Medical management of GI bleeding


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Medical management of GI bleeding

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Medical management of GI bleeding

  1. 1. Medical Management of Upper GI Bleeding –The Evidence Dr Nola McPherson ED registrar SCGH 2014
  2. 2. Learning Objectives Background: acute upper GI bleeding (UGIB) Review MAJOR CAUSES in adults (Briefly) review general management Look at the EVIDENCE for specific MEDICALTHERAPIES used in management
  3. 3. Background UGIB  Common medical emergency with associated high morbidity, mortality(6-11%)* and medical expenditure  Most commonly presents with haematemesis and/or melena (much less commonly with haematochezia – 3x higher risk of death*)  Requires rapid assessment (particularly evaluation of haemodynamic stability) and then prompt multi-team management * Source: Cameron P, Jelinek G, Kelly AM, Murray L, Brown A.Textbook of Adult Emergency Medicine. 3rd Edition.Churchill Livingston Elsevier 2009
  4. 4. Bleeding Manifestations Haematemesis = bleeding proximal to Ligament ofTreitz Frank bloody emesis vs coffee ground Melena = majority due to bleeding proximal to Ligament ofTreitz, remainder from small bowel or right side of LI Haematochezia = usually in lower GIT bleed, only if massive UGIB
  5. 5. Factors Predictive of Upper GI bleed* Melena on PR examination (LR 25) Blood or coffee ground vomit on NG lavage (LR 9.6) Ratio of blood urea nitrogen to creatinine >30 (LR 7.5) Self reported history of melena (LR 5.1-5.9) Blood clots seen in stool (LR 0.05) * Source: Srygley FD, Gerardo CJ,TranT, Fisher DA. Does this patient have a severe upper gastrointestinal bleed? JAMA 2012; 307:1072
  6. 6. Assessment  Aims assess severity of bleed identify potential cause identify co-morbidities that may alter management decisions
  7. 7. Factors Predictive of a Severe Bleed  History orthostatic dizziness, confusion, angina, severe palpitations  Examination tachycardia, orthostatic hypotension or supine hypotension (even worse), cold/clammy peripheries  Bedside and Laboratory Investigations Hb <80 g/L, high Ur:Cr ratio, high red blood found on NG lavage
  8. 8. Mortality/Morbidity Factors*  Advanced age  Cause of the bleed (particularly varices)  Presence of shock  Fresh bright red blood  Low Hb  Re-bleed presentation  Comorbid disease  Endoscopic findings *Source:
  9. 9. Ulcerative or Erosive Disease Peptic Ulcer Disease *MOST COMMON CAUSE UGIB* Idiopathic Drug induced Aspirin NSAID (approx doubles risk) Infectious H.pylori,CMV, HSV Stress induced ulcer (burns, major trauma, sepsis, hypotension, HI) Zollinger-Ellison Syndrome
  10. 10. Ulcerative or Erosive Disease Oesophagitis Peptic Infectious C. albican, CMV, HSV miscellaneous Pill induced alendronate tetracycline quinidine KCL aspirin NSAID
  11. 11. Portal Hypertension OesophagealVarices GastricVarices DuodenalVarices Portal Hypertensive Gastropathy Large amounts of dark venous blood…
  12. 12. Arterial,Venous or OtherVascular Malformations Idiopathic angiomas Hereditary haemorrhagic telangectasia Dieulafoy’s Lesion Gastric AntralVascular Ectasia Radiation-induced telangiectasia Blue rubber bleb nevus syndrome
  13. 13. Traumatic or Post Surgical Mallory-WeissTear (classic N+V then bleeding in 1/3) Post surgical anastomosis FB ingestion Post gastric/duodenal polypectomy Aortoenteric fistula (Hx aortic surgery + bright red haematemesis + haematochezia)
  14. 14. GITTumours BENIGN: leiomyoma, lipoma, polyps MALIGNANT: adenocarcinoma, mesenchymal neoplasm, lymphoma, Kaposi sarcoma, carcinoid, melanoma, metastatic tumour
  15. 15. General Management  General Management Principles 1. supplemental oxygen 2. crystalloid/colloid fluid resuscitation 3. +/- blood transfusion 4. consider correcting coagulopathy (?benefit vs risk) 5. medical management 6. endoscopic (pretreat with erythromycin) / embolisation / surgical management
  16. 16. General Management  BloodTransfusion consider on individual basis (particularly comorbidities) indication: Hb <70 g/L (except unstable CHD aim Hb > 90 g/L)1-3 avoid transfusing patients with suspected variceal bleeding to Hb >100 g/L (portal P may worsen bleeding)4, 5-8 give one unit FFP for each four units of packed RBC transfused9
