Do adjuvants add to the efficacy and tolerance of bowel preparations? A meta-analysis of randomized trials

Abstract

Background and study aims Recommendations on adjuvant use with bowel preparations remain disparate. We performed a meta-analysis determining the clinical impact of adding an adjuvant to polyethylene glycol (PEG), sodium phosphate, picosulfate (PICO), or oral sulfate solutions (OSS)-based regimens.

Methods Systematic searches were made of MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials from January 1980 to April 2016 that assessed preparations with or without adjuvants, given in split and non-split dosing, and PEG high- (> 3 L) or low-dose (≤ 2 L) regimens. Bowel cleansing efficacy was the primary outcome. Secondary outcomes included patient willingness to repeat the procedure, and polyp and adenoma detection rates.

Results Of 3093 citations, 77 trials fulfilled the inclusion criteria. Overall, addition of an adjuvant compared with no adjuvant, irrespective of the type of preparation and mode of administration, yielded improvements in bowel cleanliness (odds ratio [OR] 1.23 [1.01 – 1.51]) without greater willingness to repeat (OR 1.40 [0.91 – 2.15]). Adjuvants combined with high-dose PEG significantly improved colon cleansing (OR 1.96 [1.32 – 2.94]). The odds for achieving adequate preparation with low-dose PEG with an adjuvant were not different to high-dose PEG alone (OR 0.95 [0.73 – 1.22]), but yielded improved tolerance (OR 3.22 [1.85 – 5.55]). However, split high-dose PEG yielded superior cleanliness to low-dose PEG with adjuvants (OR 2.53 [1.25 – 5.13]). No differences were noted for OSS and PICO comparisons, or for any products regarding polyp or adenoma detection rates.

Conclusions Critical heterogeneity precludes firm conclusion on the impact of adjuvants with existing bowel preparations. Additional research is required to better characterize the methods of administration and resulting roles of adjuvants in an era of split-dosing.

^* Both authors contributed equally.

• References

• 1 Connor A, Tolan D, Hughes S. et al. Consensus guidelines for the safe prescription and administration of oral bowel-cleansing agents. Gut 2012; 61: 1525-1532
• 2 Ness RM, Manam R, Hoen H. et al. Predictors of inadequate bowel preparation for colonoscopy. Am J Gastroenterol 2001; 96: 1797-1802
• 3 Belsey J, Crosta C, Epstein O. et al. Meta-analysis: the relative efficacy of oral bowel preparations for colonoscopy 1985–2010. Aliment Pharmacol Ther 2012; 35: 222-237
• 4 Hassan C, Bretthauer M, Kaminski MF. et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) guideline. Endoscopy 2013; 45: 142-150
• 5 Johnson DA, Barkun AN, Cohen LB. et al. Optimizing adequacy of bowel cleansing for colonoscopy: recommendations from the US multi-society task force on colorectal cancer. Gastroenterology 2014; 147: 903-924
• 6 Martel M, Barkun AN, Menard C. et al. Split-dose preparations are superior to day-before bowel cleansing regimens: a meta-analysis. Gastroenterology 2015; 149: 79-88
• 7 Tongprasert S, Sobhonslidsuk A, Rattanasiri S. Improving quality of colonoscopy by adding simethicone to sodium phosphate bowel preparation. World J Gastroenterol 2009; 15: 3032-3037
• 8 Dickersin K, Scherer R, Lefebvre C. Identifying relevant studies for systematic reviews. BMJ 1994; 309: 1286-1291
• 9 Hookey LC, Depew WT, Vanner S. The safety profile of oral sodium phosphate for colonic cleansing before colonoscopy in adults. Gastrointest Endosc 2002; 56: 895-902
• 10 Abdullah M, Rani AA, Fauzi A. et al. A randomized, controlled, double-blind trial of the adjunct use of Clebopride in polyethylene glycol electrolyte (PEG) solution for colonoscopy preparation. Acta medica Indonesiana 2010; 42: 27-30
