Effectiveness of the pharmacological therapy to prevent post ERCP acute pancreatitis: a network meta-analysis

Figures & data

Figure 1. Clinical study selection flow diagram.

Table 1. Clinical trials included in the network meta-analysis.

Author-year	Country	Age	N	M	F	Placebo group	AP (%)	Intervention group	AP (%)	Intervention 1	Intervention 2	Intervention 3	lost of follow-up %.
Abu-Safieh 2014 [22]	Palestine	54	182	71	111	93	10.4	89	4.7	Diclofenac 75 mg IM	Placebo	No	8.5
Alizadeh 2016) [92]	Iran	56.4	372	175	197	95	12.4	102	3.6	Diclofenac 100 mg Rectal	Indometacin 100 mg rectal	Naproxen 500 Mg rectal	17.3
Andrade-Dávila 2015 [23]	Mexico	52.7	166	56	110	84	20.23	82	4.8	Indometacin 100 mg Rectal	Placebo	No	0
Bai 2015 [63]	China	60	900	434	466	445	12.3	445	4.5	Somatostatin 250UI Hr IV	Placebo	No	0.9
Barkay 2008 [60]	Israel	64.6	105	43	62	54	7.8	51	7.4	Heparin 5000UI SC	Placebo	No	0.9
Beauchant 2008 [54]	France	52	208	58	150	103	17	105	17	Nitroglicerin 0.1 mg bolus − 35 UI/Kg/min IV	Placebo	No	5
Bhatia 2011 [24]	India	41	371	123	248	123	15	245	16	Valdecoxib 20 mg IV	Gliceril trinitrato 10 mg twice a day	Control	2.4
Bordas 1988 [64]	Spain	65	33	15	18	16	94	17	8	Somatostatin 4 UI/Kg IV	Placebo	No	0
Bordas 1998 [65]	Spain	59	160	96	64	80	10	80	2.5	Somatostatin 4 UI/Kg IV	Placebo	No	16.7
Budzyńska 2001 [49]	Poland	58.5	300	87	213	101	7.9	199	12	Prednisone 40 mg Oral	Allopurinol 200 mg Oral	Placebo	0
Buxbaum 2014 [89]	EEUU	44	62	30	32	39	17	23	-	Lactato ringer 3 lm/kg 8 hr + bolus 20 ml/kg IV	Lactato ringer (3 ml Kg Iv 8 hours)	no	12.7
Cavallini 1996 [66]	Italy	60.4	435	199	236	210	14	208	6	Gabexate 1gr IV	Placebo	No	0
Chan 2008 [72]	China	62.6	133	72	61	49	40.8	84	13	Somatostatin 250 mcg IV pre y post	Somatostatin 250 mg	Placebo	0
Cheon 2007 [25]	EE. UU.	45.8	207	69	138	112	16.7	111	16.2	Diclofenac 50 Mg VO	Placebo	No	7.2
Chik 2018 [26]	Malaysia	52.5	122	61	61	61	14	61	3.8	Diclofenac 75 Mg IV	Placebo	No	4.7
Choi 2009 [68]	Corea	65.1	704	365	339	350	7.4	354	3.3	Nafamostat 20 mg IV	Placebo	No	2.6
Choi 2017 [15]	Corea	57.6	510	278	232	250	9.8	205	4.3	Lactato ringer IV (10 ml/kg pre +3 ml/kg during y 8 hr +10 ml/kg post)	Lactato ringer (1.5 ml/kg during the procedure and during 8 hr)	No	0
Concepción-Martín 2013 [69]	SPAIN	73	510	241	269	255	6.7	255	7.5	Somatostatin IV 250Ui h total 1250 Ui	Placebo	No	58.9
De Quadros Onófrio 2016 [27]	Brazil	57	477	141	336	253	7.1	244	6.5	Ketoprofen 100 Mg IV	Placebo	No	4.6
De Palma 1999 [52]	Italy	58.6	529	279	250	266	9.1	263	4.6	Hidrocortisone 100 Mg IV	Placebo	No	1.1
Devie’re 2001 [93]	Belgica	60.6	137	59	78	68	5.4	69	3.8	interleukin 10 4Ui/kg	interleukin 10 20 UI/Kg	Placebo	4.9
Döbrönte 2014 [28]	Hungary	66.6	665	239	426	318	6.3	347	5.1	Indometacin 100 Mg rectal	Placebo	No	3.1
Dumot 1998 [50]	EEUU	52	255	107	148	176	8.7	129	6.7	Metilprednisolona 125 Mg IV	Placebo	No	10.8
Elmunzer 2012 [9]	EEUU	45	602	126	476	307	16.1	295	9.7	Indometacin 100 Mg Rectal	Placebo	No	24.7
Fujishiro 2006 [94]	Japan	64.8	139	75	64	69	4.5	70	2.3	Gabexate 900 mg	Unilastatin 450mil UI	Unilastatin 150mil UI	7.3
Fujita 2016 [29]	Japan	63.6	100	72	28	53	17	47	4.3	Flurbiprofeno 50 Mg IV	Placebo	No	30.6
