Approach to Upper GI Bleeding

Bryan Sauer, MD, MSc
Approach to Upper GI Bleeding
Bryan G. Sauer, MD, MSc (Clin Res)
Assistant Professor of Medicine
Co-Medical Director of Endoscopy
University of Virginia
Division of Gastroenterology and Hepatology
Natural History
■ In 1970, during the BC (before
cimetidine) era, 79% of bleeding
stopped without intervention
■ Our job as gastroenterologists:
■ Stop
St
any remaining
i i
bleeding
bl di
■ Reduce risk of rebleeding
Schiller et al. BMJ 1970
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Bryan Sauer, MD, MSc
Background
■ GI bleeding is a significant medical
problem
 300,000 hospitalizations annually
 Incidence increases with age
 Rebleeding rates range from 7-16%
despite endoscopic treatment
 Variceal rebleeding (25-29%)
 PUD rebleeding (20-22%)
 Mortality: 10-14%
ASGE Guideline: The role of endoscopy in the management of acute non-variceal upper GI bleeding 2012; van Leerdam ME, Best
Practice & Res Clin Gastro 2008; Barkun AN et al. Ann Intern Med 2010.
Sources of UGIB
■ Non-variceal UGIB
■ Ulcer (33-56%)
■ Erosions (19%)
■ Mallory-Weiss tear (4%)
■ Vascular lesions (3%)
■ Tumor (1%)
■ Portal-hypertension
■ Esophageal varices
• Hemosuccus pancreaticus
• Hemobilia
• Iatrogenic (post-sphincterotomy, etc)
• Dieulafoy's lesion
• Fistula (aortoenteric, etc)
• Polyps
• Gastric or duodenal varices
• Gastric antral vascular ectasia (GAVE)
Enestvedt et al. Nonvariceal upper-GI hemorrhage. GIE 2008 (CORI), Barkun A et al. RUGBE, Am J Gastro 2004
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Bryan Sauer, MD, MSc
Scoring Systems for Risk
Assessment
■ Blatchford,
Blatchford Rockall
■ In general, high risk includes
■ Age >65
■ Shock
■ Poor overall health status,, comorbidities
■ Low hemoglobin
■ Fresh blood, elevated urea
Transfusion in UGIB
RCT 921 patients
Restrictive (Hgb <7g/dl)
vs
Liberal (Hgb <9g/dl)
Restrictive Group:
- improved survival
- lower
l
rebleeding
bl di rate
t
(10% v 16%)
- fewer adverse events
- shorter hospital stay
Villanueva C et al, NEJM 2013
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Bryan Sauer, MD, MSc
Before Endoscopy
OUTCOMES
IV PPI
Prokinetics
Gastric
lavage*
Early
endoscopy**
Cochrane
Review
Metaanalysis
RCT
RCT,
retrospective
Mortality
X (retrospective)
Rebleeding
X (retrospective)
Progression to Surgery
X (retrospective)
Rate of high risk stigmata
XX
Repeat EGD/Visualization
XX
X (fundus)
Length of stay/charges
XX
Transfusion requirements
X
* 40 Fr tube with up to 15L of lavage ** for high risk patients, <24 hours
Sreedharan A et al. Cochrane 2010, Barkun AN et al. GIE 2010, Lee SD, et al. J Clin Gastro 2004, Spiegel et al.
Arch Intern Med 2001, Anantharkrishnan AN, et al. CGH 2009
Before Endoscopy
OUTCOMES
IV PPI
Prokinetics
Gastric
lavage*
Early
endoscopy**
Cochrane
Review
Metaanalysis
RCT
RCT,
retrospective
Mortality
X (retrospective)
Rebleeding
X (retrospective)
Progression to Surgery
X (retrospective)
Rate of high risk stigmata
Repeat EGD/Visualization
XX
XX
Length of stay/charges
Transfusion requirements
X (fundus)
XX
X
* 40 Fr tube with up to 15L of lavage ** for high risk patients, <24 hours
Sreedharan A et al. Cochrane 2010, Barkun AN et al. GIE 2010, Lee SD, et al. J Clin Gastro 2004, Spiegel et al.
