Updated bowel preparation regimens for colonoscopy: benefits and drawbacks

Abstract

Optimal bowel preparation is critical for high-quality colonoscopy and the effective prevention of colorectal cancer. Although traditional high-volume polyethylene glycol (PEG) electrolyte lavage solutions are effective and safe, they are frequently limited by poor patient tolerability. To improve adherence, several low- and ultra-low-volume PEG-based regimens, particularly 2 L and 1 L PEG plus ascorbate, have demonstrated noninferior efficacy and better patient compliance. Hyperosmotic alternatives, including oral sulfate solution and sodium picosulfate with magnesium citrate, provide comparable bowel-cleansing efficacy and are often favored for their improved palatability and tolerability. The recent introduction of oral sulfate tablets offers the convenience of a tablet form while maintaining efficacy similar to that of PEG-based regimens and significantly enhancing tolerability. However, a few cases of gastric mucosal irritation have been reported. Adjunctive simethicone also improves mucosal visibility by reducing intraluminal bubbles. With the growing diversity of bowel preparation options, regimen selection should be tailored to individual patient characteristics, including age, comorbidities, prior experiences, and personal preferences. A personalized evidence-based approach, guided by patient-specific factors and supported by emerging clinical data, can improve adherence, ensure adequate bowel cleansing, and enhance the diagnostic yield and procedural efficiency of colonoscopy.

INTRODUCTION

Colorectal cancer (CRC) remains a major global health concern due to its high mortality rate and substantial socioeconomic burden. Despite advances in screening and treatment, CRC remains one of the leading causes of cancer-related deaths worldwide. CRC poses a significant public health burden in Korea, with a crude prevalence of 569.8 per 100,000 in 2020.1 The steady rise in the incidence, from 45.4 per 100,000 in 2006 to 54.5 in 2014, mirrors global trends and underscores the need for effective screening strategies, including high-quality colonoscopy. Globally, the burden is projected to increase to 3.2 million new cases by 2040.2 Colonoscopy is the gold standard for the early detection and prevention of CRC, enabling both the diagnostic assessment and removal of precancerous lesions in a single procedure. It has been shown to significantly reduce both the CRC incidence and mortality.3,4 However, the effectiveness of colonoscopy is highly dependent on bowel preparation quality.

The quality of colonoscopy is commonly assessed using objective indicators such as the adenoma detection rate and cecal intubation rate.5 While these metrics are influenced by endoscopist performance, high-quality bowel preparation is an equally essential determinant. Currently, no standardized approach exists for bowel preparation, with multiple available lavage agents that differ in efficacy, safety, palatability, and cost-effectiveness. In addition, the timing of purgative administration varies, with the split-dose regimen, typically halving the dose the evening before and the remainder on the morning of the procedure, which is the most widely recommended method for optimal bowel preparation.6,7

Inadequate bowel preparation (occurring in up to ±25% of colonoscopies) is associated with reduced detection of polyps and adenomas, prolonged procedure times, and the need for earlier repeat examinations (Table 1).6-9 Recognizing this, expert consensus guidelines now emphasize achieving ≥90% adequacy in bowel prep as a key quality benchmark.6,7 An ideal bowel preparation agent should consistently clear more than 90% of the mucosal surface while remaining safe, well-tolerated, and acceptable to patients.6,7 However, poor patient compliance with traditional high-volume preparations has long represented a major barrier.10 In recent years, several new bowel preparation agents and formulations have been introduced to improve patient experience without compromising efficacy. These include low-volume or ultra-low-volume polyethylene glycol (PEG)-based solutions, sulfate-based preparations, and combination regimens incorporating osmotic and stimulant laxative mechanisms. This review classifies new bowel preparation regimens by their mechanism of action, summarizes their benefits and drawbacks (efficacy, safety, tolerability, patient adherence, and cost), and compares recent evidence. A summary of these agents and their key characteristics is provided in Table 2.

Table 1.