• 11 Rostom A, Jolicoeur E. Validation of a new scale for the assessment of bowel preparation quality. Gastrointest Endosc 2004; 59: 482-486
• 12 Calderwood AH, Jacobson BC. Comprehensive validation of the Boston Bowel Preparation Scale. Gastrointest Endosc 2010; 72: 686-692
• 13 Lai EJ, Calderwood AH, Doros G. et al. The Boston bowel preparation scale: a valid and reliable instrument for colonoscopy-oriented research. Gastrointest Endosc 2009; 69: 620-625
• 14 Halphen M, Heresbach D, Gruss HJ. et al. Validation of the Harefield Cleansing Scale: a tool for the evaluation of bowel cleansing quality in both research and clinical practice. Gastrointest Endosc 2013; 78: 121-131
• 15 Aronchick C, Lipshutz W, Wright S. et al. Validation of an instrument to assess colon cleansing [abstract]. Am J Gastroenterol 1999; 94: 2667
• 16 Martinek J, Hess J, Delarive J. et al. Cisapride does not improve precolonoscopy bowel preparation with either sodium phosphate or polyethylene glycol electrolyte lavage. Gastrointest Endosc 2001; 54: 180-185
• 17 Sudduth RH, DeAngelis S, Sherman KE. et al. The effectiveness of simethicone in improving visibility during colonoscopy when given with a sodium phosphate solution: a double-bind randomized study. Gastrointest Endosc 1995; 42: 413-415
• 18 McNally PR, Maydonovitch CL, Wong RK. The effectiveness of simethicone in improving visibility during colonoscopy: a double-blind randomized study. Gastrointest Endosc 1988; 34: 255-258
• 19 Corporaal S, Kleibeuker JH, Koornstra JJ. Low-volume PEG plus ascorbic acid versus high-volume PEG as bowel preparation for colonoscopy. Scand J Gastroenterol 2010; 45: 1380-1386
• 20 Di Palma JA, Rodriguez R, McGowan J. et al. A randomized clinical study evaluating the safety and efficacy of a new, reduced-volume, oral sulfate colon-cleansing preparation for colonoscopy. Am J Gastroenterol 2009; 104: 2275-2284
• 21 Bitoun A, Ponchon T, Barthet M. et al. Results of a prospective randomised multicentre controlled trial comparing a new 2-L ascorbic acid plus polyethylene glycol and electrolyte solution vs. sodium phosphate solution in patients undergoing elective colonoscopy. Aliment Pharmacol Ther 2006; 24: 1631-1642
• 22 Ell C, Fischbach W, Layer P. et al. Randomized, controlled trial of 2 L polyethylene glycol plus ascorbate components versus sodium phosphate for bowel cleansing prior to colonoscopy for cancer screening. Curr Med Res Opin 2014; 30: 2493-2503
• 23 Haas S, Andersen LM, Sommer T. Randomized controlled trial comparing Moviprep^® and Phosphoral^® as bowel cleansing agents in patients undergoing colonoscopy. Tech Coloproctol 2014; 18: 929-935
• 24 Jeon SR, Kim HG, Lee JS. et al. Randomized controlled trial of low-volume bowel preparation agents for colonic bowel preparation: 2-L polyethylene glycol with ascorbic acid versus sodium picosulfate with magnesium citrate. Int J Colorectal Dis 2015; 30: 251-258
• 25 Lee KJ, Park HJ, Kim HS. et al. Electrolyte changes after bowel preparation for colonoscopy: A randomized controlled multicenter trial. World J Gastroenterol 2015; 21: 3041-3048
• 26 Manes G, Amato A, Arena M. et al. Efficacy and acceptability of sodium picosulphate/magnesium citrate vs. low-volume PEG-ascorbic acid for colon cleansing: a randomized controlled trial. Colorectal Dis 2013; 15: 1145-1153
• 27 Marmo R, Rotondano G, Riccio G. et al. Effective bowel cleansing before colonoscopy: a randomized study of split-dosage versus non-split dosage regimens of high-volume versus low-volume polyethylene glycol solutions. Gastrointest Endosc 2010; 72: 313-320
