Acute variceal bleeding (AVB) is a severe complication of portal hypertension (PHT) and causes 70% of all upper gastrointestinal (GI) bleeding episodes in patients with liver cirrhosis. Thus, it should be suspected in any patient with cirrhosis and GI bleeding. The diagnosis is established by emergency endoscopy when one of the following is observed: active variceal bleeding (blood spurting or oozing from a varix), a white nipple or clot adherent to a varix, or the presence of blood in stomach and varices without other potential sources of bleeding.
Mortality resulting from AVB has greatly decreased in the last 3 decades to the current rate of 15% to 20%. This is probably because of effective treatments [endoscopy, vasoactive drugs, and transjugular intrahepatic portosystemic shunt (TIPS)] as well as improved general medical care (antibiotic prophylaxis, careful replacement of volemia, etc.).[2, 3] Most deaths in patients with AVB are not directly related to bleeding but rather are related to liver failure, infections, or hepatorenal syndrome (Fig. 1). The most consistent death risk indicators are the Child-Pugh classification (or its components), blood urea nitrogen or creatinine levels, active bleeding at endoscopy, hypovolemic shock, hepatocellular carcinoma, early rebleeding, bacterial infection, and renal failure.[1, 4] Thus, the management of AVB should be aimed not only at controlling bleeding but also at preventing early rebleeding, infection, and hepatic or renal derangement associated with GI bleeding.
AVB should be managed in an intensive care setting by an experienced medical team including well-trained nurses, clinical hepatologists, endoscopists, interventional radiologists, and surgeons. A lack of these facilities demands an immediate referral.
Initial resuscitation should follow the classic airway, breathing, and circulation scheme with the goal of maintaining or restoring appropriate tissue oxygenation. The airway should be secured immediately (with endotracheal intubation if necessary), especially in encephalopathic or hypovolemic patients because they are at risk of bronchial aspiration, which is further exacerbated by endoscopic procedures.
Blood volume replacement is aimed at maintaining a systolic blood pressure of approximately 100 mm Hg to avoid prolonged hypotension; this is important for preventing infection and renal failure. Transfusions should be conservative with a targeted hematocrit level of 0.21% to 0.24% (hemoglobin level = 70-80 g/L), except for patients with rapid ongoing bleeding or ischemic heart disease. The roles of platelet transfusions and fresh frozen plasma remain unclear in AVB.
Infection is a strong prognostic indicator in patients with AVB and may help to perpetuate bleeding, renal failure, and liver dysfunction (Fig. 2). The more frequent infections are spontaneous bacterial peritonitis (50%), urinary tract infections (25%), and pneumonia (25%). The use of prophylactic antibiotics (quinolones or ceftriaxone for advanced liver disease) is mandatory because they reduce the risk of rebleeding and mortality.
The current therapeutic recommendation for AVB is based on a combination of vasoactive drugs and endoscopic therapy. Rescue therapies for failure include balloon tamponade and portal-systemic shunts (either surgical or TIPS; Fig. 3).
Vasoactive drugs reduce PHT by decreasing the portal blood flow. Terlipressin should be the first choice if it is available because it is the only drug that has been shown to improve survival. Somatostatin or its analogues (octreotide and vapreotide) are the second choice. Vasoactive therapy must be initiated as soon as AVB is suspected (ideally during the transfer to the hospital) because early administration facilitates endoscopy and improves the control of bleeding and rebleeding. Vasoactive therapy should be maintained for at least 2 days.
Terlipressin is a long-acting derivative from vasopressin and has shown a better safety profile than vasopressin. It is the most active drug in diminishing portal pressure. It is usually initiated at a dose of 2 mg/4 hours for the first 48 hours, and it can be maintained for up to 5 days at a dose of 1 mg/4 to 6 hours. The most common side effect is abdominal pain; serious side effects (peripheral or myocardial ischemia) occur in less than 3% of the patients. Hyponatremia is a common side effect in patients with preserved liver function.
Somatostatin is administered as a bolus of 250 μg, which is followed by a 250-μg/hour infusion. The bolus can be repeated (up to 3 times) if bleeding is uncontrolled. Major side effects are rare. Minor side effects are nausea, vomiting, or hyperglycemia (in up to 30% of patients). The use of higher doses (500 μg/hour) causes a greater fall in the hepatic venous pressure gradient (HVPG), and this results in increased efficacy in patients with active variceal bleeding at endoscopy.
Octreotide is a somatostatin analogue with a longer half-life. It is usually given as a bolus of 50 μg, which is followed by an infusion of 25 to 50 μg/hour. The safety profile of octreotide is close to that of somatostatin.
Endoscopic therapy should be performed early after admission (preferably within the first 12 hours) and after the initial resuscitation when the patient is stable. Sclerotherapy and endoscopic band ligation (EBL) are both effective in the control of bleeding, although a meta-analysis has favored EBL in the initial control of bleeding, and it is associated with fewer adverse events and improved mortality.[10, 11] Therefore, EBL is the endoscopic therapy of choice, although sclerotherapy is acceptable if EBL is not feasible or is technically difficult.
Rescue Therapies and Role of Early TIPS Placement in High-Risk Patients
In 10% to 20% of patients, AVB is unresponsive to the initial combined treatment. If the bleeding is mild and the patient is stable, a second endoscopic treatment may be attempted. If this fails or the bleeding is severe, a derivative treatment (TIPS or surgical shunt) should be offered before further deterioration. TIPS placement with polytetrafluoroethylene (PTFE)-covered stents is the first choice because it is less invasive and has a better cost-effectiveness ratio. However, despite its high efficacy in controlling bleeding (approximately 95%), the use of TIPS as a rescue therapy is associated with a high mortality rate (30%-50%) because of the severe disease conditions that patients exhibit when it is applied.
Recent data have shown that early TIPS placement in patients with a high risk of treatment failure is associated with improved outcomes when the standard treatment with drugs and EBL is applied. These high-risk patients, who are defined by an HVPG of 20 mm Hg or more, Child class B plus active bleeding at endoscopy, or Child C class (up to 13 points), benefit from early TIPS placement within the first 72 hours (preferably 24 hours). In comparison with standard care, early TIPS placement decreases the rebleeding rate and mortality without increasing the encephalopathy rate,[13, 14] and it currently is recommended as the first-choice treatment for these high-risk patients (Fig. 4).
Balloon tamponade achieves hemostasis in 60% to 90% of variceal bleeding cases, but it should be used only in patients with massive bleeding as a temporary bridge (<24 hours) to derivative treatment. The use of esophageal covered stents is a promising alternative for refractory bleeding that currently is under evaluation.