II. Definitions

  1. Upper Gastrointestinal Bleeding
    1. Bleeding proximal to the ligament of treitz (suspends the distal duodenum) at the duodenojejunal flexure

III. Epidemiology

  1. Incidence: 48 to 160 cases per 100,000
  2. Accounts for 300,000 to 400,000 hospitalizations in U.S. yearly

IV. Risk factors

  1. History of prior Upper Gastrointestinal Bleeding (Relative Risk 13.5)
  2. Anticoagulant use (Relative Risk 12.7)
    1. Apixaban (Eliquis) appears to have the lowest risk of bleeding compared with other DOACs and Warfarin
  3. Helicobacter Pylori infection (present in 64% of cases)
    1. Upper Gastrointestinal Bleeding Odds Ratio: 1.7
    2. Adheres to gastric epithelium, predisposing underlying mucosa to injury by toxins
    3. Together, Helicobacter Pylori and/or NSAID use accounts for 80% of Upper GI Bleeding cases
  4. Antiplatelet Agents
    1. Aspirin alone increases risk of GI Bleeding by 37%
    2. Clopidogrel (Plavix) increases the GI Bleeding risk
      1. Monotherapy: 1.9% per patient year
      2. With Aspirin (Dual Therapy): 3.1% per patient year
      3. With Aspirin and Warfarin (Triple Therapy): 5.1% per patient year
    3. Concurrent Proton Pump Inhibitor lowers the GI Bleeding Odds Ratio
      1. PPI and Aspirin OR Clopidogrel monotherapy: 0.2 Odds Ratio
      2. PPI and Aspirin AND Clopidogrel: 0.36 Odds Ratio
  5. NSAID use (most common cause)
    1. See NSAID Gastrointestinal Adverse Effects for Relative Risk of specific NSAIDs
    2. Upper Gastrointestinal Bleeding Odds Ratio: 4.8 to 5.8
    3. Upper Gastrointestinal Bleeding Odds Ratio: 6.1 if Helicobacter Pylori positive in addition to NSAID use
    4. Celecoxib (Celebrex) and NaproxenSodium (Naprosyn) are the lowest risk of Upper Gastrointestinal Bleeding
  6. Elderly (especially over age 70 years) with Relative Risk 5.6
  7. Male gender (twice as common as women)
  8. Acid suppression therapy does not reduce bleeding risk
  9. End Stage Renal Disease (esp. first year of Dialysis)
  10. Selective Serotonin Reuptake Inhibitors
    1. SSRIs increase GI Bleeding risk by 55%, especially when combined with NSAIDs or antiplatelet agents

V. Causes: Adults

  1. Adults with acute massive GI Bleeding
    1. Peptic Ulcer Disease (62%)
      1. Associated with NSAID use or Helicobacter Pylori infection
      2. Gastric Ulcer (up to 55%)
      3. Duodenal Ulcer (30-38%)
    2. Esophageal Varices (6-10%)
    3. Gastritis or Duodenitis (5-10%)
    4. Esophagitis or esophageal ulcer (5-10%)
    5. Mallory-Weiss tear (3-7%)
    6. Gastrointestinal malignancy (1-4%)
    7. Arteriovenous Malformation (10%)
    8. Dieulafoy's Lesion (1%)
      1. Artery at gastric fundus may bleed heavily
      2. Difficult to identify on endoscopy
    9. Gastric antral vascular ectasia (0.5 to 2%)
      1. Longitudinal erythematous stripes on gastric mucosa
      2. Known as Watermelon Stomach
    10. Aortoenteric Fistula
      1. Associated with prior aortic surgery or grafting
    11. Conditions associated with Angiodysplasia of Stomach or duodenum
      1. Chronic Renal Failure
      2. Aortic Stenosis
      3. Cirrhosis
      4. Von Willebrand's Disease
  2. Chronic intermittent GI Bleeding
    1. Gastritis (18 to 35%)
    2. Esophagitis (18 to 35%)
    3. Gastric Ulcer (18 to 21%)
    4. Duodenal Ulcer (3 to 15%)
    5. Angiodysplasia (5 to 23%)
    6. Gastric Cancer
  3. Most commonly missed upper GI sources
    1. Large Hiatal Hernia erosions
    2. Arteriovenous Malformation
    3. Peptic Ulcer Disease

