Upper GI Bleeding

HH Tsai MD FRCP FECG Consultant Gastroenterologist

Financial Disclosures

• I have no financial relationship with any manufacturer or supplier of any product mentioned in this talk. GI Audits:

• Q: What was the mortality of UGIB in audits carried out in following years: • 1945 • 1994 • 2007 GI Audits:

• Q: What was the mortality of UGIB in audits carried out in following years: • 1945 A:11% • 1994 A: 14% • 2007 A: 10% What scoring system best predicts clinical outcome? • Rockall score? (1994) • Batchford Score? (2000) • Another? • My clinical judgement Both poor, but better than nothing

• The Blatchford score had 54% accuracy for predicting the need for intervention or death within 30 days. The Rockall score had 53% pre-endoscopy accuracy and 61% accuracy post-endoscopy. Both scores were described as having suboptimum sensitivity and specificity. • Blatchford score had better overall prognostic ability than the pre-endoscopy Rockall score (area under curve [AUC]=0.79 versus 0.62 respectively, p=0.0001). However, the Blatchford score and the post-endoscopy Rockall score had similar prognostic ability (AUC=0.79 versus 0.72 respectively, p=0.26).

• Chandra 2014 Case 1

• 70 yr old hypertensive patient on NSAID’s with H&M: Admission P 90 BP 120/90 Hb 7.2 g/dL • Do you transfuse? • What Hb do you aim for? Villanueva 2013

• Single-centre randomised controlled trial (n=921) of liberal versus restrictive blood transfusion strategies in adults admitted with haematemesis or bloody nasogastric aspirate, or melaena. • In the restrictive group, the transfusion threshold was haemoglobin of 7 g/dl with a post-transfusion target of 7–9 g/dl. • In the liberal group, the transfusion threshold was 9 g/dl with a post-transfusion target of 9–11 g/dl. • The primary outcome was death from any cause in the first 45 days Villanueva 2013 NEJM

Mortality % 10 9 8 7 6 5 Mortality % 4 3 2 1 0 Restrictive Liberal 921 UGIB pts randomized to trfX thresholds of Hgb<7 or 9gm/dL, stratified by cirrhosis 15% vs 51% trfX rates, P<0.001

95% vs 91%*, OR=0.55, 0.33-0.92

Villanueva, NEJM, 2013 Villanueva, NEJM, 2013

1.1 Risk assessment

• 1.1.1 Use the following formal risk assessment scores for all patients with acute upper gastrointestinal bleeding: • the Blatchford score at first assessment, and • the full Rockall score after endoscopy. • 1.1.2 Consider early discharge for patients with a pre-endoscopy Blatchford score of 0.

Blood products:

• 3. Transfuse patients with massive bleeding with blood, platelets and clotting factors in line with local protocols for managing massive bleeding. • 4. Base decisions on blood transfusion on the full clinical picture, recognising that over-transfusion may be as damaging as under-transfusion.

• 5. Do not offer platelet transfusion to patients who are not actively bleeding and are haemodynamically stable.

• 6. Offer platelet transfusion to patients who are actively bleeding and have a platelet count of less than 50 x 109/litre.

• 7. Offer fresh frozen plasma to patients who have either • a fibrinogen level of less than 1g/litre or • a prothrombin time (international normalised ratio) or activated partial thromboplastin time greater than 1.5 times normal. • 8. Offer prothrombin complex concentrate to patients who are taking warfarin and actively bleeding. • 9. Treat patients who are taking warfarin and whose upper gastrointestinal bleeding has stopped in line with local warfarin protocols. • 10. Do not use recombinant factor Vlla except when all other methods have failed. Timing of endoscopy • 11. Offer endoscopy to unstable patients with severe acute upper gastrointestinal bleeding immediately after resuscitation. • 12. Offer endoscopy within 24 hours of admission to all other patients with upper gastrointestinal bleeding. • 13. Units seeing more than 330 cases a year should offer daily endoscopy lists. Units seeing fewer than 330 cases a year should arrange their service according to local circumstances. Management of non-variceal bleeding

• Endoscopic treatment: • 12. Do not use adrenaline as monotherapy for the endoscopic treatment of non-variceal upper gastrointestinal bleeding.

