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Surgical Endoscopy

, Volume 30, Issue 6, pp 2155–2168 | Cite as

Endoscopic hemostasis for peptic ulcer bleeding: systematic review and meta-analyses of randomized controlled trials

  • Felipe BaracatEmail author
  • Eduardo Moura
  • Wanderley Bernardo
  • Leonardo Zorron Pu
  • Ernesto Mendonça
  • Diogo Moura
  • Renato Baracat
  • Edson Ide
Review

Abstract

Background

Peptic ulcer represents the most common cause of upper gastrointestinal bleeding. Endoscopic therapy can reduce the risks of rebleeding, continued bleeding, need for surgery, and mortality. The objective of this review is to compare the different modalities of endoscopic therapy.

Methods

Studies were identified by searching electronic databases MEDLINE, Embase, Cochrane, LILACS, DARE, and CINAHL. We selected randomized clinical trials that assessed contemporary endoscopic hemostatic techniques. The outcomes evaluated were: initial hemostasis, rebleeding rate, need for surgery, and mortality. The possibility of publication bias was evaluated by funnel plots. An additional analysis was made, including only the higher-quality trials.

Results

Twenty-eight trials involving 2988 patients were evaluated. Injection therapy alone was inferior to injection therapy with hemoclip and with thermal coagulation when evaluating rebleeding and the need for emergency surgery. Hemoclip was superior to injection therapy in terms of rebleeding; there were no statistically significant differences between hemoclip alone and hemoclip with injection therapy. There was considerable heterogeneity in the comparisons between hemoclip and thermal coagulation. There were no statistically significant differences between thermal coagulation and injection therapy, though their combination was superior, in terms of rebleeding, to thermal coagulation alone.

Conclusions

Injection therapy should not be used alone. Hemoclip is superior to injection therapy, and combining hemoclip with an injectate does not improve hemostatic efficacy above hemoclip alone. Thermal coagulation has similar efficacy as injection therapy; combining these appears to be superior to thermal coagulation alone. Therefore, we recommend the application of hemoclips or the combined use of injection therapy with thermal coagulation for the treatment of peptic ulcer bleeding.

Keywords

Non-variceal upper gastrointestinal bleeding Gastrointestinal hemorrhage Peptic ulcer Endoscopy Endoscopic hemostasis 

Notes

Compliance with ethical standards

Disclosures

Drs Felipe Baracat, Eduardo Moura, Wanderley Bernardo, Leonardo Zorron Pu, Ernesto Mendonça, Diogo Moura, Renato Baracat, and Edson Ide have no conflicts of interest or financial ties to disclosure.

Supplementary material

464_2015_4542_MOESM1_ESM.zip (1.2 mb)
Supplementary material 1 (ZIP 1224 kb)

