Colorectal cancer has become one of the most common cancers in eastern and western countries (Chen, Zheng, Zeng, Zhang, & He, 2015; Cronin et al., 2018; Goh, 2017; Lee et al., 2019) and the second leading cause of cancer death worldwide (Bray et al., 2018). Colonoscopy is the gold standard method for detecting polyps and adenomas, reducing the morbidity and incidence of colorectal cancer (Lee et al., 2019; Navarro, Nicolas, Ferrandez, & Lanas, 2017; Quintero et al., 2012; Ribeiro et al., 2018; Zauber et al., 2012). However, the effectiveness of colonoscopy depends largely on the quality of bowel preparation (Burke & Church, 2007; Provenzale et al., 2020; Rex et al., 2009).
Adequate bowel preparation is a key factor in detecting colorectal tumors and reducing the risk of missing lesions (Clark, Rustagi, & Laine, 2014; Provenzale et al., 2020; Rutter et al., 2018; Sulz et al., 2016). It can improve bowel cleansing, surveillance intervals, and cecal intubation rates (Anderson et al., 2017; Bucci et al., 2014; Johnson et al., 2015; Kim, 2012) and reduce the procedural time, overall colonoscopy cost, the risk of colonoscopy-related complications, and need for repeated colonoscopy (Hillyer et al., 2013; Kingsley, Karanth, Revere, & Agrawal, 2016; Rex, Imperiale, Latinovich, & Bratcher, 2002).
Large-volume polyethylene glycol electrolyte solution (PEG-ES) and oral sodium phosphate (NaP) preparations are widely used. Although they have been shown to be effective for bowel preparation (Castro et al., 2019; Dang et al., 2021; Gweon et al., 2020; Seo, Gweon, Huh, Ji, & Choi, 2019; Yang et al., 2020), PEG-ES and Oral NaP are still far from ideal. The large volume of PEG and unpleasant taste often cause poor compliance and serious dissatisfaction with the procedure (DiPalma, Wolff, Meagher, & Cleveland, 2003; El Sayed et al., 2003; Hookey, Depew, & Vanner, 2004). Oral NaP solutions usually have better tolerance and compliance than PEG-ES. However, in an open-access system, their use is often limited due to the lower therapeutic index in subsets of patients with cirrhosis or renal failure and congestive heart failure (Curran & Plosker, 2004; Heher, Thier, Rennke, & Humphreys, 2008; Katz et al., 2013; Rocha et al., 2018; Russmann et al., 2008; Wexner et al., 2006). These existing limitations continue to drive the search for alternatives to optimal bowel preparation.
Senna laxatives containing sennosides are an anthraquinone derivative, which are activated by colonic bacteria after ingestion. They have a direct effect on intestinal mucosa increasing bowel motility, promoting accumulation of water and electrolytes in the colonic lumen (Park & Lim, 2014; Wexner et al., 2006). An oral senna solution has recently been shown to be a valid alternative compared with PEG-based bowel preparation regimens for elective colonoscopy. The results were better bowel preparation quality, patient compliance, and overall tolerance (Park & Lim, 2014; Radaelli et al., 2005; Shavakhi et al., 2011; Wexner et al., 2006; Ziegenhagen, Zehnter, Tacke, & Kruis, 1991). Although senna bowel preparation seems to be more effective than PEG, patient discomfort and adverse events especially abdominal pain become the main obstacle for its acceptance by patients in clinical practice (Amato, Radaelli, Paggi, & Terruzzi, 2010).
Thus, it is necessary to assess whether senna bowel preparation regimens are equally effective as other standard bowel preparation regimens (NaP, PEG, and Citramag) to implement their use in clinical practice. Most of the previous meta-analyses focused on same-day preparations, split-dose preparations, or adding adjuvants regimens (Bucci, Zingone, Schettino, Marmo, & Marmo, 2019; Cheng et al., 2018; Martel et al., 2015; Restellini, Kherad, Menard, Martel, & Barkun, 2018). There is currently a paucity of data comparing senna regimens and other regimens. To date, several studies have evaluated the efficacy of senna for bowel cleansing before colonoscopy (Amato et al., 2010; Coskun & Yuksel, 2020; Haapamaki, Lindstrom, & Sandzen, 2011; Hookey, Depew, & Vanner, 2006; Manukyan et al., 2011; Poyrazoglu & Yalniz, 2015; Radaelli et al., 2005; Schanz et al., 2008; Shavakhi et al., 2011; Valverde et al., 1999; Vradelis et al., 2009), but the evidence remains controversial and has not yet been collated. The primary aim of this systematic review and meta-analysis is to assess whether senna preparation regimens are equally efficacious as other preparation regimens.
