【正文】 oencephalogram in Hepatic Encephalopathy ELECTROENCEPHALOGRAM IN HEPATIC ENCEPHALOPATHY Minimal Hepatic Encephalopathy ? Occurs in 3070% of cirrhotic patients without overt hepatic encephalopathy ? Detected by psychometric and neuropsychological testing ? May improve with lactulose or synbiotics (probiotics and fermentable fiber) MINIMAL HEPATIC ENCEPHALOPATHY Minimal Hepatic Encephalopathy Abnormalities on testing ? Attention and cognitive deficits ? Visualspacial perception impaired ? Defects in visual constructive ability ? Impaired driving ability ? Evoked potentials and spectral electroencephalography abnormal MINIMAL HEPATIC ENCEPHALOPATHY – ABNORMALITIES ON TESTING Treatment of Hepatic Encephalopathy ? Identify and treat precipitating factor ? Infection ? GI hemorrhage ? Prerenal azotemia ? Sedatives ? Constipation ? Lactulose (adjust to 23 bowel movements/day) ? Protein restriction, shortterm (if at all) TREATMENT OF HEPATIC ENCEPHALOPATHY Hepatic Encephalopathy Precipitants GI bleeding Excess protein Sedatives / hypnotics TIPS Diuretics Serum K+ Plasma volume Azotemia Temp Infections HEPATIC ENCEPHALOPATHY PRECIPITANTS Actions of Lactulose Lactulose Lactic acid Decreased pH NH3 Ureaseproducing bacteria Increase cathartic effect NH3 NH4+ ACTIONS OF LACTULOSE Hepatic Encephalopathy Treatment: Summary Decrease ammonia production in gut: ? Lactulose ? Antibiotics ? Adjustment in dietary protein Increase ammonia fixation in liver: ? Ornithine aspartate ? Benzoate Shunt occlusion or reduction HEPATIC ENCEPHALOPATHY – TREATMENT SUMMARY Flumazenil 。 23:164 MAJOR CRITERIA IN DIAGNOSING HEPATORENAL SYNDROME Urine Sodium and Urine Volume are Minor Criteria in the Diagnosis of HRS Minor criteria ? Urine sodium 10 mEq/L ? Urine osmolality plasma osmolality ? Serum sodium 130 mEq/L ? Urine volume 500 ml/day ? Urine RBCs 50/HPF Arroyo et al., Hepatology 1996。 12:716 NORFLOXACIN REDUCES RECURRENCE OF SPONTANEOUS BACTERIAL PERITONITIS (SBP) Indications for Prophylactic Antibiotics to Prevent Spontaneous Bacterial Peritonitis ? Cirrhotic patients hospitalized with GI hemorrhage (shortterm) ? Norfloxacin 400 mg . BID x 7 days ? Patients who have recovered from SBP (longterm) ? Norfloxacin 400 mg . daily, indefinitely ? Weekly quinolones not remended (lower efficacy, development of quinoloneresistance) INDICATIONS FOR PROPHYLACTIC ANTIBIOTICS TO PREVENT SPONTANEOUS BACTERIAL PERITONITIS (SBP) 50 Characteristics of Hepatorenal Syndrome ? Renal failure in patients with cirrhosis, advanced liver failure and severe sinusoidal portal hypertension ? Absence of significant histological changes in the kidney (“functional” renal failure) ? Marked arteriolar vasodilation in the extrarenal circulation ? Marked renal vasoconstriction leading to reduced glomerular filtration rate CHARACTERISTICS OF HEPATORENAL SYNDROME (HRS) Two Types of Hepatorenal Syndrome Type 1 ? Rapidly progressive renal failure (2 weeks) ? Doubling of creatinine to or halving of creatinine clearance (CrCl) to 20 ml/min Type 2 ? More slowly progressive ? Creatinine mg/dL or CrCl 40 ml/min ? Associated with refractory ascites Arroyo et al., Hepatology 1996。 117:215 SERUMASCITES ALBUMIN GRADIENT (SAAG) IS HIGH IN PORTAL HYPERTENSIVE CAUSES OF ASCITES Activation of neurohumoral systems Site of Action of Different Therapies for Ascites Cirrhosis Intrahepatic resistance Arteriolar resistance (vasodilation) Sinusoidal pressure Ascites Sodium and water retention TIPS TIPS Diuretics PVS PVS Albumin LVP Effective arterial blood volume MECHANISM OF ACTION OF THE DIFFERENT THERAPIES FOR ASCITES Management of Unplicated Ascites Definition: Ascites responsive to diuretics in the absence of infection and renal dysfunction Sodium restriction ? Effective in 1020% of cases ? Predictors of response: mild or moderate ascites, Urine Na excretion 50 mEq/day Diuretics ? Should be spironolactonebased ? A progressive schedule (spironolactone ? furosemide) requires fewer dose adjustments than a bined therapy (spironolactone + furosemide) MANAGEMENT OF UNCOMPLICATED ASCITES Sodium Restriction ? 2 g (or g of dietary salt) a day ? Fluid restriction is not necessary unless there is hyponatremia (125 mmol/L) ? Goal: negative sodium balance ? Side effect: unpalatability may promise nutritional status Management of Unplicated Ascites MANAGEMENT OF UNCOMPLICATED ASCITES: SODIUM RESTRICTION 40 Diuretic Therapy Dosage ?Spironolactone