生長抑素及其類似物奧曲肽預防內鏡逆行胰膽管造影術后胰腺炎的系統評價_《中國循證醫學雜志》

作者：

潘濤 , 王一平 , 楊錦林 , 吳宗英 , 曾超

四川大學華西醫院消化內科,成都,610041;

關鍵詞：

內鏡逆行胰膽管造影術后胰腺炎生長抑素奧曲肽 Meta分析系統評價

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目的　評價生長抑素及其類似物能否降低內鏡逆行胰膽管造影術(ERCP)后胰腺炎(PEP)的發生率及嚴重程度,以及臨床應用的安全性.
方法　計算機檢索、Cochrane臨床對照試驗試驗資料庫(2004年第1期)、MEDLINE(1966～2004.4)、EMBASE(1985～2004.4)、中國生物醫學文獻數據庫(1970～2004.4)和中國循證醫學中心隨機對照試驗資料庫,并輔以手工檢索,全面收集全世界關于生長抑素及其類似物預防PEP的RCT,按Cochrane協作網推薦的方法進行系統評價.
結果　共31篇RCT包括4 728例患者被納入評價.Meta分析結果顯示,生長抑素可降低PEP的發生率[OR 0.33,95%CI (0.20,0.54);P=0.000 01;NNT＝13];與安慰劑或空白對照試驗相比,生長抑素類似物奧曲肽可降低ERCP術后高淀粉酶血癥的發生率[OR=0.54,95%CI (0.38,0.77);P=0.000 7],但對PEP、重度PEP和ERCP術后腹痛的發生率無影響.
結論　生長抑素可降低PEP的發生率,可能是預防PEP的有效方法.由于納入的研究數量較多,有4篇為高質量的研究,且敏感性分析的結果與Meta分析的結果一致,上述結論具有一定的可信度.但目前的證據不支持奧曲肽降低PEP的發生率,故不推薦臨床用于PEP的預防.鑒于敏感性分析的結果提示奧曲肽甚至有增高PEP發生率的趨勢,是否有必要進行進一步的臨床試驗需審慎看待.

引用本文： 潘濤,王一平,楊錦林,吳宗英,曾超. 生長抑素及其類似物奧曲肽預防內鏡逆行胰膽管造影術后胰腺炎的系統評價. 中國循證醫學雜志, 2005, 05(10): 767-777. doi: 復制