VI. Causes: Children

VII. History

VIII. Symptoms

  1. Lightheadedness, Dizziness or Syncope
  2. Abdominal Pain
  3. Hematemesis with Coffee-ground Emesis
    1. Distinguish from the frothy, smaller volume blood seen in Hemoptysis
    2. Hematemesis is associated with higher mortality rates
  4. Blood per Rectum
    1. Black tarry stools or Melena
    2. Bright Red Blood Per Rectum as Maroon Stool or Hematochezia (if Upper GI Bleeding is brisk)

IX. Signs

  1. Vital Signs
    1. Do not be reassured by normal Vital Signs
      1. In contrast, Abnormal Vital Signs mandate emergent management
    2. Tachycardia
      1. Heart Rate may be initially normal despite significant Hemorrhage
    3. Hypotension or Orthostasis
      1. Late finding, requires 20% loss of Blood Volume
    4. Shock Index (SI = HR/SBP)
      1. Shock Index >0.8 is considered abnormal (hemodynamic instability)
  2. Cardiovascular Exam
    1. Signs of poor perfusion (e.g. thready pulses, cool and pale extremities, lethargy)
  3. Respiratory Exam
    1. Exclude Epistaxis source
    2. Exclude Hemoptysis source
  4. Abdominal exam
    1. Observe for signs of Cirrhosis and Esophageal Varices risk (e.g. Jaundice, Ascites, Hepatomegaly, Spider Nevi)
    2. Hyperactive Bowel Sounds
    3. Hematemesis
      1. Large volume, coffee ground or brownish Emesis
      2. Contrast with Hemoptysis (cough with smaller volume, bright red, frothy Sputum)
    4. Rebound Tenderness, involuntary guarding (or other signs of peritonitis)
      1. Consider viscus perforation with Acute Abdomen
  5. Nasogastric aspirate or lavage bloody
    1. False Negative Rate is at least 15% and likely higher (negative aspirate does not exclude GI Bleed)
    2. Fresh blood suggests persistant bleeding and suggests a high risk lesion
    3. Lavage offers higher Test Sensitivity but increases risk of aspiration and is controversial
    4. Lavage does not alter mortality, surgery or transfusion requirements
      1. Huang (2011) Gastrointest Endosc 74(5):971-80 [PubMed]
    5. Lavage positive for coffee ground material or bright red blood confirms upper gastrointestinal source
      1. However a negative lavage does not exclude Upper Gastrointestinal Bleeding
    6. Gastric Lavage may also help clear the Stomach of blood prior to endoscopy and improve the evaluation
    7. Allows for monitoring of ongoing upper gastrointestinal GI Bleeding

X. Labs

  1. Complete Blood Count
    1. Baseline Hemoglobin (trails bleeding by 8 to 24 hours)
    2. Obtain serial Hemoglobins every 6 to 8 hours after initial Hemoglobin
  2. Blood Type and Cross-match
  3. Coagulation Factors
    1. Prothrombin Time (INR)
    2. Partial Thromboplastin Time (PTT)
    3. Platelet Count
    4. Consider Fibrinogen level
    5. Consider Viscoelastic Assay (if available)
  4. Comprehensive metabolic panel
    1. Liver Function Tests
    2. Renal Functions tests
      1. Blood Urea Nitrogen (BUN)
      2. Serum Creatinine
      3. BUN to Creatinine ratio
        1. Does not reliably distinguish upper GI source
        2. However some studies show ratio >36 has Test Sensitivity 90%

XI. Imaging

  1. CT Angiography (CTA)
    1. See CT Angiography in Gastrointestinal Bleeding
    2. Consider in patients unable to undergo upper endoscopy with rapid bleeding
    3. CTA may localize sites of Massive Hemorrhage, allowing for management by Interventional Radiology or surgery