Multifactorial contributors to inadequate bowel preparation quality

Patient characteristics	Clinical conditions	Social/behavioral features
Old age (>65 years)	Chronic constipation	Tobacco use
Male sex	Diabetes mellitus	Reduced health literacy
Obesity with high body mass index (>30 kg/m2)	Hypertension	Low education level
Inpatient status	Liver cirrhosis	Low patient activation
Prior history of poor preparation	Neurological conditions: stroke, Parkinson disease, dementia
	Immobility
	Spinal cord injury
	Previous abdominal and/or pelvic surgery
	Constipating medicine: tricyclic antidepressants, narcotics, opioid use

Table 2.

Comparison of bowel preparation regimens: mechanisms, volumes, efficacy, and their benefits and drawbacks

Regimen	Type (mechanism)	Volume	Cleansing efficacy	Key contraindications	Special populations	Benefits	Drawbacks
PEG-ELS 4 L	Iso	4 L	High: reference standard	Bowel obstruction	Older adults, patients who are pregnant, IBD, R.I, ascites	High efficacy; good safety profile	Poor tolerability
PEG-ascorbate 2 L	Iso	3 L (regimen 2 L+water 1 L)	Noninferior to 4 L PEG and non-PEG regimens	Bowel obstruction, G6PD deficiency, phenylketonuria, unstable angina; or acute myocardial infarction, R.I, CHF	Older adults, patients who are pregnant (caution), IBD	Better taste, smaller volume	Risk of hemolysis in G6PD
PEG-ascorbate 1 L	Iso	2 L (regimen 1 L+water 1 L)	Noninferior to 4 L or 2 L PEG	Bowel obstruction, G6PD deficiency, Phenylketonuria, R.I, CHF	Volume-sensitive patients; adequate hydration must be maintained.	High tolerability, convenient	Dehydration and hypernatremia risk in frail or older adults
Oral sulfate solution	Hyper	2.9 L (regimen 0.9 L+water 2 L)	Noninferior to 4 L or 2 L PEG	Bowel obstruction, R.I, CHF, ascites	Young average-risk patients, patients who are pregnant (caution)	Lower volume	Risk of hyperuricemia and dehydration
			Comparable to SPMC	Hyperuricemia or Gout (caution)
Oral sulfate tablet	Hyper	3 L (28 tablet+water 3 L)	Noninferior to PEG (any volume); comparable to SPMC	Bowel obstruction, Dysphagia, Post-bariatric surgery	Tablet-tolerant patients	Tablet form, High tolerability, less nausea	Gastric mucosal injury risk
				R.I, CHF, Ascites
				Hyperuricemia or Gout (caution)
SPMC	Dual	2.34 L (regimen 0.17 L+water 2 L)	Noninferior to 4 L or 2 L PEG	Bowel obstruction, R.I, CHF, ascites	Patients desiring taste/convenience	Excellent taste	Risk of hyponatremia and hypermagnesemia
				Hypermagnesemia; or rhabdomyolysis.
PEG+bisacodyl	Iso+stimulant	3 L (regimen 2 L+water 1 L)	Comparable to 4 L PEG	Bowel obstruction, CHF, older adults with vascular disease (caution)	Young/healthy or prior poor prep	More tolerable than 4 L PEG	Rare ischemic colitis

PEG, polyethylene glycol; ELS, electrolyte lavage solution; IBD, inflammatory bowel disease; G6PD, glucose-6-phosphate dehydrogenase; R.I., renal insufficiency (creatinine clearance <30 mL/min); CHF, congestive heart failure (New York Heart Association class III or IV); SPMC, sodium picosulfate, magnesium oxide, and citric acid; PEG+bisacodyl, polyethylene glycol combined with bisacodyl; PEG+linaclotide, polyethylene glycol combined with linaclotide; Iso, iso-osmotic; hyper, hyperosmotic; dual, stimulant plus osmotic combination.

