Esophageal Varices

See Also

Epidemiology

Incidence: 30-70% of Cirrhosis cases
Bleeding occurs within first year of Esophageal Varices diagnosis in 30% of cases

Pathophysiology

See Portal Hypertension
Complication of Cirrhosis (and Portal Hypertension)
1. Typically involves distal 2-5 cm of Esophagus
2. Correlated with severity of disease

Evaluation
Screening Protocol

Initial: Endoscopy for all patients with Cirrhosis
Repeat screening
1. No Varices: Repeat every 3 years
2. Small Varices: Yearly
3. Large Varices: Per endoscopist discretion

Management
Acute Variceal Bleeding Medical Management

See Gastrointestinal Bleeding Management
Notify GI or surgery on presentation, to ready for emergent endoscopy
See Upper GI Bleed
1. Proton Pump Inhibitors are not recommended for Variceal Bleeding
ABC Management
1. Consider Endotracheal Intubation to prevent blood aspiration
Replace blood and Coagulation Factors as needed
1. Consider Tranexamic Acid (TXA)
2. Packed Red Blood Cell (pRBC) Transfusion Indications
  1. Restrictive transfusion strategy is preferred (keeping Hemoglobin >7 g/dl) at tertiary centers
  2. However, remote hospitals should initiate blood pruducts per local discretion
  3. Target mean arterial pressure (MAP) >65 mmHg
3. Massive Transfusion Protocol
  1. Indicated if 3 or more units of pRBC are required within an hour
4. Platelet Trasfusion Indications
  1. Platelet Count <50,000/uL
  2. Massive Transfusion Protocol
5. Other Blood components to consider
  1. Fresh Frozen Plasma
  2. Prothrombin Complex Concentrate (PCC4)
  3. Factor 7 (also in PCC4)
  4. Vitamin K
Upper Endoscopy emergently (within 12 hours)
1. See below under invasive management
Vasoactive agents
1. Continue for 3 to 5 days
2. Do not decrease mortality or re-bleeding risk
  1. Gotzsche (2008) Cochrane Database Syst Rev (3): CD000193 [PubMed]
3. Octreotide or Sandostatin (preferred)
  1. Decreases splanchnic Blood Flow (slows Variceal Bleeding)
  2. Dose: 50-100 mcg IV bolus, then 50 mcg/hour
  3. Long-acting Somatostatin analog
  4. Preferred vasoactive agent in Upper GI Bleed
    1. Avgerinos (1995) J Hepatol 22(2):247-8 [PubMed]
4. Intravenous Vasopressin
  1. Vasopressin 0.3 to 0,.4 units/min
  2. If not hypotensive, consider with Nitroglycerin (Risk of coronary ischemia)
  3. Stop for cerebral, cardiac, intestinal or extremity ischemia
Non-selective Beta Blocker
1. Examples: Propranolol, Nadalol, Timolol
2. Start when stable and continue indefinitely (see dosing below under prevention)
3. Titration of dose endpoint
  1. Heart Rate at 25% reduction from baseline or
  2. Heart Rate 55 beats per minute or
  3. Adverse Beta Blocker related symptoms
Prophylactic Antibiotics (per AASLD)
1. Reduces rebleeding, Spontaneous Bacterial Peritonitis (SBP), and mortality rates
2. Higher infection risk in Child-Pugh Class B-C, longterm Proton Pump Inhibitor, SBP Prophylaxis
3. Start at bleeding presentation and continue for up to 5-7 days
4. First-Line Antibiotic options
  1. Norfloxacin 400 mg orally twice daily OR
  2. Ciprofloxacin 400 mg IV (or 500 mg orally twice daily) every 8 to 12 hours
5. Alternative Antibiotic options
  1. Ceftriaxone 2 gram IV every 24 hours (or other third generation cephaloporin)
6. References
  1. Moon (2016) Clin Gastroenterol Hepatol 14:1629-37 +PMID:27311621 [PubMed]
  2. O'Leary (2015) Clin Gastroenterol Hepatol 13:753-9 +PMID:25130937 [PubMed]
Balloon tamponade
1. See Esophageal Balloon Tamponade (Sengstaken-Blakemore Tube, Linton Tube)
2. Tamponade Varices in refractory cases (60-90% effective)
  1. Esophageal Varices
  2. Gastric fundus Varices
3. Rebleeding occurs in up to 50% of cases
  1. More definitive therapy needed after bleeding stops
4. High complication rate (15%)
  1. Perforation
  2. Aspiration
  3. Pressure-induced ulceration
5. Balloon types
  1. Sengstaken-Blakemore Tube
  2. Linton-Nachlas tube
  3. Minnesota tube

