Volume of fluid consumption during preparation for colonoscopy is possibly the single most important determinant of bowel preparation adequacy

Introduction

The efficacy and safety of colonoscopy is highly dependent on the adequacy of bowel preparation [1-3]. Inadequate bowel preparation (IBP) is associated with lower detection rates of both benign and malignant lesions, longer procedure times and a more frequent need for a repeat procedure, with a resulting loss of work days, additional colonoscopic procedural risk to the patient and greater cost [3-6]. The rate of IBP varies among multiple studies, ranging from 5-67%. A recently published, large-scale meta-analysis showed a calculated IBP rate of 19.9% [7]; therefore, improvement in preparation adequacy rate is crucial.

Previous studies have identified multiple risk factors associated with IBP [8-12]: e.g. sex and older age are weak predictors of IBP. Diabetes and underlying neurologic conditions—mainly dementia, stroke and Parkinson’s disease—were consistently shown to be strong predictors of IBP in large-scale studies [9,10]. Various medications are associated with a higher risk of IBP, with opioids and tricyclic antidepressants being the strongest and most consistent in large-scale studies [10,11,13]. Factors associated with the preparation protocol (especially the effectiveness of split dose preparation and adding bisacodyl or senna to the standard preparation) were assessed in other studies, and were found to be mostly associated with better rates of adequate bowel preparation [14-17]. It has also been suggested that a delay between the end of preparation and the colonoscopy confers a higher risk for IBP [18-20]. However, most of the factors suggested by these studies are currently not modifiable, with the exception of shortening the time interval to the procedure (not always possible due to time of day) and splitting the dose of the medication chosen for preparation. In the current study, we sought to prospectively collect multiple patient characteristics, including modifiable factors associated with bowel preparation that have not been previously reported but could potentially be used to reduce IBP and improve the quality of colonoscopy.

Patients and methods

Results

Of the 1172 subjects who participated, 452 answered the original questionnaire and 720 the extended questionnaire; 619 (52.8%) were males, and the mean age was 55.8 years. Baseline demographic characteristics of the subjects are presented in Table 1. Twenty-four endoscopists performed the examinations, with a median number of 33 colonoscopies per endoscopist.

Table 1 Baseline characteristics of the entire patient cohort (n=1172)

IBP was found in 227 (19.4%) subjects. A comparison of the demographic information, medical history and medications in the adequately and inadequately prepared subject groups, along with the ORs, is presented in Table 2. Typical colonoscopy images of adequately and inadequately prepared bowel segments seen during the study are presented in Fig. 1. In the univariate analysis, subjects with IBP were significantly older (mean age 60 vs. 58 years in the inadequately and adequately prepared groups, respectively; P=0.013) and weighed more than adequately prepared subjects (80 vs. 76 kg, respectively; P<0.001). Diabetes (35.2% of inadequately prepared vs. 19.4% of adequately prepared subjects, OR 2.26, 95% confidence interval [CI] 1.6-3.14; P<0.001), history of psychiatric disease (11% of the IBP vs. 5.6% of adequately prepared subjects, OR 2.08, 95%CI 1.21-3.5; P=0.007), and heart disease (22% of the IBP vs. 14.2% of adequately prepared subjects, OR 1.71, 95%CI 1.16-2.49; P=0.006) were shown to be significantly associated with IBP. In addition, the use of several medication groups was also significantly associated with a higher risk of IBP. These included proton pump inhibitors, anti-hypertensives, statins, and diuretics, among others (Table 2).

Table 2 Patient demographic and clinical variables. Univariate comparison between adequate and inadequate preparation

Figure 1 Typical colonoscopy images of adequately and inadequately prepared bowel segments seen during the study. Images taken in the Rambam healthcare campus endoscopy suite. Images include adequately and inadequately prepared left colon (A and B respectively); adequately and inadequately prepared transverse colon (C and D respectively); and, adequately and inadequately prepared left colon (E and F respectively)

A similar comparison of adequately and inadequately prepared patients for variables subsequently added to the second questionnaire (n=720) is presented in Table 3. Education level significantly affected the risk of IBP; subjects with <12 years of education had a significantly higher risk for IBP (OR 3.06, 95%CI 1.88-4.33) than those with academic education (bachelor’s or an associate degree). In addition to weight, included in the original cohort, body mass index (BMI) was added to the extended questionnaires; as with weight, obesity (BMI ≥30 kg/m²) conferred a higher risk for IBP (OR 1.84, 95%CI 1.2-2.78). A subgroup analysis of various antidiabetic medications in diabetic patients did not reveal significant differences in the risk of IBP for any of the medications, including insulin. The use of 5 or more medication groups, not limited to those specifically mentioned above, was considered as polypharmacy and was associated with a significantly higher risk of IBP (OR 2.49, 95%CI 1.65-3.75). These associations were not found in the multivariate analysis.

