Systematic review and meta-analysis: Sodium picosulphate with magnesium citrate as bowel preparation for colonoscopy

Abstract

Background

An effective and tolerable bowel preparation is important to secure quality of colonoscopies. It remains unclear if sodium picosulphate with magnesium citrate (SPMC), which is considered a tolerable bowel preparation agent, is also an effective alternative for polyethylene glycol (PEG) and sodium phosphate (NaP).

Aim

The aim of this article is to compare effectiveness of SPMC to PEG and NaP through assessment of quality of bowel cleansing measured by validated tools.

Methods

We searched electronic databases up to January 2015. Only randomised controlled trials (RCTs) were included. Two authors independently performed selection of studies, risk of bias assessment and data extraction.

Results

Thirteen RCTs were included, with overall good quality, but large heterogeneity. SPMC had slightly better quality of bowel cleansing than PEG (pooled RR 1.06; 95% CI 1.02 to 1.11). In most trials SPMC was significantly better tolerated than PEG. There were no significant differences in effectiveness or tolerability between SPMC and NaP. Side effects were similar between agents, except for dizziness (pooled RR 1.71; 95% CI 1.32 to 2.21 in favour of PEG vs. SPMC) and vomiting (pooled RR 0.35; 95% CI 0.13 to 0.95 in favour of single-dose SPMC vs. split-dose).

Conclusions

SPMC is equally effective to NaP and little superior to PEG in terms of bowel cleansing. SPMC preparations were better tolerated than PEG preparations. SPMC may be considered as standard bowel preparation for colonoscopy.

Introduction

Colonoscopy accuracy and therapeutic safety depends heavily on the quality of bowel cleansing.¹ All current preparation strategies use a combination of dietary restrictions and laxative agents.²

In Europe, three bowel preparation agents are commonly used, namely high-volume, osmotically balanced polyethylene glycol (PEG), low-volume, hyperosmotic sodium phosphate (NaP) and sodium picosulphate with magnesium citrate (SPMC), a low-volume osmotic laxative.^2,3 Because of its taste and large volume, 5% to 15% of the patients do not complete PEG preparations.¹ Patients have less difficulty completing NaP preparations, but there are concerns regarding the safety of this agent.⁴ SPMC is effective, and due to its small volume, is also easy to administer and a well-tolerated bowel preparation agent.⁵

There are five previously published systematic reviews that compare SPMC with PEG and NaP as bowel preparation for colonoscopy.^2–4,6 In four of them it remains unclear if SPMC is more, less or equally effective compared to PEG and NaP.^2,3,6,7 Only Tan and Tjandra⁴ found better effectiveness in favour of NaP. There are two previously published reviews that compare single-dose with split-dose bowel cleansing regimens.^8,9 Both reviews found superiority of a split-dose regimen over a single-dose regimen, but these reviews mainly included studies about bowel cleansing regimens other than SPMC. However, all seven reviews included studies that used non-validated measurement tools for the assessment of the quality of bowel cleansing. Validated and standardised measurement tools are important to ensure an objective assessment of the quality of bowel cleansing by the endoscopist performing the colonoscopy. When studies with different and non-validated bowel cleansing measurement tools are included in a meta-analysis, it is very hard to compare results between these studies and draw reliable conclusions. As a result it remains unclear if SPMC is an effective alternative for PEG and NaP as bowel preparation for colonoscopy and if split-dose SPMC is more effective than single-dose SPMC.

Therefore, the present systematic review aims to assess the effectiveness of SPMC in comparison with PEG and NaP and single-dose SPMC in comparison with split-dose SPMC measured by validated tools. Secondarily we compare tolerability and side effects of these agents.

Materials and methods

Eligibility criteria

Only randomised controlled trials (RCTs) were included in this review. Selected studies included adults (>18 years), outpatients and hospitalised patients, who had to be prepared for colonoscopy. RCTs were included if they compared SPMC, or SPMC in combination with an additional laxative, with either PEG or NaP. RCTs comparing single-dose SPMC with split-dose SPMC were also included in this review. All included studies had to report the quality of bowel preparation assessed by a validated tool, namely the Ottawa Bowel Preparation Scale (OBPS),¹⁰ the Boston Bowel Preparation Scale (BBPS)¹¹ or the Aronchick scale.¹² Unfortunately there are no validated measurement tools for tolerability or severity of side effects, so we made no restrictions to the use of the measurement tools for these outcomes. Furthermore, there were no restrictions with regard to publication date in our search, but we included RCTs published only in the English language.

Information sources

We searched the following electronic databases up to January 2015: MEDLINE (Appendix 1), EMBASE (Appendix 2) and the Cochrane Central Register of Controlled Trials – CENTRAL (Appendix 3). The references of the included RCTs were searched manually to ensure no pertinent articles were missed.

Study selection

Two authors (IvL and IM) independently evaluated titles and, when available, abstracts for eligibility in this review. When more information was required to determine whether a trial met the inclusion criteria, we obtained full-text. We resolved disagreement by discussion, and when consensus was not reached, we involved a third author (AE) for decision.

Data collection process

Two authors (IvL and IM) independently extracted data from the included trials. Again, we resolved disagreement by discussion, and when consensus was not reached, we involved a third author (AE) for decision. Data items were collected digital on the Cochrane data collection form for intervention reviews.

Data items

We decided a priori to extract the following data from each article: (1) general study information (e.g. author(s), title, study period, country, location); (2) characteristics of the study (e.g. age and sex), in- and exclusion criteria and numbers of patients in each group; (3) characteristics of the intervention (e.g. type, dosing and timing of the preparation); (4) outcome measures and measurement tools.

Our primary outcome measure is effectiveness of bowel preparation, defined as quality of bowel cleansing measured by a validated tool.

Our secondary outcome measures are: quality of bowel cleansing in each colon segment, tolerability, side effects (nausea, vomiting, abdominal pain, bloating, headache and dizziness), ability to complete the preparation and willingness to repeat the same preparation in the future. Secondary outcomes were reported only from studies that also reported our primary outcome measurement.

Risk of bias in individual studies

Two authors (IvL and IM) independently assessed the risk of bias of the included studies using the Cochrane Collaboration tool for assessing risk of bias.¹³ This tool contains the following components: sequence generation, allocation concealment, blinding, incomplete outcome data, selective reporting and other potential threats to validity. We focused the assessment on the primary outcome measure and for each individual study we judged each component to be low, high or unclear risk of bias. Again, we resolved disagreement by discussion and involved a third author (AE) if necessary. Finally, we present a risk of bias summary figure to overview risk of bias assessment in all included studies.

Summary measures

Outcome measures are presented using the data and p values from the original articles. Where studies evaluated similar interventions in a similar population we formally tested heterogeneity of the data using the I² test. Where pooling seemed appropriate in view of clinical similarities between studies, we planned to use a fixed-effect model where I² was below 30% and a random-effect model where I² was between 30% and 60%.¹⁴ We did not intend to pool studies where I² was greater than 60%. For continuous outcomes, mean differences (MD) and 95% confidence intervals (CI) were calculated. For dichotomous outcomes, relative risk (RR) and 95% CI were calculated. We presented the results as described in the original articles and did not perform any recalculations.

Results

Study selection

The search yielded 776 potentially relevant titles. Two authors (IvL and IM) independently evaluated titles and, when available, abstracts for eligibility in this review. After a consensus meeting 52 articles were selected. All of these were read full-text. We excluded 40 articles, if they were non-randomised trials, investigated another bowel preparation agent, investigated a preparation for another intervention or used a non-validated measurement tool for assessing the quality of bowel cleansing. One of the articles was excluded because it was not published in English. There was no disagreement between authors on in- and exclusion of articles. We checked the references of the remaining studies and previously published reviews and that revealed three more articles. One of them met all inclusion criteria and was also included in this review. Finally, 13 RCTs were included in this review. The process of study selection is shown in the flow diagram in Figure 1, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.¹⁵

Figure 1.

Flow diagram of the study selection.

Overview of study selection process. RCTs: randomised controlled trials; SPMC: sodium picosulphate with magnesium citrate.

Study characteristics

Table 1 shows the characteristics of included RCTs. All trials were recently published (between 2009 and 2015). Most of the trials are of large size, ranging from 173 to 872 participants. The mean age of participants ranges from 48.4 years to 65.0 years and the proportion of men ranges from 35.1% to 58.6%.