Hauser 2016 [86]	Croatia	71.9	272	144	128	129	14.5	143	8.7	Diclofenac Rectal 100 mg	Ceftazidime 1 gr IV	No	4.9
Hosseini 2016 [95]	Iran	49	406	202	204	203	18	203	5.6	Indometacin 100 mg Rectal	Ssn 0.9% 1lt Iv single dose	Indometacin 100 rectal + 1lt ssn	32.3
Ishiwatari 2016 [18]	Japan	69	407	227	180	214	20.3	216	21.3	Diclofenac 100 Mg oral	Placebo	No	5.3
Jowell 2011 [70]	EEUU	55	869	372*	494*	443	15.1	426	8.7	Secretine 16 UI IV	Placebo	No	4.6
Kaffes 2006 [55]	Australia	53.2	318	124	194	163	7.4	155	7.7	glyceryl trinitrate 5 mg Transdérmic patch	Placebo	No	9.4
Kapetanos 2007 [56]	Grecia	65.8	320	169	151	162	3	158	5.6	Pentoxifiline 400 mg vo	Control	No	0
kato 2017 [30]	Japon	70.5	170	101	69	85	5.6	85	5	Celecoxib oral 400 mg	Placebo	No	6.1
Katsinelos 2005 [43]	Greece	66	243	117	126	118	17.8	125	3.2	Allopurinol 600 mg Vo	Placebo	No	2.8
Katsinelos 2011 [47]	Greece	68.5	515	232	283	260	23	255	4.5	Diclofenac 100 mg Rectal + Somatostatin 0.25 mg/h IV	Placebo	No	4.6
Khoshbaten 2008 [31]	Iran	58.5	100	47	53	50	13	50	2	Diclofenac 100 mg Rectal	Placebo	No	44.4
Kim 2016 [100]	Korea	66.7	371	195	176	186	25	185	23	Nafamostat 20 mg IV	Nafamostat 20 mg IV	No	2.9
Lavy 2004 [48]	Israel	66	321	122	199	180	9.4	141	10	Beta carotene 2 g Oral	Placebo	No	5.6
Lee 2008 [71]	Korea	62.5	391	200	191	196	9.6	197	3.6	Somatostatin 3 mg IV +500 ml Ssn	Placebo	No	2.3
Lee 2015 [62]	Korea	54.8	216	122	94	109	15.8	107	16.5	Udenafil 200 mg + aceclofenac 100 mg	Placebo	No	0
Levenick 2016 [32]	EEUU	54.7	449	213	236	226	4.9	223	7.2	100 mg Indometacin rectal	Placebo	No	0
Li 20075 [70]	China	54.8	832	432	400	418	20.7	414	12.3	Octreotide 0.3 mg IV	Placebo	No	13.4
Lua 2015 [33]	Malaysia	50	144	59	85	75	7	69	4	Diclofenac 100 mg rectal	Control	No	10.6
Luo 2016 [96]	China	62.5	2600	1237	1363	1300	12.3	1300	4.5	100 mg Indometacin Rectal Pre-procedure	100 mg Indometacine Rectal Post-procedure	No	0
Manes 2007 [97]	Italy	63.5	608	328	280	304	12.3	304	10.2	Gabexate 500 mg IV pre-procedimiento	Gabexate 500 mg Iv post procedimiento	Placebo	2.3
Manolakopoulos 2002 [72]	Greece	64	340	138	202	115	13.8	225	9.1	Octreotid 100 mcg Sc	Hidrocortisone 100 mg Iv	Placebo	4
Mansour-ghanaei 2016 [34]	Iran	45.5	324	173	151	162	28	162	12	Naproxen 500 mg Rectal	Placebo	No	0
Martinez-Torres 2009 [44]	Mexico	53.1	170	70	100	85	9.4	85	2.3	Allopurinol 600 mg Vo	Placebo	No	43.3
Masci 2003 [98]	Italia	63.9	434	201	233	217	10.2	217	4.5	Gabexate 500 mg IV *6.5 h + Gabexate 500 mg *6.5 h	Gabexate 500 mg IV *6.5 h + placebo	No	7.4
Masjedizadeh 2017 [87]	Iran	56.1	186	84	102	62	43.7	124	21	Ringer lactate 20 ml/kg pre +3 ml/kg durante 8 hr	Indometacin 50 mg rectal pre + 50 Indometacina 50 mg rectal 12 hrs post	No	0
Montano 2016 [42]	Mexico	54.2	117	38	79	58	11.3	59	4.6	Indometacin 100 mg Rectal	Placebo	No	0
Montaño Loza 2007 [35]	Mexico	55.3	150	50	100	75	37.3	75	28.3	Indometacin 100 mg Rectal	Placebo	No	0
Moreto 2003 [57]	Spain	65.9	144	87	57	70	23.5	74	24.5	Glyceryl trinitrate Transdermal Patch	Placebo	No	26.9
Mosler 2005 [45]	EEUU	51.7	701	194	507	346	12.14	355	12.96	Allopurinol 600 mg 4 h pre + Allopurinol 300 mg 1 h pre Vo	Placebo	No	0