MECHANISM-BASED CLASSIFICATION OF BOWEL PREPARATION AGENTS

Bowel preparation regimens exert their effects through two primary pharmacologic mechanisms: osmotic action, which promotes fluid retention within the intestinal lumen, and stimulant action, which increases colonic motility. Many modern preparations combine these two mechanisms to enhance efficacy and patient tolerability. Bowel preparation regimens are commonly classified according to the total volume of purgative administered. High-volume regimens, typically consisting of 4 liters of solution, may be administered as day-before, same-day, or split-dose protocols, a strategy often referred to as “full-volume” in the literature. Low-volume regimens (2 to <4 L) and ultra-low-volume regimens (<2 L) can also be delivered using similar timing formats, with ultra-low-volume strategies generally favored for same-day or split-dose administration owing to improved tolerability. The following sections summarize the major regimen categories and highlight key examples of newly approved or recently investigated agents within each class.

Osmotic laxatives

1) Isosmotic agents

(1) PEG-electrolyte lavage solution: mechanism, efficacy, and clinical considerations

Osmotic laxatives are the cornerstone of bowel preparation and exert their effects by drawing water into the intestinal lumen to facilitate colonic cleansing. Among these agents, PEG-electrolyte lavage solution (PEG-ELS) has long been regarded as the standard preparation because of its isotonic composition and negligible systemic absorption.11 High-volume PEG regimens (4 L) are United States (US) Food and Drug Administration (FDA)-approved and are considered highly effective and safe across a broad spectrum of patients, including those with renal insufficiency or congestive heart failure (CHF). However, the large fluid volume and unpalatable taste often compromise patient adherence, with reported discontinuation rates ranging from 5% to 15%.12 Common adverse effects associated with high-volume PEG-based bowel preparation regimens include abdominal bloating, cramping, nausea, vomiting, and insomnia. These volume-related side effects may be alleviated by reducing the total purgative volume.

To improve tolerability and patient adherence, several low-volume PEG-based bowel preparation regimens have been developed that incorporate hyperosmotic adjuncts such as ascorbic acid, citrate, or simethicone. Representative examples include 2 L PEG plus ascorbate formulations and ultra-low-volume 1 L PEG plus ascorbate regimens, both of which are US FDA-approved and have demonstrated noninferior bowel preparation efficacy with improved patient acceptability compared to traditional 4 L PEG-ELS protocols.6 However, it is important to note that the term “low-volume” refers specifically to the purgative solution and does not account for the additional water intake (typically 1–2 L) required to ensure adequate hydration and colonic flushing.

A novel 2 L PEG-based formulation containing citrate and simethicone was approved by the US FDA. Citrate enhances both palatability and osmotic activity, whereas simethicone minimizes intraluminal foam formation, collectively improving bowel preparation and patient tolerability. In a multicenter randomized trial comparing 2 L PEG/citrate to 4 L PEG-ELS, both regimens demonstrated comparable overall bowel preparation success rates (73.6% vs. 72.3%), but the PEG/citrate group showed significantly better tolerability (72.8% vs. 63.0%, p=0.0314) and greater willingness to reuse (93.9% vs. 82.2%, p=0.0002), with similar compliance rates (91.1% vs. 90.9%) and no serious adverse events reported.13 Another trial comparing 2 L PEG/citrate with 2 L PEG/ascorbate showed no significant differences in bowel preparation efficacy (78.3% vs. 74.3%, p=0.37), patient-reported tolerability (81.4% vs. 80.8%, p=0.74), or the incidence of mild adverse effects.14 Despite these favorable outcomes, the hyperosmolar nature of citrate raises concerns regarding potential electrolyte disturbances and dehydration, warranting caution in patients with severe renal impairment.

Additionally, a low-volume regimen combining 2 L of PEG with bisacodyl has been investigated as an alternative to traditional high-volume preparations. Recent meta-analyses and randomized controlled trials (RCTs) support the non-inferiority of low-volume regimens compared to that of high-volume PEG in terms of bowel preparation efficacy, while also demonstrating superior patient tolerability. For example, a large RCT (n=2,314) comparing 4 L split-dose PEG with 2 L split-dose PEG plus bisacodyl found no clinically meaningful difference in bowel preparation adequacy (90% vs. 89%, p=0.02), although patient willingness to repeat the regimen was significantly higher in the low-volume group (91.9% vs. 66.9%, p<0.01).15 However, rare instances of ischemic colitis have been reported,16 leading to the revocation of US FDA approval for bisacodyl-containing bowel preparation products in 2011.