Table 1.

Characteristics of included studies.

Author	Country	No. of patients	Age (mean ± SD or range)	Sex (% male)	Intervention groups	Exclusion criteria
Flemming et al.,16 2012	Canada	236	1) 57.3 ± 9.4 2) 55.4 ± 12.5	1) 47.9% 2) 45.5%	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3 DB 2) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl 2 + 3DB	Ileus, bowel obstruction, significant constipation, previous colorectal surgery, ascites, previously recognised renal impairment, active inflammatory bowel disease, pregnancy, recent myocardial infarction or unstable angina.
Hookey and Vanner,17 2009	Canada	351	1) 54.4 ± 9.5 2) 54.9 ± 10.1 3) 55.6 ± 9.5	1) 48.6% 2) 52.2% 3) 45.6%	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3 DB 2) Two sachets SPMC split-dose DB 3) 90 ml NaP split-dose DB	Recognised renal impairment, recent myocardial infarction or angina, congestive heart failure, ascites, previous colorectal resection, pregnancy.
Kao et al.,18 2011	Canada	790	1 + 2) 48.4 3 + 4) 49.8 5 + 6) 50.8 7 + 8) 49.6	1 + 2) 40.7% 3 + 4) 41.7% 5 + 6) 35.2% 7 + 8) 39.8%	1) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DB (MC) 2) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DO (AC) 3) 4 l single-dose PEG DB (MC) 4) 4 l split-dose (2/2) PEG DB + DO (AC) 5) 2 l single-dose PEG DB + 20 mg bisacodyl DB (MC) 6) 2 l single-dose PEG DO + 20 mg bisacodyl DB (AC) 7) 90 ml NaP split-dose 1 + 2 DB (MC) 8) 90 ml NaP split-dose DB + DO (AC)	Renal insufficiency, abnormal creatinine clearance, congestive heart failure, recent acute coronary syndrome or unstable angina, liver cirrhosis, ascites, chronic furosemide therapy, previous colorectal resection, known or suspected bowel obstruction, megacolon, ileus.
Katz et al.,19 2013	USA	603	1) 56.8; 21–78 2) 56.2; 18–79	1) 35.1% 2) 37.4%	1) Two sachets SPMC split-dose DB 2) 2 l PEG-3350 single-dose DB + 10 mg bisacodyl DB	Acute surgical abdominal conditions, active inflammatory bowel disease, colon disease including toxic megacolon, toxic colitis, idiopathic pseudo-obstruction and hypomotility syndrome, ascites, active ulcers, gastric outlet obstruction, retention, gastroparesis, ileus, uncontrolled angina or myocardial infarction within the last three months, congestive heart failure or uncontrolled hypertension, renal insufficiency, history of colorectal surgery, upper gastrointestinal surgery, clinically significant abnormalities in screening laboratory values.
Kim et al.,20 2014	Korea	200	Not described	Not described	1) Two sachets SPMC split-dose DB + DO 2) Three sachets SPMC split-dose (2/1) DB + DO 3) 4 l single-dose PEG DO 4) 4 l split-dose PEG DB + DO	Gastrointestinal obstruction or perforation, toxic megacolon, severe uncontrolled inflammatory bowel disease, previous colorectal resection, congestive heart failure, recent acute myocardial infarction or unstable angina, uncontrolled arterial hypertension, renal insufficiency, liver cirrhosis, ascites, pregnancy, lactation, history of hypersensitivity to any bowel cleansing agent.
Kim et al.,21 2015	Korea	387	1) 53.5 ± 10.7 2) 53.8 ± 10.4	1) 51.9% 2) 54.4%	1) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl DB 2) 4 l split-dose PEG DB + DO	Previous colorectal surgery, ileus or bowel obstruction, significant constipation, ascites, heart failure, ischemic heart disease or coronary vessel disease within the last six months, inflammatory bowel disease, pregnancy, cognitive impairment, renal impairment.
Kojecky et al.,22 2014	Czech Republic	600	1) 56.4 ± 15.3 2) 56.8 ± 16.1 3) 59.5 ± 14.1 4) 65.0 ± 14.7	1) 52.3% 2) 50.4% 3) 57.7% 4) 58.5%	1) Two sachets SPMC single-dose DB 2) Two sachets SPMC split-dose DB + DO 3) 4 l single-dose PEG DB 4) 4 l split-dose (3/1) PEG DB + DO	Ileus, known or suspected bowel obstruction, pregnancy, presence of serious medical conditions, such as severe cardiac, renal or liver diseases, active bowel inflammation and history of prior colonic or rectal surgery.
Lawrance et al.,23 2011	Australia	634	1 + 2) 55.3 ± 12.6 3 + 4) 52.7 ± 12.1 5) 53.2 ± 13.1	1 + 2) 48% 3 + 4) 46% 5) 45%	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 90 ml NaP split-dose DB (MC) 4) 90 ml NaP split-dose DB + DO (AC) 5) 4 l single-dose PEG DB (MC + AC)	Confirmed or suspected inflammatory bowel disease, current nonsteroidal anti-inflammatory drug use, heart failure, renal failure, >75 years.
Leitao et al.,24 2014	Norway	368	1) 61 (18–85) 2) 64 (19–84) Median (range)	1) 47.1% 2) 49.7%	1) 3 l split-dose (2/1) PEG DB + DO 2) Two sachets SPMC split-dose DB + DO	Active colitis, suspicion of renal insufficiency or ileus/subileus, previous colonic surgery, pregnancy, inability to adhere to the cleansing instructions and inability to consent.
Manes et al.,25 2013	Italy	293	1) 60.9 ± 12.3 2) 57.8 ± 14.4	1) 54.3% 2) 58.6%	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 2 l single-dose PEG + ascorbic acid DB (MC) 4) 2 l split-dose PEG + ascorbic acid DB + DO (AC)	Previous colonic resection, ileus, intestinal obstruction, toxic megacolon, severe heart failure, acute cardiovascular disease, uncontrolled arterial hypertension, severe liver cirrhosis, renal failure, ascites, phenylketonuria and glucose-6-phosphate dehydrogenase deficiency, pregnant or breastfeeding women.
Manes et al.,26 2014	Italy	872	1) 58.5 ± 14.4 2) 59.8 ± 14.5	1) 49.2% 2) 51.9%	1) Two sachets SPMC split-dose DB 2) Two sachets SPMC split-dose DB + DO	Previous colonic resection, ileus, intestinal obstruction, toxic megacolon, severe heart failure, acute cardiovascular disease, uncontrolled arterial hypertension, severe liver cirrhosis, renal failure, ascites, phenylketonuria and glucose-6-phosphate dehydrogenase deficiency, pregnant or breastfeeding women.
Munsterman et al.,27 2015	Netherlands	173	1) 57.39 ± 12.2 2 + 3) 55.26 ± 13.7	1) 45.9% 2 + 3) 53.4%	1) Two sachets SPMC split-dose DB + DO (MC + AC) 2) 4 l split-dose (3/1) PEG DB + DO (MC) 3) 4 l split-dose (2/2) PEG DB + DO (AC)	Ileus, significant constipation, previously recognised allergy for preparation products, severe heart failure, previously recognised renal failure, previous colorectal surgery, active inflammatory bowel disease, pregnancy, lactating.
Rex et al.,28 2013	USA	603	1) 54.8; 22–77 2) 55.7; 19–80	1) 40.7% 2) 41.6%	1) Two sachets SPMC split-dose DB + DO 2) 2 l single-dose PEG DB + 5 mg bisacodyl DB	Acute surgical abdominal conditions, active inflammatory bowel disease, colon disease including toxic megacolon, toxic colitis, idiopathic pseudo-obstruction and hypomotility syndrome, ascites, active ulcers, gastric outlet obstruction, retention, gastroparesis, ileus, uncontrolled angina or myocardial infarction within the past three months, congestive heart failure or uncontrolled hypertension, renal insufficiency, history of colorectal surgery, upper gastrointestinal surgery.

PEG: polyethylene glycol; NaP: sodium phosphate; SPMC: sodium picosulphate with magnesium citrate; DB: day before colonoscopy; DO: day of colonoscopy; MC: morning colonoscopy; AC: afternoon colonoscopy.

