Endoscopic techniques have become increasingly important in recent years, particularly in the treatment of colorectal flat lesions[58,59].
At the same time, the significance of accurate detection and assessment of such lesions in predicting malignancy has become clear. Indeed, proper bowel preparation is critical for colonoscopy because it allows for visualization of the entire colonic mucosa and improves the safety of therapeutic maneuvers[6,60].
In contrast, poor preparation lengthens the procedure, increases the risk of complications, and increases the likelihood of missing lesions.
The percentage of colonoscopies performed with inadequate bowel cleansing ranges between 5% and 35%[12,44,62-66].
Because a proper bowel cleansing regimen increases the likelihood of success, identifying risk factors for inadequate bowel cleansing is critical. Patient-related predictors of colonoscopy preparation failure include prior inadequate bowel cleansing, a history of constipation, increasing age (> 65 years), male gender, low health literacy (e.g., cognitive skills), inpatient status, obesity, diabetes mellitus (DM), inflammatory bowel disease (IBD), unexplained chronic diarrhea, megacolon, cirrhosis, stroke, dementia or Parkinson’s disease, patients at increased risk for electrolyte abnormalities (e.g., patients on diuretics), uncontrolled hypertension, severe congestive heart failure (New York Heart Association class III or IV), severe CKD (creatinine clearance < 30 mL/min/1.73 m), previous colorectal surgery, use of constipation-related medications (narcotics and tricyclic antidepressants), severe colonic stricture or obstructing tumor or perforation, dysphagia, gastroparesis, or gastric outlet obstruction, pregnancy or lactation[12,64,65,67-69].
Administration of the entire preparation the night before the colonoscopy, rather than split-dosing, and a later start time for the colonoscopy are procedure-related risk factors for inadequate bowel preparations. The presence of one or more of these risk factors can influence bowel cleansing regimens and choices.
ESGE recommends the use of high-volume or low-volume PEG-based regimens, as well as non-PEG-based agents that have been clinically validated for routine bowel preparation. For elective colonoscopy, split-dose bowel preparation (with or without additional measures) should be used, as it has been linked to improved preparation quality.
In 2015, Dik et al conducted a Dutch study that included only patients who who received a split-dose regimen. In total, 1331 colonoscopies were included in the study, with 12.9% having insufficient bowel preparation. Diabetes, chronic constipation, a history of abdominal or pelvic surgery, and recent hospitalization are all risk factors for poor bowel cleansing quality.
Gandhi et al conducted a meta-analysis of independent risk factors in over 75,000 people receiving a split-dose bowel preparation. Constipation, diabetes, and medication use were identified as predictors of colonoscopy preparation failure despite the studies’ heterogeneity. In a 2018 meta-analysis by Mahmood et al, age, male sex, inpatient status, DM, hypertension, cirrhosis, narcotic use, constipation, stroke and tricyclic antidepressants were associated with inadequate bowel cleansing (OR = -1.20, OR = 0.85, OR = 0.57, OR = 0.58, OR = 0.58, OR = 0.49, OR = 0.59, OR = 0.61, OR = 0.51, respectively). Furthermore, in Western countries, diabetes, cirrhosis, male sex, stroke history, and tricyclic antidepressant use were found to be stronger risk factors for inadequate bowel preparation than in Asian countries.
In a 2022 United States retrospective study of 1029 patients, Agrawal et al discovered the following factors to be associated with colonoscopy cancellations: Graduate school education, Hispanic ethnicity, a hemoglobin level of 10 g/dL, and if the colonoscopy was done for other indications (OR = 1.93, P = 0.04; OR = 0.47, P = 0.01; OR = 1.41, P = 0.05; OR = 0.53, P = 0.04, respectively). Dementia (OR = 2.44, P = 0.02) and gastroparesis (OR = 3.97, P = 0.01) were factors associated with poor bowel preparation in a multivariate analysis.
Ultimately, in a 2016 United States study of 2401 colonoscopies, African Americans were 70% more likely to have suboptimal preparation (95%CI 1.2-2.4); DM, tricyclic antidepressant use, narcotic use, and Miralax-Gatorade prep vs 4-L PEG 3350 were all associated with suboptimal preparation quality in a multivariable analysis (OR = 2.3, 95%CI 1.6-3.2; OR = 2.5, 95%CI 1.3-4.9; OR = 1.7, 95%CI 1.2-2.5; OR = 0.6, 95%CI 0.4-0.9, respectively).
