Variceal Bleeding
Susan Hongha T. Vu
C. Prakash Gyawali
I. GENERAL PRINCIPLES
A. Variceal bleeding is the most common lethal complication of cirrhosis.
B. The mortality of an acute bleeding episode is 20% at 6 weeks. The mortality approaches 40% at 2 years without liver transplantation.
C. Varices are present in 50% of patients with cirrhosis. This proportion increases with severity of liver disease, with 85% of Child-Pugh class C cirrhotics manifesting varices.
D. Spontaneous bleeding occurs at a rate of 5% to 15% per year.
E. While exsanguination remains the most immediate threat to life, mortality is often related to liver decompensation, aspiration, hepatic encephalopathy, hepatorenal syndrome, spontaneous bacterial peritonitis, septicemia, or alcohol withdrawal.
F. Survival is dependent on maintaining a high index of suspicion, aggressive resuscitation and stabilization of hemodynamics, early endoscopy for diagnosis and treatment, and prevention of superimposed complications and recurrent bleeding.
II. PATHOPHYSIOLOGY
A. Portal hypertension.
1. Portal hypertension is caused by intrahepatic resistance to portal venous flow from the hepatic fibrosis and architectural distortion that is seen in cirrhosis.
a. Other causes include portal vein and hepatic vein thrombosis, congenital hepatic fibrosis, and schistosomiasis.
2. Secondary hemodynamic changes associated with cirrhosis may contribute to increased portal pressure, including intrahepatic vasoconstriction and splanchnic arteriolar vasodilatation, decreased systemic vascular resistance, and increased cardiac output.
B. Development of varices.
1. Portosystemic collateral circulation develops to decompress the portal venous system. The most clinically significant locations where collaterals develop are the junctions of squamous and columnar mucosae (gastroesophageal, anal, and peristomal). These collateral vessels progressively enlarge to form varices when the portosystemic pressure gradient exceeds 10 mm Hg.
a. Esophageal varices are graded based on size, with large ones measuring ≥5 mm.
b. Gastric varices are classified as GOV (extension of esophageal varices) or IGV (isolated gastric varices in the absence of esophageal varices). GOV are treated similarly to esophageal varices, whereas there are limited data on managing IGV.
2. Risk factors for variceal rupture include large size, portosystemic pressure gradient ≥12 mm Hg, red wale marks, decompensated cirrhosis, and active infection.
III. DIAGNOSIS
A. Clinical presentation.
1. Variceal bleeding presents as hematemesis, melena, or hematochezia when brisk, and is often accompanied by varying degrees of hemodynamic instability.
2. Acute bleeding is self-limited in 40% to 50% of cases; however, these may represent sentinel bleeds that may precede massive bleeding with high rebleeding rates.
3. Nonvariceal sources of hemorrhage account for 10% to 50% of upper gastrointestinal bleeding in cirrhotics, so endoscopic verification is recommended.
B. Endoscopy.
1. The gold standard of diagnosing variceal bleeding is upper endoscopy.
2. Endoscopic findings supporting variceal bleeding include active bleeding, a fresh fibrin clot protruding from a varix, a nipple-like protrusion from a varix, red wale marks, or large varices with no other potential bleeding source.
3. Nonbleeding varices are more commonly found than bleeding varices on endoscopy; in such instances, in the absence of an alternate bleeding source, variceal band ligation is warranted because of the high rate of early recurrent bleeding.
IV. TREATMENT
A. Initial resuscitation.
1. Appropriate resuscitative efforts should be initiated without delay and before endoscopic evaluation. Endotracheal intubation may be required for airway protection, especially in the massively bleeding or obtunded patient. The patient should be hemodynamically stabilized with fluid resuscitation, transfusion, and vasopressors if needed.
2. Packed red blood cell transfusion, fresh frozen plasma, and platelet infusion may be necessary before endoscopy, depending on initial laboratory test results. When massive transfusions are necessary, the patient should be monitored for resultant hypocalcemia and thrombocytopenia.
3. Nasogastric aspiration may be necessary when the diagnosis of an upper gastrointestinal hemorrhage is in doubt; fears of trauma to a varix from the tube largely are unfounded, but good lubrication and careful technique should be exercised. Nasogastric aspiration also aids in clearing the stomach and esophagus of blood before upper endoscopy for better visualization.
B. Pharmacotherapeutic agents.
1. Octreotide is the pharmacotherapeutic vasoconstrictor of choice in acute variceal bleeding. It is a long-acting analog of somatostatin that inhibits the release of vasodilators, thus reducing splanchnic blood flow and portal pressure.
a. Octreotide should be initiated immediately when variceal bleeding is suspected. A bolus of 50 µg is followed by a continuous infusion of 50 µg/hour for 3 to 5 days.
b. Octreotide is effective in stopping active bleeding from varices and has an important role in the prevention of early recurrent bleeding after initial hemostasis.
c. Transient nausea and abdominal pain may occur, but significant adverse effects are rare.
d. Somatostatin is not available in the United States, but, when available, should be given as 250-µg bolus followed by 250-µg/hour infusion.
2. Vasopressin, when infused intravenously, is a potent vasoconstrictor that reduces splanchnic blood flow and portal pressure. It is currently used only when octreotide is not available.
a. The use of vasopressin is limited by adverse cardiac effects (including myocardial ischemia, arrhythmias, hypertension, and peripheral and bowel ischemia), which interfere with treatment in approximately 30% of patients.
b. The starting dose is 0.2 to 0.4 units/minute, titrated to a maximum of 0.8 units/minute for a maximum of 24 hours to minimize the side effects.
c. Concurrent intravenous nitroglycerin infusion, starting at 40 µg/minute and titrated to maintain a systolic blood pressure of 90 mm Hg, has been shown to reduce the systemic side effects of vasopressin.
d. Terlipressin, a synthetic analog of vasopressin with slower release, is not available in the United States, but has fewer side effects. It is administered at a dose of 2 mg every 4 hours and can be titrated down.
C. Endoscopic therapy.
1. Band ligation is the technique of choice for endoscopic control of bleeding varices. It is effective at controlling bleeding in 80% to 90% of cases.