Risk of bias within studies

Overall, the methodological quality of the 13 RCTs is similar and good (Figure 2). Sequence generation was unclear in two trials (15%), and concealment of allocation was not described in four trials (31%). Blinding of participants and personnel was impossible because of the nature of the intervention, but it is not likely that this affected the primary outcome in any of the trials, because this outcome was scored by the endoscopist, for whom blinding of the outcome assessment was ensured in all trials. Seven trials (54%) mentioned use of an intention-to-treat (ITT) analysis, two trials (15%) possibly contain selective reporting bias and in four trials (31%) insufficient information about possible influence of funders was given, resulting in an ‘unclear risk of bias’ score. The risk of bias summary is presented in Figure 2.

Figure 2.

Risk of bias summary.

For all included studies, each component of the risk of bias assessment is scored with: low risk of bias (green, + symbol), high risk of bias (red – symbol) or unclear risk of bias (yellow, ? symbol).

Heterogeneity

The studies vary in clinically and methodological terms. First of all, the intervention groups vary in dosing and timing of the bowel preparation agent, with or without bisacodyl and single-dose or split-dose. In addition, some outcome measures are measured with different measurement tools and most of the outcome measures are reported in different ways. Because of that, meta-analysis was feasible only with studies that used the same measurement tools and reported the results in the same way.

Synthesis of results

Quality of bowel preparation

Four trials found a significant difference in quality of bowel preparation in favour of SPMC compared to PEG^19,28 or NaP.^18,23 Eight trials reported no significant difference between SPMC and PEG^{18,20–22,24,25,27} or NaP.¹⁷ We were able to pool four studies,^19,20,22,28 resulting in a small significant difference between SPMC and PEG in favour of SPMC (pooled RR 1.06; 95% CI 1.02 to 1.11). Stratifying this into SPMC compared to 4 litre PEG, no significant difference was found between the two (see Figure 3).

Figure 3.

Relative risk for each study and pooled relative risk with 95% CI to excellent/good on the Aronchick scale for SPMC versus PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Two trials found a significant difference in favour of split-dose SPMC compared to single-dose SPMC.^16,26 Kojecky et al.²² reported no significant difference between the two (Table 2).

Table 2.

Quality of bowel preparation.

Author	Measurement tool	Intervention groups	Results	p value
Flemming et al.,16 2012	OBPS + Aronchick	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3 DB 2) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl 2 + 3DB	1) 5.51 ± 2.74 2) 4.05 ± 2.37 (mean OBPS ± SD) 1) 94% 2) 67% (% excellent/good on Aronchick scale)	<0.001 in favour of 2 <0.001
Hookey and Vanner,17 2009	OBPS	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3 DB 2) Two sachets SPMC split-dose DB 3) 90 ml NaP split-dose DB	1) 5.0 ± 2.4 2) 5.1 ± 2.8 3) 5.1 ± 2.6 (mean ± SD)	0.96
Kao et al.,18 2011	OBPS	1) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DB (MC) 2) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DO (AC) 3) 4 l single-dose PEG DB (MC) 4) 4 l split-dose (2/2) PEG DB + DO (AC) 5) 2 l single-dose PEG DB + 20 mg bisacodyl DB (MC) 6) 2 l single-dose PEG DO + 20 mg bisacodyl DB (AC) 7) 90 ml NaP split-dose 1 + 2 DB (MC) 8) 90 ml NaP split-dose DB + DO (AC)	1 + 2) 3.46 (3.08–3.84) 3 + 4) 3.72 (3.29–4.14) 5 + 6) 3.36 (2.99–3.73) 7 + 8) 4.83 (4.35–5.32) (mean; 95% CI)	<0.0001 in favour of 1, 2, 3, 4, 5 and 6
Katz et al.,19 2013	OBPS + Aronchick	1) Two sachets SPMC split-dose DB 2) 2 l PEG-3350 single-dose DB + 10 mg bisacodyl DB	1) 4.2 2) 4.8 (mean OBPS) 1) 83% 2) 79.7% (% excellent/good on Aronchick scale)	0.0086 in favour of 1 NS
Kim et al.,20 2014	OBPS + Aronchick	1) Two sachets SPMC split-dose DB + DO 2) Three sachets SPMC split-dose (2/1) DB + DO 3) 4 l single-dose PEG DO 4) 4 l split-dose PEG DB + DO	1) 5.66 ± 2.10 2) 5.04 ± 2.09 3) 4.98 ± 1.78 4) 4.98 ± 1.57 (mean OBPS ± SD) 1) 80% 2) 92% 3) 82% 4) 84% (% excellent/good on Aronchick scale)	0.209 0.366
Kim et al.,21 2015	BBPS	1) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl DB 2) 4 l split-dose PEG DB + DO	1) 7.3 ± 1.6 2) 7.2 ± 1.7 (mean ± SD)	0.329
Kojecky et al.,22 2014	Aronchick	1) Two sachets SPMC single-dose DB 2) Two sachets SPMC split-dose DB + DO 3) 4 l single-dose PEG DB 4) 4 l split-dose (3/1) PEG DB + DO	1) 82.6% 2) 81.6% 3) 73% 4) 87.3% (% excellent/good on Aronchick scale)	0.024 in favour of 1, 2 and 4
Lawrance et al.,23 2011	OBPS	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 90 ml NaP split-dose DB (MC) 4) 90 ml NaP split-dose DB + DO (AC) 5) 4 l single-dose PEG DB (MC + AC)	1 + 2 vs. 3 + 4) 1.84 (0.65–3.02) 3 + 4 vs. 5) 1.62 (0.52–2.73) 1 + 2 vs. 5) not described (least square mean difference; 95% CI)	<0.001 in favour of 1 + 2 <0.001 in favour of 5 NS
Leitao et al.,24 2014	OBPS	1) 3 l split-dose (2/1) PEG DB + DO 2) Two sachets SPMC split-dose DB + DO	1) 5.0 (0–14) 2) 5.0 (0–13) (median; range)	0.30
Manes et al.,25 2013	BBPS	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 2 l single-dose PEG + ascorbic acid DB (MC) 4) 2 l split-dose PEG + ascorbic acid DB + DO (AC)	1 + 2) 6.8 ± 1.76 3 + 4) 6.6 ± 1.70 (mean ± SD)	NS
Manes et al.,26 2014	BBPS	1) Two sachets SPMC split-dose DB 2) Two sachets SPMC split-dose DB + DO	1) 6.33 ± 2.19 2) 7.25 ± 1.67 (mean ± SD)	0.0001 in favour of 2
Munsterman et al.,27 2015	BBPS	1) Two sachets SPMC split-dose DB + DO (MC + AC) 2) 4 l split-dose (3/1) PEG DB + DO (MC) 3) 4 l split-dose (2/2) PEG DB + DO (AC)	1) 8 (6–9) 2 + 3) 8 (7–9) (median; IQR)	0.182
Rex et al.,28 2013	OBPS + Aronchick	1) Two sachets SPMC split-dose DB + DO 2) 2 l single-dose PEG DB + 5 mg bisacodyl DB	1) 4.6 2) 5.5 (mean OBPS) 1) 84.2% 2) 74.4% (% excellent/good in Aronchick scale)	0.0002 in favour of 1 Not described

PEG: polyethylene glycol; NaP: sodium phosphate; SPMC: sodium picosulphate with magnesium citrate; DB: day before colonoscopy; DO: day of colonoscopy; MC: morning colonoscopy; AC: afternoon colonoscopy; OBPS: Ottawa Bowel Preparation Scale; BBPS: Boston Bowel Preparation Scale; CI: confidence interval; IQR: interquartile range.

Quality of bowel preparation in separate colon segments

Three trials reported a significant difference in quality of bowel preparation in the right colon segment in favour of SPMC compared to PEG²⁸ or NaP.^17,18 Eight trials found no significant difference in quality of bowel preparation in the right colon segment between SPMC and PEG^{18–21,23–25,27} or NaP.²³ We were able to pool two studies, but no significant difference between SPMC and PEG was found (see Figure 4).

Figure 4.

Mean difference for each study and pooled mean difference with 95% CI in quality of bowel preparation in the right colon segment on the Boston Bowel Preparation Scale for SPMC versus PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Two trials also reported a significant difference in quality of bowel preparation in the mid- and rectosigmoid colon segment in favour of SPMC compared to PEG²⁸ or NaP.¹⁸ Eight trials found no significant difference in quality of bowel preparation in the mid- and rectosigmoid colon segment between SPMC and PEG^{18–21,23,24,27} or NaP.^17,23 We were able to pool two studies, resulting in a small significant difference between SPMC and 2 litre PEG in favour of SPMC in both the mid- and rectosigmoid colon (see Figures 5 and 6).