Obesity: Obesity, when combined with other risk factors, is an independent predictor of poor bowel preparation during a colonoscopy in practice.
In a 2013 retrospective study of 2163 consecutive patients, mostly men, who had colonoscopies in Indiana, one of the independent risk factors for inadequate preparation was a body mass index (BMI) of ≥ 30 Kg/m2 (OR = 1.46, 95%CI 1.21-1.75, P < 0.0001).
Sharara et al discovered that BMI was an independent risk factor for inadequate preparation in a 2016 Arabic study involving 541 patients. Obesity was associated with an OR of 5.3 (95%CI 1.4-19.8, P = 0.01) when compared to normal BMI. In a prospective study of 195 patients, obese patients had comparable rates of inadequate preparation to normal-weight individuals (OR = 0.7, 95%CI 1.10-3.96, P = 0.68). Patients who were underweight performed significantly worse than those with normal BMI (OR = 8.0, 95%CI 1.1-58.0, P = 0.04).
A high BMI had a significant difference in the effect of bowel cleansing between studies with mostly female patients (OR = 1.05) and studies with mostly male patients (OR = 1.30) (P = 0.013 for the difference), according to a 2018 systematic review and meta-analysis. Inadequate bowel preparation was linked to diabetes (OR = 1.79) and hypertension (OR = 1.25), among other risk factors.
According to a recent study by Passi et al in the United States, 49.4% of 27696 colonoscopies had insufficient bowel preparation, which was most common in the class III obesity group. When compared to the normal body mass index (BMI) group, a BMI of 30 kg/m2 and 40 kg/m2 was associated with an increased risk of an incomplete colonoscopy (P = 0.001 for overweight, P = 0.0004 for class I/II obesity), a longer procedure (P < 0.05 for all), and poorer tolerance (P < 0.0001 for class I/II obesity, P = 0.016 for class III obesity).
According to some studies, distinct bowel preparations are beneficial and safe for obese patients. In a 2012 prospective Australian study of 104 patients showing a similar bowel preparation quality after using sodium picosulphate, 90% of non-obese and 89% of obese patients had good bowel preparation (P > 0.99).
Patients were randomized to receive split-dosing of either NER1006, 2-L PEG-ASC, or OSS in a recent (2021) two phases III Spanish trials. Split-dose NER1006 (1-L-PEG-ASC) was associated with high levels of cleansing, ranging from 87% to 94% in a total of 551 patients, including those who were obese or diabetic. Obese males aged above 60 had significantly higher overall and high-quality bowel-cleansing success rates with 1-L-PEG-ASC, at 100.0% and 72.7%, respectively, compared to 86.7% and 50.0% in the control group (P = 0.015 and P = 0.033, respectively).
Diabetes mellitus: Due to the high prevalence of gastrointestinal symptoms and the increased risk of CRC, diabetic patients have a higher demand for colonoscopies than the general population[78-80].
As a result, adults with diabetes should be properly screened, and a longer bowel preparation may be necessary to ensure an adequate endoscopic examination.
Due to dietary/medication regimen changes, narcotic use, and diabetes-related complications/comorbidities such as hypoglycemia, electrolyte imbalance, acute renal failure, and ketoacidosis, diabetic patients are at risk of poor bowel preparation[82,83].
DM has been identified as an independent risk factor influencing bowel preparation quality by decreasing colonic motility[71,84-86].
The rate of insufficient bowel preparation in diabetic patients ranges from 9% to 30%[84,87,88], which should be significantly reduced by implementing a multifactorial strategy. Surprisingly, even though DM patients are notoriously difficult to prepare, few studies have looked into the best bowel preparation management strategy in this setting. In diabetic patients, taking 10 ounces of magnesium citrate two days before colonoscopies, in addition to a single 4-L PEG dose, improved colon cleansing (from 54% to 70%).
Another single-blind prospective trial on DM patients discovered that adding lubiprostone, a highly selective locally-acting activator of chloride channels used in functional constipation, to a single 4-L PEG the day before the procedure improved colon cleansing; however, the improvement was statistically non-significant due to the small sample size. A small trial in DM outpatients examined additional bowel cleansing strategies with 6-L PEG, but the results were not encouraging.
