Advertisement

Should Oral Sodium Phosphate Solution Return as the First-Line Preparation for Colonoscopy?

Published:February 19, 2014DOI:https://doi.org/10.1016/j.cgh.2014.02.015
      Although cohort and case-control studies have shown that screening colonoscopy with polypectomy reduces colorectal cancer incidence and mortality (the latter by about 50%), gastroenterologists have been humbled to find that 1% to 9% of colon cancers represent so-called interval cancers, typically found within 3 years of a previous endoscopy.
      • Zauber A.G.
      • Winawer S.J.
      • O'Brien M.J.
      • et al.
      Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.
      • Lieberman D.
      Screening for colorectal cancer in individuals at average risk: current methods and emerging issues.
      • Cooper G.S.
      • Xu F.
      • Sloan J.S.B.
      • et al.
      Prevalence and predictors of interval colorectal cancers in Medicare beneficiaries.
      • Arain M.A.
      • Sawhney M.
      • Sheikh S.
      • et al.
      CIMP status of interval colon cancers: another piece to the puzzle.
      Interval colon cancers can result in malpractice actions against the endoscopist.
      • Rex D.K.
      Avoiding and defending malpractice suits for postcolonoscopy cancer: advice from an expert witness.
      They are much more likely to occur in the proximal colon, and many likely represent missed flat lesions. This has helped lead to one of the most important developments in gastroenterology in the past decade, namely improving the quality of screening and surveillance colonoscopy to ensure the detection and removal of all premalignant polyps, and to decrease the likelihood of developing interval cancer. Of key importance for quality colonoscopy is the necessity of careful withdrawal technique and the helpfulness of monitoring withdrawal times and adenoma detection rates. Technologic advances, such as high-definition colonoscopes, narrow-band imaging, chromoendoscopy, and colonoscopes with wider fields of view, also have helped in the detection of right-sided and flat lesions.
      However, there remains a key player to the effectiveness of colonoscopy as a cancer prevention tool, and that is the quality of bowel cleansing. Inadequate bowel preparations doom even the best colonoscopist and the best equipment. Conversely, high-quality bowel preparations achieve the following: (1) improve polyp detection (including more difficult to see flat lesions, generally in the right colon), (2) should help prevent right-sided cancers, and (3) will reduce the necessity of early repeat examinations. The US Multi-Society Task Force on Colorectal Cancer has defined an adequate bowel preparation as one capable of detecting polyps greater than 5 mm.
      Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.
      In recent years, all top practices have switched to the use of split-dose preparations, in which part of the preparation is given on the morning of the colonoscopy. Split-dose preparations improve colon cleansing and are better tolerated by patients.
      • Kilgore T.W.
      • Abdinoor A.A.
      • Szary N.M.
      • et al.
      Bowel preparation with split-dose polyethylene glycol before colonoscopy: a meta-analysis of randomized controlled trials.
      The issue of the best bowel preparation for colonoscopy is a matter of debate, study, and personal preference. Although we now have a smorgasbord of options, there is in fact no one best preparation, all have some limitations. At a Digestive Diseases Week lecture in 2011, Lawrence Cohen quoted an unknown patient, “If they can put a man on the moon, why can't they come up with a better bowel prep?” (unpublished data, 2011). The answer to this question is the difficulty of balancing the 3 main requirements of the ideal bowel preparation: quality of bowel cleansing, patient tolerability, and safety. Cost, as we will mention, is also a consideration.
      Throughout the 1980s, taking 4 L of polyethylene glycol (PEG)-electrolyte lavage solution on the evening before the examination was the dominant preparation. Unfortunately, many patients could not tolerate drinking this much fluid in a short time, felt sick, and could not complete their preparations. Low-volume colonoscopy preparations with a hyperosmolar oral sodium phosphate (OSP) solution came into use in the early 1990s.
      • Vanner S.J.
      • MacDonald P.H.
      • Paterson W.G.
      • et al.
      A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-based lavage solution (Golytely) in the preparation of patients for colonoscopy.
      Randomized controlled trials showed efficacy at least as good as PEG solutions with better tolerability. The OSP preparations initially used over-the-counter (OTC) agents, such as Fleet Phospho-Soda solution (C.B. Fleet Company, Inc, Lynchburg, VA), and were quite inexpensive. One common regimen was to give 2 doses of OSP solution, each mixed with at least 8 oz of water, one on the evening before the colonoscopy and the other on the morning of the examination. OSP preparations were avoided in elderly patients, patients with renal insufficiency, and in some other situations because of concerns about fluid and electrolyte shifts and nephrocalcinosis. Later, OSP preparations using 2 prescription drugs in tablet form, first Visicol and later OsmoPrep (Salix Pharmaceuticals, Raleigh, NC), became available (by the same manufacturer). However, Visicol contained microcrystalline cellulose (a tablet binder), which could deposit in the right colon and interfere with mucosal inspection. OsmoPrep was residue free.
      Task force from the American Society of Colon and Rectal Surgeons (ASCRS), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)
      A consensus document on bowel preparation before colonoscopy.
      Both products were vastly more expensive than OTC OSP solutions.
      OSP preparations (solution and pills) were in widespread use until December 2008 when the Food and Drug Administration (FDA) issued a warning and required new safety measures for OSP products. They had received reports of cases of acute kidney injury (AKI), as well as reports in the literature.