Figure 5.

Relative risk for each study and pooled relative risk with 95% CI to excellent/good/fair in the mid-colon segment on the Ottawa Bowel Preparation Scale for SPMC versus 2 litre PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Figure 6.

Relative risk for each study and pooled relative risk with 95% CI to excellent/good/fair in the rectosigmoid colon segment on the Ottawa Bowel Preparation Scale for SPMC versus 2 litre PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Flemming et al.¹⁶ reported a significant difference in quality of bowel preparation in the right, mid- and rectosigmoid colon segment in favour of split-dose SPMC compared to single-dose SPMC. For the right colon, this was confirmed by Manes et al.,²⁶ but they found no significant difference in quality of bowel preparation in the mid- and rectosigmoid colon segment between split-dose SPMC and single-dose SPMC (Table 3).

Table 3.

Quality of bowel preparation in each colon segment.

Author	Measurement tool	Intervention groups	Results	p value
Flemming et al.,16 2012	OBPS + Aronchick	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3 DB 2) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl 2 + 3 DB	Right colon 1) 2.14 ± 0.97 2) 1.22 ± 0.86 Mid-colon 1) 1.52 ± 0.99 2) 1.15 ± 0.79 Rectosigmoid colon 1) 1.43 ± 0.95 2) 1.13 ± 0.80 (mean OBPS ± SD)	<0.001 in favour of 2 0.002 in favour of 2 0.012 in favour of 2
Hookey and Vanner,17 2009	OBPS	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3DB 2) Two sachets SPMC split-dose DB 3) 90 ml NaP split-dose DB	Not described	Right colon 0.003 in favour of 1 Mid colon NS Rectosigmoid colon NS
Kao et al.,18 2011	OBPS	1) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DB (MC) 2) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DO (AC) 3) 4 l single-dose PEG DB (MC) 4) 4 l split-dose (2/2) PEG DB + DO (AC) 5) 2 l single-dose PEG DB + 20 mg bisacodyl DB (MC) 6) 2 l single-dose PEG DO + 20 mg bisacodyl DB (AC) 7) 90 ml NaP split-dose 1 + 2 DB (MC) 8) 90 ml NaP split-dose DB + DO (AC)	Right colon 1 + 2) 1.37 3 + 4) 1.35 5 + 6) 1.10 7 + 8) 2.04 Mid-colon 1 + 2) 0.88 3 + 4) 0.89 5 + 6) 0.82 7 + 8) 1.24 Rectosigmoid colon 1 + 2) 0.71 3 + 4) 0.96 5 + 6) 0.86 7 + 8) 1.13 (mean)	<0.0001 in favour of 1, 2, 3, 4, 5 and 6 0.001 in favour of 1, 2, 3, 4, 5 and 6 0.007 in favour of 1 + 2 compared to 7 + 8
Katz et al.,19 2013	OBPS + Aronchick	1) Two sachets SPMC split-dose DB 2) 2 l PEG-3350 single-dose DB + 10 mg bisacodyl DB	Right colon 1) 81.3% 2) 84.0% Mid-colon 1) 93.2% 2) 88.7% Rectosigmoid colon 1) 92.2% 2) 89.0% (% excellent/good/fair on OBPS)	Not described Not described Not described
Kim et al.,20 2014	OBPS + Aronchick	1) Two sachets SPMC split-dose DB + DO 2) Three sachets SPMC split-dose (2/1) DB + DO 3) 4 l single-dose PEG DO 4) 4 l split-dose PEG DB + DO	Right colon 1) 1.50 ± 0.82 2) 1.47 ± 0.79 3) 1.66 ± 0.80 4) 1.69 ± 0.69 Mid-colon 1) 1.54 ± 0.70 2) 1.46 ± 0.65 3) 1.28 ± 0.61 4) 1.32 ± 0.63 Rectosigmoid colon 1) 1.50 ± 0.93 2) 1.31 ± 0.77 3) 1.24 ± 0.69 4) 1.25 ± 0.79 (mean OBPS ± SD)	0.624 0.157 0.333
Kim et al.,21 2015	BBPS	1) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl DB 2) 4 l split-dose PEG DB + DO	Right colon 1) 2.3 ± 0.7 2) 2.2 ± 0.8 Mid-colon 1) 2.5 ± 0.6 2) 2.5 ± 0.6 Rectosigmoid colon 1) 2.5 ± 0.6 2) 2.4 ± 0.7 (mean ± SD)	0.144 0.834 0.507
Lawrance et al.,23 2011	OBPS	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 90 ml NaP split-dose DB (MC) 4) 90 ml NaP split-dose DB + DO (AC) 5) 4 l single-dose PEG DB (MC + AC)	Not described	Right colon NS Mid-colon NS Rectosigmoid colon NS
Leitao et al.,24 2014	OBPS	1) 3 l split-dose (2/1) PEG DB + DO 2) Two sachets SPMC split-dose DB + DO	Right colon 1) 2 (0–4) 2) 2 (0–4) Mid-colon 1) 2 (0–4) 2) 2 (0–4) Rectosigmoid colon 1) 2 (0–4) 2) 2 (0–4) (median; range)	0.18 0.98 0.29
Manes et al.,25 2013	BBPS	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 2 l single-dose PEG + ascorbic acid DB (MC) 4) 2 l split-dose PEG + ascorbic acid DB + DO (AC)	Right colon 1 + 2) 1.95 ± 0.73 3 + 4) 1.96 ± 0.71 (mean ± SD)	NS
Manes et al.,26 2014	BBPS	1) Two sachets SPMC split-dose DB 2) Two sachets SPMC split-dose DB + DO	Right colon 1) 1.78 ± 0.94 2) 2.15 ± 0.75 (mean ± SD)	0.0001 in favour of 2
Munsterman et al.,27 2015	BBPS	1) Two sachets SPMC split-dose DB + DO (MC + AC) 2) 4 l split-dose (3/1) PEG DB + DO (MC) 3) 4 l split-dose (2/2) PEG DB + DO (AC)	Not described	Right colon 0.051 Mid-colon 0.563 Rectosigmoid colon 0.352
Rex et al.,28 2013	OBPS + Aronchick	1) Two sachets SPMC split-dose DB + DO 2) 2 l single-dose PEG DB + 5 mg bisacodyl DB	Right colon 1) 89.5% 2) 78.8% Mid-colon 1) 92.4% 2) 85.9% Rectosigmoid colon 1) 92.4% 2) 87.2% (% excellent/good/fair on OBPS)	Described as superiority for 1 Described as superiority for 1 Described as superiority for 1

PEG: polyethylene glycol; NaP: sodium phosphate; SPMC: sodium picosulphate with magnesium citrate; DB: day before colonoscopy; DO: day of colonoscopy; MC: morning colonoscopy; AC: afternoon colonoscopy; OBPS: Ottawa Bowel Preparation Scale; BBPS: Boston Bowel Preparation Scale.

Tolerability

Ten trials reported a significant difference in tolerability in favour of SPMC compared to PEG^{18–22,24,25,27,28} or NaP.¹⁷ One trial found no significant difference in tolerability between SPMC and PEG or NaP.¹⁸ The other two trials found no significant differences in tolerability between single-dose SPMC and split-dose SPMC^16,26 (Table 4).

Table 4.

Tolerability.