Table 3 Summary and comparison between patients with adequate and inadequate preparation. Demographic and clinical variables collected in the second (extended) questionnaire only

Multiple parameters of the bowel preparation process were analyzed. A comparison of these variables between adequately and inadequately prepared patients is shown in Table 4. Adequate cleaning of the right colon (BBPS ≥2) was recorded in all adequately prepared patients and in only 42/227 (18.5%) of the inadequately prepared patients.

Table 4 Summary and comparison of bowel preparation related variable between patients with adequate and inadequate bowel preparation

An interval of more than 8 h from the end of preparation to the beginning of the examination conferred a significantly higher risk for IBP, irrespectively of the time of the procedure (54.6% of the inadequately prepared vs. 41.3% of adequately prepared subjects, OR 1.71, 95%CI 1.27-2.32; P<0.001). In addition, higher rates of IBP were seen as the time from end of preparation to colonoscopy increased (Fig. 2A). An analysis comparing the volume of fluids consumed during preparation and adequacy showed that compared to subjects who drank 1.4L-2.0L of clear liquids subjects who drank <1.4 L after each sachet had a significantly higher risk of IBP (OR 3.62, 95%CI 2.65-4.95). Subjects who drank >2 L of liquids were substantially more likely to have a successful preparation (OR 0.09, 95%CI 0-0.42). Moreover, out of 66 subjects who drank >2 L of fluids after each sachet, only one had inadequate preparation. A logistic regression of the rate of IBP plotted against volume of liquids consumed within a short time interval to colonoscopy, compared to all other patients, is shown in Fig. 2B. The IBP rate dropped consistently as the volume of liquids consumed increased, with a further drop of up to an approximate 50% for subjects who also had a short interval between end of preparation and colonoscopy.

Figure 2 Predicted probability of inadequate bowel preparation (IBP) adjusted for variables significantly associated with IBP. A function of time (h) from end of preparation to colonoscopy (A) and volume of clear liquids consumed after each sachet of picosulfate, stratified by time to colonoscopy (B). Grey outlines represent the standard errors of the models

Multivariate regression analysis that included multiple factors significantly associated with IBP on univariate analysis, along with the performing endoscopist, showed that only weight, presence of diabetes, psychiatric disease, volume of fluids consumed, and time interval to colonoscopy were significantly associated with an elevated risk for IBP in the entire cohort (n=1172). ORs and 95%CIs of the multivariate regression analysis results are shown in Table 5.

Table 5 Multivariate analysis of factors significantly associated with inadequate bowel preparation

We further analyzed a subgroup of patients with favorable preparation features (drank ≥1.6 L of liquids and waited ≤8 h between end of preparation and beginning of examination). In this group, only 41/487 (8.4%) failed bowel preparation, compared to an IBP rate of 27% in the 685 patients who either drank <1.6 L of fluid or had their examination delayed (P<0.001). A subgroup analysis of patients at high risk for IBP, such as diabetics or individuals weighing more than 90 kg, revealed that among 96 diabetic individuals with both favorable features, inadequate preparation was seen in only 11 (11.5%), while 69/167 (36.9%) of diabetic patients who did not have both features failed preparation (P<0.001). Only 10/114 (8.8%) subjects with both favorable features who weighed 90 kg or more failed preparation, in comparison to a failed preparation in 61/167 (36.5%) subjects with this weight but without both favorable parameters (P<0.001).

Discussion

Adequate bowel preparation is essential for ideal endoscopic diagnostic yield. In this study, we prospectively studied 1172 patients in order to: 1) identify features associated with a high risk for IBP; 2) compare these findings to previous reports; and 3) search for bowel preparation features that can easily be modified and implemented into bowel preparation protocols to potentially lower the rate of IBP, particularly in high-risk individuals.

