Best Practices for Split Dosing Bowel Preparation
Neal K Osborn, MD, MSc
Volume 5, December 23, 2011
Colorectal cancer (CRC) is the second leading cause of cancer-related death in the United States, irrespective of gender, and the third most common cancer in men and women,1 yet it is the most preventable cancer.2 More than 90% of all CRC cases can be prevented with routine colonoscopy, the “gold standard” for early detection and removal of polyps and precancerous lesions in average-risk adults starting at age 50.2 While routine screening of asymptomatic adults significantly decreases CRC deaths, and early stage CRC detection is associated with a 90% 5-year cancer survival rate,3 only about 50% of eligible people in the United States have been screened.2,4 Several studies suggest that this is in large part because patients have reservations about the bowel preparation regimen.3,5,6 Reports of abdominal pain, cramping, bloating, nausea, and vomiting are common.7
Of patients who are screened, approximately 26% have suboptimal bowel preparation, which can compromise CRC detection rates.4,8 More specifically, suboptimal bowel preparation can potentially result in prolonged procedure times, lower rates of cecal intubation, incomplete visualization of the colon, missed diagnoses, and a need for early repeat screening. The latter is typically associated with additional time off work for the patient and increased costs.3,7,9 Inadequate bowel cleansing is an important factor contributing to undetected polyps and CRC following a negative colonoscopy.10 Two large studies have demonstrated that thorough bowel preparation significantly improves detection rates of all adenomas, including those that are small and flat.4,8
In an effort to improve both the efficacy and tolerability of bowel preparation, the American College of Gastroenterology (ACG) recommends a split-dose regimen (also referred to as a 2-day or PM/AM regimen), where half of the bowel preparation is taken the night before the colonoscopy and the other half is taken the day of the procedure.7 This newsletter will discuss the benefits of split dosing and provide suggestions to help healthcare providers incorporate it into their practice.
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The concept of split dosing arose in response to concerns regarding impaired visualization of the colon during colonoscopy if bowel preparation occurs entirely the day prior to the procedure. When the last dose of a purgative is administered within 8 to 12 hours of a colonoscopy, stool is cleared from the colon, but mucus and chyme subsequently released from the small intestine may adhere to the cecum and right colon, making a thorough examination difficult (Figure 1).
A 
B 
Figure 1. Conventional PM-only dosing versus PM/AM split-dosed bowel preparations.
A) Cecum after PM-only dosing and B) cecum after PM/AM split dosing.7
A recent meta-analysis of randomized controlled trials comparing split-dosed polyethylene glycol (PEG) to single-day PEG determined that the latter significantly increased the number of satisfactory bowel preparations, as well as patients’ willingness to repeat the same preparation.11 In response to such studies, current ACG guidelines recommend that patients take the first purgative dose the evening prior to the colonoscopy and the second dose no more than 6 hours prior to the start of the procedure (Figure 2).
Figure 2. The PM/AM split-dosing regimen. NPO = nothing by mouth.
In addition to potentially increasing the proportion of satisfactory preparations, split dosing may help to improve patient compliance, decrease the number of preparation discontinuations, and increase the detection of flat lesions.11 It has also been proposed that split dosing may be safer than a regimen completely administered the day prior to the colonoscopy, since any concomitant electrolyte disturbances are less likely to become severe when the preparation is ingested over an increased amount of time.12
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In spite of its benefits, physicians may be hesitant to prescribe a split-dose regimen, often because of the assumption that patients will be unwilling to wake up early enough on the day of the procedure to take the second dose or will refuse because of concerns regarding urgency or incontinence on their way to the procedure. However, such concerns appear to be unfounded. For example, a study by Unger et al demonstrated that 85% of patients (N=300)13 were willing to get up during the night to take the second dose of their bowel preparation (Figure 3).14
Figure 3. A majority of patients are willing to rise early to take the second dose of the preparation in a survey.14 Survey participants included endoscopy patients and drivers of colonoscopy patients.
Other research has determined that the rate of incontinence and the percentage of patients who need to stop en route to a colonoscopy was the same whether a single-day or split-dose preparation was used.13,15 A study also found that, when compared to patients who used a single-dose purgative, a higher percentage of patients who used a split dose were satisfied with the preparation and reported no or minimal difficulty in completing the regimen (Figure 4).13
Figure 4. Patients report less difficulty and greater satisfaction with PM/AM split dosing.13
When prescribing a split-dosed preparation, patient education is critical, and nurses can play a pivotal role.16 For example, in a prospective, randomized, controlled study, the rate of failed preparations fell from 26% to 4% when a patient education session conducted by a departmental nurse accompanied bowel preparation prescription.17 Many endoscopy centers provide some sort of patient education when scheduling an individual for a colonoscopy. While such education typically focuses on describing the procedure, possible adverse affects, and preparation instructions, it is important to also discuss the positive impact that successful, thorough bowel preparation can have on colonoscopy success.