References

  1. 1.
    American Society for Gastrointestinal Endoscopy (2004) ASGE Guide line: the role of endoscopy in acute non-variceal upper-GI hemorrhage. Gastrointest Endosc 60:497–504CrossRefGoogle Scholar
  2. 2.
    Wilcox CM, Alexander LN, Cotsonis G (1997) A prospective characterization of upper gastrointestinal hemorrhage presenting with hematochezia. Am J Gastroenterol 92:231–235PubMedGoogle Scholar
  3. 3.
    Yavorski RT, Wong RK, Maydonovitch C, Battin LS, Furnia A, Amundson DE (1995) Analysis of 3,294 cases of upper gastrointestinal bleeding in military medical facilities. Am J Gastroenterol 90:568–573PubMedGoogle Scholar
  4. 4.
    Rockall TA, Logan RF, Devlin HB, Northfield TC (1995) Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. Steering Committee and members of the National Audit of Acute Upper Gastrointestinal Haemorrhage. BMJ 311:222–226CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Blocksom JM, Tokioka S, Sugawa C (2004) Current therapy for nonvariceal upper gastrointestinal bleeding. Surg Endosc 18:186–192CrossRefPubMedGoogle Scholar
  6. 6.
    Cappell MS, Friedel D (2008) Initial management of acute upper gastrointestinal bleeding: from initial evaluation up to gastrointestinal endoscopy. Med Clin North Am 92:491–509CrossRefPubMedGoogle Scholar
  7. 7.
    Kovacs TO (2008) Management of upper gastrointestinal bleeding. Curr Gastroenterol Rep 10:535–542CrossRefPubMedGoogle Scholar
  8. 8.
    Gralnek M, Jensen DM, Gorbein J, Kovacs TO, Jutabha R, Freeman ML, King J, Jensen ME, Cheng S, Machicado GA, Smith JA, Randall GM, Sue M (1998) Clinical and economic outcomes of individuals with severe peptic ulcer hemorrhage and nonbleeding visible vessel: an analysis of two prospective clinical trials. Am J Gastroenterol 93:2047–2053CrossRefPubMedGoogle Scholar
  9. 9.
    Pedroto I, Dinis-Ribeiro M, Ponchon T (2012) Is timely endoscopy the answer for cost-effective management of acute upper gastrointestinal bleeding? Endoscopy 44:721–722CrossRefPubMedGoogle Scholar
  10. 10.
    Blatchford O, Davidson LA, Murray WR, Blatchford M, Pell J (1997) Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study. BMJ 315:510–514CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Simoens M, Rutgeerts P (2001) Non-variceal upper gastrointestinal bleeding. Best Pract Res Clin Gastroenterol 15:121–133CrossRefPubMedGoogle Scholar
  12. 12.
    Bleau BL, Gostout CJ, Sherman KE, Shaw MJ, Harford WV, Keate RF, Bracy WP, Fleischer DE (2002) Recurrent bleeding from peptic ulcer associated with adherent clot: a randomized study comparing endoscopic treatment with medical therapy. Gastrointest Endosc 56:1–6CrossRefPubMedGoogle Scholar
  13. 13.
    Sung J (2006) Best endoscopic hemostasis for ulcer bleeding: Is there such a treatment? Gastrointest Endosc 63:774–775CrossRefPubMedGoogle Scholar
  14. 14.
    Sung JJ, Luo D, Wu JC, Ching JY, Chan FK, Lau JY, Mack S, Ducharme R, Okolo P, Canto M, Kalloo A, Giday SA (2011) Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding. Endoscopy 43:291–295CrossRefPubMedGoogle Scholar
  15. 15.
    Giday SA, Kim Y, Krishnamurty DM et al (2011) Long–term randomized controlled trial of a novel nanopowder hemostatic agent (TC–325) for control of severe arterial upper gastrointestinal bleeding in a porcine model. Endoscopy 43:296–299CrossRefPubMedGoogle Scholar
  16. 16.
    Smith LA, Stanley AJ, Bergman JJ, Kiesslich R, Hoffman A, Tjwa ET, Kuipers EJ, von Holstein CS, Oberg S, Brullet E, Schmidt PN, Igbal T, Mangiavillano B, Masci E, Prat F, Morris AJ (2014) Hemospray Application in Nonvariceal Upper Gastrointestinal Bleeding; results of the Survey to Evaluate the Application of Hemospray in the Luminal Tract. J Clin Gastroenterol 48:89–92Google Scholar