      FDA News Release December 11, 2008: FDA requires new safety measures for oral sodium phosphate products to reduce risk of acute kidney injury: risk associated with both prescription and over-the-counter products. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116988.htm. Accessed January 29, 2014.

      FDA Alert December 11, 2008: information for healthcare professionals: oral sodium phosphate products for bowel cleansing (marketed as Visicol and OsmoPrep, and oral sodium phosphate products available without a prescription). Available at: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm126084.htm. Accessed January 29, 2014.

      OSP preparations clearly are associated with transient hyperphosphatemia. Phosphate can bind, and in some patients precipitate with calcium, leading to dystrophic deposition in the kidneys and AKI. This can be irreversible, requiring dialysis in some cases. Several of the patients reported to the FDA underwent a kidney biopsy showing acute phosphate nephropathy. Milder degrees of renal impairment, such as a mild increase in the serum creatinine level or a mild decrease in the glomerular filtration rate, also has been seen.
      • Khurana A.
      • McLean L.
      • Atkinson S.
      • et al.
      The effect of oral sodium phosphate drug products on renal function in adults undergoing bowel endoscopy.
      Potential risk factors for adverse renal outcomes include underlying renal impairment, advanced age, diabetes, and certain drugs (eg, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, nonsteroidal anti-inflammatory drugs). Interestingly, a recent review of adverse drug reactions reported to the FDA suggested that adverse renal outcomes from OSP tablets are also more common in women with a mean body weight lower than the national average.
      • Ehrenpreis E.D.
      • Parakkal D.
      • Semer R.
      • et al.
      Renal risks of sodium phosphate tablets for colonoscopy preparation: a review of adverse drug reactions reported to the U.S. Food and Drug Administration.
      Therefore, in December 2008, the FDA required that the manufacturer of Visicol and OsmoPrep add a boxed warning to the labeling of these products. (Visicol was discontinued in 2012.) The FDA warned that OTC OSP products should not be used for colonoscopy bowel preparation. This led to the manufacturer of OTC Fleet Phospho-Soda solution and its packaged bowel preparation kits to immediately recall its products. OSP solution is no longer available. The FDA acknowledged at the time of the 2008 warning that although serious adverse events were rare, in some cases they “occurred in patients with no pre-existing health factors that would have put them at risk for developing kidney injury. We cannot rule out, however, that some of these patients were dehydrated prior to ingestion of OSP products, or they did not drink sufficient fluids after ingesting OSP products.”

      FDA News Release December 11, 2008: FDA requires new safety measures for oral sodium phosphate products to reduce risk of acute kidney injury: risk associated with both prescription and over-the-counter products. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116988.htm. Accessed January 29, 2014.