Arch Intern Med 2001, Anantharkrishnan AN, et al. CGH 2009
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Bryan Sauer, MD, MSc
Before Endoscopy
OUTCOMES
IV PPI
Prokinetics
Gastric
lavage*
Early
endoscopy**
Cochrane
Review
Metaanalysis
RCT
RCT,
retrospective
Mortality
X (retrospective)
Rebleeding
X (retrospective)
Progression to Surgery
X (retrospective)
Rate of high risk stigmata
XX
Repeat EGD/Visualization
XX
X (fundus)
Length of stay/charges
Transfusion requirements
XX
X
* 40 Fr tube with up to 15L of lavage ** for high risk patients, <24 hours
Sreedharan A et al. Cochrane 2010, Barkun AN et al. GIE 2010, Lee SD, et al. J Clin Gastro 2004, Spiegel et al.
Arch Intern Med 2001, Anantharkrishnan AN, et al. CGH 2009
Timing of Endoscopy
ACG Practice Guidelines
“Patients with UGIB should g
generally
y undergo
g endoscopy
py within
24 hours of admission, following resuscitative efforts to optimize
hemodynamic parameters and other medical problems”
“In patient with higher risk clinical features (e.g., tachycardia,
hypotension, bloody emesis or NG aspirate) endoscopy within
12h may be considered to potentially improve clinical outcomes”
International Consensus Recommendations
“In patients receiving anticoagulants, correction of coagulopathy
is recommended but should not delay endoscopy”
2012 ACG Practice Guidelines; Barkun AN et al. Ann Intern Med 2010
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Bryan Sauer, MD, MSc
Endoscopic Stigmata of Ulcers &
Rebleed Risk
Stigmata
g
Active bleed
Forrest Prevalence(%)
( ) Rebleed(%)*
( )
1a, 1b
10-20
90
Visible vessel
2a
15-25
50
Adherent clot
2b
10-20
25
Flat spot
2c
10-20
10
Clean base
3
35
5
* Without treatment
Laine L, Peterson WL. Bleeding Peptic Ulcer. NEJM 1994. Freeman ML Gastrointest Endosc Clin North Am 1997
Results of Endoscopic Therapy
Where it all began…
Sham ((n=23))
MPEC ((n=21)*
)
p-value
p
Hemostasis (%)
3 (13)
19 (90)
<0.0001
Blood Transfusions
5.4 + 0.9
2.4 + 0.9
0.002
Emergency Intervention (%)
13 (57)
3 (14)
0.005
Hospital Stay (days)
7 2 + 1.1
7.2
11
4 4 + 0.8
4.4
08
0 02
0.02
Hospital Cost ($)
7,550 + 1,480
3,420 + 750
0.001
Deaths (%)
3(13)
0
NS
For actively bleeding lesions, * MPEC=multipolar electrocoagulation
Laine L. N Engl J Med 1987;316:1613
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Bryan Sauer, MD, MSc
Endoscopic Therapy
■ Endoscopic therapy reduces
■ Bleeding (active or recurrent)
■ Need for surgery
The Big Three
■ Mortality
■ Results driven by high risk stigmata:
■ Active bleeding (NNT 2)
2)*
* recurrent bleeding
■ Visible vessels (NNT 5)*
■ Adherent clot & flat spot—not reduced*
Sacks et al. JAMA 1990, Cook et al. Gastroenterology 1992, Laine and McQuaid, CGH 2009
Endoscopic Stigmata of Bleeding
Adherent Clot
Stigmata
g
Active bleed
Forrest Prevalence(%)
( ) Rebleed(%)
( )
1a, 1b
10-20
90
Visible vessel
2a
15-25
50
Adherent clot
2b
10-20
25
Flat spot
2c
10-20
10
Clean base
3
35
5
Laine L, Peterson WL. Bleeding Peptic Ulcer. NEJM Sept 15 1994. Volume 331:717-727
Freeman ML Gastrointest Endosc Clin North Am 1997; 1:229.
