Discussion
polyps, renal insufficiency
RECRUITMENT, RENAL INSUFFICIENCY, HYPOTONIC
Our prospective, non-blinded study of high doses of PEG (459 g to 612 g) and Gatorade given as part of a multi-step escalating extended cleansing protocol is the first to report the efficacy, tolerance and safety of any high-dose preparation for subjects whose colons were inadequately cleansed for a previous colonoscopy.Compared to historical control subjects who had no history of inadequate preparations who consumed standard doses of PEG (306 g to 357 g) and Gatorade, subjects had no significant difference in the colon cleanliness as measured by any of the bowel preparation scales including: (1) the Chicago BPS total score [Our definition of adequate cleansing (seeing 95% of the colonic mucosa after cleaning maneuvers) is better defined and sets a higher threshold than many other bowel preparation studies making our findings even more clinically relevant. It is important to note that the quality of the preparations was not just adequate but outstanding. All 10 subjects who used a Step 2 preparation (2.0 times the standard-dose of PEG) had perfect scores on the modified Chicago BPS and Boston BPS. Of the 59 subjects who used a Step 1 preparation (1.5 times the standard-dose of PEG): (1) 51 (86.4%) were not felt to require a higher dose of their bowel cleansing solutions for their next colonoscopy; and (2) 8 were felt to require a Step 2 preparation for their next colonoscopy including 5 (8.5%) who required extensive cleaning maneuvers to make their preparations adequate and 3 (4.3%) had inadequate preparations despite the cleaning maneuvers. Compared to historical controls, subjects had significantly more perfect Chicago BPS total scores of 36 (colons that needed no washing to visualize the mucosa).Another primary end point of this study was the safety of high doses of bowel cleansing preparations. The doses of PEG used as part of our Step 1 (459 g) and Step 2 (612 g) preparations are 1.5 to 2 times higher than our standard moderate split-dose of (306 g) PEG and Gatorade and 1.9 to 2.6 times higher than low doses (238 g to 255 g) of PEG and Gatorade. Unlike PEG-ELS, Gatorade is a hypotonic electrolyte solution (Table When the baseline BMPs were compared to the BMPs drawn as the IV was started and after subjects had consumed their preparation (Table Secondary endpoints of this study were tolerability and patient acceptance of high-dose bowel preparations. Including historical controls allowed us to compare the tolerance of high-dose preparations compared to standard dose preparations. The study preparations were well tolerated by all measures with subjects able to consume 98.9% of their high-dose cleansing solutions which was not significantly different than controls who consumed standard doses. Compared to controls, subjects had no significant increase in side effects, were just as willing to use the same preparation again for future colonoscopies, did not find the liquid more difficult to drink than their previous preparation, but did find the overall preparation more difficult.In order to understand the clinical relevance of studies such as this one that look at difficult to cleanse colons, it is necessary to understand the efficacy of the failed preparations and how selective the criteria were for inclusion. If the failed preparations were only 80% efficacious, then switching those with inadequate preparations to a standard preparation that is 98% efficacious would be expected to cleanse 90% of colons adequately (assuming the same patients would fail both preparations). Studies enrolling patients with a single prior borderline inadequate preparation would not be as informative as studies that enrolled subjects with multiple prior poor preparations.Two previous studies [In our study, 18 of 79 (22.8%) previous inadequate preparations (excluding the unknown ones) were given as a split-dose which might suggest that they were not highly efficacious. 85.5% of subjects had their last inadequate preparations in our clinic with all these colonoscopies performed since 2008. Since 2008, we have enrolled our patients in a series of 3 bowel preparation studies that documented the efficacy of the preparations we used during those eras. Before 2008, 4 L sulfate-free PEG-ELS given the day-prior was our standard preparation with a demonstrated efficacy of 94.5% [Our subjects were a very select group with very difficult to cleanse colons because: (1) most had already failed highly efficacious preparations; (2) over the past 12 years, patients with previous preparations that were borderline inadequate received 374 g of PEG and Gatorade given as a split-dose which seemed to work well and those who were successful with this preparation were ineligible to enroll in this study; and (3) 27.1% of subjects had 2 to 4 previous inadequate preparations.Subjects were significantly older than controls which was expected since they required a previous inadequate colonoscopy preparation to qualify for the study. Compared to controls, subjects were less likely to be undergoing a screening examination and more likely to have polyps found which suggests that a higher risk, more motivated group of patients chose to have a subsequent colonoscopy after an inadequate preparation.This study did not address the safety and efficacy of a Step 3 bowel preparation (2.5 times the standard-dose of PEG) since no subjects requiring this very high-dose preparation were seen during the recruitment period. Before this study began, we used protocols similar to Step 3 for a few patients who received PEG-ELS and MagCitrate. To date, we have not encountered a patient who had an inadequate Step 2 preparation (2.0 times the standard-dose of PEG). All our subjects used PEG and Gatorade as their bowel cleansing solutions; therefore, this study does not address the safety and efficacy of high doses of other bowel cleansing solutions.There were some limitations to this study. (1) The study was not a randomized trial and subjects might be more careful to follow any cleansing protocol after a previous inadequate preparation. (2) Only 7 patients with renal insufficiency were enrolled. (3) The study was not blinded. (4) Historical controls were used.