
In solutions where PEG is associated with citrate and simethicone, caution is suggested
if the products are administered in patients with creatinine clearance < 30 mL/min,
NYHA III or IV congestive heart failure, unstable angina, or acute myocardial infarction.
In the case of symptoms of electrolyte disturbances or in an at-risk patient, laboratory
evaluation of electrolytes and renal function must be considered before and after
the regimen. As these are low volume hyperosmotic formulations, attention must be
paid to encourage the intake of additional liquids to prevent dehydration and electrolyte
imbalance.
Even though specific or statistically significantly different adverse events have
not been reported in the bisacodyl arms of the aforementioned RCTs, cases of ischemic
colitis have been reported following the intake of > 5 mg bisacodyl [113]
[114]
[115].
Magnesium citrate with sodium picosulfate (MCSP) ([Table 1], Table 9s)
Efficacy
Magnesium citrate with sodium picosulfate was compared with PEG and with OSP in two
meta-analyses [116]
[117], including 6 and 13 studies, respectively. In the study by Tan & Tjandra [116], MCSP provided satisfactory colon cleansing in a similar proportion of patients
compared with PEG, with less frequent adverse events. However OSP produced better
colon cleansing than MCSP. In the study by Lieshout et al. [117], which included only RCTs in which colon cleansing was rated according to a validated
scale, MCSP provided a slightly better quality of bowel cleansing compared with PEG
(RR 1.06, 95 %CI 1.02 – 1.11); this was lost however when MCSP was compared with 4 L
PEG only. Moreover, MCSP was better tolerated than PEG, with a higher capability of
completing the preparation.
In the most up-to-date meta-analysis [118], including 25 RCTs comparing MCSP with PEG (but with different regimens), no difference
was found in colon cleansing, polyp detection rate, and ADR. However adverse events
were less frequent in the MCSP group (RR 0.78, 95 %CI 0.66 – 0.93; i. e. nausea, vomiting,
bloating, but not dizziness), and a higher proportion of patients were likely to complete
the MCSP regimen (RR 1.08, 95 %CI 1.04 – 1.13) and willing to repeat the same regimen
(RR 1.44, 95 % CI, 1.25 – 1.67).
Since the most up-to-date meta-analysis, four RCTs [94]
[95]
[96]
[97] have been published that included comparisons between split-dose MCSP vs. split-dose
2 L PEG plus ascorbate (with/without 10 mg bisacodyl); these demonstrated overall
high rates of adequate preparation without significant differences between the two
regimens. One recent RCT [119] compared 4 L PEG vs. MCSP in a primary screening setting, including 13 497 patients.
Adequate bowel preparation was more frequent in the PEG than in the MCSP group (86.4 %
vs. 79.0 %; P < 0.001). However, a split regimen was not systematically recommended for either
product.
Safety
Because of hyperosmolarity and magnesium content, solutions containing MCSP are contraindicated
in patients with congestive heart disease, hypermagnesemia, rhabdomyolisis, gastrointestinal
ulcerations, and severe impairment of renal function, which can lead to magnesium
accumulation. In a retrospective population-based study, using administrative data
and enrolling > 65-year-old patients, compared with PEG, MCSP was associated with
an increased risk of hospital admission due to hyponatremia [120]. In a post hoc analysis of two RCTs investigating MCSP regimens (excluding patients
with basal renal insufficiency), 10 % of patients had slightly above normal magnesium
levels, but this produced no clinically significant effect on monitored cardiac conduction,
including in those patients with mild-to-moderate renal impairment [121]. There have been reports of acute gastric and esophageal injury caused by undissolved
or poorly dissolved MCSP powder [122].
Oral sulfate solution (OSS) (trisulfate; [Table 1])
Efficacy
Recently, a formulation of magnesium sulfate, sodium sulfate, and potassium sulfate
(also called oral sulfate solution [OSS] or trisulfate) has become available in Europe.
This preparation was compared with 4 L PEG in three RCTs [123]
[124]
[125]. Overall, these trials showed the noninferiority of split OSS versus split high
volume PEG in terms of efficacy, a high OSS safety, and better tolerability. In addition,
three RCTs compared OSS with 2 L PEG plus ascorbate and showed similarly high efficacy
when both regimens were used in split or same-day regimens [126]
[127]
[128].
