Role of Gabexate Mesylate in Prevention of Post-ERCP Pancreatitis： a Meta Analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Jun ,  LI Fei.

Department of General Surgery， Xuan Wu Hospital of Capital Medical University， Beijing 100053， China;

Corresponding author：

LI Fei., Email: feili36@hotmail.com

Keywords：

Gabexate mesylate; Prevention; Post-ERCP pancreatitis; Meta analysis

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Objective 　To evaluate the effectiveness and safety of gabexate mesylate in the prevention of post-endoscopic retrograde cholangiopancreatography （ERCP） pancreatitis （PEP）.
Methods 　The literatures and corresponding references of randomized controlled trials （RCT） on gabexate mesylate in the prevention of PEP were searched from Cochrane library （1970 to December 2010），PubMed （1966 to December 2010），EMBASE （1966 to December 2010），and CBM （1978 to December 2010）.Literature screening，data extraction and methodological quality assessment were individually performed by two researchers.The software RevMan 4.2 of Cochrane Collaboration was used for statistical analysis.
Results 　A total of 11 trails involving 3 012 patients were included. Meta analysis showed that high dose （≥1 000 mg）of gabexate mesylate with slow intravenous infusion （≥12 h） could effectively prevent from PEP （OR=0.27，95%CI： 0.11-0.64, P=0.003） and post-ERCP abdominal pain （OR=0.44，95%CI： 0.25-0.79，P=0.005） when compared with placebo. The low dose （≤500 mg） of gabexate mesylate with quick intravenous infusion （≤6.5 h） could not effectively prevent from PEP （OR=0.85, 95%CI： 0.59-1.34, P=0.570），post-ERCP hyperamylasemia （OR=0.86，95%CI： 0.69-1.07，P=0.180），and post-ERCP abdominal pain （OR=0.66，95%CI： 0.32-1.35，P=0.250）.When compared gabexate mesylate with ulinastatin, there was no statistical difference between them in the prevention of PEP （OR=1.57，95%CI： 0.39-6.24，P=0.520） and post-ERCP hyperamylasemia （OR=1.85, 95%CI： 0.83-4.13，P=0.130）.
Conclusions 　The high dose （≥1 000 mg） of gabexate mesylate with slow intravenous infusion （≥12 h） other than low dose （≤500 mg） with quick intravenous infusion （≤6.5 h） is effective to prevent from PEP and post-ERCP abdominal pain，and can also prevent from post-ERCP hyperamylasemia to some extent.The effect which ulinastatin prevents PEP and post-ERCP hyperamylasemia is same to gabexate mesylate.The above conclusions remain to confirm by RCT with large sample and long-term follow-up of high-quality.

Citation： ZHANG Jun,LI Fei.. Role of Gabexate Mesylate in Prevention of Post-ERCP Pancreatitis： a Meta Analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2012, 19(1): 48-57. doi: Copy