• 13. For the endoscopic treatment of non-variceal upper gastrointestinal bleeding, use one of the following: • • a mechanical method (for example, clips) with or without adrenaline • • thermal coagulation with adrenaline • • fibrin or thrombin with adrenaline

Proton Pump Inhibitors:

• 14. Do not offer acid-suppression drugs (proton pump inhibitors or H2-receptor antagonists) before endoscopy to patients with suspected non-variceal upper gastrointestinal bleeding.

• 15. Offer proton pump inhibitors to patients with non-variceal upper gastrointestinal bleeding and stigmata of recent haemorrhage shown at endoscopy.

Treatment options after first or failed endoscopic treatment • 16. Consider a repeat endoscopy, with treatment as appropriate, for all patients at high risk of rebleeding, particularly if there is doubt about adequate haemostasis at the first endoscopy. • 17. Offer a repeat endoscopy to patients who rebleed with a view to further endoscopic treatment or emergency surgery. • 18. Offer interventional radiology to unstable patients who re-bleed after endoscopic treatment. Refer urgently for surgery if interventional radiology is not promptly available. Management of variceal bleeding

• Terlipressin: • 11. Offer terlipressin to patients with suspected variceal bleeding at presentation. Stop treatment after definitive haemostasis has been achieved, or after 5 days, unless there is another indication for its usea . • Antibiotics: • 19. Offer prophylactic antibiotic therapy at presentation to patients with suspected or confirmed variceal bleeding • Oesophageal varices • 20. Use band ligation in patients with upper gastrointestinal bleeding from oesophageal varices. • 21. Consider transjugular intrahepatic portosystemic shunts (TIPS) if bleeding from oesophageal varices is not controlled by band ligation. • Gastric varices • 22. Offer endoscopic injection of N-butyl-2-cyanoacrylate to patients with upper gastrointestinal bleeding from gastric varices • 23. Offer transjugular intrahepatic portosystemic shunts (TIPS) if bleeding from gastric varices is not controlled by endoscopic injection of N-butyl-2-cyanoacrylate. Control of bleeding and prevention of re-bleeding • 24. Continue low-dose aspirin for secondary prevention of vascular events in patients with upper gastrointestinal bleeding in whom haemostasis has been achieved • 25. Stop other non-steroidal anti-inflammatory drugs (including cyclooxygenase-2 [COX-2] inhibitors) during the acute phase in patients presenting with upper gastrointestinal bleeding. • 26. Discuss the risks and benefits of continuing clopidogrel (or any other thienopyridine antiplatelet agents) in patients with upper gastrointestinal bleeding with the appropriate specialist (for example, a cardiologist or a stroke specialist) and with the patient. Primary prophylaxis

• 27. Offer acid-suppression therapy (H2-receptor antagonists or proton pump inhibitors) for primary prevention of upper gastrointestinal bleeding in acutely ill patients admitted to critical care. If possible, use the oral form of the drug. • 28. Review the ongoing need for acid-suppression drugs for primary prevention of upper gastrointestinal bleeding in acutely ill patients when they recover or are discharged from critical care.

Information and support for patients and carers • 29. Establish good communication between clinical staff and patients and their family and carers at the time of presentation, throughout their time in hospital and following discharge. This should include: • • giving verbal information that is recorded in medical records • • different members of clinical teams providing consistent information • • providing written information where appropriate • • ensuring patients and their families and carers receive consistent information.

Mortality with or without rebleed Initially created to check the need for inpatient or outpatient treatment

www.mdcalc.com/glasgow-blatchford-bleeding-score-gbs Resuscitation

• Immediate: Venous access and crystaloids/colloids • Transfuse blood if: active severe bleed/exsanguination risk • In stable patients, only if Hb <7 g/dl, target 9 g/dl 921 UGIB pts randomized to trfX thresholds of Hgb<7 or 9gm/dL, stratified by cirrhosis 15% vs 51% trfX rates, P<0.001

95% vs 91%*, OR=0.55, 0.33-0.92

Villanueva, NEJM, 2013 Endoscopy

• When? • Where? • How? Upper GI Tract

Site

• Oesophagus • Stomach • Doudenum • Hepatic • Pancreatic

58 year-old man presented with upper gastrointestinal bleeding – hematemesis and melena The visible vessel", which was bleeding intermittently was successfully eradicated with the heater probe. There was no recurrent bleeding.