It is also important to ensure that all clinic staff members understand the importance of split dosing. Because nurses and assistants are at the front line, their opinions will matter to patients. They must be able to anticipate the concerns and reservations that patients may express and be ready to respond in a manner that is reassuring, yet firm. For example, for patients who are unwilling to wake up early for the second half of their split dose, staff can offer to schedule the colonoscopy appointment later in the day. Interestingly, in our office, we find that we receive fewer phone calls from patients who split their bowel preparation dose than we receive from patients who take the full dose on the day prior to the procedure. This is likely due to the fact that patients experience less discomfort with split dosing due to the lower fluid volume.
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Physicians may also be hesitant to prescribe a split-dose regimen because of concern that the second dose violates the American Society of Anesthesiologists (ASA) preprocedure fasting guidelines related to aspiration risk. Many healthcare professionals believe that a patient undergoing anesthesia should have nothing by mouth after midnight the day prior to the procedure. However, ASA guidelines support a minimum fasting period of 2 hours for clear liquids and 6 hours for light meals prior to sedation (Table).18
These guidelines are based on a meta-analysis of randomized controlled trials demonstrating that gastric volume was smaller in patients who had been allowed clear liquids up to 2 hours before anesthesia than in patients who were required to fast longer. Similarly, in a study of upper endoscopy and/or colonoscopy in 712 patients, there was no significant difference in mean residual gastric volumes between patients receiving a split-dosed bowel preparation and those receiving a single-dose preparation administered the night prior to the procedure.19 Finally, an evidence-based review by the American College of Emergency Physicians concluded that “recent food intake is not a contraindication for administration of procedural sedation and analgesia, but should be considered in choosing the timing and target level of sedation.”20
This can be a difficult topic for gastroenterologists and anesthesiologists to discuss, since each group has its own views on the topic and concerns for the patient. The best approach is to first meet with your anesthesia support team and confirm that they understand that you and your staff are committed to split dosing and that it is in the patients’ best interests. It is important to reach an agreement on an acceptable cutoff time for patients to complete their preparation regimen prior to anesthesia. Many anesthesiologists personally do not support the ASA guidelines, so it is critical for there to be a consensus among the entire anesthesia support staff to abide by the approved cutoff time, with the understanding that there may be case-by-case situations where a patient may not safely undergo sedation.
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Colonoscopy is the “gold standard” for CRC screening, but its accuracy depends on thorough bowel preparation, which is significantly enhanced by split dosing the preprocedure purgative. In addition to improving the quality of bowel preparation, split dosing may increase patients’ satisfaction with the bowel preparation process. Patients and anesthesiologists may express reservations regarding a PM/AM regimen, but educating both groups about its benefits, as well as confirming that the anesthesiology team is familiar with current ACG and ASA guidelines, can help address such concerns and improve colonoscopy efficacy.
If you found this article interesting, you may also be interested in previous issues of The GI Digest newsletter:
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| About the author |
 |  Neal K Osborn, MD, MSc Dr Osborn is the medical director of the Hemorrhoid Clinic at Atlanta Gastroenterology Associates. He is a summa cum laude graduate of Creighton University in Omaha, NE, where he also attended medical school. Following his internship and residency in internal medicine at the Mayo Clinic in Scottsdale, AZ, he completed a fellowship in gastroenterology and hepatology at the Mayo Clinic in Rochester, MN. While in Rochester, Dr Osborn earned a master's degree in clinical science and research with a specialty concentration in noninvasive methods of colon cancer screening in average-risk patients and inflammatory bowel disease. He is a member of the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. |
| About the author |
|  Neal K Osborn, MD, MSc Dr Osborn is the medical director of the Hemorrhoid Clinic at Atlanta Gastroenterology Associates. He is a summa cum laude graduate of Creighton University in Omaha, NE, where he also attended medical school. Following his internship and residency in internal medicine at the Mayo Clinic in Scottsdale, AZ, he completed a fellowship in gastroenterology and hepatology at the Mayo Clinic in Rochester, MN. While in Rochester, Dr Osborn earned a master's degree in clinical science and research with a specialty concentration in noninvasive methods of colon cancer screening in average-risk patients and inflammatory bowel disease. He is a member of the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. |
| About the author |
