The Management of Acute Upper Gastrointestinal Bleeding James Irwin Gastroenterology Department Palmerston North Hospital Acute Medicine Meeting Hutt Hospital June 21, 2015
Outline Common Definitions and Risk Scores in Upper Gastrointestinal Bleeding Epidemiology Basic Management Decision points Long term mangagment Slide 2 of 33
Common Definitions and Risk Scores in Upper Gastrointestinal Bleeding Upper GI bleeding is defined as: Bleeding proximal to ligament of Trietz Forrest Classification 1 of peptic ulceration Rockall Score 2 Blatchford Score 3 1 Forrest, Finlayson, and Shearman 1974. 2 Rockall et al. 1996. 3 O. Blatchford, Murray, and M. Blatchford 2000. Slide 3 of 33
Forrest classification 4 Grading of acuity of peptic ulceration 1a Spurting bleeding 1b Oozing bleeding 2a Visible vessel 2b Adherent clot 2c Red spot 3 Clean base 4 Forrest, Finlayson, and Shearman 1974. Slide 4 of 33
Rockall Score 5 Pre-endoscopy and post-endoscopy score Designed to predict mortality 0 1 2 3 Age <60 Years 60-79 Years 80 Shock BP 100,pulse<100 Pulse 100 BP<100 Comorbidity No major Heart failure, Renal/liver failure comorbidity IHD, any major Disseminated comorbidity malignancy Diagnosis Mallory Weis, All other Malignancy No lesion seen, diagnoses No SRH Major SRH None or Blood in lumen, dark spot visible or spurting vessel, adherent clot Table: Rockall score. SRH = stigmata of recent haemorrhage 5 Rockall et al. 1996. Slide 7 of 33
Blatchford score 6 Designed to predict combined endpoint of death, surgery, blood transfusion, performance of endoscopic therapy at endoscopy. 1 2 3 4 6 Blood Urea mmol/l 6.5-7.9 8.0-9.9 10-24.9 25 Hb (g/l, men) 12.0-12.9 10.0-11.9 <10 Hb (g/l, women) 10-11.9 <10 Systolic BP mmhg 100-109 90-99 <90 Pulse (per min) >100 Clinical Melaena Syncope Comorbidity Hepatic disease Cardiac failure Table: Blatchford score. 6 O. Blatchford, Murray, and M. Blatchford 2000. Slide 8 of 33
Epidemiology Age Standardized Incidence between 40 and 200 per 100,000 per year 7 30 day mortality 5-10% 8 Associated with H. pylori infection 9 NSAID use 10 Anticoagulant use 11 Increasing age 12 Male sex 13 Maori ethnicity 14 7 Lewis et al. 2002; O. Blatchford, Davidson, et al. 1997; Loperfido et al. 2009; Rockall et al. 1995; Irwin et al. 2014b. 8 O. Blatchford, Davidson, et al. 1997; Loperfido et al. 2009; Irwin et al. 2014b. 9 Schöttker et al. 2012. 10 García Rodríguez L 1998. 11 Hallas et al. 2006. 12 O. Blatchford, Davidson, et al. 1997. 13 O. Blatchford, Davidson, et al. 1997; Rockall et al. 1995. 14 Irwin et al. 2014b. Slide 9 of 33
Findings at Endoscopy Gastric Ulcer 19 Duodenal Ulcer 21 Gastric Cancer 2.5 Oesophogeal Cancer 0.9 Gastric Erosions 14 Duodenal Erosions 8.4 Vascular Lesion 3.1 Oesophogeal Varices 5.1 Oesophagitis 15 Mallory Weiss Tear 4.05 Normal Endoscopy 15 Slide 10 of 33
Basic Management Algorithm Safe IV access - 2 large bore lines Crossmatch Resuscitation Monitor and maintain end organ perfusion blood pressure, urine output, level of consciousness Correct coagulation defects PPI Endoscopy Address risk factors H. pylori status NSAID use Antiplatelet and anticoagulant therapy Home! Slide 11 of 33
Decision Points When to transfuse? PPI therapy Continue or stop antiplatelet therapy? Continue or stop anticoagulant therapy? Timing of endoscopy? What endoscopic therapy? Discharge criteria? What is a rebleeding episode? Slide 12 of 33
When to transfuse? Evidence of massive bleeding Haemodynamic instability Haemodynamically stable anaemia? Evidence in trauma and in variceal bleeding of survival benefit from lower transfusion targets 15 No clear data in undifferentiated GI bleed 16 Hb<70 g/l 15 Hébert et al. 1999; Villanueva et al. 2013. 16 Villanueva et al. 2013. Slide 13 of 33
Sub-group analysis 17 17 Villanueva et al. 2013.