OSS has also been compared with MCSP in one RCT [129], using the two products in split-dose fashion, and demonstrated better cleansing
success in the OSS group.
Safety
OSS is contraindicated in patients with congestive heart disease, ascites, and severe
renal insufficiency (glomerular filtration rate < 30 mL/min). Data are scarce regarding
OSS in the setting of renal insufficiency and liver failure. Clinically significant
electrolyte disturbances and kidney injury or significant creatinine elevation have
not been reported to date [130]. However real-life clinical experience with these solutions is limited and prudence
is mandatory. Because of the potential risk of hydroelectrolytic disturbances, laboratory
evaluation of electrolytes and renal function may be appropriate before and after
the procedure in at-risk patients. Adequate hydration must be encouraged in all patients.
These solutions may also cause transient elevation of uric acid levels, which must
be considered in patients affected with hyperuricemia or gout.
Laxatives in elderly people
There is insufficient evidence to recommend a specific product for elderly people.
Osmotically balanced PEG solutions are theoretically the safest, and are preferred
in these patients [153]. However high volume products are thought to be particularly poorly tolerated in
elderly patients. Even if compliance may be increased with specific measures, the
most relevant being the adoption of a split-dose regimen, future research must focus
on the safety profile of low volume regimens in the elderly population.
Two RCTs specifically enrolled elderly patients. In one study [60] comparing 2 L PEG ascorbate with 4 L PEG and enrolling more than 200 patients aged
> 65 years with normal renal function and electrolytes, no increases in adverse events
were found (but no laboratory evaluation was done after the regimen), along with comparable
cleansing efficacy and higher willingness to repeat the regimen. One RCT [125] randomized almost 200 patients, aged between 65 and 75 and without systemic co-morbidities,
to receive OSS or 4 L PEG both in a split-dose fashion. No differences in frequency
of acute kidney injury or significant electrolyte changes were found, along with very
high and not different cleansing success between the two groups and significantly
higher willingness to repeat the OSS regimen.
RCTs of 1 L PEG ascorbate against OSS [103], MCSP [102], and 2 L PEG ascorbate [104] included a proportion of patients aged between 65 – 85 years without systemic co-morbidities,
but safety outcomes were not specifically reported for these subgroups.
At-risk patients and laxatives
Even if all cleansing regimens are associated with the risk of dehydration and potential
electrolyte imbalances (even caused only by vomiting), hyperosmotic preparations may
further increase these risks in at-risk populations, such as patients with chronic
renal insufficiency, congestive heart failure, or liver failure with ascites. Although
the majority of RCTs exclude such patients, PEG solutions with osmotically balanced
electrolytes are often selected, on account of their safety profiles, for patients
in these categories [154].
Only retrospective cohorts have found relative safety of PEG in patients with impaired
renal function compared to other formulations (e. g. vs. OSP [155]). In one retrospective cohort, patients with glomerular filtration rate < 60 mL
/min ingested either 4 L PEG or 2 L PEG ascorbate solutions [156]. No statistically significant change in electrolytes or blood urea nitrogen or increase
in creatinine was found after intake of either preparation. Comparing the regimens,
a transient > 30 % increase in creatinine levels was found in 7.5 % of 4 L PEG patients
and in 11.5 % of 2 L PEG plus ascorbate patients; this was not statistically significantly
different [156].
Patients with creatinine clearance > 30 mL/min have generally been included in RCTs
evaluating PEG plus ascorbate solutions. Further data are needed to recommend a specific
regimen in this setting.
Oral sodium phosphate (OSP)
ESGE recommends against the routine use of oral sodium phosphate for bowel preparation.
Strong recommendation, low quality evidence.