      The incidence of clinically important adverse renal outcomes has been difficult to quantify, both in the general population and in high-risk subgroups, because most of the serious problems have represented isolated case reports. Millions of patients have received OSP preparations. A systematic review and meta-analysis concluded that it was not possible to discern whether there was an association between OSP preparations and kidney injury based on the availability of trials.
      • Brunelli S.M.
      Association between oral sodium phosphate bowel preparations and kidney injury: a systematic review and meta-analysis.
      The study by Layton et al,
      • Layton J.B.
      • Klemmer P.J.
      • Christiansen C.F.
      • et al.
      Sodium phosphate does not increase risk for acute kidney injury after routine colonoscopy, compared with polyethylene glycol.
      published in this issue of Clinical Gastroenterology and Hepatology, represents an impressive attempt to better define the risk of AKI associated with OSP tablets compared with PEG for colonoscopy preparation. They conducted a large retrospective cohort study, using a US-based administrative claims database, of middle-aged and older adults undergoing outpatient colonoscopy from 2000 to 2008. OTC OSP preparations were not studied because the investigators could examine only prescription drug use. Besides examining the risk of AKI among OSP and PEG participants, they also looked at subgroups at high risk for AKI. The number of patients in the study was impressive: 121,266 received OSP pill preparations and 429,430 received PEG. Patients were followed up for 6 months for AKI, renal failure, and dialysis. The investigators found no increased risk of AKI in OSP pill users compared with PEG (0.2% vs 0.3%), and increased AKI was not seen in the high-risk clinical subgroups. The investigators acknowledged that the study of administrative claims for AKI outcomes may be an insensitive measure of renal dysfunction. For instance, they were not able to assess estimates of glomerular filtration rate or urinary biomarkers, which have a better ability to assess early or mild changes in renal function. The investigators also mentioned that the results of their study may not be able to be generalized to uninsured populations. Perhaps the latter populations have more difficulty following preparation instructions and maintaining as good hydration, thereby resulting in more AKI.
      Where does this leave us in 2014 regarding the role of OSP bowel preparations? For one thing, this well-done study helps to reassure us further that serious adverse renal effects from OSP preparations seem to be rare. We are less certain about the frequency of them causing mild long-term impairment in renal function. Prescription OsmoPrep is the option currently available. However, I do not believe that the time is here for OSP preparations to again become a first-line bowel preparation. OSP preparations still have a boxed warning and that is reason enough, and that is not likely to change in the near future. How much motivation there will be toward performing further studies of renal injury associated with OSP preparations is unclear. Healthy patients being considered for an OSP preparation should be told that they are generally safe, although they are not used in patients with renal impairment, kidney disease, or in the elderly. Patients also need to be given explicit instructions to maintain good hydration before and during the preparation, as well as after the procedure. The boxed warning states that other risk factors for AKI include the use of medications that affect rectal perfusion/function, including diuretics, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and possibly nonsteroidal anti-inflammatory drugs. Ideally, OSP preparations should not be used in these patients.
      Another downside of OSP pills is that they are quite expensive. Insurance companies do not always pay for OSP pill preparations, so in our practice we warn patients who want them that they are expensive if they must pay out of pocket. In writing this editorial, I priced a generic 4 L jug of PEG and 32 tablets of OsmoPrep at 3 major local pharmacies in Columbia, MO. The price for the PEG preparation ranged from $16 to $20. (Proprietary PEG preparations were more expensive.) The price for the OsmoPrep ranged from $150 to $186.
      Thankfully, we have figured out ways to make PEG preparations much more tolerable by using split dosing. Four-liter split-dose PEG preparations are relatively inexpensive and provide good colon cleansing in most patients.
      • Enestvedt B.K.
      • Tofani C.
      • Laine L.A.
      • et al.
      4-liter split-dose polyethylene glycol is superior to other bowel preparations, based on systematic review and meta-analysis.
      There is also no boxed warning regarding their use. In our practice, OSP pill preparations (OsmoPrep) serve more of a niche role. We use them in healthy individuals without risk factors who in the past either could not tolerate a split-dose PEG preparation or who refused them or some other fluid-based preparation. We also discuss prep costs with our patients.
      Gastroenterologists have made colonoscopy a better cancer prevention tool by using a better (and slower) withdrawal technique, by quality monitoring of our practices, and by demanding high-quality bowel preparations. The use of split-dose preparations certainly has helped to achieve good colon cleansing in most patients, although the search for even better preparations continues. Although OSP preparations are generally quite safe in healthy patients when hydration is maintained, there is little to suggest that they will return to their former glory days of the 1990s and early 2000s. Although expensive, OSP pill preparations can be helpful in select patients.