Murray 2003 [36]	Scotland	56.5	220	77	143	110	37.4	110	15.4	Diclofenac 100 mg Rectal	Placebo	No	0
Nøjgaard 2009 [59]	International	66	806	332	474	401	7.1	405	4.5	glyceryl trinitrate parche 15 Mg.Td	Placebo	No	1.7
Ohuchida 2014 [73]	Japan	68.8	809	502	307	404	6.7	405	3.5	Nafamostat 20 mg en 500 ml de DAD5%	Placebo	No	7.6
Otsuka 2012 [37]	Japan	73.5	104	53	51	53	18.9	51	3.9	Diclofenac 50 mg rectal	Control	No	32.9
Park 2011 [74]	Korea	63	595	319	276	220	14	475	5.1	Nafamostat 50 mg IV + DAD 5% 500cc	Nafamostat 20 mg IV + DAD 5% 500cc	Placebo	2.1
Park 2014 [41]	Korea	64.5	343	204	139	180	11.8	163	12.7	Diclofenaco 90 mg IM	Placebo	No	9.7
Park 2017 [99]	Korea	59	395	179	216	129	6.7	134	3	Lactato Ringer IV (3 ml/kg/h pre +20 ml/kg post +3 ml/kg/h *8 h)	Solucón Salina IV (3 ml/kg/h pre +20 ml/kg post +3 ml/kg/h)	Lactato R (1.5 ml/kg/h y post procedimiento 8 horas)	2.7
Poon 1999 [75]	China	62.8	220	102	118	109	16	111	8	Somatostatina 3 mg IV +500 ml Ssn	Placebo	No	4.3
Poon 2003 [76]	China	68	270	137	133	135	14.4	135	3	Somatostatina 250Ui IV	Placebo	No	4.3
Rabenstein 2004 [61]	Germany	58	448	135	313	227	8.8	221	8.1	HBPM 3000 ui IV	Placebo	No	0
Romagnuolo 2008 [46]	Canada	54.7	586	242	344	293	4.4	293	5.3	allopurinol 300 mg V	Placebo	No	0
Sand 1993 [53]	Finland	61.5	166	68	98	84	4	82	4	Nifedipine 20 mg * 3 dosis Vo	Placebo	No	0
Senol 2009 [38]	Turkey	60	80	43	37	40	17.5	4	7.5	Diclofenac 75 Mg Im	Placebo	No	12.1
Shaygan 2015 [83]	Iran	50.8	150	51	99	75	5.6	75	3.4	ringer Lactato 20 ml/kg pre +3 ml/kg/h *8 h	ringer Lactato (1.5 ml/kg/8*h)	No	0
Sherman 2003 [51]	EEUU	51.2	1115	396	719	555	13.6	560	16.6	prednisone Oral 40 mg	Placebo	No	0
Sherman 2009 (101)	International	51	305	74	231	153	12.5	152	10.5	IL10 (8Ui/kg)	IL10 (20 Ui/kg)	Placebo	10
Sotoudehmanesh 2007 [39]	Iran	58.2	490	226	264	245	15	245	7	Indometacin 100 mg rectal	Placebo	No	9.8
Sotoudehmanesh 2014 [88]	Iran	58	300	146	154	150	15.3	150	6.7	Indometacine 100 mg rectal + Isosorbide dinitrate 5 mg Sl	Indometacin 100 mg Rectal + placebo	No	0
Testoni 2001 [77]	Italy	51.8	120	49	71	58	14.3	56	12	Octreotid 200 Ug Sc/4 dosis	Control	No	0
Thomopoulos 2006 [78]	Grecce	69.8	201	99	102	101	8.9	101	2	Octreotid 500 Ug Sc * 3 dosis	Placebo	No	0.5
Tsujino 2005 [79]	Japan	65	406	244	162	204	7.4	202	2.9	Ulinastatin 150 mil Ui IV	Placebo	No	2.4
Tsujino 2012 [91]	Japan	60	226	148	78	113	8.8	113	5.3	Ulinastatin 150 mil Ui IV + risperidone 2 mg Vo	Ulinastatin 150 mil Ui Iv	No	0
UÇAR 2015 (102)	Turkey	60.2	150	50	100	75	12.5	75	11.8	Diclofenac 75 mg IM	Diclofenaco 100 mg rectal	Control	0
Uchino 2013 [85]	Japan	65	483	295	188	250	8.8	250	10	Risperidona 2 mg Vo	Placebo	No	3.4
Upendra Shah 2012 [80]	EEUU	48	73	18	55	37	12.5	36	13.2	Aprepitant 125 mg Vo	Placebo	No	20.7
Xiong 2006 [81]	China	62	193	90	103	95	10	98	3.1	Gabexato 300 mg IV	Placebo	No	3.5
Yoo 2008 [83]	Korea	63.5	227	123	104	108	5.6	119	6.7	Unilastatina 100.000 Ui IV + 500 cc ssn	Placebo	No	0
Yoo 2011 [82]	Korea	62.5	286	143	143	143	21	143	16.1	Nafamostat 50 mg IV + DAD 5% 500cc	Placebo	No	2.1
Yu Hao 2009 [58]	China	64	74	31	43	37	17	37	12	glyceryl trinitrate 5 mg SL	Placebo	No	0
Zhao 2014 [40]	China	59	120	52	68	60	20	60	13	Dilofenac 75 mg Im	Control	No	0