Current United States guidelines do not endorse any of these recommendations, instead recommending a split-dose bowel cleansing regimen for DM patients with no adjustments. A subsequent European randomized, single-blind, superiority trial compared a conventional bowel preparation protocol with a diabetic-specific preparation protocol, which included a low-fiber diet for three days, a clear liquid diet for one day, and a 4-L split-dose PEG regimen.
The latter group was given a special education program that included diet, laxative intake, and blood glucose-lowering agent adjustment instructions. In the conventional protocol, inadequate bowel cleansing was statistically more common than in the diabetic-specific protocol (20% vs 7%; RR = 3.1, 95%CI 1.2-8.0, P = 0.014).
Chronic constipation: The most prevalent type of constipation, functional chronic constipation, frequently affects women and the elderly who undergo colonoscopies often and ranges in prevalence from 2% to 27% in Western countries[91-93]. Constipation has been identified as a risk factor for inadequate bowel preparation[13,94]. Currently, ESGE does not recommend any specific bowel preparation in patients suffering from constipation chronically.
In elderly patients, slow transit constipation, defined by decreased bowel movements, may result in insufficient laxative wash-out and bowel preparation. This hypothesis was confirmed in a 2015 Korean study, which discovered that colonic transit time of more than 30 h was associated with inadequate bowel preparation. Furthermore, slow-transit constipation, as determined by radiopaque marker colonic transit testing, was linked to a more than 2-fold increased risk of poor bowel preparation in a 2022 study of 274 American patients with chronic constipation (OR = 2.2, 95%CI 1.1-4.4).
In patients with a history of constipation, additional bowel purgatives should be considered. Numerous studies in recent years have suggested different bowel preparation regimens in patients with chronic constipation, with good results using a variety of laxatives.
In a double-blind 2008 United States trial, 200 CRC screening patients were randomly assigned to receive a 24 g dose of lubiprostone or placebo before a split-dose PEG with electrolytes bowel preparation in the absence of dietary restriction.
Split-dose PEG, electrolytes, and lubiprostone pretreatment was found to be more effective (P = 0.001) and tolerable (P = 0.003) than placebo, most likely due to a reduction in abdominal bloating (P = 0.049).
In a 2015 Italian randomized, single-blind study, 400 constipated patients were enrolled and randomly assigned to one of two arms: Split 2-L PEG-citrate-simethicone plus 2-day bisacodyl or split 4-L PEG. In a 2016 Chinese RCT, the addition of lactulose one day before colonoscopy in combination with 4-L split-dose PEG was shown to be significantly superior (P < 0.05) to the conventional preparation with oral PEG and electrolytes for colonoscopy bowel preparation.
In terms of ease of administration (P < 0.001), willingness to repeat (P < 0.001), and compliance (P = 0.002), the 2-L PEG-citrate-simethicone/bisacodyl solution was found to be significantly more acceptable. According to a 2019 RCT, the optimal dose of crystalline lactulose for Japanese constipated patients is 26 g/day. A short therapy cycle of PEG plus electrolytes was effective and safe in improving bowel preparation in chronic constipation patients in a 2020 and 2021 Japanese study[101,102]. In 2016, a larger Asian population was studied in a randomized, double-blind, placebo-controlled trial. Surprisingly, when lower doses of PEG were combined with lubiprostone, no significant difference in preparation quality was observed.
In a 2021 systematic review and meta-analysis of three RCTs, Dang et al enrolled 225 chronically constipated patients, with 47.6% receiving sodium phosphate and 52.4% receiving PEG. Despite the low quality of evidence, patients who received sodium phosphate before their colonoscopy had cleaner colons than those who received PEG (OR = 1.87, 95%CI 1.06-3.32, P = 0.003).
IBD: Inadequate bowel preparation has also been linked to comorbidities such as IBD. This was demonstrated in an Italian multicenter, randomized, single-blind study of 211 adult outpatients with ulcerative colitis (UC) undergoing colonoscopy and receiving either 2-L PEG plus bisacodyl or 4-L PEG. Low-volume PEG was not inferior to 4-L PEG for bowel cleansing in UC (P = NS), but it was better tolerated (P < 0.0001) and accepted (P < 0.0001). The split dosage was associated with better cleansing regardless of preparation. A period of more than 6 h between the end of preparation and the colonoscopy predicted poor cleansing.
In a 2021 retrospective analysis of a prospective cohort, Maida et al demonstrated the efficacy and safety of 1-L PEG-ASC in 45% of 411 patients.
