gi bleeding mark topazian, m.d. december 16, 2010

GI Bleeding

Mark Topazian, M.D.December 16, 2010

Has responded with a disclosure

Will discuss off-label/investigative use(s): Sandoz, Ethicon Octreotide, Dermabond

Critical Care Grand Rounds Disclosure Summary

Mark D. Topazian, MD

Planning committee members who have nothing to disclose:

Sean M. Caples, DO, Co-Director

Juan N. Pulido, MD, Co-Director

J. Christopher Farmer, MD

Kim Jones, Program Coordinator

Disclosure SummaryAs a provider accredited by ACCME, College of Medicine, Mayo Clinic (Mayo School of CME), must ensure balance, independence, objectivity and scientific rigor in its educational activities. Course Director(s), Planning Committee Members, Faculty, and all others who are in a position to control the content of this educational activity are required to disclose all relevant financial relationships with any commercial interest related to the subject matter of the educational activity. Safeguards against commercial bias have been put in place. Faculty also will disclose any off label and/or investigational use of pharmaceuticals or instruments discussed in their presentation. Disclosure of this information will be published in course materials so those participants in the activity may formulate their own judgments regarding the presentation.

Critical Care Grand Rounds Disclosure Summary Continued

Learning Objectives

• Identify predictors of morbidity and mortality in patients with acute gastrointestinal hemorrhage

• Describe the management approach to gastrointestinal hemorrhage

• Understand the evidence basis for pharmacologic and endoscopic therapies

• Review important recent developments in this field

GI Bleeding is an important clinical problem

Incidence: 100/100,000/year

Mortality: 3% to 10%

Silverstein GIE 2002; Cutler DDS 1981; Lanas AJG 2009

Risk stratificationPharmacologyInterventional StrategiesPrevention


RebleedingMortalityEarly intervention



PPIOctreotideASA/clopidigrel




EndoscopyAngiography




EndoscopyAngiography

PrimarySecondary

Predictors of re-bleeding and death

Variceal Bleeding

Size of the initial bleed

Severity of liver disease

Infection (SBP)

Non-Variceal Bleeding

Size of the initial bleed

Age > 65 years

Comorbidities

Endoscopic stigmata

Schiller, Truelove, Williams. Hematemesis and melena with special reference to factors affecting outcome, BMJ 1970

Bedside estimation of hypovolemia

• No bedside test is reliable for diagnosis of moderate acute blood loss

• Supine tachycardia and/or hypotension are specific but insensitive (often absent) in severe acute blood loss (630-1150 ml)

• 2 signs are sensitive and specific for diagnosis of severe acute blood loss:– Postural pulse increment ≥ 30 bpm– Severe postural dizziness (unable to stand for VS)

McGee JAMA 1999

Bedside diagnosis of hypovolemia

• No bedside test is reliable for diagnosis of moderate acute blood loss

• Supine tachycardia and/or hypotension are specific but insensitive (often absent) in severe acute blood loss (630-1150 ml)

• 2 signs are sensitive and specific for diagnosis of severe acute blood loss:– Postural pulse increment ≥ 30 bpm– Severe postural dizziness (unable to stand for VS)

McGee JAMA 1999

Melena, hematemesis, hematochezia

• Melena implies acute loss of at least 250 ml blood in the UGI tract– Pace of melena

• Hematemesis implies rapid UGI bleeding– Fatality rate doubled c/w melena

• Hematochezia is usually due to LGIB– May be due to duodenal ulcer

Schiff AJMS 1942, Schiller 1970, Jensen 2005, and others

Blatchford, Lancet 2000

Blatchford Score

Low riskAll of the following:

Normal pulse and BP

Near-normal BUN and Hb

No liver, heart disease

High risk2 or more of the following:

BUN > 30 mg/dL

Hb < 10

Hypotension

Hepatic or cardiac disease

Endoscopic stigmata in peptic ulcers

Clean-based ulcerFlat spotVisible vesselAdherent clotActive bleeding



Rebleeding: 3%



Rebleeding: 10%



Rebleeding: 50%



Rebleeding: 25% - 40%



Rebleeding: 90%

PPI therapyPPI before endoscopy

Fewer endoscopic stigmataNo effect on rebleeding, surgery, or mortality

Sreeharan (Cochrane) 2010; Wu WJG 2010; Wang AIM 2010 ; and others



PPI after endoscopyImproves outcomes in pts requiring endoscopic RxNo difference between high

and regular dose RxSreeharan (Cochrane) 2010; Wu WJG 2010; Wang AIM 2010 ; and others



PPI after endoscopyImproves outcomes in pts requiring endoscopic RxNo difference between high

and regular dose RxSreeharan (Cochrane) 2010; Wu WJG 2010; Wang AIM 2010 ; and others

PPI dose1-4x daily dose

vs.2-6x daily dose IV plus cont. infusion

Octreotide therapy

Gotzsche (Cochrane) 2006; and others

MechanismPrevents post-prandial increase in mesenteric blood flow

Octreotide therapyOctreotide vs. placebo

Less transfusion (0.7 units)Less failure of initial endoscopic Rx (RR 0.7)Balloon tamponade rareNo difference in rebleeding or mortality