Predictors of re-bleeding  Endoscopic findings

Location of the ulcer (post DU, High lesser curve)

Age > 60

Shock / anaemia on admission

Size of the ulcer

Other causes Angiodysplasia

• Angiodysplasia, arteriovenous malformations and vascular ectasia are used synonymously • Argon Therapy – Use argon gas to arc current to tissue, allows directed superficial ‘burn’ ~1mm deep – Good for large areas like GAVE or tumors – Very low risk of perforation

Mucosal Tear (Mallory – Weiss)

Mallory-Weiss tears present in a classic pattern ( Emesis followed by Haematemesis )

90% of Mallory-Weiss bleeding resolves spontaneously and require no further therapy. If bleeding persists, endoscopic therapy may be required

Dieulafoy’s vascular malformations

They are dilated arterial lesions usually amendable to endoscopic therapy

Other Causes Gastric Neoplasms both malignant and benign can cause bleeding which is usually mild and chronic. However, certain benign tumours (GIST) may present with life threatening GI bleeding Also Malignant ulcer may case severe bleeding due to blood vessel erosion

• Aorto-enteric fistulas It can present as a herald bleed followed by a massive bleed in patients with prior aortic reconstructions. May present as upper or lower GI bleed

High mortality. • Hematobilia It can be found in patients following hepatic injuries or manipulations. It can happen after cholecystectomy due to pseudoaneurysm Intervention Radiology is the key element in management

Which Endoscopic Treatment ?

• Injection with Adrenaline – Endoscopic injection of Adrenaline 1:10,000 around and into the bleeding point reduces the rate of rebleeding • in patients with non-bleeding visible vessels from approximately 50% to 15-20%. • in patients with ulcers with adherent blood clot is also significantly reduced from approximately 35 to 10%. – Dose • >13mls is recommended as associated with less rebleeding than 5-10ml (RCT) • >40mls associated with increased perforation rates and pain

Which Endoscopic Treatment ?

• Thermal – Coagulation using the heater probe is associated with similar efficacy to injection • Complications, including perforation are rare • Therapy should be administered until the treated area is black and cavitated • Use a squirt of the water to lift the probe off the tissues after heat applied • Mechanical – Clips • Recent meta-analysis suggests better than injection for acute control and rebleeding (RR0.49)but no difference in mortality • No difference noted against thermocoagulation INJECTION

http://www.nejm.org/doi/full/10.1056/NEJMra0706113 CONTACT THERMAL THERAPY

http://www.nejm.org/doi/full/10.1056/NEJMra0706113 Endoscopic clips Which Endoscopic Treatment ?

• Combination Therapies – Either Adrenaline and clips or Adrenaline and thermal – Two meta-analysis demonstrate better than single therapy with no increase in complications – Mortality fell from 5.1% to 2.6% Which is the best modality?

Rebleeding Odds Ratio (95% CI)

0.27 Not Thermal + Epi vs. Epi alone (2*) Injection alone 0.38 Clips + Epi vs. Epi alone (3*) Thermal alone 0.79 or clips alone Thermal + Epi vs. Thermal alone (4*) as good as 1.30 combination Clips+ Epi vs. Clips alone (2*) with Epi? *Number of trials

0.2 0.5 1 2 5 . Treat only high-risk lesions Favors dual Favors . Equivocal data for “adherent clots” therapy monotherapy

Calvet Gastroenterology 2004, Marmo Am J Gastro 2007, Sung Gut 2007, Laine CGH 2008, Barkun GIE 2009 New Modalities to control Bleeding

