Same-day single-dose vs large-volume split-dose regimens of polyethylene glycol for bowel preparation: A systematic review and meta-analysis

Table 1 Characteristics of included studies

Ref.	Type of study	Participants and years of age	Bowel preparation	Patients with SSD/SpDs, n	Diet instruction	Colonoscopy timing	Outcomes	Interval, PC	Jadad score, modified	Use of adjuvant
Zhang et al[11], 2021	Single-center, single-blind, RCT	Outpatients 18-70 yr	SSD (A): 2 L PEG 6 h before procedure; SSD (B): 290 µg Lin 7 h before + 0.5 L water, 2 L PEG 6 h before colonoscopy; SpDs: 2 L PEG at 21:00 the day prior, 2 L PEG 6 h before colonoscopy	139A/141B/140	1-d LRD	Morning: 8:00-11:30; Afternoon: 13:30- 17:00	BBPS	6 h	4	SSD (B): Linaclotide
Barkun et al[12], 2020	Multicenter, single-blind, RCT	Outpatients ≥ 18 yr	SSD: 2 L PEG 4 h before colonoscopy + 15 mg bis at 14:00 the day before; SpDs: 2 L PEG at 19:00 the day before, 2 L PEG 4-5 h before colonoscopy	583/582	Not described	10:30-16:30	BBPS	2-3 h	5	Bisacodyl
Castro et al[13], 2019	Single-center, single-blind, RCT	Outpatients ≥ 18 yr	SSD: 4 L PEG at 6:00; SpDs: 2 L PEG at 18:00 the day before, 2 L PEG 6 h before colonoscopy	142/158	CLD after regular breakfast the day before	13:00-16:30	OBPS	Not described	5	No
Seo et al[14], 2019	Single-center, single-blind, RCT	Outpatients 40–75 yr	SSD (Mor): 4 L PEG at 5:00; SSD (Aft): 2 L PEG at 7:00 + 2 L PEG at 10:00; SpDs: 2 L PEG at 21:00 the day before, 2 L PEG at 7:00 (Mor) or at 10:00 (Aft)	172/167	LFF for 2 d, soft diet dinner the day prior	Morning 10:00-12:00; Afternoon 13:30-17:00	BBPS	Not described	3	No
Kang et al[15], 2018	Single-center, single-blind, RCT	Patients 18-70 yr	SSD: 2 L PEG 4-6 h before colonoscopy; SpDs: 2 L PEG at 19:00-21:00 the day before, 2 L PEG 4-6 h before colonoscopy	470/470	Regular meal for lunch and CLD or LRD for dinner the day before	Morning 8:30-12:00; Afternoon 13:00-16:00	BBPS	2-4 h	5	No
Zhang et al[16], 2015	Multicenter, single-blind, RCT	Patients 18-75 yr	SSD: 2 L PEG 4-6 h before colonoscopy; SpDs: 1 L PEG at 21:00 the day before, 2 L PEG 4-6 h before colonoscopy	159/159	1-d LRD	Not described	OBPS	2-4 h	3	No
Shah et al[17], 2014	Single-center, single-blind, RCT	Patients ≥ 18 yr	SSD: 2 L PEG at 5:00-7:00; SpDs: 1 L PEG at 18:00-19:00 the day before, 1 L PEG at 6:00-7:00	103/97	1-d liquid diet and CLD after midnight	11:00-16:00	OBPS	≥ 4 h	5	No
Tellez-Avila et al[18], 2014	Single-center, single-blind, RCT	Inpatients ≥ 18 yr	SSD: 2 L PEG at 6:00-8:00; SpDs: 2 L PEG at 17:00-19:00 the day before, 2 L PEG at 6:00-8:00	61/67	Not described	Not described	BBPS	≥ 3 h	5	No
Kotwal et al[19], 2014	Single-center, single-blind, RCT	Inpatients 18-80 yr	SSD: 4 L PEG at 5:00-9:00; SpDs: 2 L PEG at 19:00-21:00 the day before, 2 L PEG at 7:00-9:00	60/60	1-d CLD	After 11:00	OBPS	≥ 2 h	5	No
Kim et al[20], 2014	Single-center, single-blind, RCT	Outpatients 18-75 yr	SSD: 4 L PEG 6 h before colonoscopy; SpDs: 2 L PEG at 18:00 the day before, 2 L PEG 4-6 h before colonoscopy	50/50	Avoid high-fiber foods 3 d prior	Not described	OBPS	Not described	2	No
Seo et al[21], 2013	Single-center, single-blind, RCT	Outpatients 18-85 yr	SSD: 2 L PEG 5 h before colonoscopy; SpDs: 2 L PEG at 18:00 the day before, 2 L PEG 5 h before colonoscopy	103/102	3-d LRD	9:00-17:00	OBPS	≥ 3 h	5	No
Cesaro et al[22], 2013	Single-center, single-blind, RCT	Outpatients 18-85 yr	SSD: 2 L PEG-CS at 6:00 + bis 10-20 mg at 22:00 the day before; SpDs: 3 L PEG at 19:00 the day before, 1 L PEG at 7:00	50/51	3-d LRD	11:00-18:00	OBPS	Not described	5	Bisacodyl
Kwon et al[23], 2016	Multicenter, single-blind, RCT	Outpatients ≥ 18 yr	SSD: 1 L PEG-ASc + 0.5 L water at 6:00, 20 mg bis + 0.5 L water at 20:00 the day before; SpDs: 1 L PEG-ASc + 0.5 L water at 20:00 the day before, 1 L PEG-ASc + 0.5 L water at 6:00	92/97	LFF for 3 d, soft meal on the day prior	Not described	BBPS	≥ 3 h	5	Bisacodyl
Kang et al[24], 2017	Single-center, single-blind, RCT	Outpatients 20-75 yr	SSD: 1 L PEG-ASc 4 h before colonoscopy + 1 L water, 10 mg bis at 21:00 the day before; SpDs: 1 L PEG-ASc at 20:00 the day before + 0.5 L water, 1 L PEG-ASc 4 h before colonoscopy + 0.5 L water	100/100	3-d LRD	9:00-13:00	BBPS	> 2 h	3	Bisacodyl
Choi et al[25], 2018	Single-center, single-blind, RCT	Outpatient 18-80 yr	SSD: 1 L PEG-ASc 5 h before colonoscopy + 0.5 L water, Pru at 19:00 the day before + 0.5 L water; SpDs: 1 L PEG-ASc at 19:00 the day before + 0.5 L water, 1 L PEG-ASc 5 h before colonoscopy + 0.5 L water	130/130	3-d LRD	9:00-13:00	BBPS	Not described	5	Prucalopride
Kim et al[26], 2019	Single-center, single-blind, RCT	Outpatients 20-70 yr	SSD: 1L PEG-ASc at 5:00 + 1 L water + 20 mg bis; SpDs: 1 L PEG-ASc at 21:00 the day before + 0.5 L water, 1 L PEG-ASc at 5:00 + 0.5 L water	83/85	1-d CLD	8:30-12:00	BBPS	Not described	4	Bisacodyl
Kim et al[27], 2020	Single-center, single-blind, RCT	Patients 18-74 yr	SSD: 1 L PEG-ASc 5 h before endoscopy + 1 L water, 10 mg bis at 21:00 the day before; SpDs: 1 L PEG-ASc at 21:00 the day before + 0.5 L water, 1 L PEG-ASc 5 h before endoscopy + 0.5 L water	99/99	3-d LRD	9:00-17:00	BBPS	Not described	4	Bisacodyl
de Leone et al[28], 2013	Multicenter, single-blind, RCT	Outpatients 18-85 yr	SSD: 3-4 tablets bis at bedtime, 2 L PEG-CS 5 h before endoscopy; SpDs: 2 L PEG at 18:00 the day before, 2 L PEG 5 h before endoscopy	78/79	LFF for 3 d, CLD the day before	Morning	OBPS	Not described	4	Bisacodyl