Safety
The most feared adverse event following oral sodium phosphate (OSP) intake is kidney
injury. The largest report of kidney injury (21 patients) described the development
of acute renal failure within a few weeks after colonoscopy; this modestly improved
over time and required renal replacement therapy in four of the patients [131]. A meta-analysis of 7 controlled studies (12 168 patients) that compared the effect
of OSP vs. another bowel preparation on kidney function found no statistically significant
association between OSP and kidney injury [132]. However, these studies were usually not powered to detect rare serious complications
and their tight control of inclusion criteria tended to exclude individuals at risk
for complication development. Moreover, between January 2006 and December 2007, 171
cases of renal failure were reported to the United States Food and Drug Administration
(FDA) following the use of OSP and 10 following the use of PEG [131]. A retrospective, population-based national analysis in Iceland estimated that the
risk of biopsy-proven acute phosphate nephropathy is approximately 1 per 1000 OSP
doses sold [131]. Another severe complication of OSP for bowel preparation consists of acute disruption
of electrolyte homeostasis, including hyperphosphatemia, hypocalcemia, hypokalemia,
and hyper- or hyponatremia. The spectrum of clinical presentation varies from mild
symptoms related to hypocalcemia to death [131].
Generally accepted contraindications specific to OSP for bowel preparation include
the following as absolute contraindications: pregnancy, age < 18 years, stage 3 – 5
chronic kidney disease (glomerular filtration rate < 60 mL/min/1.73 m2), inability to maintain adequate fluid intake, pre-existing electrolyte disturbances,
ascites, symptomatic congestive heart failure, and recent (within < 6 months) symptomatic
ischemic heart disease (unstable angina or myocardial infarction). Relative contraindications
include active inflammatory bowel disease, parathyroidectomy, and delayed bowel transit
[133]
[134]
[135]
[136]
[137]. In addition, recognized risk factors for acute phosphate nephropathy following
the use of OSP include age > 55 years, hypovolemia, baseline kidney disease, bowel
obstruction, or active colitis, as well as intake of drugs that affect renal perfusion
or function such as diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin
receptor blockers and, possibly, nonsteroidal anti-inflammatory drugs [133]
[134]
[135]
[136]
[137].
Care should be taken in individuals with presumably normal renal function because
unrecognized chronic kidney disease may affect a large proportion of older individuals
(up to 23 % – 36 % of people aged 65 years or older) [138]
[139].
Strategies recommended to prevent acute phosphate nephropathy include: avoidance of
OSP in high risk patients; screening for unrecognized chronic kidney disease and electrolyte
imbalances; avoiding dehydration before, during, and after OSP administration; minimizing
the dose of OSP; and maintaining a minimum of 12 hours between the administration
of the two OSP doses [140]. It is the prescribers’ responsibility to ensure that the patient understands the
importance of maintaining an adequate fluid intake [134]. Renal function should be checked as close to the colonoscopy appointment as practically
possible, but in any case within 3 months.
Efficacy (Table 10s)
Overall, seven meta-analyses, published over an 18-year period (1998 – 2016), have
compared oral sodium phosphate with PEG [116]
[141]
[142]
[143]
[144]
[145]
[146]. In the latest meta-analysis including only RCTs comparing OSP and PEG [146], the two regimens demonstrated no difference in the rate of adequate preparation
(7 studies, 1128 patients for efficacy assessment), but better scores for OSP when
only studies using the Ottawa Bowel Preparation scale were considered. With the OSP
regimen, compliance was higher as well as acceptability, with better taste and with
less nausea, vomiting, and abdominal pain, and with no statistically significant difference
in post-procedural electrolyte imbalance and creatinine levels between the two regimens.
Since the latest meta-analyses, one RCT [147] has been published that compares OSP tablets vs. 4 L PEG, both prescribed in split-dose
fashion in a selected population without contraindications and severe co-morbidities.
The trial showed no difference in colon cleansing efficacy, in polyp detection rate,
or in the rate of any adverse events; compliance to the regimen was slightly in favor
of OSP tablets, and ingestion was considered significantly easier in that group. Thus,
if OSP is used, 90 mL solution or 32 tablets each containing 1.5 g sodium phosphate,
both in a split-dose regimen, is to be preferred [148]
[149]
[150]
[151]
[152].
Specific categories of patients
Specific categories of patients
Patients with constipation
ESGE does not suggest any specific bowel preparation in patients with constipation.
Weak recommendation, low quality evidence.
Chronic constipation has been identified as one of the risk factors for inadequate
bowel preparation. Despite the low quality of the evidence, additional bowel purgatives
are often considered in patients with chronic constipation who are about to undergo
colonoscopy. Since 2013, only five studies have specifically addressed special regimens
for constipated patients. However, these few studies are heterogeneous, comparing
different bowel preparations, volumes, timings, and adjunctive treatments. There is
neither any meta-analysis nor multicenter RCT.
