Hepatic Encephalopathy

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Hepatic Encephalopathy. Presented by: Mohannad A. Almikhlafi Ahmed M. Aljabri Supervised by: Prof. Dr.Mahmood Abdulmenem. Key Points. Epidemiology & definition Etiology Pathogenesis Stages of H.E. Sign and Symptoms Diagnosis Ascites Case presentation .
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Hepatic Encephalopathy Presented by: Mohannad A. Almikhlafi Ahmed M. Aljabri Supervised by: Prof. Dr.MahmoodAbdulmenem Key Points
  • Epidemiology & definition
  • Etiology
  • Pathogenesis
  • Stages of H.E.
  • Sign and Symptoms
  • Diagnosis
  • Ascites
  • Case presentation
  • Epidemiology
  • Cirrhosis affects 3.6 per 1000 adults in the United States and is responsible for 26,000 deaths per year.
  • Chronic liver disease represents the fourth leading cause of deaths among all races and sexes in the 45- to 54-year-old age group, exceeded only by malignancy, heart disease, and accidents.
  • Definition It is a neuropsychiatric disturbances caused by liver disease. Pathogenesis
  • HE is due to cerebral intoxication by nitrogenous compounds produced by bacteria in GIT .
  • Several nitrogenous compounds have been implicated as causes of HE : they include ammonia , false transmitters & fatty acids.
  • Pathogenesis
  • In the presence of poor hepatocellular function ,nitrogenous compound in the portal venous blood pass in to the systemic circulation with out being metabolized by the liver, & cross BBB.
  • Pathogenesis Precipitaiting factors
  • Infections
  • Constipation
  • GIT bleeding
  • Excess protein intake
  • Hypokalemia, Metabolic-alkalosis (vomiting, diarrhea , dehydration)
  • Azotemia
  • Drugs( Diuretic, sedative ,hypnotic)
  • Renal failure.
  • Stages of HE:
  • Stage 4- Frank coma
  • Stage 1- Mild confusion, decreased attention, irritability, reversed sleep pattern. Stage 2- Drowsiness, personality changes, intermittent disorientation Stage 3- Somnolence , disorientation, marked confusion, slurred speech Sign and Symptom Some of the following signs and symptoms may occur in the presence of cirrhosis or as a result of the complications of cirrhosis:
  • Abdominal swelling.
  • Nausea ,vomiting.
  • Dark urine.
  • Sleep disturbances.
  • Cont.
  • Caput Medusa.
  • Fetor hepaticus .
  • Jaundice , itching.
  • Hepatomegaly , splenomegaly.
  • Flapping tremors.
  • Gynecomastia.
  • Melena , fatigue.
  • Diagnosis
  • Laboratory: CBC, LFT, Kidney function, serum electrolyte.
  • Radiology.
  • Liver biopsy.
  • Laboratory tests 1- Hypoalbuminemia 2- Elevated prothrombin time 3- Thrombocytopenia 4- Elevated alkaline phosphates 5- Elevated aspartate transaminase (AST) alanine transaminase (ALT) 6- Elevated glutamyl transpeptidase (GGT)
  • Radiology
  • X-ray , CT, US & radioisotope scan.
  • biopsy
  • Definitive diagnosis depend on biopsy & microscopic interpretation.
  • Ascites
  • Is the pathologic accumulation of lymph fluid within the peritoneal cavity.
  • It is one of the earliest and most common presentations of cirrhosis.
  • Spontaneous bacterial peritonitis (SBP) may occur & have a high mortality rate.
  • Cont. It is due to :
  • Portal hypertension.
  • Hypoalbuminemia (due to failure of liver to form plasma protein).
  • Hyperaldosteronism(due to failure of liver to inactivation of aldosterone).
  • Precipitating factors:
  • ↑Protein load in the intestine(↑protein intake, Constipation & GIT bleeding)
  • Electrolyte disturbance(hypokalemia-metabolic alkalosis)
  • Dehydration
  • CNS depressant drugs(hypnotics , opioids &sedatives)
  • Management Of HE Goal of therapy
  • To reduce nitrogen load in the GIT
  • To correct any metabolic or electrolyte disturbance that may arise.