1.	Cotton PB,Lehman G,Vennes JA,Geenen JE,Russell RCG,Meyers WC,Liguory C,Nickl N.Endoscopic sphincterotomy complications and their management:an attempt at consensus[J].Gastrointest Endosc,1991;37(3):383-393.
2.	Freeman ML,Disario JA,Nelson DB,Fennerty MB,Lee JG,Bjorkman DJ,Overby CS,Aas J,Ryan ME,Bochna GS,Shaw MJ,Snady HW,Erickson RV,Moore JP,Roel JP.Risk factors for post-ERCP pancreatitis:a prospective,multicenter study[J].Gastrointest Endosc,2001;54(4):425-434.
3.	Masci E,Toti G,Mariani A,Curioni S,Lomazzi A,Dinelli M,Minoli G,Crosta C,Comin U,Fertitta A,Prada A,Passoni GR,Testoni PA.Complications of diagnostic and therapeutic ERCP:a prospective multicenter study[J].Am J Gastroenterol,2001;96(2):417-423.
4.	Loperfido S,Angelini G,Benedetti G,Chilovi F,Costan F,De Berardinis F,De Bernardin M,Ederle A,Fina P,Fratton A.Major early complications from diagnostic and therapeutic ERCP:a prospective multicenter study[J].Gastrointest Endosc,1998;48(1):1-10.
5.	Glasbrenner B,Adler G.Pathophysiology of acute pancreatitis[J].Hepatogastroenterology,1993;40(4):517-521.
6.	Tulassay Z.Somatostatin and the gastrointestinal tract[J].Scand J Gastroenterol,1998;228(Suppl):115-121.
7.	Harris AG.Octreotide in the treatment of disorders of the gastrointestinal tract[J].Drug Invest,1992;4(Suppl 3):1-54.
8.	Binmoeller KF,Harris AG,Dumas R,Grimaldi C,Delmont PJ.Does the somatostatin analogue octreotide protect against ERCP induced pancreatitis[J]? Gut,1992;33(8):1129-1133.
9.	Sternlieb JM,Aronchick CA,Retig JN,Dabezies M,Saunders F,Goosenberg E,Infantolino A,Ionna S,Maislin G,Wright SH,Lipshutz WH.A multicenter randomized controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis[J].Am J Gastroenterol,1992;87(11):1561-1566.
10.	Arcidiacono R,Gambitta P,Rossi A,Grosso C,Bini M,Zanasi G.The use of a long-acting somatostatin analogue (octreotide) for prophylaxis of acute pancreatitis after endoscopic sphincterotomy[J].Endoscopy,1994;26(9):715-718.
11.	Tulassay Z,Papp J.The effect of long-acting somatostatin analogue on enzyme change after endoscopic pancreatography[J].Gastrointest Endosc,1991;37(1):48-50.
12.	Testoni PA,Bagnolo F,Andriulli A,Bernasconi G,Crotta S,Lella F,Lomazzi A,Minoli G,Natale C,Prada A,Toti GL,Zambelli A.Octreotide 24 h prophylaxis in patients at high risk for post-ERCP pancreatitis:results of a multicenter,randomized,controlled trial[J].Aliment Pharmacol Ther,2001;15(7):965-972.
13.	Manolakopoulos S,Avgerinos A,Vlachogiannakos J,Armonis A,Viazis N,Papadiumitriou N,Mathou N,Stefanidis G,Rekoumis G,Vienna E,Tzourmakliotis D,Raptis SA.Octreotide versus hydrocortisone versus placebo in the prevention of post-ERCP pancreatitis:a multicenter randomized controlled trial[J].Gastrointestinal Endoscopy,2002;55(4):470-475.
14.	Tulassay Z,Dobronte Z,Pronal L,Zagoni T,Juhasz L.Octreotide in the prevention of pancreatic injury associated with endoscopic cholangiopancreatography[J].Aliment Pharmacol Ther,1998;12(11):1109-1112.
15.	Badra G,Galad AS,Rowaish I,Moustafa M,Waked I,Saled SM.Allopurinol vs octreotide in the prevention of post-ERCP pancreatitis in patient with billiary obstruction.A randomized controlled trial[J].Hepatology,2000;32(4):163A.
16.	Duvnjak M,Supanc V,Simicevic VN,Hrabar D,Troskot B,Smircic-Duvnjak L,Bekavac-Beslin M.Use of octreotide-acetate in preventing pancreatitis-like changes following therapeutic endoscopic retrograde cholangiopancreatography[J].Acta Med Croatica,1999;53(3):115-118.
17.	Arvanitidis D,Hatzipanayiotis J,Koutsounopoulos G,Frangou E.The effect of octreotide on the prevention of acute pancreatitis and hyperamylasemia after diagnostic and therapeutic ERCP[J].Hepatogastroenterology,1998;45(19):248-252.
18.	Testoni PA,Lella F,Bagndo F,Buizza M,Colombo E.Controlled trial of different dosages of octreotide in the prevention of hyperamylasemia induced by endoscopic papillosphincterotomy[J].Ita J Gastroenterol,1994;26(9):431-436.
19.	Testoni PA,Lella F,Bagndo F,Caporuscio S,Cattani L,Colombo E,Buizza M.Long-term prophylactic administration of octreotide reduces the rise in serm amylase after endoscopic procedures on Vaters papilla[J].Pancreas,1996;13(1):61-65.