Management
Acute Variceal Bleeding Invasive Management

Endoscopic ligation or banding (preferred, first-line measure)
1. Recommended within 12 hours of onset
2. Erythromycin recommended before procedure
3. Ligation is superior to sclerotherapy
  1. Laine (1995) Ann Intern Med 123(4): 280-7 [PubMed]
4. Successful banding
  1. Repeat endoscopy at 3 and 6 months and annually
  2. Banding may be repeated at repeat endoscopy
5. Unsuccessful banding (continued bleeding)
  1. Balloon Tamponade (see above) and
  2. TIPS and other interventions as below
Transjugular intrahepatic Portosystemic Shunt (TIPS)
1. Shunt from hepatic vein to intrahepatic Portal Vein to lower portal pressure
2. Commonly effective measure in Variceal Bleeding
3. Preventive of future rebleeding events
Emergency Surgical portacaval shunts
1. Rarely effective and high mortality rate

Management
Primary Prevention of Variceal Bleeding

See Portal Hypertension
Indications
1. Hepatic Vein Pressure Gradient (HPVG) >5 mmHg
2. Endoscopic criteria
  1. Large Esophageal Varices
  2. Small Esophageal Varices
    1. High Child-Pugh Score
    2. Varices with red wale markings
Contraindications
1. Do not use non-selective Beta Blockers during acute bleeding episodes (until stable)
Efficacy
1. Reduce risk of bleeding from 45% to 22%
2. Do not reduce overall mortality from Esophageal Varices
Mechanism
1. Reduce portal pressure gradient
2. Reduce azygous Blood Flow and variceal pressure
Agents (target Heart Rate reduction 20 to 25%)
1. Goal: Reduce HPVG by 20% or <12 mmHg
2. Propranolol (preferred first line agent)
  1. Start at 10 mg orally three times daily
  2. Minimum effective dose: 40 mg orally twice daily
  3. Titrate to 80 mg orally twice daily if needed
3. Nadolol 20 mg orally daily
4. Isosorbide Mononitrate (alternative)
  1. Use if Propranolol contraindicated
  2. Dose: 20 mg orally twice daily
Surgery: Esophageal banding (Variceal band ligation)
1. As effective as Propranolol in bleeding prevention
2. Fewer adverse effects than medication management
3. Lui (2002) Gastroenterology 123:735-44 [PubMed]

Prevention
Secondary prevention (prior episode of bleeding)

Isosorbide Mononitrate 20 mg PO bid
Esophageal banding (Variceal band ligation)
Sclerotherapy to Varices (variable efficacy)
Transjugular intrahepatic Portosystemic Shunt (TIPS)
LeVeen Shunt (not recommended due to high mortality)
Liver Transplant

Prognosis

Predictors of mortality with Variceal Bleeding
1. Active bleeding during endoscopy
2. Encephalopathy
3. Ascites
4. Serum Bilirubin increased
5. Aspartate Aminotransferase increased
6. Prothrombin Time increased
7. Graham (1981) Gastroenterology 80:800-9 [PubMed]
Rebleeding Events after initial bleeding episode
1. Highest risk in first 72 hours
2. Rebleeding risk is 50% in first 10 days
3. Risks for re-bleeding
  1. Age over 60 years
  2. Renal Failure
  3. Large Esophageal Varices
  4. Severe initial bleeding with Hemoglobin < 8 g/dl
Overall Risk of esophageal varice bleeding: 10-30%/year
Risk of bleeding from large Varices: 40 to 45% per year
1. Higher risk with Varices with red wale markings
2. Higher risk with advanced Child-Pugh Score
Risk of death from each bleeding episode
1. In hospital event: 15%
2. Out of hospital event: Approaches 50%

References

Spangler, Swadron, Mason and Herbert (2016) EM:Rap C3, p. 1-11
Swaminathan and Weingart in Herbert (2020) EM:Rap 20(6):8-10
Swencki (2015) Crit Dec Emerg Med 29(11):2-10
Hegab (2001) Postgrad Med 109(2):75-89 [PubMed]
Keating (2022) Am Fam Physician 105(4): 412-20 [PubMed]
Villaneuva (1996) 334:1624-9 [PubMed]
De Franchis (2004) Gastroenterology 126:1860-7 [PubMed]