PPI therapy No reduction in mortality Reduction in rebleeding rates Before or after endoscopy? First large randomised placebo controlled trial demonstrated no benefit of IV PPI before endoscopy 18 Hong Kong study demonstrated IV PPI after endoscopy reduces rebleeding (not mortality) 19 IV or oral dosing? There is evidence for oral dosing 20 Dose needs to be large enough: 40mg bd omeprazole 18 Daneshmend et al. 1992. 19 Lau et al. 2000. 20 Kaviani et al. 2003; Javid et al. 2001. Slide 15 of 33
Antiplatelet therapy Aspirin, clopidogrel Usually given for atherosclerotic disease Irreversible inhibition of COX or ADP receptors Effect lasts until new platelets are formed in absence of drug (3-7 days) For continuation of aspirin: Reduced cardiovascular mortality 21 Increased risk of rebleeding 21 Sung et al. 2010. Slide 16 of 33
Survival analysis 22 22 Sung et al. 2010.
Anticoagulant therapy Anticoagulation for AF, prosthetic heart valve, venous thromboemboism Cohort with high comorbidity, however lower rates of 30 day mortality 23 No randomized controlled data regarding how to manage anticoagulation Status quo is to reverse warfarin anticoagulation acutely with vitamin K/FFP/prothrombinex Should warfarin be restarted? Restarting warfarin associated with reduction in thromboembolic stroke, no increase in recurrent bleed at 90 days 24 For patients with AF reduced mortality over subsequent 2 years associated with restarting warfarin 25 23 Irwin et al. 2014a. 24 Sengupta et al. 2015. 25 Qureshi et al. 2014. Slide 18 of 33
Timing of endoscopy For endoscopic therapy to provide benefit, bleeding must be identified and successfully treated. The earlier, the better? Resource constraint for after hours procedures Within 24 hours 26 Reduction in rebleeding, length of stay Negative studies for early endoscopy (within 6 hours) 27 DDW presentions 2015 Higher mortality with early endoscopy (<6 hours) Observational studies, likely selection bias Hypothesis that early endoscopy is detremental - effect of procedural sedation? - aspiration? - inadequate resuscutation? Riccardo Marmo, Stig Laursen 26 Cooper et al. 1999; Hwang et al. 2012. 27 Tsoi, Ma, and Sung 2009; Schacher et al. 2005; Sarin, Monga, and Adams 2009; Lin, Wang, et al. 1996. Slide 19 of 33
Timing of endoscopy Can stratify patients and select who are likely to benefit from early endoscopy Rockall score 28 Predicts death Blatchford score 29 Predicts need for: requirement of blood transfusion, requirement of endoscopic or operative intervention to control bleeding, death, rebleeding, or a substantial fall in haemoglobin Waikato analysis 30 Association of presenting features with endoscopic lesions that were treated. Presentation with fresh haematemesis, fresh melaena, high urea, low BP, male sex, history of peptic ulcer disease. 28 Rockall et al. 1996. 29 O. Blatchford, Murray, and M. Blatchford 2000. 30 Irwin et al. 2013. Slide 20 of 33
What endoscopic therapy? For peptic ulceration Adrenaline injection 31 Dual therapy Heater probe 32 Clip placement For oesophogeal varices sclerotherapy 33 banding 34 31 Cook et al. 1992. 32 Chung et al. 1997; Lin, Tseng, et al. 1999. 33 Infante-Rivard, Esnaola, and Villeneuve 1989. 34 Stiegmann et al. 1992. Slide 21 of 33
Who is safe to discharge before or after endoscopy? Before endoscopy Blatchford score = 0 35 After endoscopy post-endoscopy Rockall score 2 36 35 O. Blatchford, Murray, and M. Blatchford 2000; Stanley et al. 2009. 36 Rockall et al. 1996; Dulai et al. 2002. Slide 22 of 33
Rebleeding episode? Rebleed associated with increased risk of death 37 What is a rebleed? Fresh haematemesis or Combination of Ongoing melaena and/or Further drop in Hb and/or Haemodynamic instability Management Resuscitation Endoscopy/surgery/...interventional radiology 37 Rockall et al. 1996. Slide 23 of 33