  17. 17.
    Barkun AN, Toubouti Y, Rahme E, Bardou M (2009) Endoscopic hemostasis in peptic ulcer bleeding for patients with high-risk lesions: a series of meta-analyses. Gastrointest Endosc 69:786–799CrossRefPubMedGoogle Scholar
  18. 18.
    Vergara M, Bennett C, Calvet X, Gisbert JP (2014) Epinephrine injection versus epinephrine injection and a second endoscopic method in high-risk bleeding ulcers. Cochrane Database Syst Rev. doi: 10.1002/14651858.CD005584.pub3 PubMedGoogle Scholar
  19. 19.
    Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions : explanation and elaboration. J Clin Epidemiol 62(10):1–34CrossRefGoogle Scholar
  20. 20.
    PROSPERO Center for Revews and Dissemination, University of York. “Guidance notes for registering a systematic review with PROSPERO”. http://www.crd.york.ac.uk/PROSPERO/
  21. 21.
    Barkun A, Bardou M, Marshall JK (2003) Consensus recommendations for managing patients with nonvariceal upper gastrointestinal bleeding. Ann Intern Med 139:843–857CrossRefPubMedGoogle Scholar
  22. 22.
    Consolidated Standards of reporting Trials – CONSORT; http://www.consort-statement.org/consort-statement/
  23. 23.
    Jadad AR, Moore RA, Carrol D, Jenkinson C, Reynolds DJM, Gavaghan DJ et al (1996) Assessing the quality of reports on randomized clinical trials: Is blinding necessary? Controlled Clin Trials 17:1–12CrossRefPubMedGoogle Scholar
  24. 24.
    Center for Evidence-Based Medicine, Headington, Oxford. Critically Appraised Topics (CAT). http://www.cebm.net/catmaker-ebm-calculators/
  25. 25.
    (RevMan) [Computer program]. Version 5.3. Copenhagen: The Nordic Cochrane Center, The Cochrane CollaborationsGoogle Scholar
  26. 26.
    Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Ljubicic N, Budimir I, Biscanin A, Nikolic M, Supanc V, Hrabar D, Pavic T (2012) Endoclips vs large or small-volume epinephrine in peptic ulcer recurrent bleeding. World J Gastroenterol 18:2219–2224CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Jubicic L, Supanc V, Vrsalovic M (2004) Efficacy of endoscopic clipping for actively bleeding peptic ulcer: comparison with polidocanol injection therapy. Hepatogastroenterology 51(56):408–412Google Scholar
  29. 29.
    Shimoda R, Iwakiri R, Sakata H, Ogata S, Kikkawa A, Ootani H, Oda K, Ootani A, Tsunada S, Fujimoto K (2003) Evaluation of endoscopic hemostasis with metallic hemoclips for bleeding gastric ulcer: comparison with endoscopic injection of absolute ethanol in a prospective, randomized study. Am J Gastroenterol 98(10):2198–2202CrossRefPubMedGoogle Scholar
  30. 30.
    Chou YC, Hsu PI, Lai KH, Lo CC, Chan HH, Lin CP, Chen WC, Shie CB, Wang EM, Chou NH, Chen W, Lo GH (2003) A prospective, randomized trial of endoscopic hemoclip placement and distilled water injection for treatment of high-risk bleeding ulcers. Gastrointest Endosc 57(3):324–328CrossRefPubMedGoogle Scholar
  31. 31.
    Gevers AM, De Goede E, Simoens M, Hiele M, Rutgeerts P (2002) A randomized trial comparing injection therapy with hemoclip and with injection combined with hemoclip for bleeding ulcers. Gastrointest Endosc 55(4):466–469CrossRefPubMedGoogle Scholar
  32. 32.
    Chung IK, Ham JS, Kim HS, Park SH, Lee MH, Kim SJ (1999) Comparison of the hemostatic efficacy of the endoscopic hemoclip method with hypertonic saline-epinephrine injection and a combination of the two for the management of bleeding peptic ulcers. Gastrointest Endosc 49(1):13–18CrossRefPubMedGoogle Scholar
  33. 33.