The most recent development in this category is NER1006, an ultra-low-volume (1 L) PEG plus ascorbate formulation. Although it has been shown to provide noninferior bowel preparation efficacy compared to standard 2 to 4 L PEG regimens, a meta-analysis including ten trials (n=1,717) reported an adequate bowel preparation rate of 83%, which was somewhat lower than that observed with other low-volume regimens. Importantly, all regimens included in the meta-analysis were administered using a split-dose protocol, reinforcing the critical importance of dosing timing in achieving successful bowel preparation.17 Another ultra-low-volume strategy currently under investigation involves combining 1 L PEG with linaclotide, a guanylate cyclase-C agonist with both secretory and pro-motility properties. In a recent RCT involving 548 patients who underwent afternoon colonoscopies, the 1 L PEG plus linaclotide regimen achieved a bowel preparation adequacy rate of 90.5%, compared to 91.6% in the 2 L PEG group (p=0.64).18 Moreover, the lower-volume regimen was associated with fewer adverse effects and greater patient willingness to repeat the preparation (95.2% vs. 82.2%, p<0.01).

However, not all ultra-low-volume regimens have consistently demonstrated satisfactory outcomes. A meta-analysis evaluating regimens with volumes <1 L reported suboptimal bowel preparation adequacy rates for sodium picosulfate/magnesium citrate (SPMC) (75%) and sodium phosphate (<1 L, 82%).17 Moreover, specific safety considerations apply to certain patient populations when using low-volume PEG regimens. Aspartame, which is included in some formulations as a flavoring agent, is metabolized to phenylalanine and should be avoided in individuals with phenylketonuria. Ascorbate, a commonly used hyperosmotic adjunct, may induce hemolysis in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency and should be used cautiously in individuals with severe renal impairment (creatinine clearance <30 mL/min) or New York Heart Association class III or IV CHF.19,20 In addition, hypernatremia may occur because of the sodium content in certain formulations; therefore, adequate fluid intake is strongly recommended during the bowel preparation process.7

2) Hyperosmotic agents

(1) Oral Sulfate Solution: Mechanism, Efficacy, and Clinical Considerations

Oral sulfate solutions (OSS) are hyperosmotic laxatives composed of a trisulfate formulation that includes sodium sulfate, potassium sulfate, and magnesium sulfate, with sodium sulfate serving as the predominant active component. These non-absorbable anions exert their effects by retaining water within the intestinal lumen, thereby facilitating effective bowel preparation. Owing to their minimal intestinal absorption and absence of significant systemic electrolyte shifts, OSS is theoretically considered safe with respect to fluid and electrolyte balance. OSS has been approved by the US FDA for split-dose use only. The typical regimen involves approximately 1 L of OSS solution and 2 L of water (total intake ±3 L).

OSS has been shown to provide superior or comparable bowel preparation efficacy compared to high- and low-volume PEG-based regimens. An RCT demonstrated that split-dose OSS yielded significantly better bowel preparation outcomes compared to 4 L Sulfate-Free PEG-ELS (98.4% vs. 89.6%, p=0.04), with similar safety profiles.21 In a meta-analysis of seven studies (n=2,049),22 OSS demonstrated similar bowel preparation efficacy to low-volume PEG-ascorbate regimens, but was associated with a higher incidence of nausea (relative risk [RR], 1.35; 95% confidence interval [CI], 1.03–1.77) and vomiting (RR, 2.30; 95% CI, 1.63–2.23). Notably, OSS was associated with an increased adenoma detection rate compared to 2 L PEG-ELS (odds ratio, 1.17; 95% CI, 1.03–1.33).23 Further, a prospective comparative study evaluating OSS and SPMC demonstrated that OSS had significantly higher rates of adequate bowel preparation (94.7% vs. 85.7%, p=0.006) and excellent bowel preparation (54% vs. 26%, p<0.001). However, no significant difference was observed in the overall preparation adequacy (96.3% vs. 94.9%, p=0.614), and patients in the SPMC group reported superior taste and tolerability.24

