Post on 30-Jan-2021
John R. Saltzman, MD, FACG
The Exsanguinating Patient:New Tools and Recent Guidelines
John R. Saltzman, MD, FACGDirector of Endoscopy
Brigham and Women’s HospitalProfessor of Medicine
Harvard Medical School
Objectives• To adequately resuscitate patients with GI bleeding• To provide proper medical therapy• To know the timing and role of endoscopic therapy
for control of GI bleeding• To provide optimal care of patients with non-
variceal upper GI bleeding
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Case• 64 yo man with history of ampullary adenocarcinoma
s/p Whipple surgery one year prior to presentation• Chronic postprandial abdominal pain 7/10 since
Whipple on ibuprofen; 100 lb. weight loss past year• Presents with 2 episodes of bright red hematemesis• C/O lightheadedness, dizziness and syncope• Exam: BP 90s/60s and HR 110; black guaiac + stool• Labs: Hct 22%, BUN 30 mg/dl, Cr 1.0 mg/dl, INR-1.1
Upper endoscopy
Non-bleeding, large, cratered ulcer with a 6 mm visible vessel at the gastrojejunal anastomosis
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Initial assessment and risk stratification
• Assess hemodynamic status immediately• Insert 2 large bore IV’s and begin resuscitation• Blood transfusions
– Target hemoglobin >7 g/dL(>10 g/dL if intravascular volume depletion or CAD)
• Risk stratification into higher and lower categories– Patient triage – Timing of endoscopy
Laine L, Jensen D. Am J Gastroenterol 2012;107:345-360
IV flow rates• Angiocatheter gauge: max infusion rate
– 22 gauge: 35 mL/min– 20 gauge: 60 mL/min – 18 gauge: 105 mL/min– 16 gauge: 205 mL/min– 14 gauge: 333 mL/min
• Central triple lumen catheter• Large lumen (brown) = 52 mL/min• Other two lumens (blue/white) = 26 mL/min
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Survival according to transfusion strategy
DaysOve
rall
Surv
ival
(%)
Villanueva C. N Engl J Med 2013;368(1):11-21
Restrictive vs. liberal strategy
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Medications inUpper GI bleeding
• Proton pump inhibitors• Warfarin• DOACs
Guideline recommendations: post-endoscopic therapy
After successful endoscopic hemostasis, IV PPI therapy with 80 mg bolus followed by 8 mg/h continuous infusion for 72 h should be given to patients who have an ulcer with active bleeding, a non-bleeding visible vessel, or an adherent clot.
Strong recommendation
Laine L, Jensen D. Am J Gastroenterol 2012;107:345-60
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Continuous vs. intermittent PPI’s
Sachar H. JAMA Intern Med 2014 Nov;174(11):1755-62
Impact of anticoagulation and therapeutic endoscopy
• 233 patients post successful therapeutic endoscopy• 44% patients had an INR >1.3 (95% 1.3)– 21% in patients with normal coagulation (INR’s
John R. Saltzman, MD, FACG
• American College of Chest Physicians (2012)– 4-factor prothrombin complex concentrate (PCC) which contain factors
II, VII, IX and X – Vitamin K (5-10 mg by slow IV) – No FFP– No individual coagulation factors (recombinant factor VIIa)
• American Heart Association/American College of Cardiology (2014): valvular heart disease– 4 factor PCC or FFP– No Vitamin K (can cause hypercoagable state)
Warfarin reversal
Direct oral anticoagulants• Factor Xa or IIa (thrombin) inhibitors• At least as effective as warfarin in preventing CVA’s in
atrial fibrillation• Oral fixed dose without coagulation management are
convenient• Therapeutic anticoagulation within hours• Normal coagulation within 24-48 hours after DOAC
dose is held
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Mechanism of action of DOACs
Hu TY. Vasc Health Risk Management 2016;12:35-44
Bleeding risk of direct anticoagulants vs. warfarin
Desai. JC Am J Gastroenterol Suppl 2016;3:13-21
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Risk factors for GI bleeding• Age >65 years• Hepatorenal dysfunction• Low body weight• Concomitant anti-platelet agents or NSAIDs• Drugs that affect cytochrome P450 or
interact with P-glycoprotein
Abraham NS. Am J Gastroenterol Suppl 2016;3:2-12
Dabigatran reversal agentIdarucizumab (Praxbind)• Humanized monoclonal antibody with high affinity for dabigatran• REVERSE-AD Trial (interim analysis):
– Eliminates dabigatran effect measured by ecarin clotting time and dilute thrombin time– Reversal within 5 minutes with 2 IV doses of 2.5 g given 15 minutes apart – $3,500/dose
• Accelerated review by FDA for “life threatening hemorrhage/need for emergency surgery or procedures” approved October 16, 2015
Pollack CV. N Engl J Med 2015;373(6):511-520
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Andexanet alfa A recombinant protein specifically designed to reverse the anticoagulant
activity of both direct and indirect Factor Xa inhibitors RCT of healthy older volunteers were given 5 mg of apixaban twice daily or
20 mg of rivaroxaban daily Anti–factor Xa activity was reduced by >90% with an andexanet bolus Thrombin generation was fully restored in >96% within 2-5 minutes (P
John R. Saltzman, MD, FACG
Medical therapy summary• Medical therapy with proton pump inhibitor
given as IV bolus or orally is effective along with endoscopic therapy
• Perform endoscopy when INR
John R. Saltzman, MD, FACG
Timing of endoscopy“Early endoscopy within 24 hours of presentation is recommended for most patients with acute upper gastrointestinal bleeding” International Consensus Guidelines 2010
“Patients with upper GI bleeding should generally undergo endoscopy within 24 hours of admission, following resuscitative efforts to optimize hemodynamic parameters” ACG Practice Guidelines 2012
Emergent or urgent endoscopy?• Emergent (
John R. Saltzman, MD, FACG
Urgent endoscopy (
John R. Saltzman, MD, FACG
Mortality and time to endoscopy
Laursen SB. Gastrointest Endosc 2016; Sep 10;Kumar N. Gastrointest Endosc 2016; Sep 29
Hemodynamically stable Hemodynamically unstable
Prophylactic endotracheal intubation
• Massive hematemesis• Altered mental status• Airway protection• May increase aspiration pneumonia• May increase cardiac AE’s (shock)
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Stigmata of recent hemorrhage
Abidi W, Saltzman JR. Scientific American GI, Hepatol, & Endoscopy 2015
Indications for endoscopic therapyStigmata Endoscopic therapy?