We consulted Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement and guidelines as our reference during all stages of analysis, design, and reporting of this meta-analysis (Moher, Liberati, Tetzlaff, & Altman, 2009). The primary and secondary results, as well as the inclusion and exclusion criteria of the study, were identified on a priori basis and described later.
Study Selection Criteria
We predesignated inclusion and exclusion criteria and then screened all types of articles for inclusion in this system review if the following criteria were met:
- Population. All inpatient and outpatient adults patients (≥18 years) who underwent an elective colonoscopy.
- Intervention: All senna bowel preparation regimens administered in only senna or senna plus adjuvants.
- Comparison: All standard bowel preparation regimens administered in PEG, NaP, or Citramag.
- Outcome: The efficacy of senna in bowel preparation for colonoscopy was considered to be the primary outcome. Secondary efficacy outcomes included side effects, tolerability, and compliance with the regimens.
- Study design: Only randomized controlled trials (RCTs) of full-text English publications were considered.
The following exclusion criteria were applied:
- Unable to extract essential information and nonrandomized studies.
- Letters, case reports, review articles, or comments.
- Incorrect population: inflammatory bowel disease patients, pediatric patients as well as the use in difficult populations.
- Incorrect outcome indicators: quality of the examination as “optimal,” “acceptable,” or “to be repeated.”
- Incorrect interventions: based on senna extract combined with an enema.
A comprehensive and systematic search was conducted in PubMed, Web of Science Core Collection, MEDLINE, Cochrane Library, EMBASE and Scopus databases (up to August 2021) to identify eligible studies comparing senna regimens and standard bowel preparation regimens before colonoscopy. References included in this study were also manually searched for additional trials. If the article was not available in full text, the author was contacted for more research data (Tian et al., 2021).
This systematic review and meta-analysis used a highly sensitive search strategy to incorporate eligible RCTs with a combination of the following text words and MeSH headings: “senna,” “bowel preparation,” and “colonoscopy.” Retrieve expressions are shown in Supplementary File 1 (available at: https://links.lww.com/GNJ/A74). Recursive searches, cross-references, and subsequent manual searches were completed.
In this systematic review and meta-analysis, the primary outcome was the efficacy of senna in bowel preparation for colonoscopy. Efficacy was defined as the proportion of adequate bowel preparation patients. Considering the heterogeneity of bowel cleanliness nomenclature in different studies, we predefined an adequate bowel preparation as good or excellent bowel preparation, assessed by an endoscopic physician using the Aronchick Scale, a Boston Bowel Preparation Scale (BBPS) score of 7 or greater, an Ottawa Bowel Preparation Scale (OBPS) score of less than 5, or other unverified 4- or 5-point scales (e.g., very poor, poor, fair, good, and excellent). In several studies, patients evaluated their tolerability, compliance, and side effects of bowel preparation by their own subjectivity. These studies distributed a nonstandardized questionnaire to patients before colonoscopy. It was from the results of these questionnaires that data on palatability (tolerability), compliance, and side effects were extracted. The outcomes of bowel preparation tolerance were defined as the rate of patients who described their overall bowel preparation level as easy to perform or acceptable. Compliance with bowel preparation was defined as the amount of at least 75% of the solution required to complete the prescribed regimen. Further, other secondary outcomes were the proportion of patients who described how their entire bowel preparation process felt without symptoms/side effects (such as nausea, vomiting, abdominal pain/cramping, headache, and dizzy).