Despite these benefits, OSS should be used with caution when selecting patients. Patients with CHF, ascites, or severe renal impairment (creatinine clearance <30 mL/min) are generally advised to avoid OSS because of the potential risks of dehydration and fluid-electrolyte imbalance. Although severe adverse events, such as acute kidney injury, have been infrequently reported, maintaining adequate hydration during administration is essential. In addition, transient elevations in serum uric acid levels were observed, warranting caution in patients with a history of gout.25

(2) Oral Sulfate Tablets: Mechanism, Efficacy, and Clinical Considerations

Oral sulfate tablets (OSTs) have been developed as a convenient, solid-form alternative to the traditional OSS- and PEG-based regimens. The conventional OST formulation has been approved by the US FDA. It contains a combination of sodium sulfate, potassium sulfate, and magnesium sulfate and exerts its bowel preparation effect via an osmotic mechanism by drawing water into the intestinal lumen. The tablets are administered using a split-dose regimen, requiring the ingestion of 14 large tablets with 1 liter of water on two occasions (28 tablets in total). Importantly, OSTs (Orafang; Pharmbio Korea Co.) contain simethicone, an anti-foaming agent that reduces intraluminal bubbles and enhances mucosal visibility during colonoscopy.26

OSTs have consistently demonstrated effective and reliable bowel preparation in various clinical settings. In a multicenter RCT, OSTs showed noninferior bowel preparation efficacy compared to the 2 L PEG plus ascorbate regimen. Moreover, OSTs achieved a significantly higher mean Boston Bowel Preparation Scale score (8.2 vs. 7.8, p=0.04) and a greater proportion of high-quality bowel preparation across all colonic segments.26 In a separate study comparing OSTs with the 1 L PEG plus ascorbate regimen, both regimens met the American Gastroenterological Association adequacy criteria (>95%), but OSTs exhibited a trend toward improved adenoma detection (59.6% vs. 41.9%) and significantly improved mucosal visibility as measured by the bubble score (p<0.001).27 In a large retrospective study (n=16,971), OST use was associated with a significantly higher adenoma detection rate compared to PEG-A use (34.5% vs. 30.7%, p<0.001), especially in the right colon (13.5% vs. 11.2%, p<0.001). Although nausea was more frequent with OSTs (3.08% vs. 1.47%), insufficient intake was less common, suggesting good overall tolerability.28

The safety profile of OSTs is consistently favorable across various patient populations. Among older adults (aged ≥70 years), OSTs not only resulted in significantly higher rates of high-quality bowel preparation (55.7% vs. 28.4%, p<0.001) and adenoma detection (54.8% vs. 35.3%, p=0.003), but also exhibited a favorable safety profile, with no serious adverse events reported.29 In patients with inflammatory bowel disease (IBD), OSTs have been shown to be both safe and effective, with no serious adverse events or disease exacerbations reported during the bowel preparation process.30 Similarly, in the setting of preoperative bowel preparation for CRC surgery, OST use did not increase the incidence of surgical site infections.31

Although OSTs have demonstrated consistent efficacy and an overall favorable safety profile across various clinical settings, recent reports have raised concerns about their potential to induce gastric mucosal injury. In a prospective study employing concurrent esophagogastroduodenoscopy, gastric erythema, edema, and hemorrhagic erosions were observed in 82% of patients who received OSTs, compared to 28% in those receiving OSS and 19% in patients who underwent PEG-based regimens (p<0.0001).32 These lesions primarily involved the greater curvature of the gastric body and occurred independently of non-steroidal anti-inflammatory drug use or Helicobacter pylori infection. Even though most patients were asymptomatic, some experienced epigastric discomfort or developed anemia. Ensuring adequate hydration and extending dosing intervals may help reduce mucosal irritation. Large-scale trials have not reported significant electrolyte abnormalities with OSTs; however, rare clinical cases of hyponatremia or neurological symptoms, such as confusion or seizure-like episodes, have been observed in real-world settings. Clinicians should accordingly monitor at-risk patients, especially older adults or those with baseline electrolyte disturbances.33

3) Sodium picosulfate and magnesium citrate

SPMC is a dual-action bowel preparation regimen that combines an osmotic laxative (magnesium citrate) with a stimulant laxative (sodium picosulfate). Sodium picosulfate is a prodrug metabolized by colonic bacteria into its active form, desacetyl bisacodyl, which stimulates colonic peristalsis. This combination achieves effective bowel preparation while maintaining a relatively low total fluid volume. The regimen typically consists of approximately 300 mL of reconstituted SPMC solution, followed by at least 2 L of additional clear fluids, resulting in a total fluid intake of approximately 2.5 to 3 L.

