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Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial

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Abstract

Background

As suggested by observational and animal studies, heparin has antiinflammatory effects that could prevent acute post–endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Low-molecular-weight heparin did not reduce the incidence of post-ERCP pancreatitis in a controlled study. The current study aimed to determine whether prophylactic administration of low-dose unfractionated heparin, which has potentially more antiinflammatory capability, can prevent acute post-ERCP pancreatitis.

Methods

Patients scheduled for ERCP in the authors’ department were randomized to receive unfractionated heparin (5,000 IU) or placebo (saline solution 0.5 ml) administered subcutaneously 20 to 30 min before the ERCP. Patients who had undergone endoscopic sphincterotomy in the past were excluded from the study. Post-ERCP pancreatitis was defined according to criteria established by Cotton: abdominal pain combined with a threefold elevation of blood amylase 24 h after the ERCP.

Results

The study enrolled 106 patients. One patient was excluded from the analysis due to inaccessible papilla of Vater, leaving 51 patients in the heparin group and 54 in the placebo group, for a total of 105 patients (62 women and 43 men) with a mean age of 64.6 years. The rate of post-ERCP pancreatitis was not different between the groups (heparin, 4 patients, 7.8%; placebo, 4 patients, 7.4%). Two patients in each group experienced mild bleeding.

Conclusions

The study did not demonstrate a significant effect of low-dose unfractionated heparin in the prevention of post-ERCP pancreatitis. A multicenter trial with a larger number of patients is needed to demonstrate a benefit from this drug.

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References

  1. Freeman ML, Nelson DB, Sherman S, Haber GB, Herman ME, Dorsher PJ, Moore JP, Fennerty MB, Ryan ME, Shaw MJ, Lande JD, Pheley AM (1996) Complications of endoscopic biliary sphincterotomy. N Engl J Med 335:909–918

    Article  PubMed  CAS  Google Scholar 

  2. Baille J (1994) Complications of endoscopy. Endoscopy 26:185–203

    Google Scholar 

  3. Huibregtse K (1996) Complications of endoscopic sphincterotomy and their prevention. N Engl J Med 335:961–963

    Article  PubMed  CAS  Google Scholar 

  4. Niederau C, Pohlmann U, Lubke H, Thomas L (1994) Prophylactic antibiotic treatment on therapeutic or complicated diagnostic ERCP: results of a randomized controlled clinical study. Gastrointest Endosc 40:533–537

    Article  PubMed  CAS  Google Scholar 

  5. Guelrud M, Mendoza S, Viera L, Guelrud D (1991) Somatostatin prevents acute pancreatitis after pancreatic duct sphincter hydrostatic balloon dilation in patients with idiopathic recurrent pancreatitis. Gastrointest Endosc 36:44–47

    Article  Google Scholar 

  6. Tulassay Z, Papp J (1991) The effect of long-acting somatostatin analogue on enzyme changes after endoscopic pancreatography. Gastrointest Endosc 37:48–50

    PubMed  CAS  Google Scholar 

  7. Weiner GR, Geenen JE, Hogan WJ, Catalano MF (1995) Use of corticosteroids in the prevention of post-ERCP pancreatitis. Gastrointest Endosc 42:579–583

    Article  PubMed  CAS  Google Scholar 

  8. De Palma GD, Catanzano C (1999) Use of corticosteroids in the prevention of post-ERCP pancreatitis: results of controlled prospective study. Am J Gastroenterol 94:982–985

    Article  PubMed  Google Scholar 

  9. Murray B, Carter R, Imrie C, Evans S, O’Suilleabhain C (2003) Diclofenac reduces the incidence of acute pancreatitis after endoscopic retrograde cholangiopancreatography. Gastroenterology 124:1786–1791

    Article  PubMed  CAS  Google Scholar 

  10. Prat F, Amaris J, Ducot B, Bocquentin M, Fritsch J, Choury AD, Pelletrier G, Buffet C (2002) Nifedipine for prevention of post-ERCP pancreatitis: a prospective, double-blind randomized study. Gastrointest Endoscopy 56:202–208