Active bleeding YesNon-bleeding visible vessel YesAdherent clot +/-Flat spot NoClean ulcer base No
Laine L, Jensen D. Am J Gastroenterol 2012;107:345-60
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Endoscopic therapeutic options• Injection• Thermal (contact)
• Bipolar probe• Monopolar
• Thermal (non-contact)• Argon plasma coagulation (APC)
• Mechanical• Hemoclips• OTSC• Banding
• Combination• Sprays
The over-the-scope clip (OTSC)
Kirschniak A. Gastrointest Endosc 2007;66:162-167
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
OTSC for primary control Series of 40 consecutive patients Indications:
Gastric ulcer with large vessel (n = 8, 20%) Oozing duodenal ulcer (n = 7, 18%) Duodenal ulcer with large vessel (n = 6, 15%) Dieulafoy's lesion (n = 6, 15%) Other secondary indications (n = 13, 32%)
Technical success and primary hemostasis achieved in all patients (100%) and no rebleeding at 30 days
Manno M. Surg Endosc 2016:30(5):2026-9
OTSC for GI bleeding after prior failures
• Primary hemostasis:– 97% (29/30)
• Rebleeding:– 7% (2/30 pts)
Manta R. Surg Endosc 2013;27:3162-3164
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Topical hemostatic agents
Barkun A. Gastrointest Endosc 2013;77:692-700
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Hemostatic spray review
Chen Y. Gastrointest Endoscopy Clin N Am 2015;25:535-552
• Immediate hemostasis: 92.3% (180/195)• Rebleed rate at 7 days: 20.6%• High risk lesions (Forrest 1a, 1b)
- Immediate hemostasis: 95% (53/56)- Rebleed rate at 7 days: 25% (13/53)
• Safety (243 cases)- 5 reported complications:
Pain (under-reported?), biliary obstruction (post-sphincterotomy bleed), perforation, hemo-peritoneum, splenic emboli (on day 29)
Hemospray considerations• Does not require special expertise• May be effective in difficult locations• Potential role for malignant bleeding• Effective only in actively oozing or spurting
bleeding lesions• Second treatment modality needed if high
risk of rebleeding• Not FDA approved
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Endpoints of endoscopic therapy
Wong RC. Gastroenterology 2009;137:1897-1902; Swain CP. Gastroenterology 1986;90:595-608
Doppler before and after endoscopic therapy
Doppler guided treatment is safe and more effective than standard visually guided endoscopic hemostasis for prevention of ulcer rebleeding
Jensen DM. Gastrointest Endosc 2016;83(1):129-36
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
GI bleeding and surgery/IR• Consult surgery and interventional radiology
(IR) early in course• “Consider surgery after 6 units of blood and
again after every 4 additional units” • Do not medically manage a patient too long
who needs surgical/IR therapy• Surgery/IR does not mean a “failure”
IR embolization vs. surgery for rebleedingOutcomes Embolization Surgery
n = 32 n = 56
Mean Age (Yr) 73 71
Mean transfusion (Units) 15.6 14.2
Mean days of hospitalization 17.3 21.6
Recurrence of bleeding 11 (34.4%) 7 (12.5%)#
Complications 40.6% 67.9%#
Death 8 (25%) 17 (30%)# P
John R. Saltzman, MD, FACG
Case conclusion
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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John R. Saltzman, MD, FACG
Major GI bleeding:Take home points
• Adequate initial resuscitation is essential• Provide proper medical therapy• Perform endoscopy in a timely manner• Use effective endoscopic treatments• Provide optimal management of your patients
ACG 2016 Southern Regional Postgraduate Course Copyright 2016 American College of Gastroenterology
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