20.	Baldazzi G,Conti C,Spotti EG,Arisi GP,Scevola M,Gobetti F,Agliardi CM,Galasso P,Bonomi E,Bianchi F.Prevention of post-ERCP acute pancreatitis with octreotide[J].G Chir,1994;15(8):359-362.
21.	Armonis A,Manolakopoulos S,Papadimitrious N,Gouma P,Avgerinos A.The effect of long acting somatostatin analogue in the prevention of post-ERCP pancreatitis[J].Gut,1994;35(suppl 4):A85.
22.	Ng KW,Jiang CF,Liang CT,Wu CS,Chen HC,Yang CL,Tan SW,Yeh CH.A prospective,randomized,controlled trial to evaluate the effect of prophylactic sandostatin on ERCP-induced hyperamylasemia and pancreatitis.Gastroenterological[J].Journal of TaiWan,1997;14(2):192-197.
23.	Russo A,Virgilio C,Aprile G.Influenza delloctreotide sulla reazione pancreatica indotta de colangiopancreatografia retrograda.Giorn[J].Ital End Dig,1992;15(2):139-145.
24.	Lin Q,Wang KD,Tang GY,Li HL.Preventive effect of octreotide on pancreatitis after ERCP[J].Journal of modern practical medicine,2001;13(1):21-22.
25.	Sun FQ,Zou DW,Li ZS,Xu GM,Sun ZX.Pevention of ERCP from pancreatitis[J].Chin J Dig Endosc,2000;17(2):81-83.
26.	Li ZS,Qian XD,Xu GM,Sun ZX,Zou XP,Xie SQ.Prophylaxis of hyperamylasemia and post-ERCP pancreatitis by octreotide[J].Chin J Hepatobiliary Surg,2000;6(1):67-68.
27.	Poon RT,Yeung C,Lo CM,Yuen WK,Liu CL,Fan ST.Prophylactic effect of somatostatin on post-ERCP pancreatitis:a randomized controlled trial[J].Gastrointest Endosc,1999;49(5):593-598.
28.	Bordas JM,Toledo-Pimentel V,Llach J,Elena M,Mondelo F,Gines A,Teres J.Effects of bolus somatostatin in preventing pancreatitis after endoscopic pancreatography:results of a randomized study[J].Gastrointest Endosc,1998;47(3):230-234.
29.	Persson B,Slezak P,Efendic S,Haggmark A.Can somatostatin prevent injection pancreatitis after ERCP[J]? Hepatogastroenterology,1992;39(3):259-261.
30.	Guelrud M,Mendoza S,Viera L,Gelrud D.Somatostatin prevents acute pancreatitis after pancreatic duct sphincter hydrostatic balloon dilation in patients with idiopathic recurrent pancreatitis[J].Gastrointest Endosc,1991;37(1):44-47.
31.	Bordas JM,Toledo V,Mondelo F,Rodes J.Prevention of pancreatic reactions by bolus somatostatin administration in patients undergoing endoscopic retrograde cholangio-pancreatography and endoscopic sphincterotomy[J].Hormone Res,1988;29(2):106-108.
32.	Saari A,Kivilaakso E,Schroder R.The influence of somatostatin on pancreatic irritation after pancreatography.An experimental and clinical study[J].Surg Res Comm,1988;2(3):271-278.
33.	Testoni PA,Masci E,Bagnolo F,Tittobello A.Endoscopic papillo-sphincterotomy:prevention of pancreatic reaction by somatostatin[J].Ital J Gastroenterol,1988;20(2):70-73.
34.	Deschner K,Kalloo A,Collen M,Cattau EL,Maher KA,Fleischer DE,Berrjamin SB.Somatostatin:an evaluation of its utility as adjunctive medication for ERCP[J].Gastrointest Endosc,1989;35(2):149-150.
35.	Circero GF,lauger R,Sahel J.Effect of somatostatin on clinical,biochemical and morphological changes following ERCP[J].Ital J Gastroenterol,1985;17(3):256-258.
36.	Poon RT,Yeung C,Liu CL,Lam CM,Yuen WK,Lo CM,Tang A,Fan ST.Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures:a randomized controlled trial[J].Gut,2003;52(12):1768-1773.
37.	Li ZS,Xu GM,Sun ZX,Zou XP,Jin ZD,Xie SQ.Clinical study on somatostatin in prevention of hyperamylasemia and pancreatitis after ERCP[J].Acad J Sec Mil Med Univ,1997;18(5):426-427.
38.	Gong L,Tang XJ,Xi M.Prophylaxis of hyperamylasemia and pancreatitis post-ERCP treated by little dosage somatostatin[J].Acad J Qiqihaer Med Col,2002;23(8):855-856.
39.	Saluja AK,Steer ML.Pathophysiology of acute pancreatitis:role of cytokines and other mediators of inflammation[J].Digestion,1999;60(1):27-33.
40.	Yuan Y,Gong Z,Lou K.Effects and mechanisms of somatostatin analogs on apoptosis of pancreatic acinar cells in acute pancreatitis in mice[J].J Gastroenterol Hepatol,2001;16(5):683-688.
41.	Binmoeller KF,Dumas R,Harris AG,Delmont JP.Effect of somatostatin analog octreotide on human sphincter of Oddi[J].Dig Dis Sci,1992;37(5):773-777.