  • 1.Lactulose:
  • Inhibit intestinal bacteria
  • absorption of nitrogenous waste product
  • Laxative effect to remove nitrogenous wastes. Dose: 20-60 ml 3 times/day, Titrated to achieve 2-4 soft stools / day without diarrhea.
  • Maximum laxative effect appear at 2-4 daysEnema should be used during the initial 2 days SE: Flatulence , Diarrhea , dehydration, Gaseous distention.
  • 2.Antibiotics:
  • Neomycin
  • 1g/6hrs
  • SE: ototoxicity and nephrotoxicity
  • Metronidazole
  • 400 mg /6hrs
  • SE: Headache, ataxia, pancreatitis .
  • Contraindicated Drugs
  • Execs diuretic
  • Sedative & hypnotic drugs
  • Drug have toxic effect on the liver
  • Parameters used to monitor Therapeutic effect: 1-Biochemical parameters: Serum ammonia Serum electrolyte levels BUN
  • 2-Clinical parameters:
  • Improvement of symptoms & physical signs of HE
  • Management Of Ascites Goal of therapy: 1- Removal of ascitic fluid. 2- Prevention of complication esp. SBP. 3- Correction of any serum biochemical abnormality. Lines of Therapy A- Rest with restriction of sodium (only 2g/d) - Serum biochemical analysis determine if fluid restriction is needed. - Restriction of water should be done if hyponatremia is present . B- Diuretics: Diuresis should be gradual because hypokalemia or intravascular volume depletion caused by aggressive therapy compromised renal function, and hepatic encephalopathy. Patients have increased serum aldosterone due to: -Increased production due to decreased intravascular volume and decreased renal perfusion Activation of RAAS. -Decreased excretion due to hepatic impairment decreased metabolism. 1- Spironolactone: Block aldosteroneredeptors. Indication: Diuretic of choice in treatment of ascites and edema due to liver cirrhosis. Dose: 100-400mg once daily. Dose Adjusted after 2 days at least because maximum effect is after 2-4 days. Adjusted according to: -Clinical parameters effective dose decreases weight by 0.5kg/d (if ascites) and 1kg/d (if ascites and lower limb edema). -Biochemical parameters hyperkalemia, hyponatremia, urea and creatinine to avoid renal impairment Precautions:
  • Hyperkalemia continuous serum potassium monitoring.
  • Urea and creatinine should be measured because spironolactone is contraindicated in renal failure.
  • 2- Furosemide:
  • If spironolactone was inadequate or no response or appearance of side effects, furosemide (20-40mg/d) is added.
  • We start with both in initial doses and increase dose by same rate.
  • C- Antibiotics:
  • Third generation cephalosporin e.g.cefotaxime 1g/12hr IV for 1 week.
  • Quinolones e.g. oral Ofloxacin or norfloxacin 400mg BID for 1 week.
  • D- Paracentesis:
  • Which is removal of ascitis fluid (4- 6L) from the abdominal cavity with a needle or catheter.
  • Indicated in tense ascites.
  • Fluid is rich in albumin  for every 1 L removed give 6-8g albumin.
  • E- TIPS (transjugularintrahepaticportosystemic shunt)
  • Indicated If paracentesis is not effective
  • Nonsurgical technique to place one or more stents between the hepatic vein and the portal vein.
  • Case presentation I.A. is a 62 years old Egyptian maleadmitted to ED of KAUH on13 May, 2009. Confusion since today morning, disorientation, lethargy, abdominal pain, constipation.
  • Past medical history: DM ( on OHG agent), CLD(LC, Hematemesis), HCV, HBV, Portal hypertension, post spleenoctomy, esophagitis.
  • Family history: No family history of similar condition.