Author	Intervention groups	Results	p value
Flemming et al.,16 2012	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3 DB 2) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl 2 + 3 DB	Not described	0.704
Hookey and Vanner,17 2009	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3 DB 2) Two sachets SPMC split-dose DB 3) 90 ml NaP split-dose DB	1) 75% 2) 78.9% 3) 47.5% (% very easy/easy to take)	<0.0001 in favour of 1 and 2
Kao et al.,18 2011	1) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DB (MC) 2) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DO (AC) 3) 4 l single-dose PEG DB (MC) 4) 4 L split-dose (2/2) PEG DB + DO (AC) 5) 2 l single-dose PEG DB + 20 mg bisacodyl DB (MC) 6) 2 l single-dose PEG DO + 20 mg bisacodyl DB (AC) 7) 90 ml NaP split-dose 1 + 2DB (MC) 8) 90 ml NaP split-dose DB + DO (AC)	1 + 2) 4.66 3 + 4) 4.19 5 + 6) 4.60 7 + 8) 4.75 (mean overall tolerability score on a seven-point Likert scale)	<0.011 in favour of 1, 2, 5, 6, 7 and 8
Katz et al.,19 2013	1) Two sachets SPMC split-dose DB 2) 2 l PEG-3350 single-dose DB + 10 mg bisacodyl DB	1) 87.4% 2) 37.2% (% very easy/easy to take)	<0.0001 in favour of 1
Kim et al.,20 2014	1) Two sachets SPMC split-dose DB + DO 2) Three sachets SPMC split-dose (2/1) DB + DO 3) 4 l single-dose PEG DO 4) 4 l split-dose PEG DB + DO	1) 0% 2) 8% 3) 32% 4) 20% (% that had difficulty with bowel preparation protocol)	0.001 in favour of 1 and 2
Kim et al.,21 2015	1) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl DB 2) 4 l split-dose PEG DB + DO	1) 94.5% 2) 63.0% (% very easy/easy to take)	<0.001 in favour of 1
Kojecky et al.,22 2014	1) Two sachets SPMC single-dose DB 2) Two sachets SPMC split-dose DB + DO 3) 4 l single-dose PEG DB 4) 4 l split-dose (3/1) PEG DB + DO	1) 60.6% 2) 56.0% 3) 24.1% 4) 23.1% (% with the best tolerance score)	<0.001 in favour of 1 and 2
Leitao et al.,24 2014	1) 3 l split-dose (2/1) PEG DB + DO 2) Two sachets SPMC split-dose DB + DO	1) 68% 2) 55% (% discomfort of any level)	0.007
Manes et al.,25 2013	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 2 l single-dose PEG + ascorbic acid DB (MC) 4) 2 l split-dose PEG + ascorbic acid DB + DO (AC)	1 + 2) 97.1% 3 + 4) 84.8% (% no/mild discomfort)	<0.0003 in favour of 1 and 2
Manes et al.,26 2014	1) Two sachets SPMC split-dose DB 2) Two sachets SPMC split-dose DB + DO	1) 7.6% 2) 8.8% (% discomfort of any level)	NS
Munsterman et al.,27 2015	1) Two sachets SPMC split-dose DB + DO (MC + AC) 2) 4 l split-dose (3/1) PEG DB + DO (MC) 3) 4 l split-dose (2/2) PEG DB + DO (AC)	1) 0 (0–1) 2 + 3) 2 (1–2.27) (median; IQR on a five-point Likert scale)	<0.001 in favour of 1
Rex et al.,28 2013	1) Two sachets SPMC split-dose DB + DO 2) 2 l single-dose PEG DB + 5 mg bisacodyl DB	1) 89% 2) 29.1% (% very easy/easy to take)	<0.0001 in favour of 1

PEG: polyethylene glycol; NaP: sodium phosphate; SPMC: sodium picosulphate with magnesium citrate; DB: day before colonoscopy; DO: day of colonoscopy; MC: morning colonoscopy; AC: afternoon colonoscopy; IQR: interquartile range.

Side effects

In 12 out of 13 trials side effects were reported. The different results across all the studies are listed in Table 5. When pooling a number of these results, the prevalence of nausea, vomiting, abdominal pain and headache was not significantly different between SPMC and PEG (see Figures 7–10). In addition we were able to pool two studies for dizziness.^23,26 The pooled RR of the incidence of dizziness shows a significant difference in favour of (4 litre) PEG compared to SPMC (pooled RR 1.46; 95% CI 1.11 to 1.92 and pooled RR 1.71; 95% CI 1.32 to 2.21) (see Figure 11). Unfortunately it was not possible to pool studies comparing SPMC with NaP.

Figure 12.

Relative risk for each study and pooled relative risk with 95% CI to get vomiting for single-dose SPMC versus split-dose SPMC. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate.

Table 5.

Side effects.

Author	Intervention groups	Results and p values
Flemming et al.,16 2012	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3DB 2) Two sachets SPMC split-dose DB + DO +  10 mg bisacodyl 2 + 3DB	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 24.8% 2) 23.9%	0.61	1) 3.4% 2) 6.8%	0.38	1) 23.1% 2) 28.2%	0.46	1) 13.7% 2) 17.9%	1.0			1) 8.5% 2) 9.4%	1.0
Hookey and Vanner,17 2009	1) Two sachets SPMC split-dose DB + 10 mg bisacodyl 2 + 3DB 2) Two sachets SPMC split-dose DB 3) 90 ml NaP split-dose DB	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 19.2% 2) 22% 3) 39.6%	0.002 in favour of 1 and 2	UNK	NS	UNK	NS	UNK	NS
Kao et al.,18 2011	1) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DB (MC) 2) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DO (AC) 3) 4 l single-dose PEG DB (MC) 4) 4 l split-dose (2/2) PEG DB + DO (AC) 5) 2 l single-dose PEG DB + 20 mg bisacodyl DB (MC) 6) 2 l single-dose PEG DO + 20 mg bisacodyl DB (AC) 7) 90 ml NaP split-dose 1 + 2DB (MC) 8) 90 ml NaP split-dose DB + DO (AC)	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1 + 2) 44% 3 + 4) 51% 5 + 6) 44% 7 + 8) 48%	0.444	1 + 2) 11% 3 + 4) 13% 5 + 6) 11% 7 + 8) 6%	0.515	1 + 2) 39% 3 + 4) 45% 5 + 6) 42% 7 + 8) 44%	0.634	1 + 2) 41% 3 + 4) 58% 5 + 6) 46% 7 + 8) 43%	0.051			1 + 2) 30% 3 + 4) 22% 5 + 6) 12% 7 + 8) 26%	0.001 in favour of 5 and 6
Katz et al.,19 2013	1) Two sachets SPMC split-dose DB 2) 2 l PEG-3350 single-dose DB + 10 mg bisacodyl DB	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 3.0% 2) 4.3%	UNK	1) 1.3% 2) 2.0%	UNK					1) 2.7% 2) 1.7%	UNK
Kim et al.,20 2014	1) Two sachets SPMC split-dose DB + DO 2) Three sachets SPMC split-dose (2/1) DB + DO 3) 4 l single-dose PEG DO 4) 4 l split-dose PEG DB + DO	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 22% 2) 22% 3) 60% 4) 44%	0.000 in favour of 1 and 2	1) 2% 2) 0% 3) 26% 4) 8%	0.000 in favour of 1 and 2	1) 6% 2) 18% 3) 36% 4) 24%	0.002 in favour of 1 and 2	1) 12% 2) 32% 3) 68% 4) 66%	0.000 in favour of 1 and 2
Kim et al.,21 2015	1) Two sachets SPMC split-dose DB + DO +  10 mg bisacodyl DB 2) 4 l split-dose PEG DB + DO	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 28.7% 2) 42.4%	0.006 in favour of 1	1) 12.7% 2) 16.9%	0.265	1) 26.5% 2) 23.9%	0.566	1) 38.7% 2) 56.0%	0.001 in favour of 1			1) 24.3% 2) 14.7%	0.020 in favour of 2
Kojecky et al.,22 2014	1) Two sachets SPMC single-dose DB 2) Two sachets SPMC split-dose DB + DO 3) 4 l single-dose PEG DB 4) 4 l split-dose (3/1) PEG DB + DO	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 6.1% 2) 18.4% 3) 32.8% 4) 14.9%	<0.001 in favour of 1 compared with 3	1) 0.8% 2) 4.8% 3) 5.8% 4) 1.5%	0.049	1) 6.1% 2) 17.6% 3) 17.5% 4) 14.9%	0.021 in favour of 1	1) 18.9% 2) 15.2% 3) 38.0% 4) 25.4%	<0.001 in favour of 1 and 2
Leitao et al.,24 2014	1) 3 l split-dose (2/1) PEG DB + DO 2) Two sachets SPMC split-dose DB + DO	Nausea/ Vomiting	p value	Nausea/ Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 57% 2) 36%	<0.001	1) 57% 2) 36%	<0.001	1) 25% 2) 27%	0.89	1) 44% 2) 40%	0.45
Manes et al.,25 2013	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 2 l single-dose PEG + ascorbic acid DB (MC) 4) 2 l split-dose PEG + ascorbic acid DB + DO (AC)	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		UNK	<0.00001 in favour of 1 and 2	UNK	0.03 in favour of 1 and 2	UNK	NS	UNK	0.006 in favour of 1 and 2	UNK	NS	UNK	NS
Manes et al.,26 2014	1) Two sachets SPMC split-dose DB 2) Two sachets SPMC split-dose DB + DO	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		UNK	NS			UNK	NS	UNK	NS	UNK	NS	UNK	NS
Munsterman et al.,27 2015	1) Two sachets SPMC split-dose DB + DO (MC + AC) 2) 4 l split-dose (3/1) PEG DB + DO (MC) 3) 4 l split-dose (2/2) PEG DB + DO (AC)	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 0 (0–1) 2 + 3) 0 (0–1)	0.011 in favour of 1	1) 0 (0–0) 2 + 3) 0 (0–0)	0.001 in favour of 1	1) 0 (0–1) 2 + 3) 0 (0–1)	0.207	1) 0 (0–1) 2 + 3) 1 (0–2)	<0.001 in favour of 1	1) 0 (0–1) 2 + 3) 1 (0–1)	0.003 in favour of 1	1) 0 (0–0.25) 2 + 3) 0 (0–1)	0.260
Rex et al.,28 2013	1) Two sachets SPMC split-dose DB + DO 2) 2 l single-dose PEG DB + 5 mg bisacodyl DB	Nausea	p value	Vomiting	p value	Abd. pain	p value	Bloating	p value	Headache	p value	Dizziness	p value
		1) 2.6% 2) 3.7%	UNK	1) 1.0% 2) 3.4%	UNK					1) 1.6% 2) 1.7%	UNK