|  Neal K Osborn, MD, MSc Dr Osborn is the medical director of the Hemorrhoid Clinic at Atlanta Gastroenterology Associates. He is a summa cum laude graduate of Creighton University in Omaha, NE, where he also attended medical school. Following his internship and residency in internal medicine at the Mayo Clinic in Scottsdale, AZ, he completed a fellowship in gastroenterology and hepatology at the Mayo Clinic in Rochester, MN. While in Rochester, Dr Osborn earned a master's degree in clinical science and research with a specialty concentration in noninvasive methods of colon cancer screening in average-risk patients and inflammatory bowel disease. He is a member of the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. |
Important Safety Information about MOVIPREP
MOVIPREP® (PEG-3350, sodium sulfate, sodium chloride, potassium chloride, sodium ascorbate and ascorbic acid for oral solution) is an osmotic laxative indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. MOVIPREP is contraindicated in patients with gastrointestinal (GI) obstruction, bowel perforation, gastric retention, ileus, toxic colitis or toxic megacolon, and patients who have had a severe hypersensitivity reaction to any of its components. MOVIPREP should be used with caution in patients at risk of or with fluid and electrolyte abnormalities, hyponatremia, arrhythmias, seizures, in patients with impaired renal function or patients taking concomitant medications that affect renal function, patients with known or suspected inflammatory bowel disease, patients with suspected GI obstruction or perforation, patients at risk for aspiration, and patients with glucose-6-phosphate dehydrogenase deficiency. Most common adverse reactions for split dosing (incidence ≥ 5%) are malaise, nausea, abdominal pain, vomiting, and upper abdominal pain. The most common adverse reactions for evening only dosing (incidence ≥ 5%) are abdominal distension, anal discomfort, thirst, nausea, abdominal pain, sleep disorder, rigors, hunger, malaise, vomiting, and dizziness. MOVIPREP contains 233 mg of phenylalanine per treatment. Advise patients to hydrate adequately before, during, and after the use of MOVIPREP.
For complete Prescribing Information.
Important Safety Information about OSMOPREP
There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long–term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti–inflammatory drugs [NSAIDs]).
It is important to use the dose and dosing regimen as recommended (PM/AM split dose).
OSMOPREP® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. Considerable caution should be advised before OSMOPREP is used in patients with severe renal insufficiency, congestive heart failure, ascites, unstable angina, gastric retention, ileus, severe chronic constipation, bowel perforation, toxic megacolon, gastric bypass or stapling surgery, or hypomotility syndrome. Use with caution in patients with impaired renal function, patients with a history of seizures or at higher risk of seizure, patients with higher risk of cardiac arrhythmias, known or suspected electrolyte disturbances (such as dehydration), or people taking drugs that affect electrolyte levels. Patients with electrolyte abnormalities such as hypernatremia, hyperphosphatemia, hypokalemia, or hypocalcemia should have their electrolytes corrected before treatment with OSMOPREP.
OSMOPREP is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients, and in patients with biopsy–proven acute phosphate nephropathy. In clinical trials, the most commonly reported adverse reactions (reporting frequency >3%) were abdominal bloating, nausea, abdominal pain, and vomiting. It is recommended that patients receiving OSMOPREP be advised to adequately hydrate before, during, and after the use of OsmoPrep.
For complete Prescribing Information for OSMOPREP including BOXED WARNING.
Important Safety Information about VISICOL
There have been rare, but serious reports of acute phosphate nephropathy in patients who received oral sodium phosphate products for colon cleansing prior to colonoscopy. Some cases have resulted in permanent impairment of renal function and some patients required long-term dialysis. While some cases have occurred in patients without identifiable risk factors, patients at increased risk of acute phosphate nephropathy may include those with increased age, hypovolemia, increased bowel transit time (such as bowel obstruction), active colitis, or baseline kidney disease, and those using medicines that affect renal perfusion or function (such as diuretics, angiotensin converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], and possibly nonsteroidal anti-inflammatory drugs [NSAIDs]).
It is important to use the dose and dosing regimen as recommended (PM/AM split dose).
VISICOL® (sodium phosphate monobasic monohydrate, USP, and sodium phosphate dibasic anhydrous, USP) Tablets are indicated for cleansing of the colon as a preparation for colonoscopy in adults 18 years of age or older. VISICOL is not to be used in patients with congestive heart failure, ascites, unstable angina pectoris, gastric retention, ileus or acute obstruction or pseudo-obstruction, severe chronic constipation, bowel perforation, acute colitis, toxic megacolon, or hypomotility syndrome. Use with caution in patients with impaired renal function, pre-existing electrolyte disturbances, or people taking drugs that affect electrolyte levels. VISICOL is contraindicated in patients with a known allergy or hypersensitivity to sodium phosphate salts or any of its ingredients. In clinical trials, the most commonly observed (≥1%) adverse reactions occurring with use of VISICOL were generally transient and self-limited and included nausea, vomiting, abdominal bloating, abdominal pain, dizziness and headache.
