An estimated 134,490 new cases and 49,190 deaths due to colorectal cancer are expected through 2016 in the United States, ranking third in both incidence and mortality among all cancers in men and women (1). High-quality colonoscopy is considered the gold standard for the detection and prevention of colorectal cancer, and its efficacy is predicated on optimal colon cleansing (2, 3). Adequate bowel preparation enhances the detection of colonic lesions, minimizes the likelihood of a more technically difficult and prolonged procedure, and limits delays in diagnosis (4, 5).
The timing of bowel preparation administration significantly impacts the adequacy of preparation. Split-dose (SPD) regimens, defined as ingesting at least one half of the preparation on the day of the examination, improves colonic cleansing along with adenoma detection rates (6, 7, 8, 9). The US Multi-Society Task Force on Colorectal Cancer guidelines recommend SPD rather than single-dose (SID) regimens (10). However, many physician and patient barriers remain to the acceptance of SPD regimens including perceived patient inconvenience, with disruption in sleep and travel due to the timing of the second dose.
Surprisingly, there are little data regarding the impact of bowel preparation on the kinetics of bowel movements. Accurate bowel movement kinetic data regarding onset, duration, intensity, and cessation of bowel activity could provide evidence to dispel concerns regarding split dosing on patient inconvenience.
We compared bowel movement kinetics, sleep and travel disruption, bowel preparation quality, and polyp detection rates in patients randomly assigned to 2-L SPD vs. SID bowel preparation regimens.
Patients and study protocol
This study was approved by the Institutional Review Board. Patients scheduled for outpatient colonoscopy were recruited to participate. Enrolled patients were randomly assigned to a 2-L regimen of polyethylene glycol electrolyte lavage solution with ascorbic acid (PEG-ELS+asc; MoviPrep; Salix Pharmaceuticals, Raleigh, NC) either as an evening before single-dose (SID) or as a SPD regimen (half dose the evening before (SPD1) and half dose the day of the procedure (SPD2)). Only native English speakers were included. Patients unwilling or unable to follow the preparation instructions were excluded from participation.
Standardized bowel preparation instructions were provided in writing and reviewed with the patient by the study coordinator. Patients in the SID arm were instructed to begin bowel preparation at 1800 hours the evening before the procedure, consuming one-fourth of the liter every 15 min until completion. The second liter dose commenced at 1930 hours in a similar manner. Patients in the SPD group began their first dose between 1800 and 2000 hours, consuming one-fourth of the liter every 15 min until completion. The second liter was completed in a similar manner, beginning 4 h prior to the scheduled procedure.
Patients completed a survey during the bowel preparation process querying the duration of clear liquid diet, time required for preparation ingestion, and onset, duration, cessation, and subjective intensity of bowel movements every 15 min (on a scale of 1–10). The study coordinator advised the subjects that “Intensity” was their subjective global assessment regarding abdominal discomfort, number of bowel movements, and urgency of bowel activities. Additional questions assessed the tolerability of the bowel preparation, hours of sleep and number of awakenings for bowel activity, and travel time and number of stops for bowel movements en route to the endoscopy center. Demographic information and past medical history were also ascertained by patient report on the survey.
Endoscopists were blinded to the study arm assignment. The number, size, histology and location of polyps, and quality of colon cleansing as documented by the endoscopists’ usual clinical practice were obtained from pathology and colonoscopy reports.
A univariable analysis was performed to assess differences between SID and SPD groups; analysis of variance or the non-parametric Kruskal–Wallis tests were used to assess differences in continuous or ordinal variables and Pearson’s χ2-tests or Fisher’s exact tests were used for categorical factors. Polynomial regression with a quadratic fit was used to assess time pattern of bowel movement intensity across groups. Average intensity per time period was modeled as the outcome with group, time, and time squared as the independent predictor; the interaction between group and time was assessed. SAS (version 9.4, The SAS Institute, Cary, NC) was used for all analyses, and a P<0.05 was considered statistically significant.
A total of 341 patients with a mean age of 54 years were enrolled in the study, including 173 (51%) in the SPD arm and 168 (49%) in the SID arm. No significant difference was observed between groups regarding indication for procedure (data not shown), gender, or percentage of patients with any specific major comorbid diseases, except for cirrhosis of the liver (Table 1).
Timing of bowel preparation ingestion and bowel movement kinetics
Compared with patients in the SID arm, patients assigned to the SPD arm reported shorter intervals between the last ingestion of solid food (22.0 vs. 22.5 h; P=0.036), as well as the initiation of a clear liquid diet (11.0 vs. 12.0 h; P=0.007) and the start of bowel preparation (Table 2). The total duration of drinking the bowel preparation was also significantly shorter in the SPD regimen (1.8 h, 95% confidence interval (CI) 1.5–2.1 vs. 2.5 h, 95% CI 2.1–3.3; P<0.001). In the SPD arm, the average time between doses was 10.5 h (95% CI 9.0–11.5).
