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Peptic Ulcer Rebleeding An Evidence-Based Management

Joint Hospital Surgical Grand Round 17 January 2009. Peptic Ulcer Rebleeding An Evidence-Based Management. Dr Shirley Yuk-Wah Liu Department of Surgery Prince of Wales Hospital The Chinese University of Hong Kong. History of Peptic Ulcer Bleeding. 1881 Theodor Billroth (1829 – 1894)

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Peptic Ulcer Rebleeding An Evidence-Based Management

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  1. Joint Hospital Surgical Grand Round 17 January 2009 Peptic Ulcer RebleedingAn Evidence-Based Management Dr Shirley Yuk-Wah Liu Department of Surgery Prince of Wales Hospital The Chinese University of Hong Kong

  2. History of Peptic Ulcer Bleeding 1881 Theodor Billroth (1829 – 1894) Father of modern abdominal surgery First gastrectomy 1800 1900 2000 1983 Warren and Marshall Association of H pylori with peptic ulcer 1950-1980s Introduction of endoscopy Warren et al. Lancet 1983 Marshall et al. Lancet 1983

  3. Mortality of peptic ulcer bleeding Peptic ulcer rebleeding is the most important predictor of mortality 1. BMJ 1947;2:441-446 2. BMJ 1970;2:7-14 3. BMJ 1973;3:655-660 4. Postgrad Med J 1987;57:627-632 5. Postgrad Med J 1989;65:913-917 6. BMJ 1995;311:222-226 VanLeerdam et al. Am J Gastroenterol 2003;98:1494-1499

  4. Bleeding peptic ulcers Urgent OGD Endoscopic hemostasis Prediction of rebleeding Close monitoring Prevention of rebleeding Rebleeding 10-15% Treatment of rebleeding Death

  5. Joint Hospital Surgical Grand Round 17 Jan 2009 Peptic Ulcer Rebleeding: An Evidence-based Management PREDICTION OF ULCER REBLEEDING

  6. Q Who are at risk of rebleeding? 10 studies published Evaluation on factors predicting rebleeding after endoscopic hemostasis

  7. Predictive factors of rebleeding Meta-analysis Clinical Independent predictive factors for rebleeding: 1. hemodynamic instability 2. comorbid illness 3. active bleeding ulcers 4. large ulcer size 5. ulcers with difficult position Endoscopic Elmunzer et al. Am J Gastroenterol 2008;103:2625-2632

  8. Joint Hospital Surgical Grand Round 17 Jan 2009 Peptic Ulcer Rebleeding: An Evidence-based Management PREVENTION OF ULCER REBLEEDING

  9. To prevent ulcer rebleeding Scheduled second-look endoscopy Adjunctive Acid suppressants - Is it useful? - Type of drugs: H2-receptor antagonists or PPI - Route of administration: IV or oral - Dosage: high-dose or low-dose

  10. Adjunctive acid suppressive drugs Platelet disaggregation 0 Neutral environment 20 Acidic environment 40 60 80 pH 100 0 1 2 3 4 5 Green et al. Gastroenterology 1978;74:38-43

  11. Maximum pepsin activity (%) 100 80 60 40 20 0 1 2 3 4 0 Gastric juice pH Adjunctive acid suppressive drugs pH 6 • Pepsin can disintegrate the clots on ulcer surface • Pepsin is irreversibly inactivated at pH 6

  12. Q 1. Is acid suppressive drugs useful? 24 RCT published Comparison of PPI to placebo in preventing rebleeding

  13. First RCT on PPI vs placebo Daneshmend et al. Br Med J 1992;304:143-147

  14. First positive evidence of PPI (IV) 240 patients Forrest class Ia, Ib, IIa 120 patients PPI group 80mg bolus, then 8mg/hr for 72 hrs 120 patients Placebo group P<0.001 P=NS P=NS Lau et al. N Eng J Med 2000;343:310-316

  15. Q 1. Is PPI useful? 19 studies on IV PPI 5 studies on oral PPI Systematic review 24 RCTs 4373 patients Conclusion point: PPI is useful in reducing rates of rebleeding, emergency operation & mortality Leontiadis et al. Cochrane Databse Syst Rev 2006;3:CD002094

  16. Q 2. Should we give PPI or H2R antagonists? Meta-analysis 11 RCT PPI 681 patients 11 RCT published H2R antagonist 671 patients Comparison of PPI to H2R antagonists as adjunctive treatment to bleeding ulcers Gisbert et al. Aliment Pharmacol Ther 2001;15:917-926

  17. Q 2. Should we give PPI or H2R antagonists? Comparison on rebleeding Comparison on emergency operation Comparison on mortality Conclusion point PPI is more superior to H2R antagonists in reducing the rates of rebleeding and emergency operation Gisbert et al. Aliment Pharmacol Ther 2001;15:917-926

  18. Q 3. What should be the best route of administration? 0 RCT published No RCT performed on direct comparison of oral versus IV PPI