    Article  Google Scholar 

  11. Moreto M, Zaballa M, Casado I, Merino O, Rueda M, Ramirez K, Urcelay R, Baranda A (2003) Transdermal glyceryl trinitrate for prevention of post- ERCP pancreatitis: a randomized double–blind trial. Gastrointest Endosc 57:1–7

    Article  PubMed  Google Scholar 

  12.  Cavallini G, Tittobello A, Frulloni L, Masci E, Mariani A, DiFrancesco V (1996) Gabexate for the prevention of pancreatic damage related to endoscopic retrograde cholangio-pancreatography. N Engl J Med 335:919–923

    Article  PubMed  CAS  Google Scholar 

  13. Deviere J, Le Moine O, Van Laethem JL, Eisendrath P, Ghilain A, Severs N, Cohard M (2001) Interleukin-10 reduces the incidence of pancreatitis after therapeutic endoscopic retrograde cholangio-pancreatography. Gastroenterology 120:498–505

    Article  PubMed  CAS  Google Scholar 

  14. Tulassay Z, Döbrönte Z, Prónai L, Zágoni T, Juhász L (1998). Octreotide in the prevention of pancreatic injury associated with endoscopic cholangiopancreatography. Aliment Pharmacol Ther 12:1109–1112

    Article  PubMed  CAS  Google Scholar 

  15. Thomopoulos KC, Pagoni NA, Vagenas KA, Margaritis VG, Theocharis GI, Nikolopoulou VN (2006) Twenty-four hour prophylaxis with increased dosage of octreotide reduces the incidence of post-ERCP pancreatitis. Gastrointest Endosc 64:726–731

    Article  PubMed  Google Scholar 

  16. Tarnasky PR, Palesch YY, Cunningham JT, Mauldin PD, Cotton PB, Hawes RH (1998) Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction. Gastroenterology 115:1518–1524

    Article  PubMed  CAS  Google Scholar 

  17. Smithline A, Silverman W, Rogers D, Nisi R, Wiersema M, Jamidar P, Hawes R, Lehman G (1993) Effect of prophylactic main pancreatic duct stenting on the incidence of biliary endoscopic sphincterotomy-induced pancreatitis in high-risk patients. Gastrointest Endosc 39:652–657

    Article  PubMed  CAS  Google Scholar 

  18. Fazel A, Quadri A, Catalano MF, Meyerson SM, Geenen JE (2003) Does a pancreatic duct stent prevent post-ERCP pancreatitis? A prospective randomized study. Gastrointest Endosc 57:291–294

    Article  PubMed  Google Scholar 

  19. Sherman S, Bucksot EL, Esber E, Pezzi J, Gottlieb K, Lehman G (1995) Does leaving a main pancreatic duct stent in place reduce the incidence of precut biliary sphincterotomy induced pancreatitis? Randomized prospective study (abstract). Am J Gastroenterol 90:241

    Google Scholar 

  20. Gabryelewicz A, Kosidlo S, Prokopowicz J, Prokopowicz K (1986) Does heparin modify protease-antiprotease balance in acute experimental pancreatitis in rats? Hepatogastroenterology 33:79–92

    PubMed  CAS  Google Scholar 

  21. Kosidlo S, Gabryelewicz A, Prokopowicz J, Prokopowicz K (1986) Pancreatic proteolytic and inhibitory activity during acute experimental pancreatitis in rats with reference to heparin treatment (in Polish with English abstract). Mater Med Pol 18:136–143

    PubMed  CAS  Google Scholar 

  22. Toulon P, Chadeuf G, Bouillot JL, Amiral J, Cambillau M, Sultan Y, Aliach M (1991) Involvement of heparin cofactor II in chymotrypsin neutralization and in pancreatic–proteinase–antiproteinase interaction during acute pancreatitis in man. Eur J Clin Invest 21:303–309

    Article  PubMed  CAS  Google Scholar 

  23. Bleeker WK, Agterberg J, Rigter G, Hack CE, Gool JV (1992) Protective effect of antithrombin III in acute experimental pancreatitis in rats. Dig Dis Sci 37:280–285