The rate of IBP in our cohort was 19.4%, similar to the IBP rates found in other studies, including a recent large meta-analysis performed by Mahmood et al [7,21]. The adequacy of bowel preparation, graded according to the BBPS, was also similar to other studies where preparation was mostly with sodium picosulfate [23,24]. Multivariate adjustment revealed unmodifiable variables (e.g. obesity, diabetes, and education level) significantly associated with IBP, all of which are well-established risk factors in the literature [7,8]. Interestingly, and consistently with previous findings, a higher BMI tended to raise the risk of IBP significantly, especially in males [8], though our study had a male predominance. Moreover, when females alone were analyzed, the effects of weight and BMI were attenuated (OR for obesity as a risk factor for IBP in females alone was 1.75, 95%CI 0.93-3.24). When multiple medication groups were assessed (e.g. opiates, anti-hypertensive drugs, and lipid lowering drugs) some were shown to be associated with IBP, similarly to previous reports [7,8]. Additionally, polypharmacy was associated with an increased risk of IBP, regardless of medication type (Table 3). While this association has been demonstrated previously [19], in our study this finding was not significantly associated with IBP after adjustment for multiple other factors (Tables 3,5).

Extensive bowel preparation characteristics were collected and analyzed, including volume of clear liquids consumed during colonoscopy preparation, which to the best of our knowledge has not been previously reported. We show that the volume of liquids consumed with each sachet was independently associated with the rate of IBP, where only 1/66 patients who consumed ≥2 L after each sachet had inadequate preparation. Furthermore, this is the first study to show a direct and continuous association between volume of fluids consumed and IBP rate. This continuous reduction in rate was seen as fluid consumption exceeded the instructions provided in the picosulfate leaflet, which recommends at least 1.25 L (5 cups) and only 750 mL (3 cups or 250 mL) of clear liquids following the first and second sachets, respectively. In an effort to identify additional modifiable preparation-related features, we observed that the rate of IBP decreased further in a subgroup of patients whose colonoscopies were performed <8 h after they took the second sachet of sodium picosulfate. This finding was independent of whether the procedure took place during morning or afternoon hours. IBP rates were low even in high-risk diabetic, obese, or older patients who met this criterion. A longer time interval between bowel preparation and colonoscopy has long been shown to be a risk factor for IBP [7,8]; however, the further improvement we found with greater liquid consumption has major significance. An important reservation regarding these findings is the possible risk of electrolyte disturbances with consumption of high volumes of water during bowel preparation. Our subjects were outpatients and we did not perform any blood sample analysis. Therefore, further research is needed, and balanced fluids should be considered when high-volume preparations are recommended or studied. However, we are unaware of any hospitalizations or deaths that occurred in our cohort.

Several limitations of our study need to be addressed. Data were collected through questionnaires filled out by the patient with the assistance of a nurse practitioner immediately prior to colonoscopy, and therefore patient recall might cause bias with regard to clinical as well as preparation-associated information. Moreover, it is likely that subjects would feel some degree of unease about admitting to poor compliance with the preparation protocol. The large number of patients assessed in this study may alleviate this potential bias. Furthermore, this study was conducted in a single tertiary center in Israel, which might affect the generalizability of the results. However, our cohort was demographically diverse and included a variety of ages, ethnicities and educational backgrounds, which may have mitigated the aforementioned drawback. Since all patients were scheduled for an elective examination, the indication for colonoscopy was not recorded, though this information could have helped identify subgroups that would benefit from high-volume fluid preparation. Another substantial limitation is the difficulty of achieving full adherence to guidelines and mainly the strong recommendation of initiation of colonoscopy within 5 h of consumption of the last dose of bowel preparation [21]. The difficulty, especially with early morning examinations, is a well-known challenge. The lack of post-procedure follow up for any adverse effects is an additional limitation. However, we are unaware of any preparation-associated post colonoscopy hospitalizations. Finally, since all subjects in the study used sodium picosulfate for preparation, results might not be generalizable to other preparation protocols and further investigations are required.

In conclusion, along with previously suggested risk factors for IBP, also found in the current study, herein we show 2 modifiable bowel preparation factors, low fluid intake and a long interval to colonoscopy, that can easily be incorporated into preparation protocols to improve bowel preparation with sodium picosulfate. Further prospective interventional studies will be necessary before definitive conclusions can be drawn.