  19. Q 3. What should be the best route of administration? Oral PPI IV PPI 5 trials 658 patients 19 trials 3714 patients Meta-regression analysis: No difference on - Rebleeding - Emergency operation - Mortality Evidence is still inconclusive of which route is better Leontiadis et al. Cochrane Databse Syst Rev 2006;3:CD002094

  20. Q 4. High-dose or low-dose PPI 2 RCT published High-dose PPI vs low-dose PPI P=NS P=0.002 Cheng et al. Dig Dis Sci 2005;502:1194-1201 Udd et al. Scand J Gastroenterol 2001;36:1332-1338

  21. Q 4. High-dose or low-dose PPI High-dose PPI PPI 80mg IV bolus then 8mg/hr infusion Low-dose PPI Oral PPI or IV PPI dose <120mg/day Conclusion point: High-dose PPI should be the recommended dosage for bleeding peptic ulcer 18 trials 2052 patients 6 trials 2320 patients Emergency surgery Rebleeding Both significantly reduced 36/1149 (3.1%) 59/1171 (5.0%) Only high-dose PPI significantly reduce the need OR=0.61, 95% C.I. 0.40-0.93, P=0.02 Leontiadis et al. Cochrane Databse Syst Rev 2004;3:CD002094

  22. To prevent ulcer rebleeding Scheduled second-look endoscopy Adjunctive Acid suppressants Is it useful ?

  23. Scheduled second-look endoscopy Rationale • To treat before clinical rebleeding occurs • To perform second-look OGD within 16 – 24 hours after primary endoscopic hemostasis Villanueva et al. Gastrointest Endosc 1994;40:34-39 Saeed et al. Endoscopy 1996;28:288-294 Rutgeerts et al. Lancet 1997;350:692-696 Messmann et al. Endoscopy 1998;30:583-589 Chiu et al. Gut 2003;52:1403-1407

  24. Scheduled second-look endoscopy Systematic reviews on 4 RCTs Villanueva et al. Gastrointest Endosc 1994;40:34-39 Saeed et al. Endoscopy 1996;28:288-294 Rutgeerts et al. Lancet 1997;350:692-696 Messmann et al. Endoscopy 1998;30:583-589 Marmo et al. Gastrointest Endosc 2003;57:62-67

  25. Scheduled second look endoscopy Forrest class Ia to IIb bleeding ulcers Conclusion point: Second-look endoscopy can prevent rebleeding P=0.03 P=0.05 P=NS Chiu et al. Gut 2003;52:1403-1407

  26. Joint Hospital Surgical Grand Round 17 Jan 2009 Peptic Ulcer Rebleeding: An Evidence-based Management TREATMENT OF ULCER REBLEEDING

  27. How to treat rebleeding? Q • Endoscopic re-treatment B. Immediate surgery C. Angiographic embolization What is the best treatment option? What type of emergency operations to perform?

  28. Q Surgery vs endoscopic re-treatment - 1169 patients with bleeding ulcers requiring endoscopic hemostasis - 92 patients (8.7%) developed rebleeding 1 RCT published P=0.03 P=0.27 P=0.59 P=0.16 P=0.37 Lau et al. N Eng J Med 1999;340:751-756

  29. Factors associated with failed endoscopic re-treatment Conclusion point: - Decision between surgery or repeat endoscopy should be selective

  30. Q Surgery vs Angiographic Embolization Only one retrospective comparative study (n=70) Not enough evidence to conclude whether surgery or embolization is more superior 0 RCT published Ripoll et al. J Vasc Interv Radiol 2004;15:447-450

  31. Q Angiographic embolization vs endoscopic re-treatment No RCT evidence to compare angiographic embolization to repeat endoscopy 0 RCT published

  32. What type of surgery to do? Q Conservative surgery Definitive surgery - Vagotomy +/- drainage - Partial gastrectomy - Ulcer plication - Ulcer excision 2 RCT published Prevent rebleeding Stop bleeding Lau et al. Best Pract Res Clin Gastroenterol 2000;14:505-518

  33. Q What type of surgery to do? Multicenter trial Conservative surgery: ulcer plication + H2RA Definitive surgery: vagotomy + drainage or gastrectomy P<0.05 P<0.05 Poxon et al. Br J Surg 1991;178:1344-1345

  34. Q What type of surgery to do? French Association of Surgical Research trial [1978-1988] Conservative surgery: ulcer plication + vagotomy Definitive surgery: gastrectomy Results before the era of PPI may not be reliable P<0.05 Millat et al. World J Surg 1993;17:568-573

  35. Conclusion High-dose IV PPI infusion is useful in reducing rebleeding, emergency operation and mortality Second-look endoscopy is useful in preventing rebleeding in high-risk patients Both endoscopic re-treatment and surgery should be selectively applied to rebleeding patients The choice between conservative and definitive Surgery is still controversial

  36. Department of Surgery The Chinese University of Hong Kong

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