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Bryan Sauer, MD, MSc
After clot removal
59% would
benefit from
therapy
Bini EJ et al. GIE 2003
Adherent clot studies
■ Four RCTs published 2002-2003:
■ Endo Rx Better = 2 (Jensen (n
(n=32)
32), Bleu (n
(n=56))
56))
■ No difference = 2 (Sung (n=39), Jung (n=19))
Retrospective
Study 2003
Meta-analysis
2005
Meta-analysis
2009
n
244
240, 6 studies
189, 5 studies
Location
NYC
US,, Spain,
p , Asia
US,, UK,, Asia
Endo vs. Medical Rx 138 versus 106
112 versus 128
71 versus 118
Rebleeding
0.07 (0.02-0.22)
0.39 (0.22-0.69)
0.31 (0.06-1.77)
FAVORS
Endo Rx
Endo Rx
No Difference
Bini EJ, Cohn J. GIE 2003, Kahi et al. Gastroenterology 2005, Laine L, McQuaid KR, Clin Gastro Hep 2009
RCT: Jensen DM et al. Gastro 2002, Bleau BL et al. GIE 2002, Jung HK et al. Am J Gastro 2002, Sung JJY, et al. Ann Int Med 2003
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Bryan Sauer, MD, MSc
Adherent Clot Summary
■ Controversy exists
■ Only one study used continuous infusion
PPI as control
■ Showed no difference in rebleeding rate
■ Current Guidelines: endoscopic therapy
ma be considered,
may
considered altho
although
gh intensi
intensive
e
PPI therapy alone may be sufficient
Sung JJY, et al. Ann Int Med 2003, Barkun AN et al. Annals of Int Medicine 2010
Endoscopic therapeutic choices
■ Injection
■ Epinephrine (1:10,000)
(
) or saline
■ Sclerosant
■ Thrombin/Fibrin Glue
■ Thermal
■ Bipolar electrocoagulation (heat + pressure)
■ Heater probe (heat + pressure)
■ APC (heat only)
■ Mechanical
■ Clip (theoretical advantage of no tissue injury)
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Bryan Sauer, MD, MSc
Injection therapy
■ Epinephrine: 1:10,000 – 1:100,000
■ Less effective than:
■ Other monotherapies (NNT 9)
■ When combined with 2nd therapy (NNT 5)
■ TWO IS BETTER THAN ONE
■ Two
T
modalities—epi
d liti
i + thermal/mechanical
th
l/
h i l
■ Two procedures—2nd look endoscopy if
used as monotherapy
Laine L, McQuaid KR. CGH 2009, Park WG, et al. Technological Review, GIE 2007
Thermal Therapy
■ Bipolar electrocoagulation
■ Coaptive coagulation: compress vessel
(pressure), then coagulate (heat) to seal
■ Low wattage (15-20W) for 5-10 seconds
■ Heater Probe
■ Argon Plasma Coagulation
■ Less well-studied
■ No difference in RCT for high risk stigmata
when compared to epi + heater probe
Chau C et al. GIE 2003
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Bryan Sauer, MD, MSc
Thermal Therapy
■ When compared to no therapy, reduced:
■ Bleeding (NNT 4)
■ Surgery (NNT 8)
■ Mortality (NNT 33)
■ Can be used as monotherapy
Laine L, McQuaid KR. CGH 2009, Chau CH et al. GIE 2003
Endoscopic Hemoclips
■ Initial hemostasis lower than other
endoscopic
d
i treatments:
t t
t
■ RR 0.78 (0.64 – 0.95)
■ When clips do not work well
■ Challenging locations
■ Lesser curvature/posterior wall of stomach
■ Posterior duodenum
■ Retroflexed view
■ Fibrotic lesions
Lin H et al, Am J Gastro 2002, Lin H et al. Dig and Liver Disease 2003, Saltzman JR et al. Am J Gastro 2005
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Bryan Sauer, MD, MSc
Endoscopic Hemoclips
■ No difference in outcomes compared to
standard
t d d endoscopic
d
i therapies
th
i (thermal):
(th
l)
■ Rebleeding, surgery, mortality
■ Better than epinephrine monotherapy
■ SUMMARY: When able to be placed,
clips appear as successful as thermal
therapy
Daram SR et al. Surg Endosc 2013
Endoscopic Hemoclips
QuickClip2
(Olympus)
Resolution
(BSCI)
Instinct
(Cook)
Jaw span
11 mm
11 mm
16 mm
Rotation
Yes
No
Yes
Re-opening ability
No
Yes
Yes
MRI conditional
No
Yes
Yes
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Bryan Sauer, MD, MSc
Ulcer with active oozing
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Bryan Sauer, MD, MSc
Ulcer with visible vessel