SPMC has demonstrated high bowel preparation efficacy and superior patient tolerability compared with high-volume PEG-based regimens. In a meta-analysis of 25 RCTs, SPMC showed noninferior bowel-cleansing efficacy compared to PEG, with a RR of 0.93 (95% CI, 0.86–1.01; p=0.07), retaining over 90% of PEG’s cleansing effectiveness. There were no significant differences in polyp detection rate (RR, 0.94; 95% CI, 0.82–1.08) or adenoma detection rate (RR, 0.88; 95% CI, 0.74–1.05) between the two groups. However, patient tolerability outcomes favored SPMC, with higher regimen completion rates (RR, 1.08; 95% CI, 1.04–1.13; p<0.001) and greater willingness to reuse the regimen (RR, 1.44; 95% CI, 1.25–1.67; p<0.001). The overall incidence of adverse events was significantly lower with SPMC (RR, 0.78; 95% CI, 0.66–0.93; p=0.004).34 In a more recent meta-analysis of 13 RCTs, SPMC demonstrated slightly superior bowel preparation efficacy compared to PEG (RR, 1.06; 95% CI, 1.02–1.11).35 SPMC was significantly better tolerated than PEG in most included trials, and no significant differences in bowel preparation efficacy or tolerability were observed between SPMC and sodium phosphate. Regarding specific adverse events, dizziness was more commonly reported with SPMC than with PEG (RR, 1.71; 95% CI, 1.32–2.21), while vomiting occurred less frequently with single-dose SPMC regimens than with split-dose regimens (RR, 0.35; 95% CI, 0.13–0.95). Several RCTs conducted in Korea compared SPMC with 2 L PEG plus ascorbate, demonstrating comparable bowel preparation efficacy but superior patient-reported outcomes in the SPMC group.36-38 In one study, SPMC was associated with a lower incidence of adverse effects, including nausea, vomiting, and abdominal discomfort (47.4% vs. 62.4%, p=0.031), as well as significantly higher tolerability ratings (92.1% vs. 83.4%, p=0.001).38 In addition, patients receiving SPMC consistently rated it more favorably in terms of taste and overall satisfaction compared with PEG-based regimens.

Despite its advantages, SPMC is not without safety concerns. Due to its hyperosmolar nature, it is contraindicated in patients with severe renal impairment, CHF, or hypermagnesemia.39 While serum magnesium levels typically normalize rapidly in individuals with normal renal function, hyponatremia has been reported in older adults, with an absolute risk increase of 0.05% and a RR of 2.4 (95% CI, 1.5–3.9).40 In rare cases, improper dissolution of powdered SPMC formulations has resulted in esophageal or gastric injury, highlighting the importance of adequate reconstitution and ingestion with sufficient fluids.41 The introduction of ready-to-drink liquid formulations has mitigated this risk and enhanced ease of administration.42

SUMMARY OF MECHANISM-BASED REGIMENS

Modern bowel preparation regimens, including PEG-based solutions (high-, low-, and ultra-low-volume), OSS, OST, and SPMC, have shown variable efficacy, tolerability, and safety across populations. Low- and ultra-low-volume PEG with ascorbate and OST demonstrated favorable patient adherence. OSS and SPMC are equally effective, but require caution in patients with renal or cardiac comorbidities. Understanding the unique mechanisms and safety profiles of each agent is essential for tailoring regimens for individual patients.