Two reviewers conducted independent screening of all articles starting with the title and abstract. This was followed by full text screening of the articles marked as included and uncertain for formal review. The two reviewers independently assessed the full text using the inclusion and exclusion criteria to determine whether the article was included. If an article was excluded, they listed the reason for exclusion. Disagreements between the reviewers were resolved through consultation and discussion with a third independent reviewer.
Two authors independently implemented data extraction using predeveloped standardized tables. Any differences arising were resolved through mutual discussion and consultation, if required, by consultation with another senior author. The data extracted from the included trials were as follows: year of publication, first author, country, study design, number of patients, number of endoscopy centers, patients with successful bowel preparation, compliance, palatability (tolerability), side effects (nausea, vomiting, abdominal pain/cramping, headache, and dizziness), risk of bias criteria (random sequence generation, blinding of participants and personnel, allocation concealment, blinding of outcome assessment, selective reporting, incomplete outcome data, and other bias) (using the Cochrane Collaboration Risk of Bias tool) and senna bowel preparation details and standardized bowel preparation details (type, dose, and formulation).
The quality of RCTs was evaluated by the Cochrane risk bias tool. Two authors assessed quality of the included article and inconsistent opinions were decided through consultation and discussion. If necessary, the authors resolved the discrepancies through discussion or consultation with a third senior author.
The authors used the Cochrane Review Manager 5.4 to calculate the pooled summary estimates and expressed summary estimates as odds ratios (ORs) along with 95% confidence intervals (95% CIs). If the p value was less than .05, it was statistically significant. For all pooled rates, use of random-effects models and Mantel-Haenszel statistics were considered. OR values greater than 1 indicated that senna bowel preparation was more effective. Heterogeneity between studies was calculated using the χ2 test with n − 1 degrees of freedom (n represents the number of studies). There was significant heterogeneity if the p value < .10. Heterogeneity can also be calculated with the I2 test of inconsistency. If heterogeneity was detected (I2 > 50%), the authors performed subgroup analysis according to number of centers (i.e., monocenter or multicenter), country, and type of bowel preparation. Sensitivity analysis was conducted for the most clinically relevant variables (outpatients, validated scales, and year of publication) (Spadaccini et al., 2020). The percentage of all results reported in the study was converted to absolute values. However, the values to be extracted were not determined from charts or figures to reduce possible subjectivity.
The authors retrieved 353 articles through electronically searched databases and two potential articles were added manually. A total of 218 duplicate articles were excluded through Endnote software and manual work. Then, 107 articles were removed based on titles and abstracts and 30 articles were fully retrieved and reviewed. Eleven articles (3,343 patients) that met inclusion and exclusion criteria were included in this meta-analysis (Amato et al., 2010; Coskun & Yuksel, 2020; Haapamaki et al., 2011; Hookey et al., 2006; Manukyan et al., 2011; Poyrazoglu & Yalniz, 2015; Radaelli et al., 2005; Schanz et al., 2008; Shavakhi et al., 2011; Valverde et al., 1999; Vradelis et al., 2009) (Figure 1).
Characteristics of the RCTs were provided in Supplementary Table 1 (available at: https://links.lww.com/GNJ/A75). One trial was performed in North America (150 patients), four trials were performed in Asia (895 patients), and six trials were performed in Europe (2,170 patients). The trial populations in 10 of the 11 trials were composed of outpatients. Another trial enrolled inpatients. Three trials involved multiple centers, while eight trials were single centers. Regarding the evaluation tool of bowel cleanliness, the BBPS was used in one study (474 patients), the OBPS was used in three studies (648 patients), the Aronchick scale was used in four studies (1,129 patients), and nonvalidated scales were used in three studies (1,092 patients).
A total of 11 studies included in the analysis compared senna bowel preparation regimens versus standard bowel preparation regimens (see Supplementary Table 1, available at: https://links.lww.com/GNJ/A75). Seven studies evaluated senna versus PEG (senna vs. only PEG, n = 4; senna plus 2L PEG vs. 4L PEG, n = 2; senna vs. 2L PEG plus senna, n = 1), three studies evaluated senna versus 90-ml NaP (senna vs. only NaP, n = 2; senna vs. NaP plus senna, n = 1), and one study evaluated senna plus Citramag versus Citramag. The use of senna with low dose ranges from 24 to 300 mg, and high dose 500 to 1000 mg.