XIII. Management: Stabilization of the Actively Bleeding Patient

  1. See Acute Gastrointestinal Bleeding Management
  2. ABC Management
  3. Initial Supportive care
    1. Oxygen
    2. Two large bore IVs (14-18 gauge)
      1. Larger bore catheters have highest flow rates (250 ml/min for 14G, 100 ml/min for 18G)
      2. IO Access or Central Line access if unable to obtain timely, adequate large bore peripheral access
    3. Fluid Resuscitation and Transfusion
      1. See blood replacement below for additional factors (e.g. Massive Transfusion Protocol)
      2. May use initial crystalloid fluid (e.g. 1 Liter) to briefly temporize until blood is available
        1. However, crystalloid further dilutes Coagulation Factors
      3. Hemorrhagic Shock replacement with Blood Transfusion (pRBC) as soon as available
        1. Start with 1 to 2 units of unmatched pRBC ( O- Blood) until cross matched blood is available
      4. Target a mean arterial pressure >65 mmHg
      5. Increase transfusion rates for Shock Index >1.0, hemodynamic instability, rapid Hemorrhage
      6. Avoid Vasopressors if possible (aside from peri-intubation as below)
        1. Limit use to hemodynamic instability refractory to Massive Transfusion Protocol
    4. Consider Endotracheal Intubation (for airway protection)
      1. See Rapid Sequence Intubation
      2. Endotracheal Intubation Preoxygenation
      3. Have two large bore suctions (one with open tubing, one yanker) on and ready for vomit or blood
        1. Tip of one tube may be placed in the Esophagus for active Emesis
      4. Avoid Peri-Intubation Hypotension (high risk for peri-intubation Cardiac Arrest)
        1. Start Vasopressors (e.g. peripheral Norepinephrine) or have Push Dose Pressors drawn up and ready
  4. Monitor Vital Signs including Blood Pressure, Heart Rate and Oxygen Saturation
    1. Consider Arterial Line
    2. Avoid Hypothermia (worsens Coagulopathy)
    3. Correct Acidosis
      1. Modify mechanical Ventilator settings if intubated (e.g. Respiratory Rates)
  5. Intensive Care Unit admission for significant bleeding or hemodynamically unstable
  6. Replace blood and Coagulation Factors as needed
    1. See Gastrointestinal Bleeding Management
    2. See Massive Transfusion Protocol
    3. Unstable Patients: pRBC transfusion
      1. In acute Hemorrhage, true Hemoglobin level is delayed 8 to 24 hours
      2. Start Blood Transfusion in hemodynamically Unstable Patients with active Hemorrhage regardless of initial Hemoglobin
    4. Massive Transfusion Protocol
      1. See Massive Transfusion Protocol for indications
      2. Replace pRBC with FFP and Platelets in a balanced, 1:1:1 ratio
      3. Viscoelastic Assay may be used to direct a more specific protocol for the given patient
      4. Calcium is also replaced for every 6 units pRBC transfused
      5. Avoid over-shooting Hemorrhage volume (risk of worsening GI Hemorrhage, esp. Variceal Bleeding)
    5. Stable Patients: pRBC Transfusion indications
      1. pRBC transfusion for Hemoglobin <7 g/dl (or <8 g/dl with significant comorbidity)
      2. Stable Gastrointestinal Bleeding may target a Hemoglobin of 7 g/dl (restrictive transfusion)
      3. Slow transfusion rates (esp. in CHF, Renal Failure) to prevent Transfusion Associated Circulatory Overload (TACO)
    6. Platelets
      1. Platelet Transfusion for Platelet Count <50,000
      2. Platelets may also be increased with IV Desmopressin in CKD, antiplatelet medications, Thrombocytopenia
    7. Anticoagulant Reversal
      1. See Emergent Reversal of Anticoagulation
      2. Correct INR >2.5 for patients on Warfarin before endoscopy (e.g. PCC4 or FFP and Vitamin K)
    8. Cirrhosis
      1. Risk of Hypocalcemia and Hypomagnesemia (associated with citrate in transfusion products)
      2. Coagulopathy may benefit from Vitamin K Clotting Factor replacement in Massive Hemorrhage
        1. Consider Vitamin K 10 mg IV
        2. Consider Cryoprecipitate 10 units/kg IV
    9. Other agents
      1. Tranexamic Acid 1g IV has been used
        1. However, evidence from HALT-IT trial found no benefit and increased adverse events
        2. (2020) Lancet 395(10241):1927-36 [PubMed]
  7. Upper endoscopy urgently to emergently
    1. Notify GI or surgery on patient presentation to ready for upper endoscopy
    2. Performed in first 24 hours after fluid Resuscitation and stabilization
    3. See Upper Endoscopy Evaluation of GI Bleeding
    4. See Glasgow-Blatchford Bleeding Score
      1. May forego upper endoscopy if score <1
    5. See protocols below
    6. Erythromycin infusion immediately prior to endoscopy
      1. Prokinetic that increases endoscopy Test Sensitivity for Gastrointestinal Bleeding site
  8. Medications
    1. Intravenous Proton Pump Inhibitor (e.g. Pantoprazole IV) - see below
    2. Variceal Bleeding specific management (see below)
    3. Prokinetic Agents (e.g. Erythromycin IV before endoscopy)
      1. Controversial, but may improve endoscopy efficacy

