Somatostatin and Octreotide in Preventing Post-ERCP Pancreatitis: A Systematic Review_Chinese Journal of Evidence-Based Medicine

Authors：

PAN Tao , WANG Yiping , YANG Jinlin , WU Zongying , ZENG Chao

Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China;

Corresponding author：

Keywords：

Post-ERCP pancreatitis; Somatostatin; Octreotide; Meta-analysis; Systematic review

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Objective 　To evaluate the effectiveness and safety of somatostatin and the analogue-octreotide in preventing post-ERCP pancreatitis.
Methods 　We searched Cochrane Clinical Trial Register （Issue 1, April, 2004 ）, MEDLINE （1966- April, 2004）, EMBASE （1985- April, 2004）, CBM disc （1970- April, 2004） and The Clinical Trial Register of Chinese Evidence-Based Medicine Center and handsearched the related journals to identify Randomized Controlled Trials （RCT）of somatostatin and octreotide in post-endoscopic retrograde chnlangiopancreatography pancreatitis（PEP）prevention. Systematic review was conducted using the method recommended by The Cochrane Collaboration.
Results 　Thirty-one trials involving 4 728 patients undergoing ERCP were included. Meta-analysis showed that the incidence of post-ERCP pancreatitis [ OR 0.33, 95% CI 0. 20 to 0. 54; P =0. 000 01 ; NNT =13] was significantly reduced by somatostatin. Octreotide could only reduce the incidence of hyperamylasemia [ OR 0. 54, 95% CI 0. 38 to 0. 77 ; P =0. 000 7 ]. The inci- dence of PEP, severe PEP and post-ERCP abdominal pain could not be reduced by octreotide.
Conclusions 　Somatostatin can prevent post-ERCP pancreatitis. Four trials are of high quality in the 12 included studies and the results are consistent with the sensitive-analysis, so it is credible to some extent. However, existing evidence does not support that octreotide can reduce the incidence of PEP, so it is not recommended for this indication. Sensitive-analysis even showed that octreotide could increase the incidence of PEP. Therefore, whether it is necessary to carry out further clinical trials should be considered with caution.

Citation： PAN Tao ,WANG Yiping,YANG Jinlin,WU Zongying,ZENG Chao. Somatostatin and Octreotide in Preventing Post-ERCP Pancreatitis: A Systematic Review. Chinese Journal of Evidence-Based Medicine, 2005, 05(10): 767-777. doi: Copy

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.

Chinese Journal of Evidence-Based Medicine

Somatostatin and Octreotide in Preventing Post-ERCP Pancreatitis: A Systematic Review

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