Rectal nonsteroidal anti-inflammatory drugs, glyceryl trinitrate, or combinations for prophylaxis of post-endoscopic retrograde cholangiopancreatography pancreatitis: A network meta-analysis

Table 1 Characteristics of the included studies

Ref.	Country	Intervention	Sample size
Murray et al[11], 2003	Scotland	100 mg diclofenac after endoscopy	220
Sotoudehmanesh et al[12], 2007	Iran	100 mg indomethacin before ERCP	490
Khoshbaten et al[13], 2007	Iran	100 mg diclofenac after endoscopy	100
Elmunzer et al[14], 2012	United States	100 mg indomethacin after ERCP	602
Otsuka et al[15], 2012	Japan	50 mg diclofenac before ERCP	104
Döbrönte et al[16], 2014	Hungary	100 mg indomethacin 10-15 min before ERCP	665
Andrade-Dávila et al[17], 2015	México	100 mg indomethacin after ERCP	166
Lua et al[18], 2015	Malaysia	100 mg diclofenac after ERCP	144
Patai et al[19], 2015	Hungary	100 mg indomethacin 1 h before ERCP	539
Levenick et al[20], 2016	United States	100 mg indomethacin following attempted cannulation	449
Luo et al[21], 2016	China	100 mg indomethacin within 30 min before ERCP	2014
Mansour-Ghanaei et al[22], 2016	Iran	500 mg naproxen immediately before ERCP	324
Patil et al[23], 2016	India	100 mg diclofenac immediately before or during the ERCP	400
Mohammad et al[24], 2017	Iran	100 mg diclofenac, 100 mg indomethacin or 500 mg naproxen, 30 min before ERCP	246
Li et al[25], 2019	China	100 mg indomethacin before ERCP	100
Katoh et al[26], 2019	Japan	50 mg diclofenac before ERCP	297
Sudhindran et al[27], 2001	United Kingdom	Sublingual 2 mg GTN before ERCP	186
Moretó et al[28], 2003	Spain	Transdermal 15 mg GTN 30 to 40 minutes before ERCP	144
Kaffes et al[29], 2006	Australia	Transdermal 5 mg GTN before ERCP	318
Hao et al[30], 2009	China	Sublingual 5 mg GTN 5 min before ERCP	74
Nøjgaard et al[31], 2009	France	Transdermal 15 mg GTN before ERCP	806
Bhatia et al[32], 2011	India	Transdermal GTN 30 min before ERCP	250
Sotoudehmanesh et al[33], 2014	Iran	100 mg indomethacin, plus 5 mg of sublingual GTN before ERCP	300
Wang et al[9], 2020	China	Indomethacin plus 0.5 mg of sublingual GTN 5 min before ERCP	352

ERCP: Endoscopic retrograde cholangiopancreatography; GTN: Glyceryl trinitrate.

Table 2 Incidence and severity of post- endoscopic retrograde cholangiopancreatography pancreatitis

Ref.	Group	Case (n)	PEP		Sex (M:F)	Age (yr)
			Mild PEP	Moderate to serve PEP
Murray et al[11], 2003	Diclofenac 100 mg	110	7	0	NA	NA
	Placebo	110	15	2	NA	NA
Sotoudehmanesh et al[12], 2007	Indomethacin	245	7	0	111:134	58.4 ± 17.1
	Placebo	245	10	5	115:130	58.4 ± 16.8
Elmunzer et al[14], 2012	Indomethacin	295	14	13	66:29	44.4 ± 13.5
	Placebo	307	25	27	60:47	46.0 ± 13.1
Otsuka et al[15], 2012	Diclofenac 50 mg	51	2	0	20:31	75
	Placebo	53	7	3	33:20	72
Döbrönte et al[16], 2014	Indomethacin	347	16	4	133:214	65.66 ± 16.21
	Placebo	318	18	4	106:212	67.68 ± 15.56
Andrade-Dávila et al[17], 2015	Indomethacin	82	3	1	31:51	51.59 ± 18.55
	Placebo	84	14	4	25:59	54.0 ± 17.85
Lua et al[18], 2015	Diclofenac 100 mg	69	4	3	34:35	50.3 ± 17.6
	Placebo	75	4	0	25:50	49.6 ± 16.8
Patai et al[19], 2015	Indomethacin	270	15	3	89:181	66.25 (23-100)
	Placebo	269	33	4	88:181	64.51 (20-95)
Levenick et al[20], 2016	Indomethacin	223	16	0	105:118	64.9
	Placebo	226	9	2	108:118	64.3
Luo et al[21], 2016	Indomethacin	992	22	7	NA	NA
	Placebo	1022	48	17	NA	NA
Mansour-Ghanaei et al[22], 2016	Naproxen	162	8	4	84:78	46.3 ± 8.3
	Placebo	162	18	10	89:73	44.7 ± 9.7
Patil et al[23], 2016	Diclofenac 100 mg	200	6	0	72:128	45.44
	Placebo	200	14	9	77:23	47.86
Mohammad et al[24], 2017	Diclofenac 100 mg	124	2	3	58:66	56.5 ± 18.7
	Indomethacin	122	3	4	57:65	58.0 ± 16.8
	Naproxen	126	7	12	60:66	54.8 ± 13.7
Katoh et al[26], 2019	Diclofenac 50 mg	147	7	1	82:65	74.3 ± 11.8
	Placebo	150	4	1	95:55	74.0 ± 12.7
Moretó et al[28], 2003	tra-GTN	71	2	1	44:27	66.7 ± 2
	Placebo	73	10	1	43:30	65.2 ± 2
Kaffes et al[29], 2006	tra-GTN	155	9	2	59:96	60 (47-72)
	Placebo	163	6	4	57:106	65 (54-75)
Nøjgaard et al[31], 2009	tra-GTN	401	4	14	164:237	67(18-95)
	Placebo	405	9	20	168:237	65(19-96)
Bhatia et al[32], 2011	tra-GTN	124	12	0	36:88	42 (18-76)
	Placebo	126	13	0	47:79	42.5 (19-90)
Sotoudehmanesh et al[33], 2014	Indomethacin+sub-GTN	150	8	2	76:74	58.4 ± 17.8
	Placebo	150	19	4	70:80	58.6 ± 17.5
Wang et al[9], 2020	Indomethacin+sub-GTN	176	5	4	Female	63.5 ± 14.4
	Placebo	176	14	20	Female	66.87 ± 13

