35 36 37 (2) Portal Hypertension and Bleeding Varices.docx

Portal Hypertension and Bleeding Varices Learning Objectives For the following complications of cirrhosis, describe: Pathophysiology Non-pharmacologic management strategies Pharmacologic management strategies, including dosing Primary and secondary prophylaxis, including dosing, when applicable Comp...

Portal Hypertension and Bleeding Varices Learning Objectives For the following complications of cirrhosis, describe: Pathophysiology Non-pharmacologic management strategies Pharmacologic management strategies, including dosing Primary and secondary prophylaxis, including dosing, when applicable Complications: portal hypertension, varices, ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, and hepatorenal syndrome Describe, in detail, the mechanism of action of beta blockers in portal hypertension and varices Portal hypertension Definition High pressures within the hepatic portal vein Spleen, and pancreas Pathophysiology Causes Liver fibrosis due to cirrhosis causes resistance to blood flow in the portal vein Splanchnic vasodilation leads to arterial underfilling causing hypotension Hypotension causes a vasoconstriction reaction from the kidneys to increase sodium and water retention (RAAS) This leads to an increase in cardiac output to “increase” blood flow Diagnosis Pressure gradient >10 mmHg between the portal vein and inferior vena cava (IVC) (normal = 3 mmHg) Hepatic vein drains de-oxygenated blood from the liver into IVC Don't generally measure portal pressure – invasive Clinical presentation based on complications: ascites, esophageal & gastric varices, hepatorenal syndrome, spontaneous bacterial peritonitis Imaging: ultrasound, CT MRI showing cirrhosis, splenomegaly, collateral vessels, ascites Treatment Nonspecific beta blockers Reduce portal vein inflow by decreasing cardiac output and decreasing splanchnic blood flow ß-1 blockade decreased cardiac output ß-2 blockade splanchnic vasoconstriction, reduces portal flow and pressure unopposed alpha-1 splanchnic vasoconstriction Which all decrease portal blood flow Beta 2 and unopposed alpha-1 directly affect splanchnic system! Nadolol 20 mg PO daily titrate Propranolol 10 mg PO TID Propranolol undergoes extensive first pass, but less so in cirrhosis Titrate to 20-25% reduction in resting HR or absolute HR of 55-60, or until no longer tolerated Caution: Beta blockers can also increase risk of hepatorenal syndrome Varices Varices Definition: gastric or esophageal collateral vessels in response to increased intrahepatic pressure At risk when portal pressure exceeds hepatic vein pressure by >/= 12 mmHg Each episode of variceal bleeding 25-30% risk of death; 70% chance of recurrence within 6 months Diagnosis Endoscopy – gold standard Grade 1 varices: small (<5mm diameter) Grade 2 varices: large (>5mm diameter) Varices Primary prophylaxis Screening esophagogastroduodenoscopy (EGD) in all cirrhotic patients If no varices present, no pharmacologic ppx If varices present and at high risk for bleeding (Child-Pugh B or C), nonselective ß-blocker (propranolol, nadolol) ß-1 blockade decreased cardiac output; ß-2 blockade prevention of splanchnic vasodilation; unopposed alpha-1 splanchnic vasoconstriction Propranolol 10mg PO TID or nadolol 20mg QD titrate to 25% reduction in HR, HR of 55-60 beats/min, or max tolerable dose Bleeding varices Discontinue beta blockers in acute setting Airway management First, aggressive fluid resuscitation Colloids and blood products Goal: Hgb >8 g/dL and hemodynamic stability Then, endoscopic examination + pharmacologic agents Endoscopy Injection sclerotherapy (ethanolamine and sodium tetradecyl sulfate) Endoscopic band ligation – preferred; less complications than sclerotherapy Treatment of Bleeding Varices Banding Bleeding varices Vasoactive drugs slow/stop bleeding Somatostatin or octreotide Multiple proposed mechanisms: decreased post-prandial hyperemia, reduced splanchnic blood flow and pressure via inhibition of glucagon and other vasoactive peptides, direct local vasoconstriction Octreotide IV: bolus 50-100 mcg 25-50 mcg/hr for 3-5 days – preferred Somatostatin IV: bolus 250 mcg 250-500 mcg/hr for 3-5 days Vasopressin 0.2-0.4 units/minute titrate to a max of 0.8 units/minute + nitroglycerin 40 mcg/min titrate to a max of 400 mcg/minute for 24 h Vasopressin splanchnic vasoconstriction; can titrate to 0.8 units/min Only infuse for 24 hours max due to risk of adverse effects (cardiac and peripheral ischemia, arrhythmias, hypertension, bowel ischemia) Both drugs required + higher adverse event rate; used infrequently Antibiotics Use in patients with signs of ascites or infection decreased mortality Fluoroquinolones (ciprofloxacin 400 mg IV q12h, x7 days) If acutely bleeding select IV route Ceftriaxone 2g/day IV if high rates of FQ resistance Continue up to 7 days Varices – secondary prophylaxis ß-blockers (dose is patient-specific) Propranolol 20 mg PO TID Nadolol 20-40 mg PO daily Titrate to HR of 55-60 or 25% reduction Consider combination with isosorbide mononitrate if ß-blocker alone insufficient, although generally not recommended due to conflicting evidence and increased risk of adverse effects TIPS if medically unresponsive