• Haemospray – A highly adsorptive powder made of proprietary mineral blend. When in contact with blood, the powder becomes cohesive and forms a stable mechanical plug that covers the bleeding site. – Evidence • only series reports • first GI use in 20 patients with Forrest I bleeding peptic ulcers. During endoscopy, the powder was power-sprayed onto the bleeding site with the use of a delivery catheter connected to a carbon-dioxide canister. Short bursts of powder were applied until cessation of bleeding The site was observed for a further 5 minutes. • hemostasis achieved in 19 of 20 patients • No significant recurrent bleeding was seen in 19 treated patients. No systemic effect from Haemospray was observed as the powder was not absorbed. • More data, especially comparative ones, are required to determine the role of this powder among other available treatment modalities • Endoscopic suturing

Endoscopy findings: clips + injection + Haemostatic powder Risk Stratification at Endoscopy • Endoscopic stigmata are integral to the Rockall scoring system • Ulcers with clean base, black or red spots have negligible rebleeding risk. • The risk of rebleeding from patients who have adherent blood clot is approximately 35% • The risk of rebleeding for non-bleeding visible vessels is 40- 50% • Patients who are shocked and have active bleeding at endoscopy have an 80% risk of continuing to bleed or rebleed unless endoscopic intervention is undertaken. Acid Suppression

• Role – A meta-analysis of 24 RCTs confirmed that PPIs significantly reduce the rate of rebleeding (NNT=13), the need for surgery (NNT=34) and requirement for further endoscopic treatment (NNT=10). – PPIs did not significantly affect overall mortality – However mortality reduced in high risk patient group on sub analysis • Dose – Omeprazole 80 mg bolus injection followed by 8 mg/hour intravenous infusion for 72 hours (4 trials) – May 2010 no difference between high and low dose PPI in meta- analysis of 9 RCT trails

• PPIs are not licensed for the reduction in rate of rebleeding in patients with bleeding peptic ulcers

Acid Suppression

FAQ

• When should I re-endoscpe “to see”? • What if I find no bleeding pathology? • What if I cannot find the source of bleeding because of large amount of clot/blood? • When can the patient eat again? • What do I do about Hp? Aftercare: H pylori

• How to diagnose? • How and when do I treat H pylori? Diagnostic modalities: performance

100 90 NPV estimates 80 70 60

50 +ve Predictive value 40 -ve Predictive value 30 20 10 0 Serology Rapid Histology Culture Urea Stool Urease Breath antigen

Best to confirm a negative test outside the acute setting What about aspirin?

• Aspirin non-adherence/withdrawal carries a 3x risk of major adverse cardiac events • The delay to the thrombotic event is usually 7- 10 days Risks/benefits of immediate reintroduction of aspirin

ASA discontinuation causes significantly ASA-related bleeding ulcers, N=156 increased CV mortality

Log rank test P=0.25 Hazard ratio 1.9, 95%CI 0.6-6

Log rank test, P=0.005 (HR 0.2, 95% CI 0.06-0.6)

ASA 10.3%

Placebo 5.4% BUT Placebo 12.9%

ASA 1.3%

A statistically non significant increase in recurrent PUD bleeding, Sung AIM 2010, Editorial: Barkun AIM 2010 What about Clopidogrel?

Experimental Control Odds Ratio Odds Ratio Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI Chan 2005 1 159 13 161 57.3% 0.07 [0.01, 0.56] Lai 2006 0 86 9 84 42.7% 0.05 [0.00, 0.80] Total (95% CI) 245 245 100.0% 0.06 [0.01, 0.32] Total events 1 22 Heterogeneity: Chi² = 0.06, df = 1 (P = 0.80); I² = 0% 0.01 0.1 1 10 100 Test for overall effect: Z = 3.30 (P = 0.0010) Favours experimental Favours control Rebleeding ASA + PPI Clopidogrel alone

Recommendations for patients with high CV risk: • Eradicate Hp • Introduce low-dose aspirin plus PPI early • Stop NSAIDs • Discuss risk/ benefits of other antiplatelet agents with cardiologist. Summary

• UGIB carries a high mortality • Prompt fluid resuscitation and endoscopy ideally in a specialised unit • Restrict blood products • Endoscopic treatment with a second modality to adrenaline injection • IV PPI for those with a higher risk of rebleeding