  17. 17. General Management  Consider reversal of coagulopathy (in those actively bleeding) FFP if INR >1.5 or platelets if count <50 x 109/L simultaneous replacement + scope if INR <3 delay scope until INR <3 if it is initially higher10  Consider platelet transfusion if life threatening bleeding and taking antiplatelet agents eg aspirin or clopidogrel If stent or ACS – recommend discuss with cardiologist prior to stopping antiplatelet agent or transfusing platelets11
  18. 18. Medical Management  Acid Suppression Proton pump inhibitor H2 R antagonists  Somatostatin Analogue Octreotide  Other Terlipressin Antibiotics Tranexamic acid
  19. 19. Acid Suppression  Proton Pump Inhibitor (PPI) / H2 Receptor Antagonist Recommended Practice (Up to Date 2014):12 Give PPI (empirically) to all patients with acute UGIB: esomeprazole or pantoprazole: 80mg IV bolus, followed by 8mg/hour IVI (continued for 72 hours) Start PPI at presentation (often don’t know source of bleeding) Once source known (and treated), decision can be made before discharge home if PPI needs to be continued
  20. 20. Acid Suppression Evidence? Meta analysis (2002): Pharmacotherapies for NonVariceal UGIB13,14 : PPI (IVI) significantly reduces rate of rebleeding compared to H2 R antagonists or placebo H2 R antagonists had only modest effects in bleeding gastric ulcers and no longer recommended15: - reduced rebleeding by 7.2% - reduced surgery by 6.7% - reduced mortality by 3.2%
  21. 21. Acid Suppression Evidence cont? Peptic Ulcers: PPIs (oral and IV) have additional benefits16,17: decrease LOHS decreased need for blood transfusion (in those with high risk ulcers treated with endoscopic therapy) MAY promote haemostasis in other, non ulcer, lesions
  22. 22. Acid Suppression However, NO demonstrable effect on all cause mortality What we know (oops!) think18: Asians patients likely benefit best from PPI (related to drug metabolism and ability to raise intragastric pH) PPI may decrease rate rebleeding, LOHS, need for blood transfusion but likely doesn’t effect mortality Unfortunately no good data to guide us on best route of administration or dose Oral dose needs to be at least double std clinical dose
  23. 23. Acid Suppression What do we know about the timing of administration*?? If given PPI pre – endoscopy: reduces high risk stigmata and the need for endoscopic therapy (OR 0.67) If given PPI post – endoscopy: reduces risk of requiring surgery, risk of rebleeding and death in high risk patients (RR 0.43, 0.4, 0.41 respectively) --------------------------------------------------------------------------------------------- *Source: References: 1. Lau J, Leung W, Wu J et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. NEJM 2007; 356:1631- 40. 2. Leontiadis GI, SharmaVK, Howden CW. Proton pump inhibitor treatment for acute peptic ulcer bleeding. Cochrane Database Syst Rev 2006;1:CD002094. [2006 Reference] [2010 Reference]
  24. 24. Somatostatin Analogue  Octreotide Recommended Practice (UpTo Date 2014)12: In suspected or known cases of variceal bleeding, give octreotide 20-50 mcg bolus followed by 25-50 mcg/hr IVI may also reduce risk of bleeding due to nonvariceal causes19 (however NOT recommended for routine use in these circumstances – but can be used as an adjunct in some cases) MOA in this setting: reduces splanchnic arterial blood flow (via vasoconstriction) and portal venous pressure (while still maintaining systemic BP and cardiac output)
  25. 25. Somatostatin Analogue Octreotide Indications Suspected or known variceal bleeding controls bleeding in 74-92% cases18 comparable to injection sclerotherapy and vasopressin for bleeding control and survival, however, with less SE18 reduces rebleeding, blood transfusion requirement and surgery does NOT reduce mortality significantly (RR 0.80, 95% CI 0.63-1.01)20
  26. 26. Somatostatin Analogue Octreotide Indications continued…. (Some) bleeding peptic ulcers18: may be reduction in rebleeding may be reduction in need for subsequent surgery NO effect on mortality NOT routinely given, consider if high risk (to avoid the above complications) OR delay until emergency endoscopy
  27. 27. Vasopressin Analogue  Terlipressin Recommended Practice21: in suspected or known cases of variceal bleeding give 2mg bolus IV injection (2mg 6 hourly for 24 hours, then 1mg 6 hourly for 24 hours if bleeding stabilised, then stop) 34% relative risk reduction in mortality Systematic review has shown NO difference between21: - terlipressin and somatostatin treatment - terlipressin and endoscopy therapy MOA: synthetic analogue of vasopressin with fewer SE, vasoactive, specificity for splanchnic vessels causing vasoconstriction and reduction in portal pressure
