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

EpidemiologyCirrhosis 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.

DefinitionIt is a neuropsychiatric disturbances caused by liver disease.

• 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

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

Infections Constipation GIT bleeding Excess protein intake Hypokalemia, Metabolic-alkalosis

(vomiting, diarrhea , dehydration) Azotemia Drugs ( Diuretic, sedative ,hypnotic) Renal failure.

Precipitaiting factors

Stage 1- Mild confusion, decreased attention, irritability, reversed sleep pattern.Stage 2- Drowsiness, personality changes, intermittent disorientationStage 3- Somnolence , disorientation, marked confusion, slurred speech Stage 4- Frank coma

Stages of HE:

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- Hypoalbuminemia2- Elevated prothrombin time3- Thrombocytopenia4- Elevated alkaline phosphates5- 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: o Inhibit intestinal bacteria

o absorption of nitrogenous waste product

o Laxative effect to remove nitrogenous wastes.

Dose: 20-60 ml 3 times/day, Titrated to

achieve 2-4 soft stools / day without diarrhea.

o 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 ammoniaSerum electrolyte levelsBUN

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 TherapyA- 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 aldosterone redeptors.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 (transjugular intrahepatic portosystemic 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 male admitted to ED of KAUH on 13 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:o Glimepiride 3 mg PO OD o Metformin 500 mg PO BID Furosemide 40 mg PO OD Lactulose 30 mL PO TID ( D/C 4 days before admission)

• Diagnosis: Hepatic encephalopathy

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/LGlucose: 12.1 mmol/L CK: 2468 IU/LAlbumin: 22 g/L ALT: 69 U/LAST: 110 U/L GGT: 92 U/L Troponin-I 1.6 ug/l

13/5

Examination:o General condition: Disorientation &

Confusiono Skin: No jaundice, no skin rasho CVS: S1 + S2 + 0o CNS: Normal reflexes, flapping tremorso Chest: Bilateral basal crepitationo Abdomen: Distended, soft, lax,

hepatomegally, mild ascitits

PLAN

Lab: CBC, LFT, PT, APTT, U&E, PCR HBV DNA & HCV RNA.

Medications:Furosemide 40 IV BIDLactulose 30 mL PO TIDLactulose enema 300 mL PR ODCeftriaxone 2gm IV OD Insulin sliding scale S.C Q 6hrOrnithine (hepamerz®)1 Sachet

• Currently ptn is conscious, oriented, free of pain, no abdominal pain, no tenderness, no melena, mild ascites.

• Normal vital signs

Propranolol 10 mg PO BIDAlbumin 100 mL IV OD for 2 daysOmeprazol 40 mg PO OD

14/5

Patient is stable, conscious, oriented.

Plan:D/C Ceftriaxone, ISSAdjustment for Lactulose frequency TID QID & for Furosemide route of administration IV PO

16/5

Glimepiride 3 mg PO OD Metformin 500 mg PO BID

Discharge tomorrow

• Patient was discharged.

• Discharge medications:o Omeprazole 20 mg PO ODo Propranolol 20 mg BIDo Lactulose 30 mL PO QIDo Glimepiride 3 mg PO ODo Metformin 500 mg PO BID

17/5

Assessmento 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

Reference• http://www.nlm.nih.gov/medlineplus/en

cy/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