1. Cotton PB,Lehman G,Vennes JA,Geenen JE,Russell RCG,Meyers WC,Liguory C,Nickl N.Endoscopic sphincterotomy complications and their management:an attempt at consensus[J].Gastrointest Endosc,1991;37(3):383-393.
2. Freeman ML,Disario JA,Nelson DB,Fennerty MB,Lee JG,Bjorkman DJ,Overby CS,Aas J,Ryan ME,Bochna GS,Shaw MJ,Snady HW,Erickson RV,Moore JP,Roel JP.Risk factors for post-ERCP pancreatitis:a prospective,multicenter study[J].Gastrointest Endosc,2001;54(4):425-434.
3. Masci E,Toti G,Mariani A,Curioni S,Lomazzi A,Dinelli M,Minoli G,Crosta C,Comin U,Fertitta A,Prada A,Passoni GR,Testoni PA.Complications of diagnostic and therapeutic ERCP:a prospective multicenter study[J].Am J Gastroenterol,2001;96(2):417-423.
4. Loperfido S,Angelini G,Benedetti G,Chilovi F,Costan F,De Berardinis F,De Bernardin M,Ederle A,Fina P,Fratton A.Major early complications from diagnostic and therapeutic ERCP:a prospective multicenter study[J].Gastrointest Endosc,1998;48(1):1-10.
5. Glasbrenner B,Adler G.Pathophysiology of acute pancreatitis[J].Hepatogastroenterology,1993;40(4):517-521.
6. Tulassay Z.Somatostatin and the gastrointestinal tract[J].Scand J Gastroenterol,1998;228(Suppl):115-121.
7. Harris AG.Octreotide in the treatment of disorders of the gastrointestinal tract[J].Drug Invest,1992;4(Suppl 3):1-54.
8. Binmoeller KF,Harris AG,Dumas R,Grimaldi C,Delmont PJ.Does the somatostatin analogue octreotide protect against ERCP induced pancreatitis[J]? Gut,1992;33(8):1129-1133.
9. Sternlieb JM,Aronchick CA,Retig JN,Dabezies M,Saunders F,Goosenberg E,Infantolino A,Ionna S,Maislin G,Wright SH,Lipshutz WH.A multicenter randomized controlled trial to evaluate the effect of prophylactic octreotide on ERCP-induced pancreatitis[J].Am J Gastroenterol,1992;87(11):1561-1566.
10. Arcidiacono R,Gambitta P,Rossi A,Grosso C,Bini M,Zanasi G.The use of a long-acting somatostatin analogue (octreotide) for prophylaxis of acute pancreatitis after endoscopic sphincterotomy[J].Endoscopy,1994;26(9):715-718.
11. Tulassay Z,Papp J.The effect of long-acting somatostatin analogue on enzyme change after endoscopic pancreatography[J].Gastrointest Endosc,1991;37(1):48-50.
12. Testoni PA,Bagnolo F,Andriulli A,Bernasconi G,Crotta S,Lella F,Lomazzi A,Minoli G,Natale C,Prada A,Toti GL,Zambelli A.Octreotide 24 h prophylaxis in patients at high risk for post-ERCP pancreatitis:results of a multicenter,randomized,controlled trial[J].Aliment Pharmacol Ther,2001;15(7):965-972.
13. Manolakopoulos S,Avgerinos A,Vlachogiannakos J,Armonis A,Viazis N,Papadiumitriou N,Mathou N,Stefanidis G,Rekoumis G,Vienna E,Tzourmakliotis D,Raptis SA.Octreotide versus hydrocortisone versus placebo in the prevention of post-ERCP pancreatitis:a multicenter randomized controlled trial[J].Gastrointestinal Endoscopy,2002;55(4):470-475.