The time to onset of first bowel movement after the start of ingestion of bowel preparation was longer in SPD1 (P=0.019) and shorter in SPD2 (P<0.001) compared with the SID regimen (Figure 1). Ninety-one percent of patients began bowel movements within 60 min of drinking SPD2, compared with only 64% of patients after SID and 51% of SPD1. The average bowel movement intensity was significantly greater in the SID group than either dose of the split regimen (Figure 2, P<0.001). The peak intensity of the single dose and second dose of the split regimen occurred at ˜1 h, whereas the peak intensity of the first dose of the split regimen peaked slightly thereafter.
The proportion of patients achieving clear effluent after dosing was complete was 92% of SID patients, 66% of SPD1 patients (P<0.001), and 97% of SPD2 patients (P=0.028 vs. single dosing). The time to a clear effluent was not different between SID and SPD1 (P=0.23), with 31% and 38% not clear until after 120 min. Time to clear effluent was substantially shorter in SPD2 vs. single dosing (P<0.001), with 30% reporting clear effluent within 30 min. The time from the start of bowel preparation ingestion to the last bowel movement for the SID, SPD1, and SPD2 doses was 10 h, 5 h, and 3.3 h, respectively. When examining SPD1 and SPD2 together, the difference in time from preparation ingestion and last bowel movement between single and split dosing was not significant (SID: 10.0 h, 95% CI 5.5–13.0; SPD: 8.2 h, 95% CI 6.5–11.8; P=0.44; Supplementary Figure S1 online). However, the total duration of bowel movements was significantly greater in the SID regimen than in split dosing (9 h, 95% CI 4.6–12.1 vs. 6.7 h, 95% CI 4.7–9.7; P=0.041; Figure 3).
Patient inconvenience and preparation tolerability
Patients reported a shorter time between completion of bowel preparation and bedtime in single dosing compared with the evening dose of the split regimen (2.3 vs. 3.3 h; P<0.001; Table 3). More patients in the SID arm than the SPD arm woke up for bowel movements (66 vs. 49%, P<0.001), and there was a trend toward more nocturnal bowel movements in single dosing vs. SPD1 (P=0.087). Approximately 5% of patients in each arm stopped en route while driving to the endoscopy center for a bowel movement (P=0.63) and only one patient stopped twice (Table 4).
Patient satisfaction with bowel preparation regimen
SID preparation was reported to be more difficult to complete than SPD1 (5.0; CI 3.0–8.0 vs. 3.0; CI 1.0–7.0; P=0.001) but was not significantly different from SPD2 (P=0.13; Supplementary Figure S2). Patients endorsed less bloating and bad taste (P<0.001) after the second dose of the split regimen than after completion of SID preparation. No differences were noted in patient recommendations of regimen (P=0.35) or overall satisfaction (P=0.37) between the two study arms.
Bowel preparation quality and polyp detection
Thirty-two percent of patients in the SPD arm and 19% of patients in the SID arm underwent an afternoon colonoscopy (P<0.007; Table 5). The quality of bowel preparation was significantly better in the SPD arm (P<0.001), in spite of more patients in this arm undergoing afternoon exams (Figure 4). Excellent or good preparation was reported in 95.6 vs. 85.5% of split dosing vs. single dosing, respectively. Colonoscopy completion rates were similar with cecal intubation achieved in 98.8 and 99.4% in the SPD and SID regimens, respectively (P=0.87). There was no difference between arms in polyp or adenoma detection rate or in the location or size of polyps detected. Importantly, the sessile-serrated polyp detection rate (SSPDR) was significantly greater in the SPD arm than the SID arm (9.9 vs. 2.4%; P=0.004).
Our data detail bowel movement kinetics in response to low-volume bowel preparation. To our knowledge, our study is the first to provide this clinically relevant data. Moreover, we demonstrated important qualitative and quantitative differences between evening before SID and SPD regimens. Overall, nearly every parameter studied showed a significant benefit with the SPD regimen. This included fewer hours to complete the bowel preparation ingestion, longer hours between completing the evening dose of bowel preparation and bedtime, fewer patients waking up to move their bowels, decreased intensity of bowel movements, and no increase in the number of patients stopping during travel for bowel movements on the way to the endoscopy center. SPD preparation also provided improved colon cleansing over the evening before SID regimen and a fourfold increase in the SSPDR.
There are significant data in the literature demonstrating improved bowel preparation quality with SPD bowel preparation regimens in comparison with single dosing the evening before colonoscopy (6, 7, 11, 12, 13, 14). Correspondingly, numerous societies have published detailed guidelines endorsing SPD preparations (10, 15, 16, 17).