• 28 Mathus-Vliegen EM, van der Vliet K. Safety, patientʼs tolerance, and efficacy of a 2-liter vitamin C-enriched macrogol bowel preparation: a randomized, endoscopist-blinded prospective comparison with a 4-liter macrogol solution. Dis Colon Rectum 2013; 56: 1002-1012
• 29 Worthington J, Thyssen M, Chapman G. et al. A randomised controlled trial of a new 2 litre polyethylene glycol solution versus sodium picosulphate + magnesium citrate solution for bowel cleansing prior to colonoscopy. Curr Med Res Opin 2008; 24: 481-488
• 30 Moon CM, Park DI, Choe YG. et al. Randomized trial of 2-L polyethylene glycol + ascorbic acid versus 4-L polyethylene glycol as bowel cleansing for colonoscopy in an optimal setting. J Gastroenterol Hepatol 2014; 29: 1223-1228
• 31 Ponchon T, Boustiere C, Heresbach D. et al. A low-volume polyethylene glycol plus ascorbate solution for bowel cleansing prior to colonoscopy: the NORMO randomised clinical trial. Dig Liver Dis 2013; 45: 820-826
• 32 Rivas JM, Perez A, Hernandez M. et al. Efficacy of morning-only 4 liter sulfa free polyethylene glycol vs. 2 liter polyethylene glycol with ascorbic acid for afternoon colonoscopy. World J Gastroenterol 2014; 20: 10620-10627
• 33 Sahebally SM, Burke JP, Chu S. et al. A randomized controlled trial comparing polyethylene glycol + ascorbic acid with sodium picosulphate + magnesium citrate solution for bowel cleansing prior to colonoscopy. Irish J Med Sci 2015; 184: 819-823
• 34 Valiante F, Pontone S, Hassan C. et al. A randomized controlled trial evaluating a new 2-L PEG solution plus ascorbic acid vs. 4-L PEG for bowel cleansing prior to colonoscopy. Dig Liver Dis 2012; 44: 224-227
• 35 Yoo IK, Lee JS, Chun HJ. et al. A randomized, prospective trial on efficacy and tolerability of low-volume bowel preparation methods for colonoscopy. Dig Liver Dis 2015; 47: 131-137
• 36 Hangartner PJ, Munch R, Meier J. et al. Comparison of three colon cleansing methods: Evaluation of a randomized clinical trial with 300 ambulatory patients. Endoscopy 1989; 21: 272-275
• 37 Park SS, Sinn DH, Kim Y-H. et al. Efficacy and tolerability of split-dose magnesium citrate: low-volume (2 liters) polyethylene glycol vs. single- or split-dose polyethylene glycol bowel preparation for morning colonoscopy. Am J Gastroenterol 2010; 105: 1319-1326
• 38 Samarasena JB, Muthusamy VR, Jamal MM. Split-dosed MiraLAX/Gatorade is an effective, safe, and tolerable option for bowel preparation in low-risk patients: A randomized controlled study. Am J Gastroenterol 2012; 107: 1036-1042
• 39 Sharara AI, Harb AH, Sarkis FS. et al. Split-dose menthol-enhanced PEG vs PEG-ascorbic acid for colonoscopy preparation. World J Gastroenterol 2015; 21: 1938-1944
• 40 DiPalma JA, Wolff BG, Meagher A. et al. Comparison of reduced volume versus four liters sulfate-free electrolyte lavage solutions for colonoscopy colon cleansing. Am J Gastroenterol 2003; 98: 2187-2191
• 41 Katz PO, Rex DK, Epstein M. et al. A dual-action, low-volume bowel cleanser administered the day before colonoscopy: Results from the SEE CLEAR II study. Am J Gastroenterol 2013; 108: 401-409
• 42 Rex DK, Katz PO, Bertiger G. et al. Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: The SEE CLEAR i study. Gastrointest Endosc 2013; 78: 132-141
• 43 El Sayed AM, Kanafani ZA, Mourad FH. et al. A randomized single-blind trial of whole versus split-dose polyethylene glycol-electrolyte solution for colonoscopy preparation. Gastrointest Endosc 2003; 58: 36-40
• 44 Johanson JF, Popp Jr. JW, Cohen LB. et al. A randomized, multicenter study comparing the safety and efficacy of sodium phosphate tablets with 2L polyethylene glycol solution plus bisacodyl tablets for colon cleansing. Am J Gastroenterol 2007; 102: 2238-2246
• 45 Malik P, Balaban DH, Thompson WO. et al. Randomized study comparing two regimens of oral sodium phosphates solution versus low-dose polyethylene glycol and bisacodyl. Dig Dis Sci 2009; 54: 833-841