  28. 28. ‘Other’ MedicalTreatments  Antibiotics Recommended Practice (Up to Date 2014)12: patients with cirrhosis andUGIB (what ever the cause) – 20% will have a bacterial infection, further 50% will develop one while in hospital (assoc HIGH mortality) give ceftriaxone, quinolone or amoxyicillin-clavulanate
  29. 29. ‘Other’ MedicalTreatments Evidence? Prophylactic antibiotics in patients with cirrhosis + UGIB have been shown to 12 : reduce infectious complications decreased mortality may decrease risk of rebleeding from oesoph varices Timing? benefits shown when given both before and after endoscopy (before preferred)
  30. 30. ‘Other’ MedicalTreatments  Tranexamic Acid Recommended practice (UpTo Date 2014)12 : NO role in medical management of UGIB Evidence? A meta analysis of 7 RCTs found in those patients treated with antiulcer and /or endoscopy for UGIB (the mainstay treatment), tranexamic acid did not provide any additional beneficial effect22 MOA: Anti fibrinolytic agent which competitively inhibits activation of plasminogen to plasmin (plasmin degrades fibrin clots)
  31. 31. Summary  Careful history and examination important – consider source, assess severity, identify comorbid condition, look for signs that indicate complications  Blood transfusion for12: • Haemodynamic instability despite crystalloid resusc (at least 2L) • Hb < 70 g/L in low risk patients • Hb <90 g/L in high risk (elderly, CAD, COPD) • Give FFP for coagulopathy (IRN>1.5, PTT 3 sec greater then control) • Give platelets if < 50 x109 /L or platelet dysfunction (chronic aspirin therapy)
  32. 32. Summary  ALL patients with acute upper GI bleeding should be treated at presentation with PPI until source of bleeding is known  Majority of existing studies use omeprazole, we SUSPECT that other PPIs offer the same benefit (?dose ?route)  Evidence PPI in peptic ulcers (major cause of UGIB) reduces most things (!) EXCEPT mortality (however high risk patients may have improved mortality rates if PPI given post endoscopy)  H2 R antagonists are no longer recommended
  33. 33. Summary  Patients who present with UGIB and have known cirrhosis should have antibiotics before endoscopy
  34. 34. Summary  Patients with known or suspected gastro - oesophageal variceal bleed should have: octreotide (bolus and then IVI) PLUS antibiotics Avoid blood transfusing to Hb>100 g/L OR terlipressin boluses six hourly PLUS antibiotics *note: octreotide remains the therapy of choice18
  35. 35. Questions?
  36. 36. References 1. Laine L, Jensen DM. Management of patients with ulcer bleeding. Am J Gastroenterol 2012; 107:345 2. Duggan JM.Gastrointestinal hemorrhage: should we transfuse less? Dig Dis Sci 2009; 54:1662 3. Qaseem A, Humphrey LL, Fitterman N, et al.Treatment of anemia in patients with heart disease: a clinical practice guideline from the American College of Physicians.Ann Intern Med 2013; 159:770 4. VillanuevaC, ColomoA, BoschA, et al.Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368:11
  37. 37. References 5. Kravetz D, Bosch J, Arderiu M, et al. Hemodynamic effects of blood volume restitution following a hemorrhage in rats with portal hypertension due to cirrhosis of the liver: influence of the extent of portal-systemic shunting. Hepatology 1989; 9:808 6. Cerqueira RM,Andrade L, Correia MR, et al. Risk factors for in- hospital mortality in cirrhotic patients with oesophageal variceal bleeding. Eur J Gastroenterol Hepatol 2012; 24:551 7. Krige JE, Kotze UK, Distiller G, et al. Predictive factors for rebleeding and death in alcoholic cirrhotic patients with acute variceal bleeding: a multivariate analysis.World J Surg 2009; 33:212
  38. 38. References 8. McCormick PA, Jenkins SA, McIntyre N, Burroughs AK.Why portal hypertensive varices bleed and bleed: a hypothesis.Gut 1995; 36:100 9. Maltz GS, Siegel JE, Carson JL. Hematologic management of gastrointestinal bleeding.GastroenterolClin NorthAm 2000; 29:169. 10. Wolf AT,Wasan SK, Saltzman JR. Impact of anticoagulation on rebleeding following endoscopic therapy for nonvariceal upper gastrointestinal hemorrhage.Am J Gastroenterol 2007; 102:290. 11. ASGE Standards of Practice Committee, Anderson MA, Ben- MenachemT, et al. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc 2009; 70:1060.
