The Exsanguinating Patient: New Tools and Recent...

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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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


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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


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Survival according to transfusion strategy

DaysOve

rall

Surv

ival

(%)

Villanueva C. N Engl J Med 2013;368(1):11-21

Restrictive vs. liberal strategy


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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



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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


• 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


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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


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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


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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


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


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 (


Urgent endoscopy (


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)


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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



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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


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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


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Topical hemostatic agents

Barkun A. Gastrointest Endosc 2013;77:692-700


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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


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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


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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


Case conclusion


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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


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