Risk of Bias Assessments
Based on the Cochrane Collaboration tool, four studies were judged to have a low risk of bias and seven studies had a moderate risk of bias. Seven studies had adequate random sequence generation, for which a random number table (n = 1) or a computer-generated program (n = 6) was used. In 10 studies, allocation was adequately concealed by using block randomization (n = 1), allocation concealment (n = 3), sealed and opaque envelopes (n = 3), parallel allocation (n = 1), and random allocation software (n = 2). All studies were single-blinded (investigator-blinded). Three studies that did not report missing and excluded cases were unclear about incomplete outcome data. Eight studies reported incomplete outcome data and the number of incomplete outcome data was comparable among the intervention groups and the reason for the missing were similar (Figures 2 and 3).
Primary Outcome: Efficacy
Senna Versus All Preparations
Senna bowel preparation was compared with standard bowel preparation regimens of any product. Eleven studies compared senna versus all preparations, regardless of dosage, product, or addition of adjuvant. One of 11 studies' data on bowel cleanliness was not analyzed. Based on the data reported by all the 10 studies (3,244 patients), no significant difference in bowel preparation cleanliness was observed between patients receiving the senna bowel preparation solution and those receiving the standard bowel preparation solution (OR [95% CI]: 1.02 [0.63, 1.67], p = .93 from random effects), with considerable heterogeneity observed across the studies (I2 = 85%) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
Senna Versus PEG
Seven studies (2,547 patients) evaluated a senna bowel preparation solution versus a PEG bowel preparation solution with no evidence of a statistically significant difference in the bowel preparation cleanliness between groups (OR [95% CI]: 1.06 [0.59, 1.90], p = .83), I2 = 85% for heterogeneity (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
Senna Versus Only PEG
Four studies (1,702 patients) comparing senna solution versus only PEG solution showed no significant between-group differences in bowel cleanliness (OR [95% CI]: 1.79 [0.93, 3.45], p = .08 from random effects), with considerable heterogeneity observed across the studies (I2 = 79%) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75). Three studies (1,380 patients), except for study by Shavakhi et al. (2011), indicated significant between-group differences in bowel cleanliness (OR [95% CI]: 2.58 [1.80, 3.71], p < .00001 from random effects) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
Senna Versus 2L PEG Plus Senna
One study of 296 patients comparing senna versus 2L PEG plus senna showed significant between-group differences in bowel cleanliness (OR [95% CI]: 0.37 [0.16, 0.83], p = .02, I2 0%) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
Senna Plus 2L PEG Versus 4L PEG
Two studies of 549 patients comparing senna plus 2L PEG versus 4L PEG showed no significant between-group differences in bowel cleanliness (OR [95% CI]: 0.64 [0.29, 1.39], p = .25, I2 = 72%) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
Senna Versus NaP
Three studies (454 patients) compared senna bowel preparation solution versus NaP bowel preparation solution. Two studies with analyzable data showed no evidence of a statistically significant difference in the bowel preparation cleanliness between groups (OR [95% CI]: 0.59 [0.15, 2.33], p = .45), I2 = 85% for heterogeneity) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
Senna Versus Only NaP
Two studies (227 patients) compared senna bowel preparation solution versus only NaP bowel preparation solution, with only one study including analyzable data. Senna solution yielded a significantly greater proportion of adequate preparations (OR [95% CI]: 0.29 [0.14, 0.61], p = .001) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
Senna Versus NaP Plus Senna
One study of 227 patients comparing senna versus NaP plus senna showed no significant between-group differences in bowel cleanliness (OR [95% CI]: 1.19 [0.56, 2.56], p = .65) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75).