PEG: polyethylene glycol; NaP: sodium phosphate; SPMC: sodium picosulphate with magnesium citrate; DB: day before colonoscopy; DO: day of colonoscopy; MC: morning colonoscopy; AC: afternoon colonoscopy; Abd.: abdominal; UNK: unknown.

Figure 7.

Relative risk for each study and pooled relative risk with 95% CI to get nausea for SPMC versus 2 litre PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Figure 8.

Relative risk for each study and pooled relative risk with 95% CI to get vomiting for SPMC versus PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Figure 9.

Relative risk for each study and pooled relative risk with 95% CI to get abdominal pain for SPMC versus PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Figure 10.

Relative risk for each study and pooled relative risk with 95% CI to get headache for SPMC versus PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Figure 11.

Relative risk for each study and pooled relative risk with 95% CI to get dizziness for SPMC versus PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

The pooled RR of the incidence of vomiting between single-dose and split-dose SPMC from two studies was in favour of single-dose SPMC (pooled RR 0.35; 95% CI 0.13 to 0.95) (see Figure 13).^16,22

Figure 13.

Relative risk for each study and pooled relative risk with 95% CI to get bloating for single-dose SPMC versus split-dose SPMC. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate.

Lastly we were able to pool the two studies that measured the incidence of bloating between single-dose and split-dose SPMC, but no significant difference was found (pooled RR 1.00, 95% CI 0.67 to 1.48) (see Figure 13).^16,22

Ability to complete the preparation and willingness to repeat the same preparation in the future

Overall, ability to complete the preparation was in favour of SPMC compared to PEG or NaP and a little bit in favour of split-dose SPMC compared to single-dose SPMC (Table 6, Figures 14 and 15). Willingness to repeat the same preparation in the future was in favour of SPMC compared to PEG and no significant difference was reported between split-dose SPMC and single-dose SPMC (Table 7).

Table 6.

Ability to complete the preparation.

Author	Intervention groups	Results (% able to consume the full amount)	p value
Katz et al.,19 2013	1) Two sachets SPMC split-dose DB 2) 2 l PEG-3350 single-dose DB + 10 mg bisacodyl DB	1) 99.7% 2) 92.3%	Not described
Kim et al.,21 2015	1) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl DB 2) 4 l split-dose PEG DB + DO	1) 99.4% 2) 90.2%	<0.001 in favour of 1
Kojecky et al.,22 2014	1) Two sachets SPMC single-dose DB 2) Two sachets SPMC split-dose DB + DO 3) 4 l single-dose PEG DB 4) 4 l split-dose (3/1) PEG DB + DO	1) 77.3% 2) 76.8% 3) 85.4% 4) 80.6%	NS
Lawrance et al.,23 2011	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 90 ml NaP split-dose DB (MC) 4) 90 ml NaP split-dose DB + DO (AC) 5) 4 l single-dose PEG DB (MC + AC)	1 + 2) 100% 3 + 4) 90%	Not described
Leitao et al.,24 2014	1) 3 l split-dose (2/1) PEG DB + DO 2) Two sachets SPMC split-dose DB + DO	1) 81.2% 2) 94.2%	0.001
Manes et al.,25 2013	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 2 l single-dose PEG + ascorbic acid DB (MC) 4) 2 l split-dose PEG + ascorbic acid DB + DO (AC)	1 + 2) 83.6% 3 + 4) 77.9%	NS
Manes et al.,26 2014	1) Two sachets SPMC split-dose DB 2) Two sachets SPMC split-dose DB + DO	1) 70.4% 2) 78.9%	0.008 in favour of 2 OR: 1.57 95% CI: 1.12–2.21
Rex et al.,28 2013	1) Two sachets SPMC split-dose DB + DO 2) 2 l single-dose PEG DB + 5 mg bisacodyl DB	1) 99.0% 2) 89.9%	<0.0001 in favour of 1

PEG: polyethylene glycol; NaP: sodium phosphate; SPMC: sodium picosulphate with magnesium citrate; DB: day before colonoscopy; DO: day of colonoscopy; MC: morning colonoscopy; AC: afternoon colonoscopy; OR: odds ratio; CI: confidence interval.

Figure 14.

Relative risk for each study and pooled relative risk with 95% CI to complete the preparation for SPMC versus 2 litre PEG. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate; PEG: polyethylene glycol.

Figure 15.

Relative risk for each study and pooled relative risk with 95% CI to complete the preparation for single-dose SPMC versus split-dose SPMC. CI: confidence interval; SPMC: sodium picosulphate with magnesium citrate.

Table 7.

Willingness to repeat the same preparation in the future.

Author	Intervention groups	Results (% willingness to repeat the same preparation for a future endoscopy)	p value
Kao et al.,18 2011	1) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DB (MC) 2) Two sachets SPMC split-dose DB + 300 ml magnesium citrate DO (AC) 3) 4 l single-dose PEG DB (MC) 4) 4 l split-dose (2/2) PEG DB + DO (AC) 5) 2 l single-dose PEG DB + 20 mg bisacodyl DB (MC) 6) 2 l single-dose PEG DO + 20 mg bisacodyl DB (AC) 7) 90 ml NaP split-dose 1 + 2DB (MC) 8) 90 ml NaP split-dose DB + DO (AC)	Not described	<0.0001 in favour of 1, 2, 7 and 8
Katz et al.,19 2013	1) Two sachets SPMC split-dose DB 2) 2 l PEG-3350 single-dose DB + 10 mg bisacodyl DB	1) 93.2% 2) 59.4%	<0.0001 in favour of 1
Kim et al.,21 2015	1) Two sachets SPMC split-dose DB + DO + 10 mg bisacodyl DB 2) 4 l split-dose PEG DB + DO	1) 83.2% 2) 48.5%	<0.001 in favour of 1
Manes et al.,25 2013	1) Two sachets SPMC split-dose DB (MC) 2) Two sachets SPMC split-dose DB + DO (AC) 3) 2 l single-dose PEG + ascorbic acid DB (MC) 4) 2 l split-dose PEG + ascorbic acid DB + DO (AC)	1 + 2) 97.8% 3 + 4) 83.4%	<0.0001 in favour of 1
Manes et al.,26 2014	1) Two sachets SPMC split-dose DB 2) Two sachets SPMC split-dose DB + DO	1) 95.8% 2) 96.5%	NS
Rex et al.,28 2013	1) Two sachets SPMC split-dose DB + DO 2) 2 l single-dose PEG DB + 5 mg bisacodyl DB	1) 96.0% 2) 54.7%	<0.0001 in favour of 1

PEG: polyethylene glycol; NaP: sodium phosphate; SPMC: sodium picosulphate with magnesium citrate; DB: day before colonoscopy; DO: day of colonoscopy; MC: morning colonoscopy; AC: afternoon colonoscopy.