SSD: Same-day single-dose; SpDs: Split-dose; PC: Preparation-to-colonoscopy; LFF: Low-fiber foods; LRD: Low residual diet; CLD: Clear liquid diet; PEG-CS: Polyethylene glycol with citrates and simethicone; PEG-ASc: Polyethylene glycol ascorbic acid; RCT: Randomized controlled trial; PEG: Polyethylene glycol; Lin: Linaclotide; BBPS: Boston Bowel Preparation Scale; bis: Bisacodyl; OBPS: Ottawa Bowel Preparation Scale; Mor: Morning; Aft: Afternoon; Pru: Prucalopride.

Table 2 Subgroup analysis

Subgroup	Studies, n	SSD, n	SpDs, n	I2 , %	P value for heterogeneity	Pooled analysis (cat-RR/con-MD)	95%CI	P value
2 L SSD with adjuvant vs SpDs
Adequate bowel preparation (categorical)[11,12,22,23,25,27,28]	7	1172	1177	51	0.05	1.00	(0.95, 1.05)	0.99
BBPS score for right colon (continuous)[11,12,23-27]	7	1227	1232	41	0.12	0.00	(-0.05, 0.05)	0.93
OBPS score for right colon (continuous)[22]	1	50	51
2 L SSD without adjuvant vs SpDs
Adequate bowel preparation (categorical)[11,15,16,18,21]	5	932	938	90	< 0.00001	0.86	(0.72, 1.02)	0.07
BBPS score for right colon (continuous)[11,15]	2	611	610	0	1.00	0.00	(-0.07, 0.07)	1.00
OBPS score for right colon (continuous)[16,21]	2	262	261	89	0.003	0.26	(-0.20, 0.72)	0.26
4 L SSD without adjuvant vs SpDs
Adequate bowel preparation (categorical)[13,14,20]	3	364	375	0	0.66	0.99	(0.94, 1.05)	0.82
BBPS score for right colon (continuous)[14]	1	172	167
OBPS score for right colon (continuous)[19,20]	2	110	110	0	0.71	-0.06	(-0.30, 0.18)	0.62

SSD: Same-day single-dose; SpDs: Split-dose; BBPS: Boston bowel preparation scale; OBPS: Ottawa bowel preparation scale; cat-RR/con-MD: Categorical-relative risk ratio/continuous-mean differences; CI: Confidence interval.