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Bryan Sauer, MD, MSc
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Bryan Sauer, MD, MSc
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Bryan Sauer, MD, MSc
Mallory Weiss Tear
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Bryan Sauer, MD, MSc
Mallory Weiss Tear
Vascular Ectasia
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Bryan Sauer, MD, MSc
Vascular Ectasia
Portal Hypertensive Bleeding
■ Esophageal varices
■ Gastric varices
■ Duodenal varices
■ Gastric Antral Vascular Ectasia (GAVE)
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Bryan Sauer, MD, MSc
High Risk Esophageal Varices
Esophageal Varices with Band
Ligation
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Bryan Sauer, MD, MSc
Gastric Antral Vascular Ectasia
Gastric Varices
■ Conventional approach
(sclerosis banding)
(sclerosis,
■ TIPS (Transjugular
Intrahepatic Portosystemic
Shunt)
■ Endoscopic glue injection:
Cyanoacrylate
■ BRTO (angiographic
retrograde occlusion)
■ Surgical shunt: rarely
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Bryan Sauer, MD, MSc
BRTO (Balloon(Balloon-Occluded Retrograde
Transvenous Obliteration)
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Complications of therapy
■ Endoscopic therapy (8 of 1044, 0.8%) versus no
endoscopy (1 of 931
931, 0
0.1%):
1%): RR 2
2.12
12 (0
(0.79-5.70)
79 5 70)
Modality
n
Induced Bleeding
Perforations
Rate of Cpx
Epinephrine
958
2
0
0.2%
Sclerosant ± epi
1339
1
6
0.5%
HP ± epi
1070
2
9
1.0%
BPEC ± epi
580
1
2
0.5%
Clips ± epi
373
0
0
0.0%
Cpx = complications, epi = epinephrine, HP = heater probe, BPEC = bipolar electrocoagulation
Laine L, McQuaid KR. CGH 2009
New Endoscopic Therapies
(aka nonnon-standard therapies)
■ Hemospray/EndoClot
■ Disclaimer: Not FDA approved in the
United States
■ Over-the-Scope
Over the Scope closure devices
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Bryan Sauer, MD, MSc
Hemospray
• Mechanical tamponade
p
effect
• Absorbs water
• Activates clotting
cascade
Gastrointestinal Endoscopy 2013 77, 692-700
Hemospray
Sung JJ et al. Endoscopy 2011
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Bryan Sauer, MD, MSc
Hemospray
Sulz MC et al. Endoscopy 2014
Case series of 16 patients
Reports using Hemospray
Hemospray//Endoclot
■ Peptic ulcer bleeding, primary tx
■ 20 adults, 95% hemostasis, 2 rebleed
■ Malignant bleeding
■ 5 patients, 100% hemostasis, one rebleed
■ Variceal bleeding
■ 9 patients,
ti t 100% h
hemostasis,
t i zero rebleed
bl d
■ Post EMR
■ 20 lesions, 90% hemostasis, 3 rebleed
Sung et al. Endoscopy 2011; Chen et al. GIE 2012; Ibrahim et al. GIE 2013, Huang R et al. Dig Endoscopy 2014
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Bryan Sauer, MD, MSc
SEAL Survey
■ 10 pilot sites across Europe in
2011
■ 63 patients with UGIB
■ 30 ulcers, 33 “other” pathology
■
■
■
■
55 (87%) treated as monotherapy
Primary hemostasis: 85% (47/55)
Rebleeding rate at 7d: 15%
Second-line therapy in 8
patients, all with hemostasis
Smith LA, et al. J Clin Gastroenterol, epub ahead of print, Barkun et al GIE 2013
Over the Scope Clip
■ Retrospective study, 30
patients
■ Conventional Rx failures
■ Hemostasis—97%
Rebleed— 6%
■ Reports
p
include use in ulcers,
MW tear, dieulafoy, GIST,
anastomosis , EMR/ESD,
diverticular, post
polypectomy
Manta et al. Surg Endosc 2013; Chan et al. Endoscopy 2014; Alcaide N, et al. Rev Esp Enferm Dig 2014
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Bryan Sauer, MD, MSc
Post--endoscopic Therapy
Post
PPI after endoscopic therapy
No. of
patients
■30-day rebleed rate
■ 6.7 % for IV omeprazole
Lau et al. N Engl J Med 2000
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■ 26.5 % for placebo
27
Bryan Sauer, MD, MSc
What Dose of PPI?