PEP: Endoscopic retrograde cholangiopancreatography; M: Male; F: Female; NA: Not available; sub-GTN: Sublingual glyceryl trinitrate; tra-GTN: Transdermal glyceryl trinitrate.

Table 3 League table with OR estimates of each pair of interventions accompanied by 95%CI according to the prevention of total PEP (significant difference when OR < 1 and CI < 1)

Indomethacin+GTN	Diclofenac 100 mg	sub-GTN	Indomethacin	Diclofenac 50 mg	tra-GTN	Naproxen	Pla
0.62 (0.21, 1.82)
0.61 (0.16, 2.38)	0.99 (0.29, 3.37)
0.42 (0.18, 1.02)	0.69 (0.33, 1.43)	0.69 (0.23, 2.10)
0.30 (0.07, 1.30)	0.49 (0.13, 1.86)	0.50 (0.11, 2.34)	0.72 (0.21, 2.42)
0.30 (0.10, 0.89)	0.49 (0.20, 1.22)	0.49 (0.15, 1.66)	0.71 (0.33, 1.50)	0.99 (0.26, 3.68)
0.26 (0.08, 0.86)	0.43 (0.17, 1.10)	0.43 (0.11, 1.62)	0.62 (0.26, 1.47)	0.86 (0.21, 3.58)	0.87 (0.30, 2.50)
0.21 (0.09, 0.50)	0.34 (0.18, 0.65)	0.34 (0.12, 0.97)	0.49 (0.33, 0.73)	0.69 (0.22, 2.18)	0.70 (0.37, 1.32)	0.80 (0.35, 1.83)

GTN: Glyceryl trinitrate; sub-GTN: Sublingual glyceryl trinitrate; tra-GTN: Transdermal glyceryl trinitrate; Pla: Placebo.

Table 4 League table with OR estimates of each pair of interventions accompanied by 95%CI according to the prevention of mild PEP (significant difference when OR < 1 and CI < 1)

Indomethacin+GTN	Diclofenac 100 mg	Indomethacin	tra-GTN	Naproxen	Diclofenac 50 mg	Placebo
0.59 (0.19, 1.86)
0.46 (0.19, 1.12)	0.77 (0.35, 1.72)
0.38 (0.12, 1.20)	0.65 (0.24, 1.75)	0.84 (0.38, 1.85)
0.38 (0.11, 1.35)	0.64 (0.22, 1.87)	0.83 (0.32, 2.14)	0.99 (0.31, 3.14)
0.32 (0.08, 1.39)	0.54 (0.14, 2.11)	0.70 (0.21, 2.37)	0.84 (0.22, 3.19)	0.85 (0.19, 3.71)
0.27 (0.11, 0.67)	0.46 (0.23, 0.94)	0.59 (0.40, 0.88)	0.71 (0.36, 1.41)	0.72 (0.29, 1.78)	0.84 (0.27, 2.66)

GTN: Glyceryl trinitrate; sub-GTN: Sublingual glyceryl trinitrate; tra-GTN: Transdermal glyceryl trinitrate.

Table 5 League table with OR estimates of each pair of interventions accompanied by 95%CI according to the prevention of moderate-to-severe PEP (significant difference when OR < 1 and CI < 1)

Indomethacin+GTN	Diclofenac 100 mg	Indomethacin	Diclofenac 50 mg	tra-GTN	Naproxen	Placebo
0.71 (0.17, 2.96)
0.44 (0.17, 1.16)	0.61 (0.20, 1.87)
0.47 (0.05, 4.40)	0.66 (0.07, 6.62)	1.07 (0.13, 8.55)
0.28 (0.09, 0.85)	0.39 (0.11, 1.36)	0.63 (0.30, 1.34)	0.59 (0.07, 4.95)
0.24 (0.07, 0.82)	0.34 (0.11, 1.02)	0.55 (0.24, 1.27)	0.52 (0.06, 4.65)	0.88 (0.32, 2.46)
0.19 (0.08, 0.48)	0.27 (0.09, 0.79)	0.43 (0.28, 0.66)	0.41 (0.05, 3.11)	0.69 (0.37, 1.28)	0.78 (0.35, 1.77)

GTN: Glyceryl trinitrate; sub-GTN: Sublingual glyceryl trinitrate; tra-GTN: Transdermal glyceryl trinitrate.