Table 3 Secondary outcome

Secondary outcome	Studies (n)	SSD (n)	SpDs (n)	I2 (%)	P value for heterogeneity	Pooled analysis (cat-RR/con-MD)	95%CI	P value
Sleep disturbance	15	2591	2463	74	< 0.00001	0.52	(0.40, 0.68)	< 0.00001
2 L SSD with adjuvant vs SpDs	7	1214	1215	69	0.003	0.69	(0.43, 1.10)	0.12
2 L SSD without adjuvant vs SpDs	6	1014	1013	80	0.0002	0.45	(0.30, 0.67)	< 0.0001
4 L SSD without adjuvant vs SpDs	3	363	375	67	0.05	0.47	(0.28, 0.78)	0.004
Willingness to repeat	10	1996	1855	90	< 0.00001	1.15	(1.03, 1.29)	0.01
2 L SSD with adjuvant vs SpDs	6	1073	1078	89	< 0.00001	1.24	(1.06, 1.45)	0.008
2 L SSD without adjuvant vs SpDs	3	691	690	82	0.004	1.14	(1.01, 1.29)	0.03
4 L SSD without adjuvant vs SpDs	2	232	227	54	0.14	0.89	(0.71, 1.13)	0.34
Side effects
Nausea	17	2715	2592	68	< 0.0001	0.95	(0.78, 1.16)	0.63
Vomiting	16	2644	2521	64	0.0002	0.96	(0.66, 1.38)	0.81
Abdominal pain	17	2715	2592	38	0.06	0.75	(0,62, 0.90)	0.002
Bloating	15	2205	2077	67	0.0001	0.80	(0.63, 1.01)	0.06

SSD: Same-day single-dose; SpDs: Split-dose; cat-RR/con-MD: Categorical-relative risk ratio/continuous-mean differences; CI: Confidence interval.

Table 4 Grades of Recommendation, Assessment, Development and Evaluation rated the certainty of evidence

No. of studies	Design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	SSD	SpDs	RR (95%CI)	Effect/Absolute	Quality	Importance
Adequate bowel cleanliness
14	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	2002/2468 (81.1%)	1973/2350 (84.0%)	RR 0.97 (0.92 to 1.02)	25 fewer per 1000 (from 67 fewer to 17 more)	(+++) moderate	Critical
								85.5%		26 fewer per 1000 (from 68 fewer to 17 more)
Right colon BBPS
9	Randomized trials	No serious risk of bias	No serious inconsistency	No serious indirectness	No serious imprecision	None	1869	1869	-	Md 0 higher (0.04 lower to 0.03 higher)	(++++) high	Critical
Right colon OBPS
5	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	422	422	-	Md 0.04 higher (0.27 lower to 0.34 higher)	(+++) moderate	Critical
Sleep disturbance
15	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	348/2591 (13.4%)	651/2463 (26.4%)	RR 0.52 (0.40 to 0.68)	127 fewer per 1000 (from 85 fewer to 159 fewer)	(+++) moderate	Critical
								32.0%		154 fewer per 1000 (from 102 fewer to 192 fewer)
Willingness to repeat
10	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	1624/1996 (81.4%)	1269/1855 (68.4%)	RR 1.15 (1.03 to 1.29)	103 more per 1000 (from 21 more to 198 more)	(+++) moderate	Critical
								65.2%		98 more per 1000 (from 20 more to 189 more)
Nausea
17	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	516/2715 (19.0%)	559/2592 (21.6%)	RR 0.95 (0.78 to 1.16)	11 fewer per 1000 (from 47 fewer to 35 more)	(+++) moderate	Critical
								20.0%		10 fewer per 1000 (from 44 fewer to 32 more)
Vomiting
16	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	191/2644 (7.2%)	202/2521 (8.0%)	RR 0.96 (0.66 to 1.38)	3 fewer per 1000 (from 27 fewer to 30 more)	(+++) moderate	Critical
								7.2%		3 fewer per 1000 (from 24 fewer to 27 more)
Abdominal pain
17	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	168/2715 (6.2%)	221/2592 (8.5%)	RR 0.75 (0.62 to 0.9)	21 fewer per 1000 (from 9 fewer to 32 fewer)	(+++) moderate	Critical
								8.2%		20 fewer per 1000 (from 8 fewer to 31 fewer)
Bloating
15	Randomized trials	No serious risk of bias	Serious1	No serious indirectness	No serious imprecision	None	322/2205 (14.6%)	415/2077 (20.0%)	RR 0.8 (0.63 to 1.01)	40 fewer per 1000 (from 74 fewer to 2 more)	(+++) moderate	Critical
								18.4%		37 fewer per 1000 (from 68 fewer to 2 more)

¹Only a few different studies have shown conflicting results. SSD: Same-day single-dose; SpDs: Split-dose; CI: Confidence interval; RR: Relative risk; BBPS; Boston Bowel Preparation Scale; Md: Moderate; OBPS: Ottawa Bowel Preparation Scale.