IBD patients had higher cleansing success (92.9% vs 85.4%, P = 0.02) than controls, with a similar number of patients experiencing adverse events (22.2% vs 21.2%, P = 0.821) and treatment-emergent adverse events (51 vs 62%, P = 0.821). Furthermore, the presence of IBD (OR = 2.51, P = 0.019), lower age (OR = 0.98, P = 0.014), a split regimen (OR = 2.43, P = 0.033), the absence of diabetes (OR = 2.85, P = 0.015), and chronic constipation (OR = 3.35, P = 0.005) were all independently associated with cleansing success.
Endoscopic disease activity has recently been discovered to predict suboptimal bowel preparation, and biological therapy has been shown to protect IBD patients from it.
In a 2022 United States study by Kumar et al, the moderate-to-severe endoscopic disease was associated with higher odds of suboptimal bowel preparation vs mild or inactive disease [adjusted OR (aOR) 2.7; (95%CI 1.52-4.94)], whereas baseline biologic use was associated with a lower odds of suboptimal bowel preparation [aOR, 0.24 (0.09-0.65)] among the overall IBD cohort. Furthermore, age > 65 years and single-dose vs split-dose bowel preparation were independent predictors of suboptimal bowel preparation [aOR, 2.99 (1.19-7.54); aOR, 2.37 (1.43-3.95), respectively].
Liver cirrhosis: Liver cirrhosis predicts poor bowel preparation at screening colonoscopy[64,109].
This finding is most likely due to multiple factors impairing intestinal motility in cirrhotic patients[110,111]. The role of chronic liver disease in predisposing to inadequate bowel preparation in the absence of cirrhosis is unknown. In a 2016 United States study, Anam et al compared 120 cirrhotics to 220 non-cirrhotics with chronic liver disease, and the first group performed significantly worse on bowel preparation. Cirrhotics had lower bowel preparation scores than non-cirrhotics (P = 0.0027), with cirrhotics having the lowest (48%) and non-cirrhotics having the highest (30%), with no effect of the MELD score.
The rate of failure to complete the bowel preparation and the incidence of side effects were comparable in 53 cirrhotics compared to 52 healthy subjects undergoing screening colonoscopy, according to an Italian 2015 study by Salso et al. Despite this, nearly half of the cirrhotics (49% vs 5% control; P < 0.001) had poor bowel cleansing.
In a 2017 Chinese retrospective study, Lee et al compared the safety of two bowel-cleansing agents in patients with liver cirrhosis (2-L PEG-ASC vs 4-L PEG). Patients preferred the 2-L PEG-ASC over the 4-L PEG group for acceptability and compliance. Finally, because both groups were successfully cleansed, the authors concluded that using 2-L PEG-ASC for colonoscopy in cirrhotics was a safe option.
Decompensated cirrhosis patients are more prone to frailty, cognitive abnormalities, and decreased ambulation. Clayton et al discovered that patient educational video did not improve bowel preparations (split-prep) in the pre/post-intervention period in 121 patients with decompensated cirrhosis undergoing colonoscopy during the initial liver transplantation evaluation (29.8% vs 31.9%, respectively).
Furthermore, patients with moderate to severe ascites had a significantly higher rate of inadequate colonoscopy bowel preparation than non-ascites patients.
CKD: The use of cleansing agents in patients with CKD should be carefully evaluated due to the risk of electrolyte imbalance or worsening renal function. No significant changes in vital or biochemical parameters have been linked to high volume osmotically balanced solutions containing PEG and electrolytes capable of maintaining bowel lumen isosmosis.
According to previous research[117,118], PEG is generally safe in CKD patients; however, adequate hydration and renal function monitoring should be ensured before and after colonoscopy in some cases to avoid acute kidney failure. Individualized laxative choice is strongly advised for patients at risk of hydroelectrolyte disturbances (moderate quality evidence).
Because of hyperosmolarity and the risk of magnesium toxicity, as well as acute phosphate nephropathy, magnesium-based preparations and sodium phosphate should be avoided in CKD patients[13,120,121].
Furthermore, due to the poor tolerability of high-volume PEG-based regimens, low-volume PEG (2-L) solutions with ascorbic acid (PEG-ASC) solutions have been proposed to reduce the patient’s excessive fluid intake. Ascorbic acid can act as an osmotic agent and enhance the laxative effect of PEG due to its hexose structure, and its pleasant taste makes it easier for patients to swallow. Ascorbic acid, on the other hand, has been linked to the formation of renal stones and acidosis, with contradictory results[123,124]. As a result, low-volume preparations continue to be a challenge for many CKD patients.