  • Home medications:
  • Glimepiride 3 mg PO OD
  • Metformin 500 mg PO BID Furosemide 40 mg PO OD Lactulose 30 mL PO TID ( D/C 4 days before admission)
  • Diagnosis: Hepatic encephalopathy
  • 13/5 Vital signs: RR: 22 BP: 135/78 Pulse: 75 bpm Temp: 36.22º C Lab: Na: 144 mmol/L K: 4.1 mmol/L Bilirubin: 7 umlo/L Cr: 100 umol/L Glucose: 12.1 mmol/L CK: 2468 IU/L Albumin: 22 g/L ALT: 69 U/L AST: 110 U/L GGT: 92 U/L Troponin-I 1.6 ug/l Examination:
  • General condition: Disorientation & Confusion
  • Skin: No jaundice, no skin rash
  • CVS: S1 + S2 + 0
  • CNS: Normal reflexes, flapping tremors
  • Chest: Bilateral basal crepitation
  • Abdomen: Distended, soft, lax, hepatomegally, mild ascitits
  • PLAN Lab: CBC, LFT, PT, APTT, U&E, PCR HBV DNA & HCV RNA. Medications: Furosemide 40 IV BID Lactulose 30 mL PO TID Lactulose enema 300 mL PR OD Ceftriaxone 2gm IV OD Insulin sliding scale S.C Q 6hr Ornithine (hepamerz®)1 Sachet 14/5
  • Currently ptn is conscious, oriented, free of pain, no abdominal pain, no tenderness, no melena, mild ascites.
  • Normal vital signs
  • Propranolol 10 mg PO BID
  • Albumin 100 mL IV OD for 2 days
  • Omeprazol 40 mg PO OD
  • 16/5 Patient is stable, conscious, oriented. Plan: D/C Ceftriaxone, ISS Adjustment for Lactulose frequency TID QID & for Furosemide route of administration IV PO Glimepiride 3 mg PO OD Metformin 500 mg PO BID Discharge tomorrow 17/5
  • Patient was discharged.
  • Discharge medications:
  • Omeprazole 20 mg PO OD
  • Propranolol 20 mg BID
  • Lactulose 30 mL PO QID
  • Glimepiride 3 mg PO OD
  • Metformin 500 mg PO BID
  • Assessment
  • Furosemide is not prefer because of: Potent & rapid acting (ptn had mild ascites) hypovolemia aggravate HE SE: hypokalemia (metabolic alkalosis)
  • Spironolactone is the drug of choice for ascites (mild diuresis, antagonize aldosterone) starting with 100 mg OD titrated to 300 mg/day if no response.
  • Norfloxacin is the prophylactic drug of choice for SBP.
  • Lactulose effect will start after 2-3 days, so, giving lactulose enema is a good decision.
  • Therapeutic dose of Lactulose is the dose that produce 4 soft stool without diarrhea.
  • The right Propranolol dose is the dose that decrease pulse baseline by 25% (but not ˂ 60 bpm).
  • Diuretics and beta-blockers may increase the risk of hyperglycemia so, carful monitoring for blood sugar level.
  • Beta-blockers may mask symptoms of hypoglycemia such as tremors and tachycardia, other symptoms: headache, dizziness, drowsiness, nausea, hunger, and sweating may be unaffected.
  • Laxatives can cause significant losses of fluid and electrolytes, including Na, K, Mg and zinc, that may be additive to those of diuretics, so carful monitoring for these parameters & any signs of fluid & electrolyte depletion.
  • Most complaints about lactulose are nausea (due to sweet taste of the drug), diarrhea, flatulence.
  • THANKS electrolytes, including Na, K, Mg and zinc, that may be additive to those of diuretics, so carful monitoring for these parameters & any signs of fluid & electrolyte depletion. Reference electrolytes, including Na, K, Mg and zinc, that may be additive to those of diuretics, so carful monitoring for these parameters & any signs of fluid & electrolyte depletion.
  • http://www.nlm.nih.gov/medlineplus/ency/article/000302.htm
  • http://emedicine.medscape.com/article/186101-overview
  • http://www.gastroresource.com/gitextbook/en/chapter14/14-13.htm
  • http://www.umm.edu/ency/article/000302.htm
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