Consult with your physician to see if this product is right for you.
Complete Prescribing Information for VISICOL, including BOXED WARNING
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1. U.S. Cancer Statistics Working Group. United States cancer statistics: 1999-2007 incidence and mortality web-based report. 2010. 2. Colorectal cancer screening. American Society for Gastrointestinal Endoscopy Web site. http://www.asge.org/Pressroomindex.aspx?id=552. Updated 2010. Accessed September 11, 2011. 3. Lichtenstein GR, Cohen LB, Uribarri J. Review article: Bowel preparation for colonoscopy—the importance of adequate hydration. Aliment Pharmacol Ther. 2007;26:633-641. 4. Harewood GC, Sharma VK, de Garmo P. Impact of colonoscopy preparation quality on detection of suspected colonic neoplasia. Gastrointest Endosc. 2003;58:76-79. 5. Harewood GC, Wiersema MJ, Melton LJ III. A prospective, controlled assessment of factors influencing acceptance of screening colonoscopy. Am J Gastroenterol. 2002;97:3186-3194. 6. Burke CA, Church JM. Enhancing the quality of colonoscopy: The importance of bowel purgatives. Gastrointest Endosc. 2007;66:565-573. 7. Cohen LB, Kastenberg DM, Mount DB, Safdi AV. Current issues in optimal bowel preparation: excerpts from a roundtable discussion among colon-cleansing experts. Gastroenterol Hepatol. 2009;5(suppl 20):1-11. 8. Froehlich F, Wietlisbach V, Gonvers JJ, Burnand B, Vader JP. Impact of colonic cleansing on quality and diagnostic yield of colonoscopy: The European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study. Gastrointest Endosc. 2005;61:378-384. 9. Cohen LB, Tennyson C. Bowel preparation for colonoscopy: maximizing efficacy, minimizing risk. Gastroenterol Endosc News. March 2010. 10. Rex DK. Maximizing detection of adenomas and cancers during colonoscopy. Am J Gastroenterol. 2006;101:2866-2877. 11. Kilgore TW, Abdinoor AA, Szary NM, et al. Bowel preparation with split-dose polyethylene glycol before colonoscopy: a meta-analysis of randomized controlled trials. Gastrointest Endosc. 2011;73:1240-1245. 12. Lasisi F, Rex DK. Improving protection against proximal colon cancer by colonoscopy. Expert Rev Gastroenterol Hepatol. 2011;5:745-754. 13. Khan MA, Piotrowski Z, Brown MD. Patient acceptance, convenience, and efficacy of single-dose versus split-dose colonoscopy bowel preparation. J Clin Gastroenterol. 2010;44:310-311. 14. Unger RZ, Amstutz SP, Seo DH, Huffman M, Rex DK. Willingness to undergo split-dose bowel preparation for colonoscopy and compliance with split-dose instructions. Dig Dis Sci. 2010;55:2030-2034. 15. Furman D, Young P, Cash B. Are we asking too much? Early morning split-dose bowel preparations: a survey of patients' experiences and opinions. Am J Gastroenterol. 2010;105(suppl 1):S149-S150. 16. Palma JD, Rex D. Advances in bowel preparations: new formulation and clinical results. Gastroenterol Nurs. 2011;34(suppl 2):S2-S8. 17. Abuksis G, Mor M, Segal N, et al. A patient education program is cost-effective for preventing failure of endoscopic procedures in a gastroenterology department. Am J Gastroenterol. 2001;96:1786-1790. 18. American Society of Anesthesiologists Committee. Practice guidelines for preoperative fasting and the use of pharmacologic agents to reduce the risk of pulmonary aspiration: Application to healthy patients undergoing elective procedures: An updated report by the American Society of Anesthesiologists Committee on Standards and Practice Parameters. Anesthesiology. 2011;114:495-511. 19. Huffman M, Unger RZ, Thatikonda C, Amstutz S, Rex DK. Split-dose bowel preparation for colonoscopy and residual gastric fluid volume: an observational study. Gastrointest Endosc. 2010;72:516-522. 20. Godwin SA, Caro DA, Wolf SJ, et al. Clinical policy: procedural sedation and analgesia in the emergency department. Ann Emerg Med. 2005;45:177-196.