CLINICAL CONSIDERATIONS AND PATIENT-FOCUSED SELECTION

The expanding range of available bowel preparation options allows clinicians to individualize regimens based on each patient’s clinical characteristics, preferences, and risk factors. Contemporary clinical guidelines emphasize this patient-centered approach, acknowledging that personalized regimen selection enhances not only the efficacy of bowel preparation but also patient adherence and the overall success of colonoscopic procedures.

Efficacy versus tolerability

Although newer bowel preparation agents have demonstrated high efficacy in clinical trials, their real-world effectiveness is closely associated with patient tolerability and compliance. Adverse experiences during ingestion, such as nausea, vomiting, and abdominal discomfort, often determine whether a patient can complete the prescribed regimen. Therefore, clinicians should carefully evaluate prior patient experience with bowel preparation when selecting an appropriate regimen. For example, patients who have previously experienced nausea or vomiting with liquid purgatives may benefit from tablet-based formulations. Conversely, patients who have difficulty tolerating the total volume of traditional regimens may be better suited for ultra-low-volume options, such as 1 L PEG with ascorbate or low-volume picosulfate-based preparations.

Patient age and comorbidities

Age and comorbidities are important factors that influence both the safety and efficacy of bowel preparation regimens. Older adults, particularly those aged ≥70 years, are at increased risk for fluid and electrolyte disturbances, necessitating careful regimen selection. Therefore, SPMC should be used with caution in this population due to its potential to induce hyponatremia. In contrast, PEG-based preparations, particularly iso-osmotic 4 L PEG-ELS or low-volume PEG-electrolyte formulations, are generally regarded as safer alternatives for older adults.

Patients with significant comorbidities require special attention

In patients with chronic kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m²), hyperosmotic agents such as OSS and SPMC should be avoided due to the potential risks of electrolyte imbalance and dehydration. Iso-osmotic PEG-based regimens, particularly 4 L PEG-ELS, are considered the safest options for this population.

Patients with CHF are particularly vulnerable to fluid and electrolyte shifts. In this group, PEG-based regimens are the preferred option, whereas sulfate- or phosphate-containing agents should generally be avoided to minimize cardiovascular risk.

In patients with liver cirrhosis and ascites, bowel preparation can exacerbate fluid retention and disrupt serum electrolyte balance. PEG-ELS, which avoids abrupt osmotic shifts, is generally considered to be the safest option for this population.

Younger, medically stable individuals without significant comorbidities can generally tolerate any of the currently available bowel preparation regimens. In such cases, personal preferences, such as aversion to liquid formulations or difficulty swallowing tablets, can be prioritized to enhance compliance and overall patient satisfaction.

Specific contraindications and high-risk populations

Several clinical scenarios necessitate the avoidance of specific components in bowel preparation regimens: (1) Ascorbate-containing preparations are contraindicated in patients with G6PD deficiency owing to the risk of hemolytic anemia; (2) Flavored preparations that contain phenylalanine should be avoided in individuals with phenylketonuria; (3) Sulfate-based agents may elevate serum uric acid levels and are, therefore, suboptimal for patients with a history of gout; (4) Tablet-based regimens may be unsuitable for patients with dysphagia or those who have undergone bariatric or upper gastrointestinal surgery, due to concerns regarding gastric retention and excessive pill burden; (5) Although colonoscopy is rarely indicated during pregnancy, it may be necessary in certain clinical situations. In such cases, PEG-based regimens are considered the safest option; however, hyperosmotic or stimulant-containing agents should be avoided because of their potential for uterine stimulation and electrolyte imbalances; (6) Patients with IBD, particularly those with active disease, benefit from PEG-based regimens. OSTs have also been shown to be safe in this population, with no increased risk of flares. In patients with IBD, particularly during active disease, PEG-based preparations are preferred because of their gentle action, and OSTs have demonstrated safety without an increased risk of disease flares.

These contraindications underscore the importance of obtaining a comprehensive medical history before selecting an appropriate bowel preparation regimen.