One well-designed RCT in 400 patients with chronic constipation compared 2 L PEG plus
citrate plus simethicone plus 2-day bisacodyl vs. 4 L PEG and showed no significant
differences between groups [157]. Another RCT that included constipated and nonconstipated patients [158] compared four different regimens: OSP vs. OSP plus bisacodyl vs. PEG 4 L vs. PEG
2 L plus bisacodyl. The authors reported no statistically significant differences
between groups, but when analyzing only constipated patients (n = 65), they found
that 45 mL OSP plus 20 mg bisacodyl was significantly superior to the 4-L PEG preparation
(95 % of patients had satisfactory colon cleansing vs. 66 %, respectively; P = 0.03). One nonrandomized study including 372 patients, of whom 65 had constipation,
compared 4 L PEG vs. 2 L PEG plus ascorbate, both in split dose [159]. Based on the Aronchick scale for quality of bowel preparation, the authors did
not find statistically significant differences between groups, either in constipated
or nonconstipated patients. However, several methodological issues were not clarified.
Another nonrandomized Turkish study [160] in 227 patients with constipation (constipation not clearly defined) evaluated the
addition of a 200-mL enema to standard preparation with sennoside. They compared three
groups: enema before preparation, enema after preparation, and standard preparation
(no enema). They did not find overall differences between groups. However, in constipated
women, enema before preparation was superior to the other regimens.
In conclusion, evidence is still lacking that would allow recommendation of a special
regimen or supplemental treatment for bowel preparation in patients with chronic constipation.
Low volume PEG and OSP seem to be better tolerated than 4 L PEG with no differences
regarding efficacy. Despite good results regarding OSP preparations in terms of tolerance,
compliance, efficacy, and safety profile in one study, these results are irrelevant
in our setting given that the use of OSP is not recommended by current guidelines
because of its safety profile [14]
[161]. There is no additional evidence to recommend using bisacodyl or enemas as complementary
measures in bowel preparation. In special cases, such as cystic fibrosis, more intensive
regimens have been suggested [162], but additional evidence is needed.
Patients with inflammatory bowel disease (IBD)
ESGE recommends high volume or low volume PEG-based bowel preparation in patients
with inflammatory bowel disease (IBD).
Strong recommendation, high quality evidence.
Colon cleansing in inflammatory bowel diseases is critically important both for disease
assessment and detection of dysplasia. Recently the promotion of chromoendoscopy in
international guidelines has made high quality bowel preparation even more crucial
[163]. Patients with IBD bear a heavy burden from colonoscopy for disease assessment and
surveillance [164]. One in eight patients may experience a disease flare in the weeks following colonoscopy
that may relate to the bowel preparation [165]. In an RCT of patients without colitis, sodium phosphate- or sodium picosulfate-based
preparations resulted in a 10-fold increase in mucosal inflammation compared to PEG-based
bowel preparation [166]. An observational study of 730 patients noted a 3.3 % rate of erosions or other
inflammatory lesions in patients without IBD or without current nonsteroidal anti-inflammatory
drug (NSAID) use, that was related to sodium phosphate-based bowel preparation [167].
Limited comparative data are available for bowel preparation efficacy and tolerability
in colitis. A recent 2017 meta-analysis identified four fully published comparative
studies [168]; no more studies were identified after further searches. One study from the 1980s
compared the use of bowel preparation regimens that would not be acceptable in contemporary
practice (castor oil vs. high dose senna) [169], and one examined the use of addition of simethicone to PEG-based preparation to
reduce bubbling [170]. Two further studies looked at high volume vs. low volume PEG plus adjuvant (ascorbic
acid or bisacodyl) preparation [171]
[172]. Combining the latter two studies, which compared low volume PEG (≤ 2 L) plus adjuvant
vs. high volume PEG (> 3 L), no significant difference in bowel cleansing was observed
(OR 1.19, 0.52 – 2.71), though low volume regimes appeared more acceptable to patients
(OR for willingness to repeat 5.11, 1.31 – 20.00). In an analysis restricted to split-dose
high volume PEG vs. split-dose low volume PEG plus adjuvant, there was no difference
in preparation quality (OR 0.84, 0.37 – 1.92). A Japanese RCT, presented as an abstract,
that compared low volume PEG plus ascorbic acid vs. large volume PEG alone in patients
with ulcerative colitis and Crohn’s disease, found similar results in terms of similar
or better cleansing with PEG plus adjuvant, and better patient acceptability (author
contacted for full results) [173]. Only low volume 2 L PEG-based bowel preparations have been validated in this setting.