14. Tulassay Z,Dobronte Z,Pronal L,Zagoni T,Juhasz L.Octreotide in the prevention of pancreatic injury associated with endoscopic cholangiopancreatography[J].Aliment Pharmacol Ther,1998;12(11):1109-1112.
15. Badra G,Galad AS,Rowaish I,Moustafa M,Waked I,Saled SM.Allopurinol vs octreotide in the prevention of post-ERCP pancreatitis in patient with billiary obstruction.A randomized controlled trial[J].Hepatology,2000;32(4):163A.
16. Duvnjak M,Supanc V,Simicevic VN,Hrabar D,Troskot B,Smircic-Duvnjak L,Bekavac-Beslin M.Use of octreotide-acetate in preventing pancreatitis-like changes following therapeutic endoscopic retrograde cholangiopancreatography[J].Acta Med Croatica,1999;53(3):115-118.
17. Arvanitidis D,Hatzipanayiotis J,Koutsounopoulos G,Frangou E.The effect of octreotide on the prevention of acute pancreatitis and hyperamylasemia after diagnostic and therapeutic ERCP[J].Hepatogastroenterology,1998;45(19):248-252.
18. Testoni PA,Lella F,Bagndo F,Buizza M,Colombo E.Controlled trial of different dosages of octreotide in the prevention of hyperamylasemia induced by endoscopic papillosphincterotomy[J].Ita J Gastroenterol,1994;26(9):431-436.
19. Testoni PA,Lella F,Bagndo F,Caporuscio S,Cattani L,Colombo E,Buizza M.Long-term prophylactic administration of octreotide reduces the rise in serm amylase after endoscopic procedures on Vaters papilla[J].Pancreas,1996;13(1):61-65.
20. Baldazzi G,Conti C,Spotti EG,Arisi GP,Scevola M,Gobetti F,Agliardi CM,Galasso P,Bonomi E,Bianchi F.Prevention of post-ERCP acute pancreatitis with octreotide[J].G Chir,1994;15(8):359-362.
21. Armonis A,Manolakopoulos S,Papadimitrious N,Gouma P,Avgerinos A.The effect of long acting somatostatin analogue in the prevention of post-ERCP pancreatitis[J].Gut,1994;35(suppl 4):A85.
22. Ng KW,Jiang CF,Liang CT,Wu CS,Chen HC,Yang CL,Tan SW,Yeh CH.A prospective,randomized,controlled trial to evaluate the effect of prophylactic sandostatin on ERCP-induced hyperamylasemia and pancreatitis.Gastroenterological[J].Journal of TaiWan,1997;14(2):192-197.
23. Russo A,Virgilio C,Aprile G.Influenza delloctreotide sulla reazione pancreatica indotta de colangiopancreatografia retrograda.Giorn[J].Ital End Dig,1992;15(2):139-145.
24. Lin Q,Wang KD,Tang GY,Li HL.Preventive effect of octreotide on pancreatitis after ERCP[J].Journal of modern practical medicine,2001;13(1):21-22.
25. Sun FQ,Zou DW,Li ZS,Xu GM,Sun ZX.Pevention of ERCP from pancreatitis[J].Chin J Dig Endosc,2000;17(2):81-83.
26. Li ZS,Qian XD,Xu GM,Sun ZX,Zou XP,Xie SQ.Prophylaxis of hyperamylasemia and post-ERCP pancreatitis by octreotide[J].Chin J Hepatobiliary Surg,2000;6(1):67-68.
27. Poon RT,Yeung C,Lo CM,Yuen WK,Liu CL,Fan ST.Prophylactic effect of somatostatin on post-ERCP pancreatitis:a randomized controlled trial[J].Gastrointest Endosc,1999;49(5):593-598.
