Timing and frequency of bowel activity in patients ingesting sodium picosulphate/magnesium citrate and adjuvant bisacodyl for colon cleansing before colonoscopy

Gastrointestinal Diseases Research Unit, Kingston General Hospital, Queen’s University, Kingston, Ontario Correspondence: Dr Lawrence C Hookey, Hotel Dieu Hospital, 166 Brock Street, Kingston, Ontario K7L 5G2. Telephone 613-544-3310, fax 613-544-3114, e-mail hookeyl@hdh.kari.net Received for publication April 7, 2011. Accepted May 25, 2011 There is growing evidence that the efficacy of existing colon cleansing regimens can be significantly enhanced by adjusting the timing of the dosing of the preparation and combining the use of stimulant laxatives (1-5). For example, several studies suggest that the time interval from the final dose of a purgative to the start of the colonoscopy is very important to the efficacy of cleansing (4,6-9). These studies suggest that intervals of greater than 6 h to 12 h from the administration of the final dose of the cleansing agent, regardless of the preparation used, results in inferior cleansing. Thus, giving the final dose of a cleansing agent within approximately 6 h of the colonoscopy evaluation appears original arTicle

to provide superior colon cleansing.In addition to the timing factor, the use of stimulant laxatives, in combination with cleansing regimens, can also enhance the quality of the colon cleansing -at least in some studies.This has been most evident for the large-volume polyethylene glycol solutions (PEG) in which the ingestion of a stimulant laxative within 1 h to 2 h of taking the PEG solution enabled the volume of PEG preparations to be reduced without having a major effect on efficacy (10).More recently, we have shown that bisacodyl tablets (a stimulant laxative) given for two days before colon cleansing with sodium picosusulphate/magnesium citrate (Pico-Salax [PSLX], Ferring Pharmaceuticals Inc, Canada) also enhances the degree of colon cleansing (11).PSLX is a combination of sodium picosulphate (a stimulant laxative) and magnesium citrate (an osmotic laxative).The use of this regimen has subsequently become widespread in Canada.
To better understand and fully maximize the impact of components of a colon cleansing regimen, either through adjustment of timing or the addition of a stimulant laxative, it is essential to accurately evaluate the impact of these interventions.Understanding the colonic response to purgatives also has practical implications concerning sleep and travel time to the endoscopy suite.Surprisingly, little data are available in this regard with any of the available bowel preparations, including PSLX.Although Linden and Waye (12) examined the effects of sodium phosphate, including influence on transit and sleep, this agent has subsequently been withdrawn from the market.Hence, we undertook the current study in an effort to better document and understand the exact effects of the agents of PSLX combined with bisacodyl tablets over a three-day cleansing period.

MeTHodS
Patients were recruited from the outpatient gastroenterology clinics at Hotel Dieu Hospital (Kingston, Ontario).All of the patients' colonoscopies were ordered by their attending gastroenterologist for routine clinical indications.Exclusion criteria included the following: congestive heart failure; renal insufficiency (estimated glomerular filtration rate <90 mL/min); ileus or bowel obstruction; previous colorectal surgery; ascites; active inflammatory bowel disease; and recent (less than six months) myocardial infarction or unstable angina.All patients provided informed consent for the procedure; the study was approved by the Queen's University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (Kingston, Ontario).
All patients took PSLX combined with bisacodyl for colon cleansing.They were instructed to take one 10 mg tablet of bisacodyl at 18:00 for two consecutive nights before taking the PSLX (days three and two precolonoscopy).Patients were instructed to avoid seeds and high-fibre products for five days before examination followed by a clear fluid diet the day before colonoscopy.Patients were encouraged to drink 4 L of a carbohydrate electrolyte sports drink solution (Gatorade [QTG, Canada] or equivalent) during the day of clear fluids and continue this up until the time they left their residence for their procedure (13).The timing of PSLX ingestion was adjusted according to the scheduled time of colonoscopy.Traditional dosing regimen: Patients whose colonoscopy was scheduled before 11:00 were asked to take one dose of PSLX at 17:00 and the second dose at 22:00 the evening before colonoscopy.Spilt-dosing regimen: Patients whose colonoscopies were scheduled after 11:00 were asked to take one dose at 19:00 the evening before colonoscopy and the second dose at 06:00 on the day of colonoscopy.
These two groups were analyzed separately because, when taken in the evening, the second dose of PSLX would potentially alter or confound the effects of the first dose.
In addition to these instructions, patients were given a diary to record the study data.This included their average bowel movement frequency in the week before starting the bowel preparation, the time at which each preparation medication was taken, the time of each subsequent bowel movement, and the total amount of sports drink and overall fluids consumed starting the day before colonoscopy.
Patients underwent colonoscopy by one of eight gastroenterologists who then rated the quality of the bowel preparation using the Ottawa Bowel Preparation Scale score (14) and the Aronchick score (15).These gastroenterologists had undergone training to ensure consistency when evaluating the quality of colon cleansing (16).