In summary, the optimal bowel preparation selection should be guided by a comprehensive assessment of patient age, comorbidities, prior experience with bowel preparation, personal preferences, and risk factors for complications. By integrating these considerations, clinicians can tailor bowel preparation regimens for individual patients, thereby enhancing patient adherence and improving colonoscopic outcomes. Personalized preparation strategies not only optimize mucosal visualization and adenoma detection but also enhance safety and patient satisfaction. In the context of precision medicine and shared decision making, a patient-centered approach to bowel preparation has become a fundamental component of high-quality colonoscopic care (Table 3).

Table 3.

Patient-centered bowel preparation selection guide

Patient factors	Preferred regimen(s)	Agents not recommended
Age >70 years	PEG-ELS, PEG-ascorbate, OSS, OST	SPMC
Chronic kidney disease (eGFR <30 mL/min/1.73 m²)	PEG-ELS	OSS, OST, SPMC
Congestive heart failure	PEG-ELS	OSS, OST, SPMC
Liver cirrhosis with ascites	PEG-ELS	OSS, OST, SPMC
G6PD deficiency	PEG-ELS	PEG with ascorbate
History of gout	PEG-ELS, PEG-ascorbate, SPMC	OSS, OST
Dysphagia or post-bariatric surgery	PEG-ELS, PEG-ascorbate	OST
Pregnancy	PEG-ELS, PEG-ascorbatea), OSSa)	OST, SPMC
Active IBD	PEG-ELS, PEG-ascorbate, OSTa)	OSS, SPMC

PEG-ELS, polyethylene glycol-electrolyte lavage solution; PEG-ascorbate, polyethylene glycol combined with ascorbic acid; OSS, oral sulfate solution; OST, oral sulfate tablet; SPMC, sodium picosulfate with magnesium citrate; eGFR, estimated glomerular filtration rate; G6PD, glucose-6-phosphate dehydrogenase; IBD, inflammatory bowel disease.

^a)Agents to use with caution.

ROLE OF ADJUNCTIVE AGENTS

In addition to selecting the appropriate bowel preparation regimen, adjunctive agents play a complementary role in optimizing the bowel preparation quality and procedural outcomes. Among these, simethicone is the only adjunct, supported by moderate-quality evidence, particularly for reducing intraluminal foam and enhancing mucosal visibility. A meta-analysis and several RCTs have shown that adding simethicone to PEG-based regimens significantly improves bowel cleanliness, BBPS scores, and adenoma detection rates.43 While the optimal timing of administration remains inconclusive, earlier ingestion may shorten cecal intubation time and improve right-sided polyp detection rates.44 Other adjuncts, such as bisacodyl, lubiprostone, and mosapride, have shown limited or population-specific benefits, and dietary supplements like chewing gum or citrus extracts may enhance patient satisfaction without significantly improving bowel preparation efficacy.45-49 Based on current guidelines, the US Multi-Society Task Force conditionally recommends the adjunctive use of oral simethicone, whereas routine use of other agents is not advised due to inconsistent or low-quality evidence.6 Thus, while adjunctive agents can enhance the effectiveness and tolerability of bowel preparation, their use should be guided by patient characteristics, preparation regimen, and available evidence.

CONCLUSIONS

High-quality bowel preparation is a prerequisite for effective colonoscopy and plays a crucial role in the prevention of CRC. Over the past decade, low- and ultra-low-volume PEG-based solutions have significantly improved patient tolerability while maintaining effective bowel preparation. OSS and SPMC are effective alternatives for patients who cannot tolerate conventional preparations, although careful selection is warranted in the older adult or high-risk populations. Recently, the introduction of OSTs has improved patient convenience by addressing the discomfort associated with liquid-based regimens. OSTs have demonstrated better tolerability and more favorable cleansing outcomes than PEG-ascorbate, making it a valuable option for patients who struggle with large-volume preparations.

Each bowel preparation regimen has distinct advantages and limitations, highlighting the importance of individualized selection to ensure adherence and optimal mucosal visualization. The patient’s age, comorbidities, prior experience, and personal preferences should guide the choice of preparation. As bowel preparation strategies continue to evolve, clinicians must remain informed of the emerging evidence and adapt their practices accordingly. In the era of precision medicine, a patient-centered, evidence-based approach is essential for achieving optimal outcomes.