28. Bordas JM,Toledo-Pimentel V,Llach J,Elena M,Mondelo F,Gines A,Teres J.Effects of bolus somatostatin in preventing pancreatitis after endoscopic pancreatography:results of a randomized study[J].Gastrointest Endosc,1998;47(3):230-234.
29. Persson B,Slezak P,Efendic S,Haggmark A.Can somatostatin prevent injection pancreatitis after ERCP[J]? Hepatogastroenterology,1992;39(3):259-261.
30. Guelrud M,Mendoza S,Viera L,Gelrud D.Somatostatin prevents acute pancreatitis after pancreatic duct sphincter hydrostatic balloon dilation in patients with idiopathic recurrent pancreatitis[J].Gastrointest Endosc,1991;37(1):44-47.
31. Bordas JM,Toledo V,Mondelo F,Rodes J.Prevention of pancreatic reactions by bolus somatostatin administration in patients undergoing endoscopic retrograde cholangio-pancreatography and endoscopic sphincterotomy[J].Hormone Res,1988;29(2):106-108.
32. Saari A,Kivilaakso E,Schroder R.The influence of somatostatin on pancreatic irritation after pancreatography.An experimental and clinical study[J].Surg Res Comm,1988;2(3):271-278.
33. Testoni PA,Masci E,Bagnolo F,Tittobello A.Endoscopic papillo-sphincterotomy:prevention of pancreatic reaction by somatostatin[J].Ital J Gastroenterol,1988;20(2):70-73.
34. Deschner K,Kalloo A,Collen M,Cattau EL,Maher KA,Fleischer DE,Berrjamin SB.Somatostatin:an evaluation of its utility as adjunctive medication for ERCP[J].Gastrointest Endosc,1989;35(2):149-150.
35. Circero GF,lauger R,Sahel J.Effect of somatostatin on clinical,biochemical and morphological changes following ERCP[J].Ital J Gastroenterol,1985;17(3):256-258.
36. Poon RT,Yeung C,Liu CL,Lam CM,Yuen WK,Lo CM,Tang A,Fan ST.Intravenous bolus somatostatin after diagnostic cholangiopancreatography reduces the incidence of pancreatitis associated with therapeutic endoscopic retrograde cholangiopancreatography procedures:a randomized controlled trial[J].Gut,2003;52(12):1768-1773.
37. Li ZS,Xu GM,Sun ZX,Zou XP,Jin ZD,Xie SQ.Clinical study on somatostatin in prevention of hyperamylasemia and pancreatitis after ERCP[J].Acad J Sec Mil Med Univ,1997;18(5):426-427.
38. Gong L,Tang XJ,Xi M.Prophylaxis of hyperamylasemia and pancreatitis post-ERCP treated by little dosage somatostatin[J].Acad J Qiqihaer Med Col,2002;23(8):855-856.
39. Saluja AK,Steer ML.Pathophysiology of acute pancreatitis:role of cytokines and other mediators of inflammation[J].Digestion,1999;60(1):27-33.
40. Yuan Y,Gong Z,Lou K.Effects and mechanisms of somatostatin analogs on apoptosis of pancreatic acinar cells in acute pancreatitis in mice[J].J Gastroenterol Hepatol,2001;16(5):683-688.
41. Binmoeller KF,Dumas R,Harris AG,Delmont JP.Effect of somatostatin analog octreotide on human sphincter of Oddi[J].Dig Dis Sci,1992;37(5):773-777.

《中國循證醫學雜志》

生長抑素及其類似物奧曲肽預防內鏡逆行胰膽管造影術后胰腺炎的系統評價

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《中國循證醫學雜志》

生長抑素及其類似物奧曲肽預防內鏡逆行胰膽管造影術后胰腺炎的系統評價

摘要 全文 圖表 視頻 參考文獻 施引文獻 補充材料

Format

Content

摘要全文圖表視頻參考文獻施引文獻補充材料