Notably, ESGE guidelines do not recommend aspartame and ascorbate-containing solutions (such as 2-L and 1-L PEG-ASC solutions) for patients with renal insufficiency and creatinine clearance less than 30 mL/min. A high rate of hypernatremia has been observed following the administration of 1-L PEG-ASC, owing primarily to the product’s sodium content. If low volume PEG solutions combined with citrate and simethicone are administered to patients with creatinine clearance less than 30 mL/min, caution is advised.
In a 2016 retrospective study, a same-day 1-L low-volume PEG regimen with a previous-day low-residue diet and laxative was tested to improve tolerability. The study included 5,427 patients who were instructed to consume a low-residue fiber diet with 10 mL sodium picosulfate one day before the colonoscopy, followed by 1-L low-volume PEG and 0.5-L water four hours before the exam. In 86 CKD patients (creatinine 1.1 mg/dL), the BBPS 6 success rate was 94.1%, and there were no serious complications. Lee et al found that the 2-L PEG-ASC was a safe choice for bowel preparation before colonoscopy in patients with impaired renal function in a 2016 study.
In one retrospective cohort, patients with a GFR of 60 mL/min were given either 4-L PEG or 2-L PEG-ASC solutions. Patients in the 2-L PEG-ASC group (n = 61) rated their tolerance and acceptability higher than those in the 4-L PEG group (n = 80). After either preparation, there was no statistically significant change in electrolytes, blood urea nitrogen, or creatinine. When the regimens were compared, 7.5% of 4-L PEG patients and 11.5% of 2-L PEG-ASC patients had a transient > 30% increase in creatinine levels, though the differences were not statistically significant. Ohmiya et al discovered that same-day conventional bowel preparation with PEG electrolyte lavage solution plus Ascorbate (PEG-ELS-ASC) was safe and effective in 56 CKD patients in the Japanese 2021 study.
Only retrospective cohorts have found PEG to be safer than other formulations in patients with impaired renal function.
The most severe kidney injury case reported reversible post-colonoscopy acute renal failure within a few weeks of oral sodium phosphate (OSP) intake, necessitating renal replacement therapy in 19% of patients. Furthermore, during the 2006-2007 time period, the Food and Drug Administration received reports of 171 cases of renal failure caused by the use of OSP and 10 cases caused by the use of PEG. A 2005 retrospective population-based Iceland study found that the risk of biopsy-proven acute phosphate nephropathy is about one in every 1000 OSP doses sold.
Three RCTs comparing OSS preparation to 4-L PEG found that split OSS was noninferior to split high-volume PEG in terms of efficacy, safety, and tolerability. Although real-world data on OSS in the setting of renal insufficiency are limited, and despite no significant differences in the frequency of acute renal failure reported with this preparation, European guidelines recommend that it be avoided in patients with severe renal insufficiency (glomerular filtration rate 30 mL/min).
According to ESGE guidelines and current evidence, patients with severe renal insufficiency should be prepared with isotonic high volume PEG solutions rather than low volume PEG or non-PEG regimens.
Heart disease: Previously, it was thought that bowel preparation (particularly after administration of PEG-ELS solution) could worsen heart failure, as a result, except in urgent or emergency cases, exposing such patients to a colonoscopy was risky. Also, coronary heart disease has been identified as a risk factor for severe desaturation and relevant electrocardiographic changes during endoscopic sedation. Furthermore, several studies have found that these solutions may be harmful to patients with heart disease due to the potential increase in plasma volume and their effects on electrolyte disturbances.
Thiazide diuretics and SSRIs, which have the potential to cause fluid and electrolyte imbalances, should be avoided in at-risk patients while undergoing bowel preparation.
Heart disease and CRC were the only predictors strongly associated with poor bowel cleansing in a 2019 Spanish single-center, endoscopist-blinded RCT of 136 patients (OR = 3.37, 95%CI 1.34-8.46, P = 0.010; OR = 3.82, 95%CI 1.26-11.61, P = 0.018, respectively). In a 2020 study, Poola et al discovered that 44% of 315 inpatients’ bowel preparation was fair/poor. Poor bowel preparation was associated with elderly people who had a history of congestive heart failure.