Discussion

This meta-analysis shows a slight significant difference in quality of bowel preparation in favour of SPMC compared to PEG. However, when stratifying the subgroup SPMC compared to 4 litre PEG the significance of this result was lost. When looking at tolerability of the bowel preparation we found that SPMC preparations are better tolerated than PEG preparations. Overall, no statistically significant differences in either quality of bowel preparation or tolerability were demonstrated between SPMC and NaP. Side effects were similar between SPMC and PEG or NaP, except for dizziness. A significant difference in the incidence of dizziness was found between SPMC and PEG in favour of PEG. Side effects were also similar between single-dose SPMC and split-dose SPMC, except for vomiting. A slight significant difference in the incidence of vomiting was found in favour of single-dose SPMC.

Our main results about quality of bowel cleansing are consistent with the conclusions in the review of Barkun et al.² The better tolerability was also found in the review of Hookey and Vanner,³ Jin et al.⁶ and Tan and Tjandra.⁴ However, these latter found NaP more effective in bowel cleansing than sodium picosulphate or PEG. However, in the reviews by Hookey and Vanner and Tan and Tjandra, sodium picosulphate was compared instead of SPMC.

The flaw of these reviews is that they also included studies that used non-validated and subjective measurement tools for the assessment of overall quality of bowel cleansing. Our results, although generally consistent with the results in earlier reviews, have a stronger body of evidence due to the inclusion of only objective and validated measurement tools for effectiveness of bowel preparation.

Due to lack of homogeneity in measurement tools and the way of reporting outcome measures, pooling was possible only within studies that used the same measurement tools and reported the results in the same way. The meta-analysis conducted in this review provides additional information about the extent of the effect, but should always be considered carefully together with the non-pooled results.

We acknowledge several limitations in our study. First, not all databases were explored, although the main medical electronic databases were included. Second, the results we found may be influenced by the various dietary restrictions used in the RCTs. These varied from a low-fibre diet one, two or three days before colonoscopy to a clear liquid diet with or without a light breakfast or lunch, and with or without fasting for a certain period on the day before colonoscopy. A combination of both was also used. We have not considered these differences in this review because it makes it impossible to compare results. Thirdly, the findings of this review are restricted to the effectiveness and tolerability of SPMC as bowel preparation agent for colonoscopy. Safety is not included as outcome separately; however, in this review we took the side effects into account.

Several populations, such as children, elderly, patients with severe heart failure, renal insufficiency or previous colorectal surgery, were excluded in the RCTs. Therefore, we still have no knowledge about the effectiveness and tolerability of SPMC compared to PEG and NaP in these sensitive populations. Future research could therefore focus on the effectiveness and tolerability of SPMC compared to PEG and NaP in sensitive populations, and the most appropriate additional dietary restriction.

In conclusion, SPMC is equally effective as bowel preparation to NaP and little superior to PEG. Furthermore, the tolerability of SPMC is better than of PEG preparations. These findings are important for clinical practice, as the frequency of colonoscopies will increase due to recently introduced screening programs in multiple countries in Europe with more patients being exposed to bowel preparation agents. Because inability to complete the preparation contributes to poor cleansing, which may lead to incomplete visualisation of the colon, it is important that a bowel preparation agent is effective in cleansing and also tolerable for patients.^2,29

SPMC has the most of these properties, and may therefore be considered as a first-choice bowel preparation agent.

Appendix 1. PubMed search terms

(((Colonoscopy[Mesh] OR Colonoscop*[tiab] OR “Colonoscopic Surgery”[tiab]) AND ((“Polyethylene Glycols”[Mesh] OR “Polyethylene Glycol”[tiab] OR “Polyethylene Glycols”[tiab] OR Polyoxyethylene*[tiab] OR “Polyethylene Oxide”[tiab] OR “Polyethylene Oxides”[tiab] OR Macrogol*[tiab] OR Polyethyleneoxide*[tiab] OR Lauromacrogol*[tiab] OR Miralax*[tiab] OR Carbowax-400[tiab] OR “Carbowax 400”[tiab] OR “Polyethylene Glycol 1000”[tiab] OR “PEG 1000”[tiab] OR “Polyethylene Glycol 8000”[tiab] OR “PEG 8000”[tiab] OR “Polyethylene Glycol 2000”[tiab] OR “Polyethylene Glycol 300”[tiab] OR “Macrogol 300”[tiab] OR “Polyethylene Glycol 3350”[tiab] OR “PEG 3350”[tiab] OR “Polyethylene Glycol 400”[tiab] OR “PEG 400”[tiab] OR “PEO 400”[tiab] OR “Polyethylene Glycol 4000”[tiab] OR “Polyethylene Glycol 6000”[tiab] OR “PEG 6000”[tiab] OR Tritons[tiab] OR Vigilon[tiab] OR Golytely[Supplementary Concept] OR Golytely[tiab] OR Isocolan[tiab] OR Colyte[tiab] OR NuLytely[Supplementary Concept] OR NuLytely[tiab] OR SF-ELS[tiab] OR Halflytely[tiab] OR MoviPrep[Supplementary Concept] OR MoviPrep[tiab] OR PEG[tiab] OR Kleanprep[tiab]) OR (“picosulfate sodium”[Supplementary Concept] OR “picosulfate sodium”[tiab] OR “sodium picosulfate”[tiab] OR Picolines[Mesh] OR Picoline*[tiab] OR Picoprep[tiab] OR Picolax[tiab] OR Picosulfol[tiab] OR Laxoberal[tiab] OR “magnesium citrate”[Supplementary Concept] OR “magnesium citrate”[tiab] OR “mg citrate”[tiab] OR CitraFleet[tiab] OR Picoprep-3[tiab]) OR (“sodium phosphate”[Supplementary Concept] OR “sodium phosphate”[tiab] OR Visicol[tiab] OR Osmoprep[tiab] OR “Fleet Phospho-Soda”[tiab] OR Phosphoral[tiab]))) AND ((randomized controlled trial [pt] OR controlled clinical trial [pt] OR randomized [tiab] OR placebo [tiab] OR drug therapy [sh] OR randomly [tiab] OR trial [tiab] OR groups [tiab]) NOT (animals[mh] NOT (animals[mh] AND humans [mh])))

Appendix 2. EMBASE search terms

•  1 exp colonoscopy/ (46056)

•  2 Colonoscop*.ti,ab,kw. (33407)

•  3 “Colonoscopic Surgery”.ti,ab,kw. (2)

•  4 1 or 2 or 3 (52356)

•  5 exp macrogol derivative/ (10439)

•  6 “Polyethylene Glycol”.ti,ab,kw. (20909)

•  7 “Polyethylene Glycols”.ti,ab,kw. (892)

•  8 Polyoxyethylene*.ti,ab,kw. (2241)

•  9 “Polyethylene Oxide”.ti,ab,kw. (1181)

• 10 “Polyethylene Oxides”.ti,ab,kw. (50)

• 11 Macrogol*.ti,ab,kw. (400)

• 12 Polyethyleneoxide*.ti,ab,kw. (128)

• 13 Lauromacrogol*.ti,ab,kw. (33)

• 14 Miralax*.ti,ab,kw. (75)

• 15 Carbowax-400.ti,ab,kw. (13)

• 16 Carbowax400.ti,ab,kw. (0)

• 17 “Carbowax 400”.ti,ab,kw. (13)

• 18 “Polyethylene Glycol 1000”.ti,ab,kw. (248)

• 19 “PEG 1000”.ti,ab,kw. (208)

• 20 “Polyethylene Glycol 8000”.ti,ab,kw. (194)

• 21 “PEG 8000”.ti,ab,kw. (329)

• 22 “Polyethylene Glycol 2000”.ti,ab,kw. (146)

• 23 “Polyethylene Glycol 300”.ti,ab,kw. (76)

• 24 “Macrogol 300”.ti,ab,kw. (5)

• 25 “Polyethylene Glycol 3350”.ti,ab,kw. (211)

• 26 “PEG 3350”.ti,ab,kw. (311)

• 27 “Polyethylene Glycol 400”.ti,ab,kw. (714)

• 28 “PEG 400”.ti,ab,kw. (1060)

• 29 “PEO 400”.ti,ab,kw. (21)

• 30 “Polyethylene Glycol 4000”.ti,ab,kw. (472)