Data for very low volume (< 2 L) PEG-based bowel preparation with adjuvants are awaited.
Current consensus guidelines recommend chromoendoscopy with targeted biopsies for
IBD surveillance [161]. No study has yet focused on which preparation regimes are optimal for chromoendoscopy;
however a recent case series noted that having a clear liquid diet for 24 hours pre-procedure
led to a higher probability that preparation would be good enough to allow chromoendoscopy
(OR 0.11, 95 %CI 0.01 – 0.85; P < .034) [174].
Pregnant/lactating patients
ESGE found insufficient evidence to determine for or against the use of specific regimens
in pregnant/breastfeeding women. However, if colonoscopy is strongly indicated, PEG
regimens may be considered, with tapwater enemas preferred for sigmoidoscopy.
Insufficient evidence to determine net benefits or risks.
Colonoscopy appears feasible and relatively safe in pregnancy when strongly indicated
[175]. The use of PEG in pregnancy has not been extensively studied and it is unknown
whether it can cause fetal harm; when used for treating constipation during pregnancy,
it is considered relatively safe. Because full colonoscopy is rarely indicated during
pregnancy, tapwater enemas are recommended as bowel preparation for sigmoidoscopy.
No reported series allows any evaluation of the role of bowel preparation during lactation.
If bowel preparation is strictly recommended, interrupting breastfeeding during and
after bowel preparation may be an option.
Acute lower gastrointestinal bleeding (LGIB)
ESGE recommends PEG regimens for bowel preparation if urgent colonoscopy is scheduled
for lower gastrointestinal bleeding (LGIB).
Strong recommendation, moderate quality evidence.
Preparation of the colon in the setting of acute lower GI bleeding facilitates endoscopic
visualization, diagnosis, and treatment, and may reduce the risk of bowel perforation.
Preparation for colonoscopy should include 4 – 6 L of a PEG solution or the equivalent,
administered over 3 – 4 hours until the rectal effluent is clear [176]
[177]
[178]. The use of lower volume or alternative colon preparation solutions in the setting
of LGIB has not been specifically addressed, but preliminary data seem encouraging
[179].
Many patients with acute LGIB are unable to tolerate rapid colon preparation and thus
a nasogastric tube can be placed to facilitate this process as long as the risk of
aspiration is low. Aspiration precautions should be used particularly in older and
debilitated patients. In addition, administration of a prokinetic/antiemetic agent
immediately prior to initiating the colon preparation may reduce nausea and facilitate
gastric emptying. Unprepped sigmoidoscopy/colonoscopy in the setting of acute LGIB
is not recommended since cecal intubation rates and diagnostic yields are low, and
poor visualization may increase the risk of perforation [176]
[177].
Inadequate bowel preparation: management, inpatients, and risk factors
Inadequate bowel preparation: management, inpatients, and risk factors
Management of inadequate bowel preparation
ESGE recommends early repetition of colonoscopy within 1 year in the case of inadequate
bowel preparation, unless clinically contraindicated.
Strong recommendation, moderate level of evidence.
Same-day or next-day colonoscopy after additional preparation – with either laxative
or enema – may be suggested. The next regimen of bowel preparation should be individualized
according to the possible reasons for failure.
Weak recommendation, very low level of evidence.
Possible regimens for repeated colonoscopy
As already reported in the Introduction, patients with an inadequate cleansing must
repeat the colonoscopy because of a high risk of clinically relevant lesions having
been missed. The evidence on the efficacy of a next-day or same-day colonoscopy, after
additional bowel preparation, compared with a later colonoscopy is limited and conflicting.