Non-acute decisions Test and treat for H. pylori if peptic ulcer disease Cease NSAID Decide ongoing anticoagulation Usually restart warfarin after 1-14 days Decide ongoing antiplatelet therapy If gastric ulcer, requires repeat endoscopy to ensure ulcer healing 38 Decide long term PPI 39 38 Hansson et al. 1996. 39 Laine and Jensen 2012. Slide 24 of 33
Bibliography I Blatchford, O., L. A. Davidson, et al. (Aug. 30, 1997). Acute upper gastrointestinal haemorrhage in west of Scotland: case ascertainment study. BMJ (Clinical research ed.) 315.7107, pp. 510 514 Blatchford, O., W. R. Murray, and M. Blatchford (Oct. 14, 2000). A risk score to predict need for treatment for upper-gastrointestinal haemorrhage. Lancet 356.9238, pp. 1318 1321 Chung, S. S. et al. (May 3, 1997). Randomised comparison between adrenaline injection alone and adrenaline injection plus heat probe treatment for actively bleeding ulcers. BMJ (Clinical research ed.) 314.7090, pp. 1307 1311 Cook, D. J. et al. (Jan. 1992). Endoscopic therapy for acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis. Gastroenterology 102.1, pp. 139 148 Cooper, G. S. et al. (Feb. 1999). Early endoscopy in upper gastrointestinal hemorrhage: associations with recurrent bleeding, surgery, and length of hospital stay. Gastrointestinal endoscopy 49.2, pp. 145 152 Daneshmend, T. K. et al. (Jan. 18, 1992). Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. BMJ 304.6820, pp. 143 147 Slide 26 of 33
Bibliography II Dulai, G. S. et al. (Mar. 2002). Utilization of health care resources for low-risk patients with acute, nonvariceal upper GI hemorrhage: an historical cohort study. Gastrointestinal Endoscopy 55.3, pp. 321 327 Forrest, J. A., N. D. Finlayson, and D. J. Shearman (Aug. 17, 1974). Endoscopy in gastrointestinal bleeding. Lancet 2.7877, pp. 394 397 García Rodríguez L, C. C. (Jan. 12, 1998). RIsk of hospitalization for upper gastrointestinal tract bleeding associated with ketorolac, other nonsteroidal anti-inflammatory drugs, calcium antagonists, and other antihypertensive drugs. Archives of Internal Medicine 158.1, pp. 33 39 Hallas, J. et al. (Oct. 7, 2006). Use of single and combined antithrombotic therapy and risk of serious upper gastrointestinal bleeding: population based case-control study. BMJ 333.7571, pp. 726 Hansson, L.-E. et al. (July 25, 1996). The Risk of Stomach Cancer in Patients with Gastric or Duodenal Ulcer Disease. New England Journal of Medicine 335.4, pp. 242 249 Hébert, P. C. et al. (Feb. 11, 1999). A Multicenter, Randomized, Controlled Clinical Trial of Transfusion Requirements in Critical Care. New England Journal of Medicine 340.6, pp. 409 417 Hwang, J. H. et al. (June 2012). The role of endoscopy in the management of acute non-variceal upper GI bleeding. Gastrointestinal endoscopy 75.6, pp. 1132 1138
Bibliography III Infante-Rivard, C., S. Esnaola, and J. P. Villeneuve (Apr. 1989). Role of endoscopic variceal sclerotherapy in the long-term management of variceal bleeding: a meta-analysis. Gastroenterology 96.4, pp. 1087 1092 Irwin, J. et al. (July 18, 2013). Factors at presentation predictive of a requirement for endoscopic therapy in patients presenting with overt upper gastrointestinal haemorrhage: a retrospective observational study. Frontline Gastroenterology, (July 10, 2014a). Supratherapeutic anticoagulation at presentation is associated with reduced mortality in nonvariceal upper gastrointestinal hemorrhage. Endoscopy International Open 2.3, E148 E152 Irwin, J. et al. (Aug. 2014b). Incidence of upper gastrointestinal haemorrhage in Maori and New Zealand European ethnic groups, 2001-2010. Internal Medicine Journal 44.8, pp. 735 741 Javid, G. et al. (Sept. 2001). Omeprazole as adjuvant therapy to endoscopic combination injection sclerotherapy for treating bleeding peptic ulcer. The American Journal of Medicine 111.4, pp. 280 284 Kaviani, M. J. et al. (Jan. 1, 2003). Effect of oral omeprazole in reducing re-bleeding in bleeding peptic ulcers: a prospective, double-blind, randomized, clinical trial. Alimentary Pharmacology & Therapeutics 17.2, pp. 211 216 Laine, L. and D. M. Jensen (Mar. 2012). Management of Patients With Ulcer Bleeding. The American Journal of Gastroenterology 107.3, pp. 345 360