Statistics
Descriptive statistics with means and SD, or medians with ranges are used to describe data, depending on the distribution.The mean number of bowel movements produced by each component of the cleansing regimen was compared with baseline using paired t tests, with the patients serving as their own controls.Subgroup analysis was planned for comparison based on whether the patients took both doses of PSLX the evening before colonoscopy or one in the evening and one in the morning of the colonoscopy.Analysis was performed using the c 2 test, Mann Whitney test or Student's t test, as appropriate.Pearson correlation coefficients (r) were used to further assess whether the number of bowel movements from both doses of bisacodyl and the entire preparation related to the quality of the bowel cleansing assessed by the Ottawa Bowel Preparation Scale.One hundred patients were enrolled to allow for adequate distribution of responses and description of mechanism results.Subgroup analyses were performed as exploratory tests; however, the study was not necessarily powered to assess these questions directly.The data are presented as mean ± SD.

reSuLTS
One hundred patients (42 men) with a mean age of 60.2 years (range 19 to 82 years) participated in the present study.Only four patients met the constipation criteria of <3 spontaneous bowel movements per week.Patients ingested a mean of 4.9 L (range 1 L to 17 L) of clear fluids including a mean of 1.5 L (range 0 L to 5.25 L) of sports drink the day before colonoscopy.Five patients underwent incomplete colonoscopies: four due to abdominal discomfort and one due to a poor preparation and a sigmoid stricture, which was subsequently surgically resected.

Comparison of the effect on the frequency of bowel movements for each purgative component
The mean baseline number of bowel movements per day in the seven days before commencing the cleansing regimen was 1.7±1.1.Compared with this baseline number of bowel movements per day, the addition of bisacodyl resulted in a significant increase in the number of bowel movements on each day it was taken, with means of 3.3±2 and 3.8±2.2bowel movements on days 3 and 2 precolonoscopy, respectively (P<0.05) (Figure 1).Patients experienced a significantly greater number of bowel movements with each dose of PSLX when compared with baseline.The first dose resulted in a mean of 4.4±2.7 bowel movements.

Figure 1) Mean number of bowel movements stimulated by each component of the colon cleansing regimen compared with baseline. Pico-Salax, Ferring Pharmaceuticals Inc, Canada
Those taking a second dose the same night had a mean of 6.3±3.0 bowel movements, with those taking morning doses having 4.5±2.4bowel movements after each dose.

Comparison of the timing effect on bowel movements for each purgative component Bisacodyl:
The average time to the first bowel movement following the first dose of bisacodyl was 8.9±5 h, and the mean time to the final bowel movement was 16.5±5.1 h.The effect of the second bisacodyl dose exhibited a similar range (Table 1).evening PSLX dosing (n=68): The first dose of PSLX produced the first bowel movement at a mean of 1.5±1 h (range 0 h to 4 h) after ingestion.The final bowel movement occurred at a mean of 5.4±2.5 h (range 2 h to 14 h).

Split-dose PSLX (n=32):
The first dose produced the first bowel movement at a mean of 1.3±1.3h (range 0 h to 9 h) after ingestion, with the final bowel movement occurring at an average of 9.6±4.6 h (range 2 h to 13 h) after ingestion (Table 1).After the morning dose of PSLX, the first bowel motion occurred at 0.9±0.8h (range 0 h to 4 h), and the final at a mean of 3.9±1 h (range 2 h to 6 h) after ingesting the medication (Figure 2).