In a single-center series of 235 patients with inadequate preparation, next-day colonoscopy
vs. non-next-day rescheduled colonoscopy was associated with a reduced risk of secondary
failure (OR 0.31, 95 %CI 0.1 – 0.92) [180]. This was not confirmed in a larger single-center series of 397 patients with inadequate
procedure as recurrent failure was observed in 30 % of the next-day group and 23.5 %
of the non-next-day group (P = 0.48) [181]. However, in a retrospective study on 3047 procedures with inadequate cleansing,
patients advised to have next-day colonoscopy were more likely to adhere to the repeat
colonoscopy recommendation [182].
In a single-center prospective nonrandomized study, 87 patients with inadequate preparation
after an initial 4 L PEG received either an additional 2 L PEG on the same day or
a 4 L PEG plus bisacodyl 1 week later after 3 days of a low residue diet, with no
difference found between the two regimens [183]. In an observational study, 60 patients with inadequate preparation received a same-day
repeat colonoscopy after receiving an additional laxative of 250 mL of senna alkaloids
with 1.5 L of water [184]; the repeat colonoscopy reached the cecum in 83 % of patients.
A recent randomized trial showed the superiority of a high volume PEG-based regimen
over a low volume PEG when associated with an intensive regimen of preparation [185].
Direct enema or irrigation
Direct administration of laxative enemas through the colonoscope into the right colon
via the biopsy channel (133 mL/19 g phosphate enema plus 37 mL/10 mg bisacodyl enema,
10 patients; two 37 mL/10 mg bisacodyl enemas, 11 patients) was reported to be effective
in 21 patients with inadequate preparation after low volume PEG and bisacodyl preparation
[186]. In a similar study, 26 patients with inadequate preparation after low volume PEG
received 500 mL PEG into the right colon via the colonoscope biopsy channel. Overall,
preparation was successful in 25 patients [187].
On the other hand, a randomized trial compared 1 L PEG enema administered through
the colonoscope to the additional oral ingestion of 2 L PEG in 125 patients with inadequate
preparation. An appropriate preparation was obtained in 35 out of 66 (53 %) in the
enema group vs. 53 out of 67 (81 %) in the oral group, with respective Boston Bowel
Preparation Scale scores of 6.3 vs. 7.4 (P < 0.001) [188].
In a single-center study, 42 patients with inadequate preparation were randomized
to receive either pump irrigation with a 650 mL/min flow rate (Jetprep; Herzliya,
Israel) or syringe irrigation with 30 – 50-mL aliquots. Pump irrigation was superior
in improving per-procedure preparation with a significant difference in the right
colon [189].
Other approaches
Surveys showed that additional ingestion of the same or a different preparation, additional
instillation through the colonoscope, and additional enema are useful, as are rescheduled
subsequent colonoscopy with the same or different preparation, or the same preparation
but with better observance of diet [190]
[191]
[192]
[193].
Careful assessment of the primary reason for failure of the previous preparation,
such as vomiting, poor adherence, and risk factors for inadequate cleansing, is recommended
before prescribing a new regimen.
Bowel preparation in inpatients
ESGE recommends specific verbal or written instructions to patients and to clinic
staff caring for hospitalized patients, to improve the quality of bowel preparation.
Strong recommendation, moderate quality evidence.
One recent systematic review and meta-analysis [194] summarized the evidence from eight RCTs and nine observational cohort studies (Table 11s). In this systematic review, included studies were arbitrarily classified according
to the intervention used for improving bowel cleanliness as: (a) education of patients
and/or personnel regarding bowel preparation; (b) modification of preparation regimen;
and (c) other interventions. Colon cleansing that was adequate (or an equivalent measure
calculated from the available data) was achieved in 67 % (95 %CI [60]
[61]
[62]
[63]
[64]
[65]
[66]
[67]
[68]
[69]
[70]
[71]
[72]
[73]
[74]
[75]%) of patients overall; in 77 % (62 – 91)% of the intervention group in the studies
assessing the impact of educational interventions vs. 50 % (32 – 68)% of the controls;
in 71 % (60 – 81)% of the participants with various preparation regimens; and in 55 %
(22 – 87)% in the single study examining the administration of bowel preparation through
esophagogastroduodenoscopy. The heterogeneity of the various cathartics used and the
variation in timing of their administration, and the existence of only a single study
in the third intervention group precluded meta-analysis of study results for intervention
categories (b) and (c).
