Medical Management of Upper GI Bleeding
– The EvidenceDr Nola McPherson ED registrar SCGH 2014
Learning Objectives
Background: acute upper GI bleeding (UGIB)
Review MAJOR CAUSES in adults
(Briefly) review general management
Look at the EVIDENCE for specific MEDICAL THERAPIES used in management
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
Bleeding Manifestations
Haematemesis = bleeding proximal to Ligament of Treitz
Frank bloody emesis vs coffee ground
Melena = majority due to bleeding proximal to Ligament of Treitz, remainder from small bowel or right side of LI
Haematochezia = usually in lower GIT bleed, only if massive UGIB
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, Tran T, Fisher DA. Does this patient have a severe upper gastrointestinal bleed? JAMA 2012; 307:1072
Assessment
Aims
assess severity of bleed
identify potential cause
identify co-morbidities that may alter management
decisions
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
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: http://lifeinthefastlane.com/ebm-upper-gi-haemorrhage/
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
Ulcerative or Erosive Disease
Oesophagitis
Peptic
Infectious C. albican, CMV, HSV miscellaneous
Pill induced alendronate tetracycline quinidine KCL aspirin NSAID
Portal HypertensionOesophageal Varices
Gastric Varices
Duodenal Varices
Portal Hypertensive Gastropathy
Large amounts of dark venous blood…
Arterial, Venous or Other Vascular MalformationsIdiopathic angiomas
Hereditary haemorrhagic telangectasia
Dieulafoy’s Lesion
Gastric Antral Vascular Ectasia
Radiation-induced telangiectasia
Blue rubber bleb nevus syndrome
Traumatic or Post SurgicalMallory-Weiss Tear (classic N+V then bleeding in 1/3) Post surgical anastomosisFB ingestion Post gastric/duodenal polypectomyAortoenteric fistula (Hx aortic surgery + bright red haematemesis + haematochezia)
GIT TumoursBENIGN: leiomyoma, lipoma, polyps
MALIGNANT: adenocarcinoma, mesenchymal neoplasm, lymphoma, Kaposi sarcoma, carcinoid, melanoma, metastatic tumour
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
General Management
Blood Transfusion
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
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 <3delay 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
Medical Management
Acid Suppression
Proton pump inhibitor
H2 R antagonists
Somatostatin Analogue
Octreotide
Other
Terlipressin
Antibiotics
Tranexamic acid
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
*note: omeprazole most extensively studied, esomeprazole & pantoprazole PROBABLY acceptable alternatives
Acid Suppression
Evidence?
Meta analysis (2002): Pharmacotherapies for Non Variceal 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%
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
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
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: http://lifeinthefastlane.com/ebm-upper-gi-haemorrhage/
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, Sharma VK, Howden CW. Proton pump inhibitor treatment for acute peptic
ulcer bleeding. Cochrane Database Syst Rev 2006;1:CD002094. [2006 Reference] [2010 Reference]
Somatostatin Analogue
Octreotide
Recommended Practice (Up To 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)
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
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
Vasopressin Analogue
Terlipressin
Recommended Practice21:in suspected or known cases of variceal bleedinggive 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
‘Other’ Medical Treatments
Antibiotics
Recommended Practice (Up to Date 2014)12:patients with cirrhosis and UGIB (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
‘Other’ Medical Treatments
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)
‘Other’ Medical Treatments
Tranexamic Acid
Recommended practice (Up To 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)
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)
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
Summary
Patients who present with UGIB and have known cirrhosis should have antibiotics before endoscopy
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
Questions?
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. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper gastrointestinal bleeding. N Engl J Med 2013; 368:11
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
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. Gastroenterol Clin North Am 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-Menachem T, et al. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc 2009; 70:1060.
References
12. Saltzman, JR. Approach to acute upper gastrointestinal bleeding in adults. In: UpToDate, Feldman, M (Ed), UpToDate, Waltham, MA, 2014
13. Imperale TF. 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. Kwan V, Norton ID. Endoscopic management of non-variceal upper gastrointestinal haemorrhage. Australia and New Zealand Journal of Surgery 2007; 77: 222-230
References
16. Chan WH, Khin LW, Chung YF, 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, Kelly AM, Murray L, Brown A. Textbook of Adult Emergency Medicine. 3rd Edition. Churchill Livingston Elsevier 2009.
References
19. Imperiale TF, 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. Ripoll C, Banares R, Beceiro I, et al. Comparison of transcatheter arterial embolisation and surgery for treatment of bleeding peptic ulcer after endoscopic treatment failure. Journal of Vascular and Interventional Radiology 2004; 15; 447-450.
References
22. Gluud LL, Klingenberg SL, Langholz E. Tranexamic acid for upper gastrointestinal bleeding. Cochrane Database Syst Rev 2012; 1:CD006640.
Glasgow-Blatchford Score