• 46 Young CJ, Simpson RR, King DW. et al. Oral sodium phosphate solution is a superior colonoscopy preparation to polyethylene glycol with bisacodyl. Dis Colon Rectum 2000; 43: 1568-1571
• 47 Adams WJ, Meagher AP, Lubowski DZ. et al. Bisacodyl reduces the volume of polyethylene glycol solution required for bowel preparation. Dis Colon Rectum 1994; 37: 229-233 discussion 233–224
• 48 Brady 3rd CE, Dipalma JA, Beck DE. Effect of bisacodyl on gut lavage cleansing for colonoscopy. Ann Clin Res 1987; 19: 34-38
• 49 Clarkston WK, Smith OJ. The use of GoLYTELY and Dulcolax in combination in outpatient colonoscopy. J Clin Gastroenterol 1993; 17: 146-148
• 50 Gweon TG, Kim SW, Noh YS. et al. Prospective, randomized comparison of same-day dose of 2 different bowel cleanser for afternoon colonoscopy: picosulfate, magnesium oxide, and citric acid versus polyethylene glycol. Medicine 2015; 94: e628
• 51 Huppertz-Hauss G, Bretthauer M, Sauar J. et al. Polyethylene glycol versus sodium phosphate in bowel cleansing for colonoscopy: a randomized trial. Endoscopy 2005; 37: 537-541
• 52 Kim HG, Huh KC, Koo HS. et al. Sodium picosulfate with magnesium citrate (SPMC) plus laxative is a good alternative to conventional large volume polyethylene glycol in bowel preparation: a multicenter randomized single-blinded trial. Gut Liver 2015; 9: 494-501
• 53 Hookey LC, Depew WT, Vanner SJ. Combined low volume polyethylene glycol solution plus stimulant laxatives versus standard volume polyethylene glycol solution: a prospective, randomized study of colon cleansing before colonoscopy. Can J Gastroenterol 2006; 20: 101-105
• 54 Haapamaki MM, Lindstrom M, Sandzen B. Low-volume bowel preparation is inferior to standard 4 1 polyethylene glycol. Surg Endosc 2011; 25: 897-901
• 55 Schanz S, Kruis W, Mickisch O. et al. Bowel preparation for colonoscopy with sodium phosphate solution versus polyethylene glycol-based lavage: a multicenter trial. Diagn Ther Endosc 2008; 2008: 713521
• 56 Abdul-Baki H, Hashash JG, ElHajj II. et al. A randomized, controlled, double-blind trial of the adjunct use of tegaserod in whole-dose or split-dose polyethylene glycol electrolyte solution for colonoscopy preparation. Gastrointest Endosc 2008; 68: 294-300
• 57 Tasci I, Altinli E, Sirin F. Bowel cleansing for diagnostic colonoscopy: Which method is preferable? Istanbul experience. Tech Coloproctol 2003; 7: 18-21
• 58 Grigg E, Schubert MC, Hall J. et al. Lubiprostone used with polyethylene glycol in diabetic patients enhances colonoscopy preparation quality. World J Gastrointest Endosc 2010; 2: 263-267
• 59 Stengel JZ, Jones DP. Single-dose lubiprostone along with split-dose PEG solution without dietary restrictions for bowel cleansing prior to colonoscopy: a randomized, double-blind, placebo-controlled trial. Am J Gastroenterol 2008; 103: 2224-2230
• 60 Shaver WA, Storms P, Peterson WL. Improvement of oral colonic lavage with supplemental simethicone. Dig Dis Sci 1988; 33: 185-188
• 61 Cesaro P, Hassan C, Spada C. et al. A new low-volume isosmotic polyethylene glycol solution plus bisacodyl versus split-dose 4 L polyethylene glycol for bowel cleansing prior to colonoscopy: a randomised controlled trial. Dig Liver Dis 2013; 45: 23-27
• 62 de Leone A, Tamayo D, Fiori G. et al. Same-day 2-L PEG-citrate-simethicone plus bisacodyl vs split 4-L PEG: Bowel cleansing for late-morning colonoscopy. World J Gastrointest Endosc 2013; 5: 433-439
• 63 Saunders BP, Masaki T, Fukumoto M. et al. The quest for a more acceptable bowel preparation: Comparison of a polyethylene glycol/electrolyte solution and a mannitol/Picolax mixture for colonoscopy. Postgrad Med J 1995; 71: 476-479