Regarding the effect of specific educational intervention, patients in the intervention
arms received either brief counselling and written instructions or an educational
booklet [195]
[196], while in three studies [197]
[198]
[199] leaflets, lectures, and/or presentations were used to educate personnel involved
in patients’ preparation. Finally, in one study [200], both personnel and patients were educated. Among these studies the OR (95 %CI)
of achieving adequate colon cleansing was 3.49 (1.67 – 7.28) in the intervention group
compared to the standard practice group. Inconsistences in the reporting of ADR, adverse
events, tolerance, and willingness of patients to repeat the preparation preclude
conclusions on the value of the interventions for these outcomes.
There is evidence that the rate of inadequate bowel preparation in inpatients undergoing
colonoscopy is high, although several interventions have been implemented to address
the problem. There is moderate evidence that educational interventions provided to
patients and health care personnel may improve colon cleansing.
Risk factors for inadequate bowel cleansing
ESGE found insufficient data to recommend the use of specific predictive models for
inadequate bowel preparation in clinical practice.
Inadequate colon preparation has been reported in up to 18 % – 35 % of patients undergoing
colonoscopy [201]
[202]. Overall, 5 RCTs, 20 prospective and 12 retrospective observational studies, as
well one case-control and one study of unknown design attempted to identify predictors
of preparation failure (Table 12s) using multivariate analysis. Moreover, two recent meta-analyses including 67 and
24 studies with more than 75 000 and almost 50 000 participants, respectively, evaluated
independent risk factors identified in the literature up to 2016 [201]
[202]. The authors acknowledged the limitations of their analyses because of the high
heterogeneity for all outcomes and because of the mix of RCTs and various types of
noninterventional studies. Patients’ baseline characteristics (increasing age and
male gender), clinical conditions (constipation, diabetes mellitus, hypertension,
cirrhosis, stroke, and dementia), and medication use (narcotics and tricyclic antidepressants)
were identified as predictors of colonoscopy preparation failure in both meta-analyses.
On the other hand, both meta-analyses failed to identify previous abdominal surgery
as a predictor, while there were inconsistent results regarding body mass index (BMI)
and history of colon preparation failure (Appendix 4s).
Identification of risk factors for poor bowel cleansing would have the potential benefit
of selecting patients who need more intensive bowel preparation. Thus, three models
have been developed so far using these factors to correctly predict adequate colon
cleansing [203]
[204]
[205]. Hassan et al. built their model on patient-related risk factors identified in a
multicenter prospective study of 2811 consecutive patients who underwent colonoscopy.
The model was established in the exploratory group (randomly half of the included
population) and validated in the rest of the participants; the area under the curve
of the logistic regression model for predicting adequate bowel preparation was 0.63
[203]. A total of 1331 colonoscopies were included in the development cohort of a Dutch
study that identified American Society of Anesthesiologists (ASA) score ≥ 3, use of
tricyclic antidepressants or opioids, diabetes, constipation, previous abdominal and/or
pelvic surgery, history of inadequate bowel preparation, and hospitalization as independent
predictors for inadequate bowel preparation. These factors were included in the prediction
model with a discriminative ability indicated by an area under the curve of 0.77 in
the validation cohort [205]. Finally, another model was developed using data from 667 consecutive Spanish outpatients.
Antidepressant use, co-morbidity, constipation, and abdominal/pelvic surgery were
included in the model as independent predictors for inadequate cleansing. The model
showed an area under the curve of 0.70 in a validation cohort that included 409 individuals
[204]. So far, none of these predictive models have been tested in other than their validation
cohort populations, and no study has attempted to apply a different regimen to patients
presenting with risk factors for inadequate colon cleanliness.
There is moderate quality evidence that patients’ epidemiological and clinical characteristics
may predict colonoscopy preparation failure. However, no predictive model has been
applied in clinical practice, so far.
Disclaimers
The legal disclaimer for ESGE Guidelines [16] applies to this Guideline.
Prof. James East was funded by the National Institute for Health Research (NIHR) Oxford
Biomedical Research Centre (BRC). The views expressed are those of the author and
not necessarily those of the NHS, the NIHR or the UK Department of Health.
