Pathogenesis : The most important predictor of hemorrhage is the size of varices. There are two distinct phases in the course of variceal hemorrhage: an acute phase and a later phase in which there is a high risk of recurrent bleeding.
The acute phase starts with the onset of active hemorrhage. Patients with Child class C cirrhosis and large, actively spurting varices are less likely to achieve spontaneous hemostasis. In addition, a hepatic venous pressure gradient >20 mmHg is associated with a greater risk of continued or recurrent bleeding. Active infection is associated with an increased risk of bleeding and multiorgan failure, which forms the basis for the recommended use of antibiotics in patients with variceal bleeding.
Following cessation of active hemorrhage, there is a period of approximately six weeks in which there is a high risk of recurrent hemorrhage. The greatest risk is within the first 48 to 72 hours, and over 50% of all early rebleeding episodes occur within the first 10 days.
Supportive care of patients with active variceal hemorrhage
Hemodynamic resuscitation with crystalloids
PRBC to keep Hb>7. Avoid over transfusions as it can increase protal blood flow with resultant increased portal hypertension and bleeding.
Correct coagulopathy and thrombocytopenia as indicated. Keep platelet counts >50, INR<1.5 and fibrinogen>200.
Airway protection with intubation, in case of massive hemetemesis and suspected aspiration.
Ceftriaxone or Norfloxacin prophylaxis for 7 days in high-risk subjects with ascites
Treatment of varices: Hepatology. 2007 Sep;46(3):922-38 , Int J Hepatol. 2012;2012:750150 , Gut. 2015 Nov;64(11):1680-704.
Patients with acute variceal hemorrhage have a high incidence of infection, presumably due to bacterial translocation across the damaged variceal wall. Short-term (maximum seven days) antibiotic prophylaxis should be instituted in any patient with cirrhosis and variceal bleed. IV Ceftriaxone or Oral norfloxacin (400 mg twice daily) or intravenous ciprofloxacin is the recommended antibiotic for a total of 7 days.
Vasoactive medications decrease portal blood flow and are used for the treatment of acute variceal hemorrhage. They include vasopressin, somatostatin, and their analogs (terlipressin and octreotide, respectively.
Octreotide and somatostatin analogues: Octreotide inhibits the release of vasodilator hormones such as glucagon , indirectly causing splanchnic vasoconstriction and decreased portal inflow. Octreotide should be initiated as soon as variceal hemorrhage is suspected and continued for 72 hours after EGD.
Upper endoscopy, performed within 12 hours, should be used to make the diagnosis and to treat variceal hemorrhage either with endoscopic variceal ligation or sclerotherapy.
Transjugular intrahepatic portosystemic shunting (TIPS) is indicated in patients in whom bleeding from varices cannot be controlled or in whom bleeding recurs despite combined medical and endoscopic therapy.
Balloon tamponade should be used as a temporizing measure (maximum 24 hours) in patients with uncontrollable bleeding for whom a more definitive therapy (eg, TIPS or endoscopic therapy) is planned.
Vasopressin — Intravenous vasopressin (0.4 unit bolus followed by an infusion of 0.4 to 1 units/min) causes mesenteric artery vasoconstriction with resultant decreased portal venous blood flow and thereby decreasing protal vein pressures. However, it also causes extrasplanchnic vasoconstrictive properties and resultant myocardial, cerebral, bowel, and limb ischemia. Hence, it is rarely used for variceal bleed.
Transjugular intrahepatic portosystemic shunt — A transjugular intrahepatic portosystemic shunt (TIPS) is created by passing a needle catheter via the transjugular route into the hepatic vein and wedging it there. The needle is then extruded and advanced through the liver parenchyma to the intrahepatic portion of the portal vein and a stent is deployed.
Main indications are persistent bleeding after endoscopic interventions, recurrent variceal bleeding, hepatorenal syndrome, persistent hepatohydrothorax and refractory ascites.
Absolute contraindications for TIPSS include hepatic encephalopathy, acute heart failure, severe pulmonary hypertension and severe tricuspid regurgitation.