Bowel preparation regimens should not only effectively evacuate the colon for optimal visualization but should also minimize patient discomfort and inconvenience in order to optimize compliance (3, 15). Unfortunately, bowel preparation continues to be viewed by patients as the most unpleasant component of a colonoscopy. In two separate studies assessing deterrents for patients undergoing colonoscopy, reluctance to take the bowel preparation was cited by 41 and 66% of individuals, respectively (18, 19). In this context, many physicians may be reluctant to prescribe SPD bowel preparation regimens with the need for early morning second dose administration and concern regarding patient inconvenience during travel.
Although there are significant data emphasizing SPD bowel preparation and its association with bowel cleanliness, there are a very limited number of prior studies evaluating bowel kinetics following SPD regimens. One study did evaluate bowel activity after SPD sodium phosphate administration (since removed from the market due to safety concerns). In this analysis, bowel activity after the evening and morning doses continued for 4.6 h (CI 1–14) and 2.9 h (CI 0.5–6.5), respectively. However, no SID regimen was compared in this trial (20). Another study compared two versions of a combined bisacodyl (days 3 and 2 prior to procedure) and sodium picosulphate/magnesium citrate (PSLX) regimen. Two PSLX doses were dispensed as either (a) both during the evening prior to procedure or (b) as split dosing, half the evening before the procedure and half the morning of colonoscopy. For the evening/morning split dosing, bowel activity continued 9.6±4.6 h following the evening dose and 3.85±1.0 h after the morning dose. Information was limited for the group receiving dual evening doses, as the effects of the first administration were likely ongoing at the time of the second dose (5 h later) (21).
Our novel data provide evidence that fewer patients wake up for bowel movements during SPD bowel preparation compared with evening before SID preparation. Some patients ingesting a SPD regimen were required to wake up early to start their second dose of bowel preparation, particularly those few patients scheduled for early morning appointments. In spite of these few patients awakening early, those in the SPD group had less frequent nocturnal awakenings for bowel movements, and our data also showed a trend toward a longer period of continuous, uninterrupted sleep (5.0 h, 95% CI 3.8–6.5 vs. 4.5 h, 95% CI 3.0–6.0; P=0.18).
No differences were noted between study groups regarding the need to stop for a bowel movement during transportation to the procedure. This result supports the findings of one prior study that found no difference in travel disruptions between SPD 2-L PEG-ELS+asc and traditional evening before 4-L PEG-ELS (7).
Accurate information regarding onset, duration, and intensity of bowel activity along with sleep and travel disruptions in single- and split-dosed bowel preparation could prove to have a significant clinical benefit. Such knowledge provides a practical time frame for providers with which to counsel patients on expectations prior to the procedure. Specifically, our data demonstrate that >50% of patients had a bowel movement within 30 min of SPD2, and >50% achieved peak bowel movement intensity and reported a clear effluent within 60 min. The average time from finishing the preparation to the final bowel movement was 2.4 h in SPD2. Ninety-three percent of the SPD2 patients reported a travel time to our endoscopy center of <2 h. This duration of travel time to our tertiary referral center may not represent the typical travel time for patients undergoing colonoscopy in their local area, which is likely <1 h. Only one of our patients traveling <1 h needed to stop for a BM. In addition, the average subjective intensity of bowel movements dropped below 1 out of 10 within 2.5 h of beginning the bowel preparation. These facts lead us to suggest that patients begin SPD2 dosing 4 h prior to the procedure, leaving adequate time for transportation. This practice remains consistent with prior guidelines from the US Multi-Society Task Force on Colorectal Cancer, recommending SPD2 bowel preparation within 4–6 h of procedure time for optimal preparation quality (10).
An unexpected yet compelling finding was the substantial increase in SSPDR demonstrated in the SPD arm compared with the SID regimen. Prior studies have shown an association between split dosing and improvement in the adenoma detection rate, but ours appears to be the first prospective study to find an increase in SSPDR with a SPD regimen (8, 9). Although one retrospective study has suggested a proximal SSPDR goal of 5% for average risk people, well-established targets for serrated lesion detection are not established (22).
There are a few limitations to our study. For one, this was a single blind study, and the endoscopist could have been informed of the dosing regimen. In addition, the majority of the data were self-reported. The rating of the bowel preparation was according to the scale utilized by the individual physician in their clinical practice.
Our unique study provides additional compelling data that support the national recommendation of providing at least half of the bowel preparation on the day of the colonoscopy. We demonstrated a significant decrease in total bowel preparation ingestion time along with intensity and duration of bowel movements. Moreover, the SPD regimens were associated with less sleep disturbance and no difference in travel disruption compared with single dosing. Most importantly, split dosing resulted in a fourfold increase in the SSPDR, an important quality outcome.
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