  39. 39. References 12. Saltzman, JR. Approach to acute upper gastrointestinal bleeding in adults. In: UpToDate, Feldman, M (Ed), UpToDate,Waltham, MA, 2014 13. ImperaleTF. Birgisson S. Somatostatin or octreotide compares with H2-antagonists and placebo in the management of acute non variceal upper gastrointestinal haemorrhage: a meta-analysis. Annals of Internal Medicine 1997; 127: 1062-1071 14. Ioannou GN, Doust J, Rockey DC. Systemic review: terlipressin in acute oesophageal variceal haemorrhage. Alimentary Pharmacology and Therapeutics 2003; 17: 53-64 15. KwanV, Norton ID. Endoscopic management of non-variceal upper gastrointestinal haemorrhage. Australia and New Zealand Journal of Surgery 2007; 77: 222-230
  40. 40. References 16. ChanWH, Khin LW, ChungYF, et al. Randomized controlled trial of standard versus high-dose intravenous omeprazole after endoscopic therapy in high-risk patients with acute peptic ulcer bleeding. Br J Surg 2011; 98:640 17. Green FW Jr, Kaplan MM, Curtis LE, Levine PH. Effect of acid and pepsin on blood coagulation and platelet aggregation.A possible contributor prolonged gastroduodenal mucosal hemorrhage. Gastroenterology 1978; 74:38 18. Cameron P, Jelinek G, KellyAM, Murray L, BrownA.Textbook of Adult Emergency Medicine. 3rd Edition.Churchill Livingston Elsevier 2009.
  41. 41. References 19. ImperialeTF, Birgisson S. Somatostatin or octreotide compared with H2 antagonists and placebo in the management of acute nonvariceal upper gastrointestinal hemorrhage: a meta-analysis.Ann Intern Med 1997; 127:1062. 20. Gøtzsche PC, Hróbjartsson A. Somatostatin analogues for acute bleeding oesophageal varices. Cochrane Database Syst Rev. 2005 Jan 25;(1):CD000193. 21. RipollC, Banares R, Beceiro I, et al. Comparison of transcatheter arterial embolisation and surgery for treatment of bleeding peptic ulcer after endoscopic treatment failure. Journal ofVascular and Interventional Radiology 2004; 15; 447-450.
  42. 42. References 22. Gluud LL, Klingenberg SL, Langholz E.Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2012; 1:CD006640.
  43. 43. Glasgow-Blatchford Score Blood Urea Nitrogen <18.2 mg/dL (<6.5 mmol/L) (0 points) >=18.2 and <22.4 mg/dL (>=6.5 and <8 mmol/L) (2 points) >=22.4 and <28 mg/dL (>=8 and <10 mmol/L) (3 points) >=28 and <70 mg/dL (>=10 and <25 mmol/L) (4 points) >=70 mg/dL (>=25 mmol/L) (6 points) Hemoglobin Male >=13 gm/dL (>130 gm/L) (0 points) Male >=12 and <13 gm/dL (>=120 and <130 gm/L) (1 point) Male >=10 and <12 gm/dL (>=100 and <120 gm/L) (3 points) Female >=12 gm/dL (>120 gm/L) (0 points) Female >=10 and <12 gm/dL (>=100 and <120 gm/L) (1 point) Male or female <10 gm/dL (<100 gm/L) (6 points) Systolic BP >=110 mmHg (0 points) 100-109 mmHg (1 point) 90-99 mmHg (2 points) <90 mmHg (3 points) Other Markers Heart rate >=100 per minute (1 point) Melena at presentation (1 point) Syncope at presentation (2 points) Hepatic disease present (2 points)