XIV. Management: Specific Interventions

  1. Esophageal Varices
    1. See Bleeding Esophageal Varices
    2. Upper Endoscopy emergently
      1. Endoscopic ligation
      2. Variceal banding
      3. Sclerotherapy
      4. Obturation
      5. Esophageal stenting (refractory cases)
    3. Vasoactive Agents
      1. Octreotide 50 mcg IV bolus, followed by 50 mcg/hour IV infusion
      2. Octreotide is a splanchnic Vasoconstrictor that decreases Variceal Bleeding and decreases transfusion needs
    4. Non-selective Beta Blocker (e.g. Propranolol, Nadalol, Timolol)
    5. Prophylactic Antibiotics (e.g. Norfloxacin, Ciprofloxacin, Ceftriaxone)
      1. Ceftriaxone 2 g IV every 24 hours for 7 days (may be transitioned to oral Ciprofloxacin)
    6. Consider Esophageal Balloon Tamponade (e.g. Linton Tube, Sengstaken-Blakemore Tube)
      1. Indicated for stabilization until endoscopy
  2. Non-variceal persistent bleeding
    1. Upper endoscopy (see protocol above)
      1. See Risk stratification below
    2. Transcatheter Arterial Embolization (via Angiography) Indications for Persistent Bleeding
      1. Endoscopy not available
      2. Biliary bleeding
      3. Pancreatic bleeding
      4. Gastric Ulcer
      5. Mallory-Weiss Tear
    3. General Surgery Indications
      1. Acute Abdomen (peritonitis)
      2. Continued massive bleeding without known source
      3. Failed medical therapy, endoscopy and angiography
      4. Lower risk of rebleeding compared with transcatheter ablation
        1. Beggs (2014) Clin Exp Gastroenterol 7:93-104 [PubMed]