Comparison of the efficacy of colon cleansing in patients receiving PSLX the night before with those receiving a split dose
Previous studies examining the use of PSLX the night before colonoscopy (11) showed that the efficacy of colon cleansing was significantly lower in patients who underwent colonoscopy after 11:00.In the current study, patients who were booked for colonoscopy after 11:00 (n=32) were instructed to take their second dose of PSLX at 06:00 on the day of colonoscopy as opposed to the night before.In contrast to the previous findings, there was no difference in efficacy between the two groups, with total Ottawa Bowel Preparation Scale scores of 5.22±3.1 and 5.03±2.8for the evening dosing and split dosing, respectively (P=0.77).Similarly, no significant differences were seen between the groups using the Aronchick score (Figure 3).

relationship of bowel movement frequency and bowel cleansing quality
As the number of total bowel movements increased, the quality of the bowel cleansing, as indicated by a lower Ottawa Bowel Preparation Scale score, improved (r=0.481;P<0.001).The quality of bowel cleansing also correlated with the total number of bowel movements produced by both doses of bisacodyl (r=0.315;P=0.002).

diSCuSSion
The present study was the first to record the effects of bisacodyl and PSLX on bowel movement timing and frequency when these agents were used for colon cleansing.These data have important implications for understanding the role of each component.Both the adjuvant stimulant laxative bisacodyl and the PSLX resulted in a significantly greater number of bowel movements compared with each patient's baseline.The true effect of the second dose in the split-dose group may have been partially underestimated due to the fact that patients possibly underwent their procedure before all bowel activity had ceased.Moreover, it demonstrated how the timing of these components could be optimized to improve patient satisfaction and maximize the quality of the bowel preparation before colonoscopy.For instance, given the average of approximately 8 h between bisacodyl ingestion and onset of action, the doses could be taken earlier in the day to avoid disruption of sleep during the night.Our previous study had suggested that the addition of a stimulant laxative for two days before the ingestion of PSLX improved the quality of colon cleansing, but did not compromise patient tolerability of the preparation compared with those receiving PSLX alone (11).Although the mechanism of this effect was unclear, intuitively, we believed that it was the result of the additional laxative effect of the bisacodyl.The results of the current study document that bisacodyl significantly increases the number of bowel movements over baseline and demonstrates that the average magnitude of this effect is approximately double that of the patients' baseline bowel habit.We also showed that the total number of bowel movements produced by bisacodyl significantly correlated with the quality of bowel cleansing, confirming the role of the adjuvant stimulant in the regimen.The findings also have implications for the timing of this ingestion, implying that taking the pills either in the afternoon or at bedtime may have the least impact on interfering with the patients' sleep.Patients may wish to take the medication even earlier in the day, although this may impact on other activities such as work.
Although patients were not asked directly about sleep or travel disturbances, our results regarding the timing of the final bowel movements following the ingestion of the second doses of PSLX also have important implications for sleep if taken the night before colonoscopy or for travelling to the endoscopy suite, particularly if it involves considerable distances.Our data suggest that the second dose taken the night before will likely interrupt patients' sleep for most of the night, but will have little impact on driving to the endoscopy suite on the day of the colonoscopy.For patients who take the second dose in the morning, it appears that at least 4 h should be recommended before travelling to the endoscopy suite because the mean time to final bowel movement after the second dose was 3.9 h.

SuMMary
The present study clarifies the contribution of individual components of the bisacodyl and PSLX colon-cleansing regimen, and supports the rationale for their combined use.Moreover, it demonstrates that greater understanding of the effects of each component can help to guide instruction in their use, which can enhance patient satisfaction and the efficacy of the preparation.Additional studies are needed to better understand individual patient variables such as constipation or medication use.Additional details regarding specific sleep and travel inconveniences would also serve to enable the design of an efficacious preparation that has the minimum impact on quality of life.

ConFLiCTS oF inTereST:
Drs Vanner and Hookey have both received research funds and consulting fees from Ferring Canada in the past.This study however, was internally funded and investigator initiated, and Ferring Canada was not invovled in any way.

Figure 2 )
Figure 2) a to d Range of time from ingestion of the first and second dose of sodium picosusulphate/magnesium citrate (Pico-Salax [Ferring Pharmaceuticals Inc, Canada]) to the final bowel movement, demonstrated by dosing regimen used.Note that the effects of the first dose in the traditional regimen may be truncated by the ingestion of the second dose.Likewise, the effects of the second dose in the split-dose regimen may be truncated by the initiation of the procedure

Figure 3 )
Figure 3) Aronchick bowel preparation (Prep) scores for patients receiving sodium picosusulphate/magnesium citrate (Pico-Salax [Ferring Pharmaceuticals Inc, Canada]) the night before or the split dose (ie, night before and morning of procedure).vs Versus