Combination could be another tool for bowel preparation?

Table 1 Summary of the combination methods reviewed in this study

Combination agents	Comparable agents	Study methods	Preparation scales	Results	Weakness of combinations
PEG + osmotic agents
PEG 2 L + NaP 45 mL (n = 130)[12]	PEG 4 L (n = 141)	RCT, single center in South Korea	Ottawa	The bowel preparation quality and rate of adverse events were not different between the two groups	Serum sodium and phosphorus were increased and serum calcium and potassium were decreased in the combination group
PEG 2 L + NaP 90 mL (n = 277)[8]	PEG 4 L (n = 249)	RCT, single center in South Korea	Aronchick	The overall and segmental bowel preparation quality of the combination group was better	Occurrence of hyperphosphatemia was greater in the combination group.
PEG 2 L + oral sulfate 473 mL (n = 186)[14]	PEG 2 L with ascorbic acid (n = 185)	RCT, 24 centers in the United States	Aronchick	Successful preparation rates were identical in the two groups	Vomiting was more frequent in the combination group
PEG 2 L + magnesium citrate 250 mL (n = 73)[16]	PEG 4 L on the day before (n = 79) and in split-dose (n = 80)	RCT, single center in South Korea	Aronchick	The bowel preparation of the combination group was more satisfactory than that of the day before group. Patient satisfaction was highest in the combination group
PEG + stimulant agents
PEG 2 L + bisacodyl 15 mg (n = 78)[18]	PEG 4 L (n = 76)	RCT, 2 centers in Italy	Ottawa	The bowel cleansing quality and adenoma detection rate were equivalent in the two groups. Mucosal visibility was superior in the combination group
PEG 2 L in split dose + bisacodyl 15 mg (n = 138)[19]	PEG 4 L (n = 126)	RCT, single center in Italy	Harefield	The good or satisfactory preparation rate and adherence to the drinking instructions were higher in the combination group
PEG 2 L + bisacodyl 10-20 mg (n = 761, meta-analysis from six studies)[20]	PEG 4 L (n = 779)	RCT, 6 studies in the United States, Norway, Canada, and Australia	Aronchick and Ottawa	The preparation quality was similar in the two groups. The incidence of adverse events such as nausea, vomiting, and bloating was lower in the combination group
MiraLAX-Gatorade + bisacodyl 20 mg (n = 383)[22]	PEG 4 L (n = 395)	Retrospective database analysis in the United States	Aronchick	The rates of excellent or good bowel cleansing were similar in the two groups
PEG 2 L + sodium picosulfate 150 mL (n = 41)[23]	NaP tablets (total 50 g, n = 50)	Crossover design trial, single center in Japan	Likert	The effectiveness of colonic cleansing was not different between the two groups	Patients’ overall impressions were worse and the frequency of nausea was higher in the combination group
PEG 2 L + senna 12 tablets (n = 141)[25]	Senna 24 tablets (n = 145)	RCT, single center in Italy	Aronchick	The preparation quality was similar in the two groups. The incidence of abdominal pain was lower in the combination group
PEG + prokinetic agents
PEG 2 L + mosapride 5 mg (n = 103) or itopride 50 mg (n = 103)[28]	PEG 2 L plus placebo (n = 99)	RCT, single center in Japan	Aronchick	There were fewer uncomfortable abdominal symptoms in the PEG with prokinetic group	The addition of prokinetics did not improve the bowel cleansing effect
PEG 2 L + mosapride 15 mg (n = 124)[29]	PEG 2 L plus placebo (n = 125)	RCT, single center in Japan	Aronchick	The optimal cleansing rate of left-sided colon was higher in the PEG with mosapride group. Patients who had previous colonoscopy experience felt that the bowel preparation was easier after mosapride addition
Osmotic + stimulant agents
SP/MC 2 sachets1 (n = 140)[33]	PEG 4 L (n = 145)	RCT, 3 centers in Italy	Boston	The bowel cleansing quality was similar in the two groups. Tolerability and palatability was better in the SP/MC group
SP/MC 2 sachets1 (n = 296)[34]	PEG 2 L with bisacodyl 10 mg (n = 302)	RCT, 12 centers in the United States	Aronchick and Ottawa	The quality of bowel cleansing was similar in the two groups. Patients' acceptability and tolerability on a questionnaire were greater in the SP/MC group
SP/MC 2 sachets1 (n = 304)[35]	PEG 2 L with bisacodyl 10 mg (n = 297)	RCT, 10 centers in the United States	Aronchick and Ottawa	The overall colon cleansing was superior and the tolerability was better with the SP/MC regimen
SP/MC 2 sachets1 + PEG 2L (n = 282) or PEG 1 L (n = 303)[37]	SP/MC 3 sachets1 (n = 307)	RCT, single center in South Korea	Aronchick and Ottawa	The cleaning efficacy of the right colon of the SP/MC plus PEG 2 L group was better than that of the SP/MC group	Nausea and bloating were more frequent in the SP/MC plus PEG 2 L group than in the SP/MC group
Magnesium citrate 2 sachets2 and senna (n = 160)[40]	Magnesium citrate 2 sachets2 (n = 182)	RCT, single center in the United Kingdom	Likert	Adequate visualization of colonic mucosa was better in the combination group	Incidence of abdominal cramps was higher in the combination group

¹One packet contains 10 mg sodium picosulfate, 3.5 g magnesium oxide and 12 g citric acid;

²One sachet contains 11.6 g magnesium carbonate and 17.8 g anhydrous citric acid. PEG: Polyethylene glycol; NaP: Sodium phosphate; SP/MC: Sodium picosulfate plus magnesium citrate; RCT: Randomized controlled trial.