1.	Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis：a comprehensive review[ J]. Gastrointest Endosc, 2004, 59(7)：845-864.
2.	Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP： a prospective multicenter study [J]. Am J Gastroenterol, 2001, 96(2)： 417-423.
3.	Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pancreatitis： a prospective multicenter study [J]. Am J Gastroenterol, 2006, 101(1)： 139-147.
4.	Stanten R, Frey CF. Pancreatitis after endoscopic retrograde cholangiopancreatography.An underreported disease whose severity is often unappreciated [J]. Arch Surg, 1990, 125(8)： 1032-1035.
5.	Rolny P, Anderberg B, Ihse I, et al. Pancreatitis after sphincter of Oddi manometry [J]. Gut, 1990, 31(7)821-824.
6.	Tsujino T, Kawabe T, Omata M. Antiproteases in preventing post-ERCP acute pancreatitis [J]. JOP, 2007, 8(4 Suppl)： 509-517.
7.	Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotom ycomplications and their management： an attempt at consensus [J]. Gastrointest Endosc, 1991, 37(3)： 383-393.
8.	Higgius JPT, Green S. Cochrane handbook for systematic reviews of interventions. Updated September 2006 [M]. England： John Wiley and Sons Ltd, 2006： 202.
9.	Jadad AR， Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials： is blinding necessary? [J].Control Clin Trials， 1996, 17(1)： 1-12．.
10.	Cavallini G, Tittobello A, Frulloni L, et al. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. Gabexate in digestive endoscopy—Italian Group [J]. N Engl J Med, 1996, 335(13)： 919-923.
11.	Andriulli A, Clemente R, Solmi L, et al. Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis： a multicenter, placebo-controlled, randomized clinical trial [J]. Gastrointest Endosc, 2002, 56(4)： 488-495.
12.	Andriulli A, Solmi L, Loperfido S, et al. Prophylaxis of ERCPrelated pancreatitis： a randomized, controlled trial of somatostatin and gabexate mesylate [J]. Clin Gastroenterol Hepatol, 2004,2(8)： 713-718.
13.	熊光苏，张唏文，吴叔明，等. 加贝酯预防ERCP 术后胰腺炎的临床研究 [J]. 胰腺病学， 2005， 5(4)： 200-202．.
14.	刁凌云，沈云志，汪良芝，等. 小剂量加贝酯预防ERCP 术后胰腺炎及高淀粉酶血症的临床研究 [J]. 中华腹部疾病杂志，2006， 6(6)： 402-405．.
15.	Manes G, Ardizzone S, Lombardi G, et al. Efficacy of post procedure administration of gabexate mesylate in the prevention of post-ERCP pancreatitis： a randomized, ontrolled,multicenter study [J]. Gastrointest Endosc, 2007, 65(7)： 982-987.
16.	李邦库，邹多武，宛新建. 加贝酯、奥曲肽预防ERCP 术后高淀粉酶血症和胰腺炎的临床疗效评价 [J]. 中国实用医药，2007， 2(15)： 105-107．.
17.	孟凡冬，吴咏冬，冀明，等. 国产加贝酯预防ERCP 术后胰腺炎的临床研究 [J]. 中华消化内镜杂志， 2007， 24(2)： 100-102．.
18.	闵志钧, 施建平, 叶敏, 等. 加贝酯对ERCP 术后全身炎症反应介质的影响 [J]. 外科理论与实践， 2008， 13(4)： 359-362．.
19.	Fujishiro H, Adachi K, Imaoka T, et al. Ulinastatin shows prevent ive effect on post-endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study [J]. J Gastroenterol Hepatol, 2006, 21(6)： 1065-1069.
20.	Ueki T, Otani K, Kawamoto K, et al. Comparison between ulinastatin and gabexate mesylate for the prevention of postendoscopic retrograde cholangiopancreatography pancreatitis： a prospective,randomized trial [J]. J Gastroenterol, 2007, 42(2)：161-167.
21.	Andriulli A, Leandro G, Niro G, et al. Pharmacologic treatment can prevent pancreatic injury after ERCP： a meta-analysis [J].Gastrointest Endosc, 2000, 51(1)： 1-7.中国普外基础与临床杂志2012 年1 月第19 卷第1 期 Chin J Bases Clin General Surg, Vol. 19, No. 1, Jan. 2012 ? 57 ?.
22.	Andriulli A, Leandro G, Federici T, et al. Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP： an updated meta-analysis [J]. Gastrointest Endosc,2007, 65(4)： 624–632.
23.	Zheng MH, Chen YP, Yang XJ, et al. Gabexate in the prophylaxis of post-ERCP pancreatitis： a meta-analysis of randomized controlled trials [J]. BMC Gastroenterol, 2007, 7： 6.[ 24] Seta T, Noguchi Y. Protease inhibitors for preventing complications associated with ERCP： an updated meta-analysis [J]. Gastrointest Endosc, 2011, 73(4)： 700-706.
24.	Zhang ZF, Yang N, Zhao G, et al. Preventive effect of ulinastatin and gabexate mesylate on post-endoscopic retrograde cholangiopancreatography pancreatitis [J]. Chin Med J (Engl), 2010,123(18)： 2600-2606.
25.	李汛，朱晓亮，周文策，等. 经内镜胰管支架置入在预防ERCP术后胰腺炎高危患者中的临床应用 [J]. 中国普外基础与临床杂志， 2009， 17(10)： 1006-1007．.

1. Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis：a comprehensive review[ J]. Gastrointest Endosc, 2004, 59(7)：845-864.
2. Masci E, Toti G, Mariani A, et al. Complications of diagnostic and therapeutic ERCP： a prospective multicenter study [J]. Am J Gastroenterol, 2001, 96(2)： 417-423.
3. Cheng CL, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pancreatitis： a prospective multicenter study [J]. Am J Gastroenterol, 2006, 101(1)： 139-147.
4. Stanten R, Frey CF. Pancreatitis after endoscopic retrograde cholangiopancreatography.An underreported disease whose severity is often unappreciated [J]. Arch Surg, 1990, 125(8)： 1032-1035.
5. Rolny P, Anderberg B, Ihse I, et al. Pancreatitis after sphincter of Oddi manometry [J]. Gut, 1990, 31(7)821-824.
6. Tsujino T, Kawabe T, Omata M. Antiproteases in preventing post-ERCP acute pancreatitis [J]. JOP, 2007, 8(4 Suppl)： 509-517.
7. Cotton PB, Lehman G, Vennes J, et al. Endoscopic sphincterotom ycomplications and their management： an attempt at consensus [J]. Gastrointest Endosc, 1991, 37(3)： 383-393.
8. Higgius JPT, Green S. Cochrane handbook for systematic reviews of interventions. Updated September 2006 [M]. England： John Wiley and Sons Ltd, 2006： 202.
9. Jadad AR， Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials： is blinding necessary? [J].Control Clin Trials， 1996, 17(1)： 1-12．.
10. Cavallini G, Tittobello A, Frulloni L, et al. Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangiopancreatography. Gabexate in digestive endoscopy—Italian Group [J]. N Engl J Med, 1996, 335(13)： 919-923.
11. Andriulli A, Clemente R, Solmi L, et al. Gabexate or somatostatin administration before ERCP in patients at high risk for post-ERCP pancreatitis： a multicenter, placebo-controlled, randomized clinical trial [J]. Gastrointest Endosc, 2002, 56(4)： 488-495.
12. Andriulli A, Solmi L, Loperfido S, et al. Prophylaxis of ERCPrelated pancreatitis： a randomized, controlled trial of somatostatin and gabexate mesylate [J]. Clin Gastroenterol Hepatol, 2004,2(8)： 713-718.
13. 熊光苏，张唏文，吴叔明，等. 加贝酯预防ERCP 术后胰腺炎的临床研究 [J]. 胰腺病学， 2005， 5(4)： 200-202．.
14. 刁凌云，沈云志，汪良芝，等. 小剂量加贝酯预防ERCP 术后胰腺炎及高淀粉酶血症的临床研究 [J]. 中华腹部疾病杂志，2006， 6(6)： 402-405．.
15. Manes G, Ardizzone S, Lombardi G, et al. Efficacy of post procedure administration of gabexate mesylate in the prevention of post-ERCP pancreatitis： a randomized, ontrolled,multicenter study [J]. Gastrointest Endosc, 2007, 65(7)： 982-987.
16. 李邦库，邹多武，宛新建. 加贝酯、奥曲肽预防ERCP 术后高淀粉酶血症和胰腺炎的临床疗效评价 [J]. 中国实用医药，2007， 2(15)： 105-107．.
17. 孟凡冬，吴咏冬，冀明，等. 国产加贝酯预防ERCP 术后胰腺炎的临床研究 [J]. 中华消化内镜杂志， 2007， 24(2)： 100-102．.
18. 闵志钧, 施建平, 叶敏, 等. 加贝酯对ERCP 术后全身炎症反应介质的影响 [J]. 外科理论与实践， 2008， 13(4)： 359-362．.
19. Fujishiro H, Adachi K, Imaoka T, et al. Ulinastatin shows prevent ive effect on post-endoscopic retrograde cholangiopancreatography pancreatitis in a multicenter prospective randomized study [J]. J Gastroenterol Hepatol, 2006, 21(6)： 1065-1069.
20. Ueki T, Otani K, Kawamoto K, et al. Comparison between ulinastatin and gabexate mesylate for the prevention of postendoscopic retrograde cholangiopancreatography pancreatitis： a prospective,randomized trial [J]. J Gastroenterol, 2007, 42(2)：161-167.
21. Andriulli A, Leandro G, Niro G, et al. Pharmacologic treatment can prevent pancreatic injury after ERCP： a meta-analysis [J].Gastrointest Endosc, 2000, 51(1)： 1-7.中国普外基础与临床杂志2012 年1 月第19 卷第1 期 Chin J Bases Clin General Surg, Vol. 19, No. 1, Jan. 2012 ? 57 ?.
22. Andriulli A, Leandro G, Federici T, et al. Prophylactic administration of somatostatin or gabexate does not prevent pancreatitis after ERCP： an updated meta-analysis [J]. Gastrointest Endosc,2007, 65(4)： 624–632.
23. Zheng MH, Chen YP, Yang XJ, et al. Gabexate in the prophylaxis of post-ERCP pancreatitis： a meta-analysis of randomized controlled trials [J]. BMC Gastroenterol, 2007, 7： 6.[ 24] Seta T, Noguchi Y. Protease inhibitors for preventing complications associated with ERCP： an updated meta-analysis [J]. Gastrointest Endosc, 2011, 73(4)： 700-706.
24. Zhang ZF, Yang N, Zhao G, et al. Preventive effect of ulinastatin and gabexate mesylate on post-endoscopic retrograde cholangiopancreatography pancreatitis [J]. Chin Med J (Engl), 2010,123(18)： 2600-2606.
25. 李汛，朱晓亮，周文策，等. 经内镜胰管支架置入在预防ERCP术后胰腺炎高危患者中的临床应用 [J]. 中国普外基础与临床杂志， 2009， 17(10)： 1006-1007．.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Role of Gabexate Mesylate in Prevention of Post-ERCP Pancreatitis： a Meta Analysis

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