N = Number; M = Men; F = Women; mg = milligram; IM = Intramuscular; UI = International Units; Hr = Hour; IV = Intravenous; SC = Subcutaneous; min = minute; Kg = Kilogram; ml = milliliter; g = gram; mcg = microgram; pre = Pre-intervention; post = Post-intervention; VO = Oral route; SSN = Normal Saline Solution; DAD = Dextrose in Distilled Water; IL = Interleukin; SL = Sublingual; L = Liter; AP: acute pancreatitis.

*Incomplete data for the sex variable.

Figure 2. Post-ERCP acute pancreatitis network. A: non-steroidal analgesics (NSAIDs); AB: NSAIDs and Antibiotics; AD: NSAIDs and Isosorbide Dinitrate; AL: Allopurinol; AS: NSAIDs and somatostatin; B: beta carotenes; C: Corticosteroids; CB: Nifedipine; D: glyceryl trinitrate; H: Heparin; N: hydration with normal lactate; PDA: udenafil aceclofenac; S: somatostatin and analogs; SI: Risperidone; SSI: unilastatin-Risperidone; V: aggressive hydration with lactate ringer.

Figure 3. Assessment of risk of bias within studies.

Figure 4. Assessment of risk of bias across studies.

Figure 5. Forrest plot for post-ERCP acute pancreatitis A: non-steroidal analgesics (NSAIDs); AB: NSAIDs and Antibiotics; AD: NSAIDs and Isosorbide Dinitrate; AL: Allopurinol; AS: NSAIDs and somatostatin; B: beta carotenes; C: Corticosteroids; CB: Nifedipine; D: glyceryl trinitrate; H: Heparin; N: hydration with normal lactate; PDA: udenafil aceclofenac; S: somatostatin and analogs; SI: Risperidone; SSI: unilastatin-Risperidone; V: aggressive hydration with lactate ringer.

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