Hepatic Encephalopathy

1. Hepatic Encephalopathy Presented by: Mohannad A. Almikhlafi Ahmed M. Aljabri Supervised by: Prof. Dr.MahmoodAbdulmenem

2. Key Points • Epidemiology & definition • Etiology • Pathogenesis • Stages of H.E. • Sign and Symptoms • Diagnosis • Ascites • Case presentation

3. 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.

4. Definition It is a neuropsychiatric disturbances caused by liver disease.

5. 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.

6. 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.

7. Pathogenesis

8. Precipitaiting factors • Infections • Constipation • GIT bleeding • Excess protein intake • Hypokalemia, Metabolic-alkalosis (vomiting, diarrhea , dehydration) • Azotemia • Drugs( Diuretic, sedative ,hypnotic) • Renal failure.

9. 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

10. 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.

11. Cont. • Caput Medusa. • Fetor hepaticus . • Jaundice , itching. • Hepatomegaly , splenomegaly. • Flapping tremors. • Gynecomastia. • Melena , fatigue.

12. Diagnosis • Laboratory: CBC, LFT, Kidney function, serum electrolyte. • Radiology. • Liver biopsy.

13. 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)

14. Radiology • X-ray , CT, US & radioisotope scan. • biopsy • Definitive diagnosis depend on biopsy & microscopic interpretation.

15. 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.

16. 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).

17. Precipitating factors: • ↑Protein load in the intestine(↑protein intake, Constipation & GIT bleeding) • Electrolyte disturbance(hypokalemia-metabolic alkalosis) • Dehydration • CNS depressant drugs(hypnotics , opioids &sedatives)

18. Management Of HE

19. Goal of therapy • To reduce nitrogen load in the GIT • To correct any metabolic or electrolyte disturbance that may arise.

20. 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.

21. Maximum laxative effect appear at 2-4 daysEnema should be used during the initial 2 days SE: Flatulence , Diarrhea , dehydration, Gaseous distention.

22. 2.Antibiotics: • Neomycin • 1g/6hrs • SE: ototoxicity and nephrotoxicity • Metronidazole • 400 mg /6hrs • SE: Headache, ataxia, pancreatitis .

23. Contraindicated Drugs • Execs diuretic • Sedative & hypnotic drugs • Drug have toxic effect on the liver

24. 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

25. Management Of Ascites

26. Goal of therapy: 1- Removal of ascitic fluid. 2- Prevention of complication esp. SBP. 3- Correction of any serum biochemical abnormality.

27. 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 .

28. B- Diuretics: Diuresis should be gradual because hypokalemia or intravascular volume depletion caused by aggressive therapy compromised renal function, and hepatic encephalopathy.

29. 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.

30. 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.

31. 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

32. Precautions: • Hyperkalemia continuous serum potassium monitoring. • Urea and creatinine should be measured because spironolactone is contraindicated in renal failure.

33. 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.

34. 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.

35. 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.

36. 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.

37. Case presentation

38. 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.

39. 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.

40. 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

41. 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

42. 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

43. 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

44. 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

45. 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

46. 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

47. 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.

48. 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.

49. 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).

50. 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.