Octreotide therapyOctreotide vs. placebo

Less transfusion (0.7 units)Less failure of initial endoscopic Rx (RR 0.7)Balloon tamponade rareNo difference in rebleeding or mortality

How to use octreotidePatients with suspected variceal hemorrhageBolus of 0 to 50 mcg, infusion of 25 – 250 mcg/hrBegin before endoscopy and continue for 3 – 5 days



Other Drug Rx for Portal HTN

• Vasopressin– Absence of controlled data– Systemic risks

• Vasopressin analogues– Terlipressin is effective in European trials

• Beta blockers– Not used in the acute setting– Decrease risk of rebleeding after discharge

Antibiotics

Infectious complications increase mortality in cirrhoticsNumerous controlled trials of antibiotic Rx

Chavez-Tapia (Cochrane), 2010

Antibiotics


Improvements with antibx:Bacterial infections (RR 0.36)Rebleeding (RR 0.53)Mortality (RR 0.79)


Antibiotics


Improvements with antibx:Bacterial infections (RR 0.36)Rebleeding (RR 0.53)Mortality (RR 0.79)

Antibiotics usedOral quinolonesQuinolones + beta-lactamsCephalosporinsCarbapenems


ASA

Sung AIM 2010

Should we stop ASA in patients with acute GI bleeding?

ASA

156 patients with acute GI hemorrhageASA for cardiovascular or cerebrovascular disease

EGD: stigmata of recent hemorrhage requiring endoscopic RxRandomized to ASA 80 mg/day or placebo for 8 weeks

Sung AIM 2010


ASA



ASARecurrent bleeding: 10%

Mortality: 1%(cardiac 1)

PlaceboRecurrent bleeding: 5%

Mortality: 13%(cardiac 5, GI 3, pneumonia 2)

Sung AIM 2010


ASA



ASARecurrent bleeding: 10%

Mortality: 1%(cardiac 1)

PlaceboRecurrent bleeding: 5%

Mortality: 13%(cardiac 5, GI 3, pneumonia 2)

Sung AIM 2010


Plavix?

ClopidogrelInteraction with PPIs

Clopidogrel → active metabolite by CYP2C19 Omeprazole is also metabolized by CYP2C19

Omeprazole: ↓ levels of the active clopidogrel metabolite

Dikman APT 2009, Siller-Matula 2010, and others

ClopidogrelInteraction with PPIs

Clopidogrel → active metabolite by CYP2C19 Omeprazole is also metabolized by CYP2C19

Omeprazole: ↓ levels of the active clopidogrel metabolite

Dikman APT 2009, Siller-Matula 2010, and others

PPI together with clopidogrel:likely ↑ risk major cardiovascular events

likely↓ risk GI bleedEffect may be greatest in slow metabolizers

Furuta BJCP 2010

Clopidogrel/PPI interaction

Possible strategiesAvoid PPI when not indicatedSequence CYP2C19 genotype

Substitute H2 receptor antagonistsStagger clopidogrel and PPI doses

Increase clopidogrel doseAdd or substitute ASA

Dikman APT 2009, Siller-Matula 2010, Furuta 2010, and others

Principles of endoscopic hemostasis

• Identify and target the point source of bleeding

• Only treat lesions that have a high likelihood of rebleeding

• Endoscopic Rx decreases rebleeding rate by > 50%

• Repeat endoscopic Rx is usually effective in those who rebleed

Gastric Varices

Minnesota Tube

http://img.tfd.com/dorland/thumbs/tube_Sengstaken-Blakemore.jpg

http://er119.org/xoops_er119/uploads/photos/95.jpg

Early TIPS?TIPS prevents bleeding but is associated with liver failure

TIPS is a rescue treatment

Garcia-Pagan NEJM 2010



63 patients with variceal hemorrhageChilds-Pugh score of 7 – 13 (B or C)

All received endoscopic and pharmacologic RxRandomized to standard care or early TIPS




63 patients with variceal hemorrhageChilds-Pugh score of 7 – 13 (B or C)

All received endoscopic and pharmacologic RxRandomized to standard care or early TIPS

Standard CareRebleeding (1 year) 45%Death (1 year) 39%

Early TIPSRebleeding (1 year) 3%Death (1 year) 13%


Stress Ulcer Prophylaxis

Cook NEJM 1994, Cook CCM 1999, Lin 2010, and others

PathophysiologyIschemia (Curling’s ulcers)↑Acid (Cushing’s ulcers)




Risk factorsMechanical ventilation

CoagulopathyRenal failure

Burns, Trauma, Transplant




Risk factorsMechanical ventilation

CoagulopathyRenal failure

Burns, Trauma, Transplant

RxPPI ≥ H2RA

Prevention of late re-bleeding

Peptic UlcerTest for h pylori - C13 breath test, bx - confirm eradicationLong term antisecretory Rx

Gisbert (Cochrane) 2004, Ding WJG 2009, and others

Prevention of late re-bleeding

Variceal hemorrhageEradicate varices - Elective band ligationBeta blockers

Gisbert (Cochrane) 2004, Ding WJG 2009, and others

gi bleeding mark topazian, m.d. december 16, 2010

Documents

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death variceal bleeding

predictors of rebleeding

initial bleed age

gi bleeding mark topazian

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