TABLE 1. -
Results for the Primary Outcome: Bowel Cleanliness
|Type of Preparation
||Number of Trials
||OR [95% CI]
|Senna vs. all preparations
||1.02 [0.63, 1.67]
|Senna vs. PEG
||1.06 [0.59, 1.90]
|Senna vs. only PEG
||1.79 [0.93, 3.45]
|Senna vs. only PEG
||2.58 [1.80, 3.71]
|Senna vs. 2L PEG plus senna
||0.37 [0.16, 0.83]
|Senna plus 2L PEG vs. 4L PEG
||0.64 [0.29, 1.39]
|Senna vs. NaP
||0.59 [0.15, 2.33]
|Senna vs. only NaP
||0.29 [0.14, 0.61]
|Senna vs. NaP plus senna
||1.19 [0.56, 2.56]
|Senna plus Citramag vs. Citramag
||2.10 [1.27, 3.45]
Note. CI = confidence interval; NA = not applicable; NaP = sodium phosphate solution; OR = odds ratio; PEG = polyethylene glycol.
aOne study was removed.
Senna Plus Citramag Versus Citramag
One study of 342 patients comparing senna plus Citramag versus Citramag showed significant between-group differences in bowel cleanliness (OR [95% CI]: 2.10 [1.27, 3.45], p = .004) (see Supplementary Figure 4, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 1, available at: https://links.lww.com/GNJ/A75). All comparisons of bowel cleanliness studies are summarized in Table 1.
Secondary Outcomes: Tolerability
Senna Versus All Preparations
Four of 11 studies on tolerability (i.e., palatability/acceptability) were not analyzed. Based on the data reported by all the seven studies (2,625 patients), significant difference in bowel preparation tolerability was observed between patients receiving the senna bowel preparation solution and those receiving the standard bowel preparation solution (OR [95% CI]: 1.66 [1.08, 2.54], p = .02 from random effects), with considerable heterogeneity observed across the studies (I2 = 78%) (see Supplementary Figure 5, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 2, available at: https://links.lww.com/GNJ/A75).
Senna Versus Only PEG
Four studies (1,700 patients) investigated senna versus only PEG with no evidence of a statistically significant difference in bowel preparation tolerability in the pooled analysis in bowel preparation tolerability.
Senna Versus 2L PEG Plus Senna
One study (296 patients) evaluated senna versus 2L PEG plus senna with no evidence of a statistically significant difference between groups in bowel preparation tolerability (see Supplementary Figure 5, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 2, available at: https://links.lww.com/GNJ/A75).
Senna Plus 2L PEG Versus 4L PEG
Two studies (629 patients) included analyzable data, showing greater adequate tolerability of bowel preparation for senna plus 2L PEG (OR [95% CI]: 2.35 [1.66, 3.31], I2 = 0%, p < .00001) (see Supplementary Figure 5, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 2, available at: https://links.lww.com/GNJ/A75).
Secondary Outcomes: Compliance
Senna Versus All Preparations
In four studies (1,332 patients) assessing compliance of bowel preparation, the senna bowel preparation solution group demonstrated statistically significantly higher compliance as compared with the standard bowel preparation solution (OR [95% CI]: 3.05 [1.42, 6.55], p = .004 from random effects), with considerable heterogeneity observed across the studies (I2 = 80%) (see Supplementary Figure 6, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 2, available at: https://links.lww.com/GNJ/A75).
Senna Versus Only PEG
We found no evidence of a statistically significant difference in bowel preparation compliance among the different regimens (see Supplementary Figure 6, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 2, available at: https://links.lww.com/GNJ/A75).
Senna Plus 2L PEG Versus 4L PEG
Comparing senna plus 2L PEG with 4L PEG also resulted in no evidence of a statistically significant difference in bowel preparation compliance (see Supplementary Figure 6, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 2, available at: https://links.lww.com/GNJ/A75).
Secondary Outcomes: Adverse Events
Adverse events including vomiting, abdominal pain, headache, and dizziness revealed no significant difference in the meta-analysis. The 95% CIs were 0.81–3.35, 0.35–1.23, 0.66–1.51, and 0.50–1.56, respectively, with substantial heterogeneity. Seven studies (2,042 patients) provided information on the rates of nausea, and analysis showed a lower incidence of nausea in patients using senna bowel preparation (OR [95% CI]: 1.84 [1.45, 2.32], p < .00001) (see Supplementary Figures 7–11, available at: https://links.lww.com/GNJ/A76, and Supplementary Table 2, available at: https://links.lww.com/GNJ/A75).