    Grgov S, Radovanović-Dinić B, Tasić T (2013) Could application of epinephrine improve hemostatic efficacy of hemoclips for bleeding peptic ulcers? A prospective randomized study. Vojnosanit Pregl 70(9):824–829CrossRefPubMedGoogle Scholar
  34. 34.
    Lo CC, Hsu PI, Lo GH, Lin CK, Chan HH, Tsai WL, Chen WC, Wu CJ, Yu HC, Cheng JS, Lai KH (2006) Comparison of hemostatic efficacy for epinephrine injection alone and injection combined with hemoclip therapy in treating high-risk bleeding ulcers. Gastrointest Endosc 63(6):767–773CrossRefPubMedGoogle Scholar
  35. 35.
    Arima S, Sakata Y, Ogata S, Tominaga N, Tsuruoka N, Mannen K, Shiraishi R, Shimoda R, Tsunada S, Sakata H, Iwakiri R, Fujimoto K (2010) Evaluation of hemostasis with soft coagulation using endoscopic hemostatic forceps in comparison with metallic hemoclips for bleeding gastric ulcers: a prospective, randomized trial. J Gastroenterol 45(5):501–505CrossRefPubMedGoogle Scholar
  36. 36.
    Taghavi SA, Soleimani SM, Hosseini-Asl SM, Eshraghian A, Eghbali H, Dehghani SM, Ahmadpour B, Saberifiroozi M (2009) Adrenaline injection plus argon plasma coagulation versus adrenaline injection plus hemoclips for treating high-risk bleeding peptic ulcers: a prospective, randomized trial. Can J Gastroenterol 23(10):699–704CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Lin HJ, Perng CL, Sun IC, Tseng GY (2003) Endoscopic haemoclip versus heater probe thermocoagulation plus hypertonic saline-epinephrine injection for peptic ulcer bleeding. Dig Liver Dis 35(12):898–902CrossRefPubMedGoogle Scholar
  38. 38.
    Lin HJ, Hsieh YH, Tseng GY, Perng CL, Chang FY, Lee SD (2002) A prospective, randomized trial of endoscopic hemoclip versus heater probe thermocoagulation for peptic ulcer bleeding. Am J Gastroenterol 97(9):2250–2254CrossRefPubMedGoogle Scholar
  39. 39.
    Cipolletta L, Bianco MA, Marmo R, Rotondano G, Piscopo R, Vingiani AM, Meucci C (2001) Endoclips versus heater probe in preventing early recurrent bleeding from peptic ulcer: a prospective and randomized trial. Gastrointest Endosc 53(2):147–151CrossRefPubMedGoogle Scholar
  40. 40.
    Skok P, Krizman I, Skok M (2004) Argon plasma coagulation versus injection sclerotherapy in peptic ulcer hemorrhage - a prospective, controlled study. Hepatogastroenterology 51(55):165–170PubMedGoogle Scholar
  41. 41.
    Laine L, Estrada R (2002) Randomized trial of normal saline solution injection versus bipolar electrocoagulation for treatment of patients with high-risk bleeding ulcers: is local tamponade enough? Gastrointest Endosc 55(1):6–10CrossRefPubMedGoogle Scholar
  42. 42.
    Lin HJ, Tseng GY, Perng CL, Lee FY, Chang FY, Lee SD (1999) Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding. Gut 44(5):715–719CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Gralnek IM, Jensen DM, Kovacs TO, Jutabha R, Jensen ME, Cheng S, Gornbein J, Freeman ML, Machicado GA, Smith J, Sue M, Kominski G (1997) An economic analysis of patients with active arterial peptic ulcer hemorrhage treated with endoscopic heater probe, injection sclerosis, or surgery in a prospective, randomized trial. Gastrointest Endosc 46(2):105–112CrossRefPubMedGoogle Scholar
  44. 44.
    Llach J, Bordas JM, Salmerón JM, Panés J, García-Pagán JC, Feu F, Navasa M, Mondelo F, Piqué JM, Mas A, Terés J, Rodés J (1996) A prospective randomized trial of heater probe thermocoagulation versus injection therapy in peptic ulcer hemorrhage. Gastrointest Endosc 43:117–120CrossRefPubMedGoogle Scholar
  45. 45.