In patients with previous TIPSS and a variceal bleed, always check the patency of stent with an ultrasound.
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Prophylaxis against variceal hemorrhage in patients with cirrhosis:
An understanding of the pathophysiology of portal hypertension is important in a discussion of therapies aimed at reducing portal pressure. Portal pressure is equal to the product of the portal venous inflow and the resistance to outflow from the portal venous system. Outflow resistance from the portal system can be due to resistance to flow through the portal vein, liver, or hepatic vein; Normal portal pressure is between 5 and 10 mmHg.
Portal hypertension leads to the formation of porto-systemic collaterals. However, portal hypertension persists despite the development of these collaterals due to an increase in portal venous inflow that results from splanchnic arteriolar vasodilatation occurring concomitant with the formation of collaterals and insufficient portal decompression through collaterals as these have a higher resistance than that of the normal liver. Therefore, an increased portal pressure gradient results from both an increase in resistance to portal flow (intrahepatic and collateral) and an increase in portal blood inflow.
A normal pressure gradient between the portal and hepatic veins (the hepatic venous pressure gradient or HVPG) is 1 to 5 mm HG. Varices form when the pressure gradient between the portal and hepatic veins rises above 10 mmHg. Thus, therapies aimed at decreasing portal venous pressure may decrease the formation of varices and the risk of variceal hemorrhage.
Screeing for varices — All patients with cirrhosis should undergo screening for esophageal varices so that prophylactic therapy can be given to those with varices that are at increased risk for bleeding. In patients with compensated cirrhosis who do not have varices, screening is repeated every three years. In patients with small varices, screening is repeated every one to two years. In patients with decompensated cirrhosis (i.e., patients who have developed complications from cirrhosis), it is repeated every year or at the time of first decompensation.
Primary Prophylaxis— Primary prophylaxis refers to the prevention of a first variceal hemorrhage in a patient with varices. Typically, one of two approaches is used for primary prophylaxis: pharmacologic prophylaxis using a nonselective beta blocker, or endoscopic prophylaxis using endoscopic variceal ligation (EVL). Both beta blockers and EVL are superior to no treatment for the prevention of a first variceal hemorrhage.
Nonselective beta blockers such as propranolol and nadolol block the adrenergic dilatory tone in mesenteric arterioles, resulting in unopposed alpha adrenergic mediated vasoconstriction and therefore a decrease in portal inflow. Doses are titrated to maximum tolerated or once heart rate (HR) of 50–55 bpm is reached. Coreg is a promising alternative to nadolol or propranolol, but it is not yet recommended for routine prophylaxis. In addition to reducing portal venous inflow through nonselective beta blockade, the anti-alpha 1 adrenergic activity leads to reduced hepatic vascular tone and hepatic resistance. This in turn leads to a further reduction in portal pressure.
The AASLD recommends: Hepatology. 2007 Sep;46(3):922-38
Patients with cirrhosis who survive an episode of active variceal hemorrhage should receive therapy to prevent recurrence of variceal hemorrhage (secondary prophylaxis).
Combination of nonselective beta blockers plus endoscopic variceal ligation is the best option for secondary prophylaxis of variceal hemorrhage.
If a patient is treated with EVL, it should be repeated every 1–2 weeks until obliteration with the first surveillance EGD performed 1–3 months after obliteration and then every 6–12 months to check for variceal recurrence.
The nonselective beta blocker should be adjusted to the maximal tolerated dose. Endoscopic variceal ligation should be repeated every 1 to 2 weeks until obliteration, with the first surveillance EGD performed 1 to 3 months after obliteration and then every 6 to 12 months to check for variceal recurrence.
Transjugular intrahepatic portosystemic shunts should be considered in patients who have Child A or B cirrhosis and experience recurrent variceal hemorrhage despite combination pharmacologic and endoscopic therapy. After TIPS placement, monitor for patency of stent with serial ultrasounds.
Patients who are otherwise transplant candidates should be referred to a transplant center.