Supplementary Table 3 (available at: https://links.lww.com/GNJ/A75) summarizes the robust sensitivity analysis based on outpatients, validated scales, and year of publication. Subgroup analyses according to type of preparation, study, and country were consistent with the primary and secondary outcomes of the main analysis (see Supplementary Table 4, available at: https://links.lww.com/GNJ/A75, and Supplementary Table 5, available at: https://links.lww.com/GNJ/A75, respectively).
To the authors' knowledge, this is the first systematic review and meta-analysis evaluating the efficacy of senna bowel preparation for colonoscopy. The aim of the current meta-analysis is to summarize the existing evidence so as to better characterize the role of senna bowel preparation before colonoscopy. This is particularly timely, as the recommendations between the U.S. and European guidelines about the use of Senna are unclear (Hassan et al., 2019; Johnson et al., 2014). Considerable clinical and statistical heterogeneity has limited drawing of precise conclusions about the effects of senna use on bowel cleanliness, tolerance, and compliance.
According to our meta-analysis, both senna and other bowel preparation were equally effective in cleansing the overall colon. In addition, all the analysis of individual preparations showed that senna solution may be superior to only PEG regimes but compared to the NaP only. Regarding secondary outcomes, our analysis confirmed a better patient experience, especially in terms of tolerance, compliance, and adverse events including nausea and vomiting, with a senna regimen.
The findings from this meta-analysis indicated that compared with other preparations, senna regimen interventions can improve bowel cleanliness and have no significant difference. Our analysis further showed that the senna regimen was comparative to other regimens (all preparations plus adjuvant vs. all preparations), which was similar to the previous meta-analysis (Restellini et al., 2018). First, by including 11 more RCTs of senna regimens compared with the previous meta-analysis, we approximately increased the number of patients by fivefold. This enabled us to make more statistically significant comparison between each individual and senna preparations. Only three RCTs in total were available in the previous review (Restellini et al., 2018).
Second, we excluded nonapproved regimens of senna preparations, such as those based on the gum chewing in adjunct to senna (Ergül, Filik, Koçak, Doğan, & Sarıkaya, 2014), as well as those preparations which are based on the combination of more than three colon-cleansing product, such as PEG plus mosapride plus senna and mannitol plus simethicone plus senna (Chen et al., 2017; Kamei et al., 2018). Both of these factors may affect the superiority shown for senna regimens. Although previous meta-analyses have shown similar results (Restellini et al., 2018), the equivalence we showed between senna and other regimens was restricted to all studies pooled together.
Third, we did not limit the comparison between all preparations plus adjuvant and all preparations, but we also showed the superiority between senna and only NaP or PEG regimes. This was clinically relevant because actual practice varied from country to region. It was necessary to tailor cleaning types according to the characteristics of patients and specific clinical scenarios (in patients, nephropathy, the elderly, etc.).
Our analysis suggested that the superiority of senna regimens was different between only NaP and PEG regimens. Compared with a single NaP regimen, senna did not seem to perform bowel cleansing as effectively as NaP solution. According to the general evaluation of colonoscopy, the number of excellent bowel cleaning patients in the NaP regimen group was significantly higher than that in the senna group (p < .001) (Poyrazoglu & Yalniz, 2015). We included data on NaP preparations and noting that the Food and Drug Administration has issued a warning about its use related to nephrotoxicity (Hassan et al., 2019; Johnson et al., 2014). Due to the limited data on NaP preparations in this meta-analysis, further studies will still be needed in the future.
Compared with the single PEG regimen, the senna regimen may effectively improve bowel cleanliness, enhance intestinal mucosal visibility, and particularly increase the success rate of colonoscopy. Based on statistical analysis of data, we found that the number of patients who completed the senna solution was more than PEG preparations due to the large volume, unpleasant taste, or poor palatability. The lower tolerance and compliance can affect the acceptability and uptake of colonoscopy, especially in screening programs for healthy populations (Senore et al., 2011).