XV. Management: Acid Reduction

  1. Proton Pump Inhibitor (preferred)
    1. Start Intravenous Proton Pump Inhibitor in all Upper Gastrointestinal Bleeding cases
      1. Better outcomes with use, although mixed results (see below)
    2. Dosing
      1. Typical dosing (even in Massive Hemorrhage)
        1. Pantoprazole (Protonix) 40 mg IV every 12 hours
        2. Continue as twice daily dosing (oral or IV) for first 2 weeks after endoscopic therapy
      2. Massive Hemorrhage
        1. Pantoprazole (Protonix) 80 mg IV, then 8 mg/hour
        2. Continuous infusion has largely been replaced in most cases by intermittent bolus
    3. Effects
      1. Full protection (achlorhydria) is delayed for the 5-7 days required to deactivate the proton pump
        1. Consider H2 Blocker initially (see below)
      2. Not proven in-vivo to aid clotting
      3. Omeprazole may heal Peptic Ulcer if near-achlorhydria
      4. No proven benefit in mortality
      5. Cochrane study suggested PPI benefit in specific measures when given in endoscopy suite
        1. May reduce Incidence of re-bleeding (NNT 15)
        2. May reduce Incidence of Gastrointestinal Bleeding requiring surgery (NNT 30)
        3. Peptic Ulcer related bleeding appears to benefit from PPI in China and Japan (but possible associated worse outcomes in U.S.)
        4. Leontiadis (2006) Cochrane Database Syst Rev (1): CD002094 [PubMed]
      6. No benefit or harm seen when PPI given at Upper GI Bleeding presentation
        1. Dorward (2006) Cochrane Database Syst Rev (4): CD005415 [PubMed]
    4. References
      1. Newman in Herbert (2014) EM:Rap 14(1): 4
      2. Daneshmend (1992) BMJ 304:143-47 [PubMed]
      3. Sreedharan (2010) Cochrane Database Syst Rev (2): CD005415 [PubMed]
      4. Sung (2009) Ann Intern Med 150(7): 455-64 [PubMed]
  2. H2 Blocker
    1. Use is controversial in Acute Gastrointestinal Hemorrhage
    2. Consider starting initially concurrently with Proton Pump Inhibitor to bridge the delay in full PPI activity
    3. Ranitidine
      1. Intermittent: 50 mg IV or IM every 6-8 hours
      2. Continuous: 6.25 mg/hour IV

XVI. Management: Very low risk patients

  1. Indications
    1. Hemodynamically stable with normal lab testing
    2. No evidence of significant bleeding in last 48 hours
    3. Nasogastric Tube aspirate without blood
    4. Upper GI Bleeding Score (Glasgow-Blatchford Bleeding Score) <1
      1. Mustafa (2015) Eur J Gastroenterol Hepatol 27(5):512-5 +PMID:25822859 [PubMed]
  2. Protocol
    1. Home with follow-up within days
    2. General measures as above

XVII. Management: Low risk patients

  1. Indications
    1. Hemodynamically stable within 1 hour of Resuscitation
    2. Minimal Blood Products required (2 PRBC or less)
    3. No evidence of active bleeding
    4. Nasogastric Tube aspirate without blood
    5. No active comorbid medical conditions
  2. Protocol
    1. Consider for rapid protocol
      1. Immediate Upper Endoscopy Evaluation of GI Bleeding
      2. Discharge to home if low-risk endoscopy results
    2. Admit if rapid protocol not available
      1. Follow moderate risk patient protocol below
    3. General measures as above

XVIII. Management: Moderate risk patients

  1. Indications
    1. Tachycardia persists despite Resuscitation
    2. Blood Products required >2 PRBC
    3. Active comorbid condition
  2. Protocol
    1. General measures as above
    2. Admit to regular medical bed
    3. Upper endoscopy when patient stabilized (<24 hours)
      1. See Upper Endoscopy Evaluation of GI Bleeding
      2. Disposition based on Upper Endoscopy results
        1. Low risk endoscopy: Observe for 24 hours
        2. Moderate risk endoscopy: Observe for 48-72 hours
        3. High risk endoscopy
          1. Initially observe in ICU for at least 24 hours
          2. Observe in hospital for 72 hours total or more

XIX. Management: High risk patients

  1. Indications
    1. Active ongoing bleeding (persistent drop in Hemoglobin despite transfusion)
    2. Hypotension or other hemodynamic instability persists despite Resuscitation
    3. Severe active comorbid condition exascerbation
    4. Liver disease exascerbation
    5. Endotracheal Intubation for airway protection
  2. Protocol
    1. General measures as above
    2. Admit to Intensive Care unit for first 24 hours
    3. Observe in hospital for 48 to 72 hours or more
    4. Urgent upper endoscopy when stabilized
      1. See Upper Endoscopy Evaluation of GI Bleeding
      2. Consider repeat routine recheck upper endoscopy in 24 hours for high risk lesions
    5. Consider arteriography if source not evident