• 31 “Polyethylene Glycol 6000”.ti,ab,kw. (640)

• 32 “PEG 6000”.ti,ab,kw. (935)

• 33 “Polyox FRA”.ti,ab,kw. (1)

• 34 Tritons.ti,ab,kw. (115)

• 35 Vigilon.ti,ab,kw. (15)

• 36 “Carbowax 600”.ti,ab,kw. (0)

• 37 exp golytely/ (446)

• 38 Golytely.ti,ab,kw. (166)

• 39 Isocolan.ti,ab,kw. (8)

• 40 Colyte.ti,ab,kw. (32)

• 41 exp bicarbonate plus macrogol 3350 plus potassium chloride plus sodium

• chloride/ (15)

• 42 Nulytely.ti,ab,kw. (17)

• 43 SF-ELS.ti,ab,kw. (5)

• 44 Trilyte.ti,ab,kw. (3)

• 45 Halflytely.ti,ab,kw. (19)

• 46 exp moviprep/ (101)

• 47 Moviprep.ti,ab,kw. (75)

• 48 Glycolax.ti,ab,kw. (0)

• 49 PEG.ti,ab,kw. (37262)

• 50 Kleanprep.ti,ab,kw. (6)

• 51 5 or 6 or 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34 or 35 or 37 or 38 or 39 or 40 or 41 or 42 or 43 or 44 or 45 or 46 or 47 or 49 or 50 (59051)

• 52 exp picosulfate sodium/ (755)

• 53 “picosulfate sodium”.ti,ab,kw. (6)

• 54 “sodium picosulfate”.ti,ab,kw. (156)

• 55 exp picoline derivative/ (1058)

• 56 Picoline*.ti,ab,kw. (423)

• 57 “4,4'-(picoliliden)-bis-phenylsulphate”.ti,ab,kw. (0)

• 58 “4,4'-(2-picolylidene)bisphenylsulfuricacid”.ti,ab,kw. (0)

• 59 Picoprep.ti,ab,kw. (23)

• 60 Picolax.ti,ab,kw. (71)

• 61 Picosulfol.ti,ab,kw. (3)

• 62 Laxoberal.ti,ab,kw. (10)

• 63 exp magnesium citrate/ (1049)

• 64 “magnesium citrate”.ti,ab,kw. (407)

• 65 “mg citrate”.ti,ab,kw. (66)

• 66 CitraFleet.ti,ab,kw. (7)

• 67 Picoprep-3.ti,ab,kw. (3)

• 68 Prepopik.ti,ab,kw. (7)

• 69 Pico-Salix.ti,ab,kw. (0)

• 70 52 or 53 or 54 or 55 or 56 or 59 or 60 or 61 or 62 or 63 or 64 or 65 or 66 or 67 or 68 (3105)

• 71 exp sodium dihydrogen phosphate/ (4010)

• 72 “sodium phosphate”.ti,ab,kw. (4571)

• 73 Visicol.ti,ab,kw. (14)

• 74 Osmoprep.ti,ab,kw. (7)

• 75 “Fleet Phospho-Soda”.ti,ab,kw. (47)

• 76 Phosphoral.ti,ab,kw. (6)

• 77 71 or 72 or 73 or 74 or 75 or 76 (6814)

• 78 51 or 70 or 77 (68071)

• 79 4 and 78 (1814)

• 80 Clinical trial/ (843273)

• 81 Randomized controlled trial/ (353844)

• 82 Randomization/ (63766)

• 83 Single blind procedure/ (18939)

• 84 Double blind procedure/ (120418)

• 85 Crossover procedure/ (40701)

• 86 Placebo/ (263779)

•  87 Randomi?ed controlled trial$.tw. (104419)

•  88 Rct.tw. (15052)

•  89 Random allocation.tw. (1419)

•  90 Randomly allocated.tw. (21229)

•  91 Allocated randomly.tw. (1984)

•  92 (allocated adj2 random).tw. (873)

•  93 Single blind$.tw. (15085)

•  94 Double blind$.tw. (153969)

•  95 ((treble or triple) adj blind$).tw. (439)

•  96 Placebo$.tw. (212771)

•  97 Prospective study/ (264665)

•  98 or/80-97 (1421270)

•  99 Case study/ (37420)

• 100 Case report.tw. (291051)

• 101 Abstract report/ or letter/ (922123)

• 102 or/99-101 (1244699)

• 103 98 not 102 (1382598)

• 104 79 and 103 (561)

Appendix 3. Cochrane Central Register of Controlled Trials (CENTRAL) search terms

•  #1 Colonoscop*:ti.ab.kw

•  #2 Polyethylene Glycols:ti.ab.kw

•  #3 PolyethyleneGlycol:ti.ab.kw

•  #4 Polyoxyethylene*:ti.ab.kw

•  #5 Polyethylene Oxide:ti.ab.kw

•  #6 Polyethylene Oxides:ti.ab.kw

•  #7 Macrogol*:ti.ab.kw

•  #8 Polyethyleneoxide*:ti.ab.kw

•  #9 Lauromacrogol*:ti.ab.kw

• #10 Miralax*:ti.ab.kw

• #11 Carbowax-400:ti.ab.kw

• #12 Carbowax400:ti.ab.kw

• #13 Carbowax 400:ti.ab.kw

• #14 Polyethylene Glycol 1000:ti.ab.kw

• #15 PEG 1000:ti.ab.kw

• #16 Polyethylene Glycol 8000:ti.ab.kw

• #17 PEG 8000:ti.ab.kw

• #18 Polyethylene Glycol 2000:ti.ab.kw

• #19 Polyethylene Glycol 300:ti.ab.kw

• #20 Macrogol 300:ti.ab.kw

• #21 Polyethylene Glycol 3350:ti.ab.kw

• #22 PEG 3350:ti.ab.kw

• #23 Polyethylene Glycol 400:ti.ab.kw

• #24 PEG 400:ti.ab.kw

• #25 PEO 400:ti.ab.kw

• #26 Polyethylene Glycol 4000:ti.ab.kw

• #27 Polyethylene Glycol 6000:ti.ab.kw

• #28 PEG 6000:ti.ab.kw

• #29 Polyox FRA:ti.ab.kw

• #30 Tritons:ti.ab.kw

• #31 Vigilon:ti.ab.kw

• #32 Carbowax 600:ti.ab.kw

• #33 Golytely:ti.ab.kw

• #34 Isocolan:ti.ab.kw

• #35 Colyte:ti.ab.kw

• #36 NuLytely:ti.ab.kw

• #37 SF-ELS:ti.ab.kw

• #38 Trilyte:ti.ab.kw

• #39 Halflytely:ti.ab.kw

• #40 Moviprep:ti.ab.kw

• #41 Glycolax:ti.ab.kw

• #42 PEG:ti.ab.kw

• #43 Kleanprep:ti.ab.kw

• #44 #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or #35 or #36 or #37 or #38 or #39 or #40 or #41 or #42 or #43

• #45 picosulfate sodium:ti.ab.kw

• #46 sodium picosulfate:ti.ab.kw

• #47 Picoline*:ti.ab.kw

• #48 4,4'-(picoliliden)-bis-phenylsulphate:ti.ab.kw

• #49 4,4'-(2-picolylidene)bisphenylsulfuricacid:ti.ab.kw

• #50 Picoprep:ti.ab.kw

• #51 Picolax:ti.ab.kw

• #52 Picosulfol:ti.ab.kw

• #53 Laxoberal:ti.ab.kw

• #54 magnesium citrate:ti.ab.kw

• #55 mg citrate:ti.ab.kw

• #56 CitraFleet:ti.ab.kw

• #57 Picoprep-3:ti.ab.kw

• #58 Prepopik:ti.ab.kw

• #59 Pico-Salix:ti.ab.kw

• #60 #45 or #46 or #47 or #48 or #49 or #50 or #51 or #52 or #53 or #54 or #55 or #56 or #57 or #58

•   or 59

• #61 sodium phosphate:ti.ab.kw

• #62 Visicol:ti.ab.kw

• #63 Osmoprep:ti.ab.kw

• #64 Fleet Phospho-Soda:ti.ab.kw

• #65 Phosphoral:ti.ab.kw

• #66 #61 or #62 or #63 # or #64 or #65

• #67 #44 or #60 or #66

• #68 #1 and #67

Declaration of conflicting interests

None declared.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.