Upper Gastrointestinal Bleeding

See Also

Definitions

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

Epidemiology

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

Risk factors

History of prior Upper Gastrointestinal Bleeding (Relative Risk 13.5)
Anticoagulant use (Relative Risk 12.7)
1. Apixaban (Eliquis) appears to have the lowest risk of bleeding compared with other DOACs and Warfarin
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
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
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 Naproxen Sodium (Naprosyn) are the lowest risk of Upper Gastrointestinal Bleeding
Elderly (especially over age 70 years) with Relative Risk 5.6
Male gender (twice as common as women)
Acid suppression therapy does not reduce bleeding risk
End Stage Renal Disease (esp. first year of Dialysis)
Selective Serotonin Reuptake Inhibitors
1. SSRIs increase GI Bleeding risk by 55%, especially when combined with NSAIDs or antiplatelet agents

Causes
Adults

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
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
Most commonly missed upper GI sources
1. Large Hiatal Hernia erosions
2. Arteriovenous Malformation
3. Peptic Ulcer Disease

Causes
Children

History

See Gastrointestinal Bleeding

Symptoms

Lightheadedness, Dizziness or Syncope
Abdominal Pain
Hematemesis with Coffee-ground Emesis
1. Distinguish from the frothy, smaller volume blood seen in Hemoptysis
2. Hematemesis is associated with higher mortality rates
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)

Signs

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)
Cardiovascular Exam
1. Signs of poor perfusion (e.g. thready pulses, cool and pale extremities, lethargy)
Respiratory Exam
1. Exclude Epistaxis source
2. Exclude Hemoptysis source
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
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

Labs

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
Blood Type and Cross-match
Coagulation Factors
1. Prothrombin Time (INR)
2. Partial Thromboplastin Time (PTT)
3. Platelet Count
4. Consider Fibrinogen level
5. Consider Viscoelastic Assay (if available)
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%

Imaging

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

Evaluation

See Upper GI Bleeding Score
See Rockall Risk Score
See Upper Endoscopy Evaluation of GI Bleeding

Management
Stabilization of the Actively Bleeding Patient

See Acute Gastrointestinal Bleeding Management
ABC Management
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
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)
Intensive Care Unit admission for significant bleeding or hemodynamically unstable
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]
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
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

Management
Specific Interventions

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
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]

Management
Acid Reduction

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]
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

Management
Very low risk patients

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]
Protocol
1. Home with follow-up within days
2. General measures as above

Management
Low risk patients

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
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

Management
Moderate risk patients

Indications
1. Tachycardia persists despite Resuscitation
2. Blood Products required >2 PRBC
3. Active comorbid condition
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

Management
High risk patients

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
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

Management
Refractory and Recurrent Bleeding

Indications
1. Persistent or recurrent bleeding despite EGD
2. See Upper Endoscopy Evaluation of GI Bleeding
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

Management
Disposition

See prevention measures below
See Helicobacter Pylori management
Proton Pump Inhibitor once daily for 4-8 weeks
1. Increase to twice daily for first 2 weeks for high risk lesions
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)
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

Management
Cause Specific Approaches

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
Mallory Weiss Tear
1. Most spontaneously heal
2. However, bleeding related mortality approaches that of Peptic Ulcer Bleeding

Management
Restarting Anticoagulants and Antiplatelet agents after Upper GI Bleed

Warfarin
1. Restart 7-15 days after bleeding (7 days if high thromboembolic risk)
Non-Vitamin K Antagonist Oral Anticoagulant (e.g DOACs, Apixaban )
1. Change to Apixaban from other DOACs
2. If already taking Apixaban, decrease dose
Aspirin
1. May restart in 3 days (immediately at 0 days, if low bleeding risk )
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)

Prevention

See Helicobacter Pylori management
See GI Prophylaxis
Avoid NSAIDs
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)
Tobacco Cessation
Avoid Alcohol

Prognosis
Outcomes

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%
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)

Prognosis
Predictors

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)
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

References

Azim (2023) Crit Dec Emerg Med 37(4): 23-9
Spangler, Swadron, Mason and Herbert (2016) EM:Rap C3, p. 1-11
Gupta (1993) Med Clin North Am 77(5):973-92 [PubMed]
Fallah (2000) Med Clin North Am 84(5):1183-208 [PubMed]
Longstreth (1995) Am J Gastroenterol 90(2):206-10 [PubMed]
Peter (1999) Emerg Med Clin North Am 17(1):239-61 [PubMed]
Stanley (2019) BMJ 364:1536 +PMID:30910853 [PubMed]
Terdiman (1998) Postgrad Med 103(6):43-64 [PubMed]
Wang (2010) Ann Surg 215(1):51-8 [PubMed]
Wilkins (2012) Am Fam Physician 85(5): 469-76 [PubMed]
Wilkins (2020) Am Fam Physician 101(5):294-300 [PubMed]
Zuckerman (2000) Gastroenterology 118:201-21 [PubMed]