Bibliography IV Lau, J. Y. et al. (Aug. 3, 2000). Effect of Intravenous Omeprazole on Recurrent Bleeding after Endoscopic Treatment of Bleeding Peptic Ulcers. New England Journal of Medicine 343.5, pp. 310 316 Lewis, J. D. et al. (Oct. 2002). Hospitalization and mortality rates from peptic ulcer disease and GI bleeding in the 1990s: relationship to sales of nonsteroidal anti-inflammatory drugs and acid suppression medications. The American journal of gastroenterology 97.10, pp. 2540 2549 Lin, H. J., G. Y. Tseng, et al. (May 1999). Comparison of adrenaline injection and bipolar electrocoagulation for the arrest of peptic ulcer bleeding. Gut 44.5, pp. 715 719 Lin, H. J., K. Wang, et al. (June 1996). Early or delayed endoscopy for patients with peptic ulcer bleeding. A prospective randomized study. Journal of clinical gastroenterology 22.4, pp. 267 271 Loperfido, S. et al. (Aug. 2009). Changing trends in acute upper-gi bleeding: a population-based study. Gastrointestinal endoscopy 70.2, pp. 212 224 Qureshi, W. et al. (Feb. 15, 2014). Restarting Anticoagulation and Outcomes After Major Gastrointestinal Bleeding in Atrial Fibrillation. American Journal of Cardiology 113.4, pp. 662 668
Bibliography V Rockall, T. A. et al. (July 22, 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 : British Medical Journal 311.6999, pp. 222 226 Rockall, T. A. et al. (Mar. 1996). Risk assessment after acute upper gastrointestinal haemorrhage. Gut 38.3, pp. 316 321 Sarin, N., N. Monga, and P. C. Adams (July 2009). Time to endoscopy and outcomes in upper gastrointestinal bleeding. Canadian Journal of Gastroenterology = Journal Canadien De Gastroenterologie 23.7, pp. 489 493 Schacher, G. M. et al. (Apr. 2005). Is early endoscopy in the emergency room beneficial in patients with bleeding peptic ulcer? A "fortuitously controlled" study. Endoscopy 37.4, pp. 324 328 Schöttker, B. et al. (May 2012). Helicobacter pylori Infection Is Strongly Associated With Gastric and Duodenal Ulcers in a Large Prospective Study. Clinical Gastroenterology and Hepatology 10.5, 487 493.e1 Sengupta, N. et al. (Feb. 2015). The Risks of Thromboembolism Vs. Recurrent Gastrointestinal Bleeding after Interruption of Systemic Anticoagulation in Hospitalized Inpatients With Gastrointestinal Bleeding: A Prospective Study. The American Journal of Gastroenterology 110.2, pp. 328 335
Bibliography VI Stanley, A. et al. (Jan. 2009). Outpatient management of patients with low-risk upper-gastrointestinal haemorrhage: multicentre validation and prospective evaluation. The Lancet 373.9657, pp. 42 47 Stiegmann, G. V. et al. (June 4, 1992). Endoscopic sclerotherapy as compared with endoscopic ligation for bleeding esophageal varices. The New England journal of medicine 326.23, pp. 1527 1532 Sung, J. J. Y. et al. (Jan. 5, 2010). Continuation of low-dose aspirin therapy in peptic ulcer bleeding: a randomized trial. Annals of internal medicine 152.1, pp. 1 9 Tsoi, K. K. F., T. K. W. Ma, and J. J. Y. Sung (Aug. 2009). Endoscopy for upper gastrointestinal bleeding: how urgent is it? Nature reviews. Gastroenterology & hepatology 6.8, pp. 463 469 Villanueva, C. et al. (Jan. 3, 2013). Transfusion Strategies for Acute Upper Gastrointestinal Bleeding. New England Journal of Medicine 368.1, pp. 11 21
Incidence per 100,000 per year 0 200 400 600 800 15 40 40 50 50 60 60 70 70 80 >80 Age (years)
Incidence per 100,000 per year 0 200 400 600 800 Ethnicity Maori ( n = 268 ) NZ European ( n = 999 ) 15 40 40 50 50 60 60 70 70 80 >80 Age (years)
Incidence per 100,000 per year 0 200 400 600 800 Sex Male ( n = 804 ) Female ( n = 556 ) 15 40 40 50 50 60 60 70 70 80 >80 Age (years)