■ RCT 201 patients after endoscopic Rx with
epi + thermocoagulation (Forrest 1a/1b/IIa)
■ Compared continuous infusion versus bolus
Highdose
Stnddose
Pvalue
Recurrent bleed
(72h)
5
6
0.77
Recurrent bleed
(30d)
7
7
0.98
Surgery
0
0
1
Death (bleedingrelated)
1
1
0.99
Chen C et al. Alim Pharm & Ther, 2012
High dose versus nonnon-high dose
■ Meta-analysis of 1157 patients in 7 studies
■ High
Hi h dose
d
= continuous
ti
iinfusion
f i
■ NO difference:
■ Rates of rebleeding (OR 1.30, CI 0.88-1.91)
■ Surgery (OR1.49, CI 0.66-3.37)
■ Mortality (OR 0.89, CI 0.37-2.13)
Wang, C et al. Arch Int Med 2010
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Bryan Sauer, MD, MSc
“We found that the best dose and route of
administration of PPIs cannot yet be
determined.”
“Our results show that, with regards to deaths,
g episodes,
p
, emergency
g
y surgeries
g
and
rebleeding
need for repeat endoscopic treatments, it is not
certain if high intravenous dose of PPIs are more,
less or equally effective compared to lower (oral or
intravenous) dose of PPIs.”
Neumann I et al. Cochrane Review 2013
PPI after UGIB Treatment
■ PPI decrease rebleed rates
■ Current recommendation is for IV PPI
bolus (80mg) followed by continuous
infusion 8mg/hr for 72 hours
■ Further evidence may support noncontinuous infusions
Laine L, Jensen DM. Am J Gastroenterol 2012, Barkun AN et al Ann Int Med 2010.
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Bryan Sauer, MD, MSc
When to restart aspirin?
ACG Practice Guideline:
“Earlyy resumption
p
of antiplatelet
p
therapy
py within 1-3 days
y
after hemostasis, and certainly within 7 days, will be
appropriate in most patients with established CV disease”
Rebleeding
Mortality
Laine L, Jensen DM. Am J Gastroenterol 2012, Sung et al. Ann Int Med 2010.
What about the “highest” risk
ulcer bleed?
■ RCT ((n=105)) comparing
p
g
transcatheter arterial
embolization AFTER
endoscopic hemostasis in high
risk ulcers (Forrest Ia-IIb)
Mean transfusion
Rebleeding
Surgery
Mortality (30-d)
STAE
Control
P Value
4.3 units
4%
2%
4%
4.9 units
14%
0%
14%
NS
0.10
NS
0.10
Laursen SB et al. Scand J Gastroenterol 2014
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Bryan Sauer, MD, MSc
How to Prevent Recurrent Ulcer
Bleeding?
Laine L & Jensen DM. Management of Patients with Ulcer Bleeding, 2012 ACG Practice Guidelines
Summary:
Approach to Upper GI Bleeding



PPI therapy should be initiated upon
presentation for upper GI bleeding
Early endoscopy (<24 hours) should
be performed in most patients
Endoscopic therapy
y should be
performed for actively bleeding
lesions/visible vessels and considered
in adherent clots
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Bryan Sauer, MD, MSc
Summary:
Approach to Upper GI Bleeding


New therapies include hemospray
and over-the-scope clip
PPI after endoscopy improves
outcomes
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