    Choudari CP, Rajgopal C, Palmer KR (1992) Comparison of endoscopic injection therapy versus the heater probe in major peptic ulcer haemorrhage. Gut 33(9):1159–1161CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Panés J, Viver J, Forné M (1991) Randomized comparison of endoscopic microwave coagulation and endoscopic sclerosis in the treatment of bleeding peptic ulcers. Gastrointest Endosc 37(6):611–616CrossRefPubMedGoogle Scholar
  47. 47.
    Waring JP, Sanowski RA, Sawyer RL, Woods CA, Foutch PG (1991) A randomized comparison of multipolar electrocoagulation and injection sclerosis for the treatment of bleeding peptic ulcer. Gastrointest Endosc 37(3):295–298CrossRefPubMedGoogle Scholar
  48. 48.
    Chung SC, Leung JW, Sung JY, Lo KK, Li AK (1991) Injection or heat probe for bleeding ulcer. Gastroenterology 100(1):33–37PubMedGoogle Scholar
  49. 49.
    Sollano JD, Ang VN, Moreno JA (1991) Endoscopic hemostasis of bleeding peptic ulcers: 1:10000 adrenalin injection vs. 1:10000 adrenalin +1% aethoxysclerol injection vs. heater probe. Gastroenterol Jpn 26(3):83–85PubMedGoogle Scholar
  50. 50.
    Laine L (1990) Multipolar electrocoagulation versus injection therapy in the treatment of bleeding peptic ulcers. A prospective, randomized trial. Gastroenterology 99(5):1303–1306PubMedGoogle Scholar
  51. 51.
    Lin HJ, Lee FY, Kang WM, Tsai YT, Lee SD, Lee CH (1990) Heat probe thermocoagulation and pure alcohol injection in massive peptic ulcer haemorrhage: a prospective, randomised controlled trial. Gut 31(7):753–757CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Lin HJ, Tsai YT, Lee SD, Lai KH, Lee FY, Lin CY, Lee CH (1988) A prospectively randomized trial of heat probe thermocoagulation versus pure alcohol injection in nonvariceal peptic ulcer hemorrhage. Am J Gastroenterol 83(3):283–286PubMedGoogle Scholar
  53. 53.
    Bianco MA, Rotondano G, Marmo R, Piscopo R, Orsini L, Cipolletta L (2004) Combined epinephrine and bipolar probe coagulation vs. bipolar probe coagulation alone for bleeding peptic ulcer: a randomized, controlled trial. Gastrointest Endosc 60(6):910–915CrossRefPubMedGoogle Scholar
  54. 54.
    Chung SS, Lau JY, Sung JJ, Chan AC, Lai CW, Ng EK, Chan FK, Yung MY, Li AK (1997) Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers. BMJ 314(7090):1307–1311CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Lu Y, Chen YI, Barkun A (2014) Endoscopic Management of Acute Peptic Ulcer Bleeding. Gastroenterol Clin North Am 43(4):677–705CrossRefPubMedGoogle Scholar
  56. 56.
    Laine L, McQuaid KR (2009) Endoscopic therapy for bleeding ulcers: an evidence-based approach based on meta-analyses of randomized controlled trials. Clin Gastroenterol Hepatol 7(1):33–47CrossRefPubMedGoogle Scholar
  57. 57.
    Calvet X, Vergara M, Brullet E (2004) Addition of a second endoscopic treatment following epinephrine injection improves outcome in high-risk bleeding ulcers. Gastroenterology 126(2):441–450CrossRefPubMedGoogle Scholar
  58. 58.
    Moher D, Liberati A, Tetzlaff J, Altman DG (2009) The PRISMA Group. Preferred Reporting Items for Systematic Reviews and Meta-Analyses, The PRISMA StatementGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Felipe Baracat
    • 1
    • 3
    Email author
  • Eduardo Moura
    • 1
  • Wanderley Bernardo
    • 2
  • Leonardo Zorron Pu
    • 1
  • Ernesto Mendonça
    • 1
  • Diogo Moura
    • 1
  • Renato Baracat
    • 1
  • Edson Ide
    • 1
  1. 1.Gastrointestinal Endoscopy Unit, Gastroenterology DepartmentUniversity of Sao Paulo Medical SchoolSão PauloBrazil
  2. 2.Thoracic Surgery Department, Instituto do Coraçao (InCor)University of Sao Paulo Medical SchoolSão PauloBrazil
  3. 3.São PauloBrazil

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