      References

        • Zauber A.G.
        • Winawer S.J.
        • O'Brien M.J.
        • et al.
        Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.
        N Engl J Med. 2012; 366: 687-696
        • Lieberman D.
        Screening for colorectal cancer in individuals at average risk: current methods and emerging issues.
        JAMA Intern Med. 2014; 174: 10-11
        • Cooper G.S.
        • Xu F.
        • Sloan J.S.B.
        • et al.
        Prevalence and predictors of interval colorectal cancers in Medicare beneficiaries.
        Cancer. 2012; 118: 3044-3052
        • Arain M.A.
        • Sawhney M.
        • Sheikh S.
        • et al.
        CIMP status of interval colon cancers: another piece to the puzzle.
        Am J Gastroenterol. 2010; 105: 1189-1195
        • Rex D.K.
        Avoiding and defending malpractice suits for postcolonoscopy cancer: advice from an expert witness.
        Clin Gastroenterol Hepatol. 2013; 11: 768-773
      1. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.
        Gastroenterology. 2012; 143: 844-857
        • Kilgore T.W.
        • Abdinoor A.A.
        • Szary N.M.
        • et al.
        Bowel preparation with split-dose polyethylene glycol before colonoscopy: a meta-analysis of randomized controlled trials.
        Gastrointest Endosc. 2011; 73: 1240-1245
        • Vanner S.J.
        • MacDonald P.H.
        • Paterson W.G.
        • et al.
        A randomized prospective trial comparing oral sodium phosphate with standard polyethylene glycol-based lavage solution (Golytely) in the preparation of patients for colonoscopy.
        Am J Gastroenterol. 1990; 85: 422-427
        • Task force from the American Society of Colon and Rectal Surgeons (ASCRS), the American Society for Gastrointestinal Endoscopy (ASGE), and the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES)
        A consensus document on bowel preparation before colonoscopy.
        Gastrointest Endosc. 2006; 63: 894-909
      2. FDA News Release December 11, 2008: FDA requires new safety measures for oral sodium phosphate products to reduce risk of acute kidney injury: risk associated with both prescription and over-the-counter products. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2008/ucm116988.htm. Accessed January 29, 2014.

      3. FDA Alert December 11, 2008: information for healthcare professionals: oral sodium phosphate products for bowel cleansing (marketed as Visicol and OsmoPrep, and oral sodium phosphate products available without a prescription). Available at: http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm126084.htm. Accessed January 29, 2014.

        • Khurana A.
        • McLean L.
        • Atkinson S.
        • et al.
        The effect of oral sodium phosphate drug products on renal function in adults undergoing bowel endoscopy.
        Arch Intern Med. 2008; 168: 593-597
        • Ehrenpreis E.D.
        • Parakkal D.
        • Semer R.
        • et al.
        Renal risks of sodium phosphate tablets for colonoscopy preparation: a review of adverse drug reactions reported to the U.S. Food and Drug Administration.
        Colorectal Dis. 2011; 13: e270-e275
        • Brunelli S.M.
        Association between oral sodium phosphate bowel preparations and kidney injury: a systematic review and meta-analysis.
        Am J Kidney Dis. 2009; 53: 448-456
        • Layton J.B.
        • Klemmer P.J.
        • Christiansen C.F.
        • et al.
        Sodium phosphate does not increase risk for acute kidney injury after routine colonoscopy, compared with polyethylene glycol.
        Clin Gastroenterol Hepatol. 2014; 12: 1514-1521
        • Enestvedt B.K.
        • Tofani C.
        • Laine L.A.
        • et al.
        4-liter split-dose polyethylene glycol is superior to other bowel preparations, based on systematic review and meta-analysis.
        Clin Gastroenterol Hepatol. 2012; 10: 1225-1231

      Linked Article

      • Sodium Phosphate Does Not Increase Risk for Acute Kidney Injury After Routine Colonoscopy, Compared With Polyethylene Glycol
        Clinical Gastroenterology and HepatologyVol. 12Issue 9
        • Preview
          Oral sodium phosphate (OSP) is a common bowel purgative administered before colonoscopy; the Food and Drug Administration has warned against its use because of concerns about acute kidney injury (AKI) from the absorbed phosphate and dystrophic calcification. However, it is not clear if OSP is associated with AKI in the general population or in high-risk subgroups undergoing colonoscopy. We estimated the risk of AKI among patients undergoing a screening colonoscopy using OSP vs polyethylene glycol (PEG) for bowel cleansing in a large, US-based claims database.
        • Full-Text
        • PDF