The effectiveness and tolerance or compliance of bowel cleaning is closely related, as the former includes partial tolerance or compliance to some extent. In fact, preparations with poor tolerance and compliance are not fully ingested and may not achieve the desired bowel cleansing effect and some national guidelines also favor preparations associated with optimal patient compliance and tolerance for optimal results (Hassan et al., 2019; Johnson et al., 2014; Wexner et al., 2006).
The choice of tolerance and compliance as secondary outcomes reflects a pragmatic clinical argument. To some extent, the patient's adverse events determine bowel cleanliness. This meta-analysis showed that the better patient experience obtained by the senna regimen and efficacy were closely related. The senna regimen was superior to all preparations we selected for secondary outcomes (tolerance and compliance). When combining the equivalent efficacy with better tolerability and compliance, there is convincing evidence that the senna regimen is recommended as alternatives to other preparations. In addition, the senna preparation (one box of 42 tablets, €5.70) is less costly than PEG (one box of four sachets, €17.20) (Amato et al., 2010).
Patients' adverse events associated with bowel preparation were reported to be inconsistent and variability. This prompted a repeat symptom subgroup analysis. Statistical heterogeneity varies according to symptom subgroup analysis. The results revealed that dizziness and headache showed a nonsignificant trend toward significance in the senna preparation. More cases of vomiting and nausea were reported in patients who took the PEG and NaP preparation. The most common adverse event was abdominal pain in the senna subgroup, with the majority of patients included in this meta-analysis reporting it to be mild.
In our view, these differences can be attributed to the patient's own physical and clinical factors such as characteristics of the adopted regimen (interval of the administration of colon-cleansing product, taking time, and dosage), colonoscopy, and examination time rather than the type of cleanliness. Therefore, in prescribing bowel preparation, endoscopic physicians should fully consider these factors to optimize patient compliance and tolerance, when endoscopic physicians.
Strengths and Limitations of the Analysis and Review
Strengths of our analysis included a comprehensive literature search and the subgroup and sensitivity analysis performed in detail for primary and secondary outcomes. The limitations of this meta-analysis were that the vast majority of the results had significant statistical heterogeneity. This still existed despite multiple sensitivity analyses (outpatients, validated scales, and year of publication) (see Supplementary Table 3, available at: https://links.lww.com/GNJ/A75) (Spadaccini et al., 2020) and subgroup analyses according to intervention measures, number of centers, country, and type of bowel preparation (see Supplementary Table 4, available at: https://links.lww.com/GNJ/A75, and Supplementary Table 5, available at: https://links.lww.com/GNJ/A75), representing a vital issue and precluding clear conclusions. Variations in clinical regimens (related diets, different products, and the number of different preparations) as well as the definition of senna regimens and bowel preparation quality may partially account for this observation.
We also acknowledge differences in bowel preparation across trial studies (see Supplementary Table 1, available at: https://links.lww.com/GNJ/A75), which reflects differences in use around the world and may lead to heterogeneity between different clinical trials. Heterogeneity may also arise from the severity of the patient's condition and the time of colonoscopy; however, we could not obtain the relevant data on these factors in the included articles. Further large number and high-quality clinical trials still need to be implemented. Moreover, only a limited number of studies can be included in the analysis which all studies on this subject to date. Further trials using more sophisticated methods may affect some conclusions. In addition, a limitation of our analysis was that patient willingness to repeat bowel preparation was not included as an outcome for two reasons. First, although bowel cleanliness was reported, most of the studies included in this review did not include the willingness to repeat bowel preparation as an outcome indicator. Second, the willingness to repeat bowel preparation may be a comprehensive measure of palatability, tolerance, and compliance. In this meta-analysis, they were discussed step by step.
Significant heterogeneity does not allow clear conclusions to be made about bowel preparation for routine senna use. Analysis of our data showed the senna regimen was associated with better compliance and tolerance, less nausea and vomiting, and superior bowel cleanliness. Therefore, the senna regimen can be used as an alternative to bowel preparation for colonoscopy.
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