• 64 Enestvedt BK, Fennerty MB, Eisen GM. Randomised clinical trial: MiraLAX vs. Golytely – a controlled study of efficacy and patient tolerability in bowel preparation for colonoscopy. Aliment Pharmacol Ther 2011; 33: 33-40
• 65 Gerard DP, Holden JL, Foster DB. et al. Randomized trial of gatorade/polyethylene glycol with or without bisacodyl and NuLYTELY for colonoscopy preparation. Clin Transl Gastroenterol 2012; 3: e16
• 66 Hookey LC, Depew WT, Vanner SJ. A prospective randomized trial comparing low-dose oral sodium phosphate plus stimulant laxatives with large volume polyethylene glycol solution for colon cleansing. Am J Gastroenterol 2004; 99: 2217-2222
• 67 Brady 3rd CE, DiPalma JA, Pierson WP. Golytely lavage – is metoclopramide necessary?. Am J Gastroenterol 1985; 80: 180-184
• 68 Kim HJ, Kim TO, Shin BC. et al. Efficacy of prokinetics with a split-dose of polyethylene glycol in bowel preparation for morning colonoscopy: a randomized controlled trial. Digestion 2012; 86: 194-200
• 69 Lee H, Kim YH, Kim JH. et al. A feasibility study of probiotics pretreatment as a bowel preparation for colonoscopy in constipated patients. Dig Dis Sci 2010; 55: 2344-2351
• 70 Tajika M, Niwa Y, Bhatia V. et al. Can mosapride citrate reduce the volume of lavage solution for colonoscopy preparation?. World J Gastroenterol 2013; 19: 727-735
• 71 Afridi SA, Barthel JS, King PD. et al. Prospective, randomized trial comparing a new sodium phosphate-bisacodyl regimen with conventional PEG-ES lavage for outpatient colonoscopy preparation. Gastrointest Endosc 1995; 41: 485-489
• 72 McKenna T, Macgill A, Porat G. et al. Colonoscopy preparation: polyethylene glycol with Gatorade is as safe and efficacious as four liters of polyethylene glycol with balanced electrolytes. Dig Dis Sci 2012; 57: 3098-3105
• 73 Sanaka MR, Super DM, Mullen KD. et al. Use of tegaserod along with polyethylene glycol electrolyte solution for colonoscopy bowel preparation: a prospective, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 2006; 23: 669-674
• 74 Lever EL, Walter MH, Condon SC. et al. Addition of enemas to oral lavage preparation for colonoscopy is not necessary. Gastrointest Endosc 1992; 38: 369-372
• 75 Chakravarty BJ, Fraser A, Hamilton I. et al. A randomised blinded study in colonic lavage for colonoscopy. Aus N Z J Med 1991; 21: 769-771
• 76 Kim MS, Park J, Park JH. et al. Does polyethylene glycol (PEG) plus ascorbic acid induce more mucosal injuries than split-dose 4-L PEG during bowel preparation?. Gut Liver 2016; 10: 237-243
• 77 Ker TS. Comparison of reduced volume versus four-liter electrolyte lavage solutions for colon cleansing. Am Surg 2006; 72: 909-911
• 78 Hookey LC, Vanner SJ. Pico-salax plus two-day bisacodyl is superior to pico-salax alone or oral sodium phosphate for colon cleansing before colonoscopy. Am J Gastroenterol 2009; 104: 703-709
• 79 Harrison NM, Hjelkrem MC. Bowel cleansing before colonoscopy: Balancing efficacy, safety, cost and patient tolerance. W J Gastroint Endosc 2016; 8: 4-12
• 80 Sharma VK, Chockalingham SK, Ugheoke EA. et al. Prospective, randomized, controlled comparison of the use of polyethylene glycol electrolyte lavage solution in four-liter versus two-liter volumes and pretreatment with either magnesium citrate or bisacodyl for colonoscopy preparation. Gastrointest Endosc 1998; 47: 167-171
• 81 Sofi AA, Nawras AT, Pai C. et al. Lubiprostone plus PEG electrolytes versus placebo plus PEG electrolytes for outpatient colonoscopy preparation: a randomized, double-blind placebo-controlled trial. Am J Ther 2015; 22: 105-110
