• 首都醫(yī)科大學(xué)宣武醫(yī)院普通外科(北京 100053);

目的  評(píng)價(jià)加貝酯預(yù)防內(nèi)鏡逆行胰膽管造影術(shù)后胰腺炎(post-ERCP pancreatitis,PEP)的安全性和有效性。
方法  計(jì)算機(jī)檢索Cochrane圖書(shū)館(1970~2010年12月)、PubMed(1966~2010年12月)、EMBASE(1966~2010年12月)及中國(guó)生物醫(yī)學(xué)文獻(xiàn)數(shù)據(jù)庫(kù)(1978~2010年12月),查找加貝酯預(yù)防PEP的隨機(jī)對(duì)照試驗(yàn)及其參考文獻(xiàn)。 由2名研究者獨(dú)立選擇試驗(yàn)、提取資料和評(píng)估方法學(xué)質(zhì)量,采用Cochrane協(xié)作網(wǎng)提供的RevMan 4.2軟件進(jìn)行統(tǒng)計(jì)分析。
結(jié)果  共有11篇文獻(xiàn),包括3 012例患者納入本研究。Meta分析結(jié)果顯示:與安慰劑比較,持續(xù)(≥12 h)大劑量(≥1 000 mg)使用加貝酯可以有效預(yù)防PEP的發(fā)生(OR=0.27,95%CI為0.11~0.64,P=0.003),并可以有效預(yù)防ERCP術(shù)后腹痛的發(fā)生(OR=0.44,95%CI為0.25~0.79,P=0.005)。快速(≤6.5 h)小劑量(≤500 mg)使用加貝酯并不能有效預(yù)防PEP的發(fā)生(OR=0.85,95%CI為0.59~1.34,P=0.570),不能預(yù)防ERCP術(shù)后高淀粉酶血癥的發(fā)生(OR=0.86,95%CI為0.69~1.07,P=0.180),也不能有效地預(yù)防ERCP術(shù)后腹痛的發(fā)生(OR=0.66,95%CI為0.32~1.35,P=0.250)。加貝酯組與烏司他丁組比較,2組對(duì)PEP預(yù)防效果的差異無(wú)統(tǒng)計(jì)學(xué)意義(OR=1.57,95%CI為 0.39~6.24,P=0.520),對(duì)ERCP術(shù)后高淀粉酶血癥預(yù)防效果的差異也無(wú)統(tǒng)計(jì)學(xué)意義(OR=1.85,95%CI為0.83~4.13,P=0.130)。
結(jié)論  持續(xù)(≥12 h)大劑量(≥1 000 mg)使用加貝酯能夠預(yù)防PEP以及ERCP術(shù)后腹痛的發(fā)生,對(duì)于ERCP術(shù)后高淀粉酶血癥的預(yù)防也有一定效果。加貝酯與烏司他丁對(duì)PEP和ERCP術(shù)后高淀粉酶血癥的預(yù)防效果相同。上述結(jié)論尚需多中心、大樣本和長(zhǎng)期隨訪的高質(zhì)量隨機(jī)對(duì)照研究證實(shí)。

引用本文: 張駿,李非. 加貝酯預(yù)防ERCP 術(shù)后胰腺炎的Meta 分析. 中國(guó)普外基礎(chǔ)與臨床雜志, 2012, 19(1): 48-57. doi: 復(fù)制

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. 熊光蘇, 張唏文, 吳叔明, 等. 加貝酯預(yù)防ERCP 術(shù)后胰腺炎的臨床研究 [J]. 胰腺病學(xué), 2005, 5(4): 200-202..
14. 刁凌云, 沈云志, 汪良芝, 等. 小劑量加貝酯預(yù)防ERCP 術(shù)后胰腺炎及高淀粉酶血癥的臨床研究 [J]. 中華腹部疾病雜志,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. 李邦庫(kù), 鄒多武, 宛新建. 加貝酯、奧曲肽預(yù)防ERCP 術(shù)后高淀粉酶血癥和胰腺炎的臨床療效評(píng)價(jià) [J]. 中國(guó)實(shí)用醫(yī)藥,2007, 2(15): 105-107..
17. 孟凡冬, 吳詠冬, 冀明, 等. 國(guó)產(chǎn)加貝酯預(yù)防ERCP 術(shù)后胰腺炎的臨床研究 [J]. 中華消化內(nèi)鏡雜志, 2007, 24(2): 100-102..
18. 閔志鈞, 施建平, 葉敏, 等. 加貝酯對(duì)ERCP 術(shù)后全身炎癥反應(yīng)介質(zhì)的影響 [J]. 外科理論與實(shí)踐, 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.中國(guó)普外基礎(chǔ)與臨床雜志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, 朱曉亮, 周文策, 等. 經(jīng)內(nèi)鏡胰管支架置入在預(yù)防ERCP術(shù)后胰腺炎高?;颊咧械呐R床應(yīng)用 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 17(10): 1006-1007..
  1. 1. Freeman ML, Guda NM. Prevention of post-ERCP pancreatitis:a comprehensive review[ J]. Gastrointest Endosc, 2004, 59(7):845-864.
  2. 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. 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. 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. 5. Rolny P, Anderberg B, Ihse I, et al. Pancreatitis after sphincter of Oddi manometry [J]. Gut, 1990, 31(7)821-824.
  6. 6. Tsujino T, Kawabe T, Omata M. Antiproteases in preventing post-ERCP acute pancreatitis [J]. JOP, 2007, 8(4 Suppl): 509-517.
  7. 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. 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. 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. 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. 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. 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. 13. 熊光蘇, 張唏文, 吳叔明, 等. 加貝酯預(yù)防ERCP 術(shù)后胰腺炎的臨床研究 [J]. 胰腺病學(xué), 2005, 5(4): 200-202..
  14. 14. 刁凌云, 沈云志, 汪良芝, 等. 小劑量加貝酯預(yù)防ERCP 術(shù)后胰腺炎及高淀粉酶血癥的臨床研究 [J]. 中華腹部疾病雜志,2006, 6(6): 402-405..
  15. 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. 16. 李邦庫(kù), 鄒多武, 宛新建. 加貝酯、奧曲肽預(yù)防ERCP 術(shù)后高淀粉酶血癥和胰腺炎的臨床療效評(píng)價(jià) [J]. 中國(guó)實(shí)用醫(yī)藥,2007, 2(15): 105-107..
  17. 17. 孟凡冬, 吳詠冬, 冀明, 等. 國(guó)產(chǎn)加貝酯預(yù)防ERCP 術(shù)后胰腺炎的臨床研究 [J]. 中華消化內(nèi)鏡雜志, 2007, 24(2): 100-102..
  18. 18. 閔志鈞, 施建平, 葉敏, 等. 加貝酯對(duì)ERCP 術(shù)后全身炎癥反應(yīng)介質(zhì)的影響 [J]. 外科理論與實(shí)踐, 2008, 13(4): 359-362..
  19. 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. 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. 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.中國(guó)普外基礎(chǔ)與臨床雜志2012 年1 月第19 卷第1 期 Chin J Bases Clin General Surg, Vol. 19, No. 1, Jan. 2012 ? 57 ?.
  22. 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. 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. 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. 25. 李汛, 朱曉亮, 周文策, 等. 經(jīng)內(nèi)鏡胰管支架置入在預(yù)防ERCP術(shù)后胰腺炎高?;颊咧械呐R床應(yīng)用 [J]. 中國(guó)普外基礎(chǔ)與臨床雜志, 2009, 17(10): 1006-1007..