XX. Management: Refractory and Recurrent Bleeding

  1. Indications
    1. Persistent or recurrent bleeding despite EGD
    2. See Upper Endoscopy Evaluation of GI Bleeding
  2. Procedures
    1. Consider arteriography with embolization
      1. First-line study
      2. Equivalent efficacy to surgical intervention
    2. Surgical Intervention
      1. Gastroduodenotomy
      2. Vagotomy
      3. Peptic Ulcer resection

XXI. Management: Disposition

  1. See prevention measures below
  2. See Helicobacter Pylori management
  3. Proton Pump Inhibitor once daily for 4-8 weeks
    1. Increase to twice daily for first 2 weeks for high risk lesions
  4. Repeat Upper Endoscopy
    1. Perform at 8-12 weeks after initial endoscopy
    2. Indications
      1. Gastric Ulcer (Confirm healing and exclude cancer)
      2. Severe Esophagitis (exclude Barrett's Esophagus)
  5. Iron Deficiency Anemia
    1. Transfused blood will keep Hemoglobin increased only 2-3 weeks
    2. Ferrous Sulfate 325 mg daily to three times daily
      1. Continue until Serum Ferritin and Hemoglobin return to normal

XXII. Management: Cause Specific Approaches

  1. Erosive Disorders (Esophagitis, Gastritis or Duodenitis)
    1. Good prognosis and therapeutic endoscopy is not required
    2. Early discharge on Proton Pump Inhibitor for 8 weeks
  2. Mallory Weiss Tear
    1. Most spontaneously heal
    2. However, bleeding related mortality approaches that of Peptic Ulcer Bleeding

XXIII. Management: Restarting Anticoagulants and Antiplatelet agents after Upper GI Bleed

  1. Warfarin
    1. Restart 7-15 days after bleeding (7 days if high thromboembolic risk)
  2. Non-Vitamin K Antagonist Oral Anticoagulant (e.g DOACs, Apixaban )
    1. Change to Apixaban from other DOACs
    2. If already taking Apixaban, decrease dose
  3. Aspirin
    1. May restart in 3 days (immediately at 0 days, if low bleeding risk )
  4. Dual Antiplatelet agents
    1. First start Aspirin AND
    2. After 5-7 days, may add back Clopidogrel or other antiplatelet agent in high risk patients (e.g. cardiac stents)

XXIV. Prevention

  1. See Helicobacter Pylori management
  2. See GI Prophylaxis
  3. Avoid NSAIDs
  4. Consider longterm Proton Pump Inhibitor if Aspirin or Clopidogrel (Plavix) cannot be stopped
    1. See Clopidogrel (Plavix) for potential Proton Pump Inhibitor interactions
    2. Proton Pump Inhibitors reduce antiplatelet efficacy (increased cardiovascular events)
  5. Tobacco Cessation
  6. Avoid Alcohol

XXV. Prognosis: Outcomes

  1. Mortality: 2-15% overall (often related to comorbidity)
    1. In hospital mortality: 13%
    2. Duodenal Ulcer: 3.7%
      1. Higher risk of erosions into larger vessels
    3. Gastric Ulcer: 2.1%
  2. Course
    1. Bleeding stops and does not recur: 85% (<2% Mortality)
    2. Re-bleeding after initially stopped: 15% (10% Mortality)
    3. Continued active bleed: 5% (30% Mortality)

XXVI. Prognosis: Predictors

  1. Bleeding characteristic predictors of poor outcome
    1. See Upper GI Bleeding Score
    2. Emesis or nasogastric aspirate contains red blood
    3. Low initial Hematocrit
    4. Coagulopathy (Low Platelets or high INR)
  2. Comorbid condition predictors of poor outcome
    1. Active Coronary Artery Disease
    2. Congestive Heart Failure
    3. Active lung disease
    4. Renal Failure
    5. Sepsis
    6. Metastatic cancer
    7. Advanced liver disease
    8. Advanced age

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