• 82 McNally PR, Maydonovitch CL, Wong RK. The effect of simethicone on colonic visibility after night-prior colonic lavage. A double-blind randomized study. . J Clin Gastroenterol 1989; 11: 650-652
• 83 Reiser JR, Rosman AS, Rajendran SK. et al. The effects of cisapride on the quality and tolerance of colonic lavage: a double-blind randomized study. Gastrointest Endosc 1995; 41: 481-484
• 84 Katsinelos P, Pilpilidis I, Paroutoglou G. et al. The administration of cisapride as an adjuvant to PEG-electrolyte solution for colonic cleansing: a double-blind randomized study. Hepatogastroenterology 2005; 52: 441-443
• 85 Jansen SV, Goedhard JG, Winkens B. et al. Preparation before colonoscopy: a randomized controlled trial comparing different regimes. Eur J Gastroenterol Hepatol 2011; 23: 897-902
• 86 Abut E, Guveli H, Yasar B. et al. Administration of olive oil followed by a low volume of polyethylene glycol-electrolyte lavage solution improves patient satisfaction with right-side colonic cleansing over administration of the conventional volume of polyethylene glycol-electrolyte lavage solution for colonoscopy preparation. Gastrointest Endosc 2009; 70: 515-521
• 87 Kao D, Lalor E, Sandha G. et al. A randomized controlled trial of four precolonoscopy bowel cleansing regimens. Can J Gastroenterol 2011; 25: 657-662
• 88 Golub RW, Kerner BA, Wise Jr. WE. et al. Colonoscopic bowel preparations – which one? A blinded, prospective, randomized trial. Dis Colon Rectum 1995; 38: 594-599
• 89 Altman DG. Practical statistics for medical research. Boca Raton, Florida, USA: Chapman & Hall/CRC; 1999
• 90 Marshall JB, Pineda JJ, Barthel JS. et al. Prospective, randomized trial comparing sodium phosphate solution with polyethylene glycol-electrolyte lavage for colonoscopy preparation. Gastrointest Endosc 1993; 39: 631-634
• 91 Senore C, Ederle A, Fantin A. et al. Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting. J Med Screen 2011; 18: 128-134
• 92 Wexner SD, Beck DE, Baron TH. et al. A consensus document on bowel preparation before colonoscopy: prepared by a 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). Dis Colon Rectum 2006; 49: 792-809
• 93 Wu L, Cao Y, Liao C. et al. Systematic review and meta-analysis of randomized controlled trials of Simethicone for gastrointestinal endoscopic visibility. Scand J Gastroenterol 2011; 46: 227-235
• 94 Lazzaroni M, Petrillo M, Desideri S. et al. Efficacy and tolerability of polyethylene glycol-electrolyte lavage solution with and without simethicone in the preparation of patients with inflammatory bowel disease for colonoscopy. Aliment Pharmacol Ther 1993; 7: 655-659
• 95 Altintas E, Ucbilek E, Sezgin O. et al. Alverine citrate plus simethicone reduces cecal intubation time in colonoscopy - a randomized study. Turk J Gastroenterol 2008; 19: 174-179
• 96 Ofstead CL, Wetzler HP, Johnson EA. et al. Simethicone residue remains inside gastrointestinal endoscopes despite reprocessing. Am J Infect Control 2016; 44: 1237-1240
• 97 Clark RE, Godfrey JD, Choudhary A. et al. Low-volume polyethylene glycol and bisacodyl for bowel preparation prior to colonoscopy: a meta-analysis. Ann Gastroenterol 2013; 26: 319-324
• 98 Godfrey JD, Clark CR, Choudhary A. et al. Ascorbic acid and low-volume polyethylene glycol for bowel preparation prior to colonoscopy: A meta-analysis. W J Meta-Anal 2013; 1: 10-15
• 99 Xie Q, Chen L, Zhao F. et al. A meta-analysis of randomized controlled trials of low-volume polyethylene glycol plus ascorbic acid versus standard-volume polyethylene glycol solution as bowel preparations for colonoscopy. PLoS One 2014; 9: e99092
• 100 Ell C, Fischbach W, Bronisch HJ. et al. Randomized trial of low-volume PEG solution versus standard PEG + electrolytes for bowel cleansing before colonoscopy. Am J Gastroenterol 2008; 103: 883-893