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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
Risk stratificationPharmacologyInterventional StrategiesPrevention
RebleedingMortalityEarly intervention
PPIOctreotideASA/clopidigrel
Risk stratificationPharmacologyInterventional StrategiesPrevention
RebleedingMortalityEarly intervention
PPIOctreotideASA/clopidigrel
EndoscopyAngiography
Risk stratificationPharmacologyInterventional StrategiesPrevention
RebleedingMortalityEarly intervention
PPIOctreotideASA/clopidigrel
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
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
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
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
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 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
Endoscopic stigmata in peptic ulcers
Clean-based ulcerFlat spotVisible vesselAdherent clotActive bleeding
Rebleeding: 3%
Endoscopic stigmata in peptic ulcers
Clean-based ulcerFlat spotVisible vesselAdherent clotActive bleeding
Rebleeding: 10%
Endoscopic stigmata in peptic ulcers
Clean-based ulcerFlat spotVisible vesselAdherent clotActive bleeding
Rebleeding: 50%
Endoscopic stigmata in peptic ulcers
Clean-based ulcerFlat spotVisible vesselAdherent clotActive bleeding
Rebleeding: 25% - 40%
Endoscopic stigmata in peptic ulcers
Clean-based ulcerFlat spotVisible vesselAdherent clotActive bleeding
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 therapyPPI before endoscopy
Fewer endoscopic stigmataNo effect on rebleeding, surgery, or mortality
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 therapyPPI before endoscopy
Fewer endoscopic stigmataNo effect on rebleeding, surgery, or mortality
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
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
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
Gotzsche (Cochrane) 2006; and others
MechanismPrevents post-prandial increase in mesenteric blood flow
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
Infectious complications increase mortality in cirrhoticsNumerous controlled trials of antibiotic Rx
Improvements with antibx:Bacterial infections (RR 0.36)Rebleeding (RR 0.53)Mortality (RR 0.79)
Chavez-Tapia (Cochrane), 2010
Antibiotics
Infectious complications increase mortality in cirrhoticsNumerous controlled trials of antibiotic Rx
Improvements with antibx:Bacterial infections (RR 0.36)Rebleeding (RR 0.53)Mortality (RR 0.79)
Antibiotics usedOral quinolonesQuinolones + beta-lactamsCephalosporinsCarbapenems
Chavez-Tapia (Cochrane), 2010
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
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
ASARecurrent bleeding: 10%
Mortality: 1%(cardiac 1)
PlaceboRecurrent bleeding: 5%
Mortality: 13%(cardiac 5, GI 3, pneumonia 2)
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
ASARecurrent bleeding: 10%
Mortality: 1%(cardiac 1)
PlaceboRecurrent bleeding: 5%
Mortality: 13%(cardiac 5, GI 3, pneumonia 2)
Sung AIM 2010
Should we stop ASA in patients with acute GI bleeding?
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
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
Early TIPS?TIPS prevents bleeding but is associated with liver failure
TIPS is a rescue treatment
Garcia-Pagan NEJM 2010
Early TIPS?TIPS prevents bleeding but is associated with liver failure
TIPS is a rescue treatment
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
Garcia-Pagan NEJM 2010
Early TIPS?TIPS prevents bleeding but is associated with liver failure
TIPS is a rescue treatment
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%
Garcia-Pagan NEJM 2010
Stress Ulcer Prophylaxis
Cook NEJM 1994, Cook CCM 1999, Lin 2010, and others
PathophysiologyIschemia (Curling’s ulcers)↑Acid (Cushing’s ulcers)
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
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
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
Recommended