Medical management of GI bleeding

1. Medical Management of
Upper GI Bleeding
–The Evidence
Dr Nola McPherson ED registrar SCGH 2014

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. 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. 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. 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. Assessment
 Aims
assess severity of bleed
identify potential cause
identify co-morbidities that may alter management
decisions

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. 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/

10. 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

11. Ulcerative or Erosive
Disease
Oesophagitis
Peptic
Infectious
C. albican, CMV, HSV
miscellaneous
Pill induced
alendronate
tetracycline
quinidine
KCL
aspirin
NSAID

12. Portal Hypertension
OesophagealVarices
GastricVarices
DuodenalVarices
Portal Hypertensive Gastropathy
Large amounts of dark
venous blood…

13. Arterial,Venous or
OtherVascular
Malformations
Idiopathic angiomas
Hereditary haemorrhagic telangectasia
Dieulafoy’s Lesion
Gastric AntralVascular Ectasia
Radiation-induced telangiectasia
Blue rubber bleb nevus syndrome

14. 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)

15. GITTumours
BENIGN: leiomyoma, lipoma, polyps
MALIGNANT: adenocarcinoma, mesenchymal neoplasm, lymphoma, Kaposi sarcoma,
carcinoid, melanoma, metastatic tumour

16. 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

17. 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

18. 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

19. Medical Management
 Acid Suppression
Proton pump inhibitor
H2 R antagonists
 Somatostatin Analogue
Octreotide
 Other
Terlipressin
Antibiotics
Tranexamic acid

20. 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

21. 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%

22. 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

23. 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

24. 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, SharmaVK, Howden CW. Proton pump inhibitor treatment for acute peptic
ulcer bleeding. Cochrane Database Syst Rev 2006;1:CD002094. [2006 Reference] [2010 Reference]

25. 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)

26. 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

27. 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

28. 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

29. ‘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

30. ‘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)

31. ‘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)

32. 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)

33. 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

34. Summary
 Patients who present with UGIB and have known cirrhosis
should have antibiotics before endoscopy

35. 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

36. Questions?

37. 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

38. 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

39. 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.

40. 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

41. 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.

42. 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.

43. References
22. Gluud LL, Klingenberg SL, Langholz E.Tranexamic acid for
upper gastrointestinal bleeding. Cochrane Database Syst Rev
2012; 1:CD006640.

44. 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)