    Article  PubMed  CAS  Google Scholar 

  24. Dobosz M, Hac S, Mionskowska L, Dobrowolski S, Wajda Z (1997) Microcirculatory disturbances of the pancreas in caerulein-induced acute pancreatitis in rats with reference to L-arginine, heparin, and procaine treatment. Pharmacol Res 36:123–128

    Article  PubMed  CAS  Google Scholar 

  25. Salas A, Sans M, Soriano A, Reverter JC, Anderson DC, Pique JM, Panes J (2000) Heparin attenuates TNF-alpha induced inflammatory response through a CD11b dependent mechanism. Gut 47:88–96

    Article  PubMed  CAS  Google Scholar 

  26. Leever R, Robin J, Hoult S, Page CP (2000) The effects of heparin and related molecules upon the adhesion of human polymorphnuclear leukocytes to vascular endothelium in vitro. Br J Pharmacol 129:533–540

    Article  Google Scholar 

  27. Koenig A, Norgard-Sumnicht K, Linhardt R, Varki A (1998) Differential interactions of heparin and heparin sulfate glycosaminoglycans with the selectins: implications for the use of unfractionated and low-molecular-weight heparins as therapeutic agents. J Clin Invest 101:877–889

    Article  PubMed  CAS  Google Scholar 

  28. Bowler SD, Smith SM, Lavercombe PS (1993) Heparin inhibits the immediate response to antigen in the skin and lung of allergic subjects. Am Rev Respir Dis 147:160–163

    PubMed  CAS  Google Scholar 

  29. Rabenstein T, Roggenbuck S, Framke B, Martus P, Fisher B, Nusko G, Muehldorfer S, Hochberger J, Ell C, Hahn EG, Schneider HT (2002) Complications of endoscopic sphincterotomy: can heparin prevent acute pancreatitis after ERCP? Gastrointest Endosc 55:476–483

    Article  PubMed  Google Scholar 

  30. Rabenstein T, Fischer B, Wiessner V, Schmidt H, Radespiel-Troger M, Hochberger J, Muehldorfer S, Nusko G, Meissmann H, Scholmerich J, Schulz HJ, Schonekas H, Hahn EG, Schneider HT (2004) Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis. Gastrointest Endos 59:606–613

    Article  Google Scholar 

  31. Cotton PB, Lehman G, Vennes JA, Geenen JE, Russell RCG, Meyers WC, Liguory C, Nickl N (1991) Endoscopic sphincterotomy complications and their management: an attempt at consensus. Gastrointest Endosc 37:383–391

    PubMed  CAS  Google Scholar 

  32. Ranson JH (1979) The timing of biliary surgery in acute pancreatitis. Ann Surg 189:654–663

    Article  PubMed  CAS  Google Scholar 

  33. Balthazar EJ, Ranson JH, Naidich DP, Megibow AS, Caccavale R, Cooper MM (1985) Acute pancreatitis: prognostic value of CT. Radiology 158:767–772

    Google Scholar 

  34. Estes JW (1980) Clinical pharmacokinetics of heparin. Clin Pharmacokinet 5:204–220

    PubMed  CAS  Google Scholar 

  35. Freeman ML (2002) Adverse outcomes of ERCP. Gastrointest Endosc 56:S273–S282

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gastroenterology, Tel Aviv Sourasky Medical Center, 6 Weizmann Street, Tel Aviv, 64239, Israel

    O. Barkay, E. Niv, E. Santo, R. Bruck & A. Hallak

  2. Department of Gastroenterology and Hepatology, Meir Medical Center, 59 Tchernichovsky St., Kfar Saba, Israel

    F. M. Konikoff

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  1. O. Barkay
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  2. E. Niv
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  3. E. Santo
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  6. F. M. Konikoff
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Correspondence to O. Barkay.

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Barkay, O., Niv, E., Santo, E. et al. Low-dose heparin for the prevention of post-ERCP pancreatitis: a randomized placebo-controlled trial. Surg Endosc 22, 1971–1976 (2008). https://doi.org/10.1007/s00464-007-9738-2

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  • DOI: https://doi.org/10.1007/s00464-007-9738-2

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