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
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:

4- Drowsiness,
Stage 3-
1-
2- Frank
Mild coma personality
Somnolence
confusion,, disorientation,
decreased
changes,
attention,
marked
intermittent
irritability,
confusion,
reversedspeech
disorientation
slurred sleep pattern.
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:
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 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 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
 13/5

Vital signs:
RR: 22 BP: 135/78
Pulse: 75 bpm Temp: 36.22 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:
o General condition: Disorientation &
Confusion
o Skin: No jaundice, no skin rash
o CVS: S1 + S2 + 0
o CNS: Normal reflexes, flapping tremors
o Chest: Bilateral basal crepitation
o 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:
o Omeprazole 20 mg PO OD
o Propranolol 20 mg BID
o Lactulose 30 mL PO QID
o Glimepiride 3 mg PO OD
o Metformin 500 mg PO BID
 Assessment
o 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/enc
y/article/000302.htm

http://emedicine.medscape.com/article
/186101-overview

http://www.gastroresource.com/gitextb
ook/en/chapter14/14-13.htm

http://www.umm.edu/ency/article/00030
2.htm