58738096 Fulminant Hepatic Failure

7/30/2019 58738096 Fulminant Hepatic Failure

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Fulminant Hepatic Failure

Nattaphol Uransilp


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Fulminant Hepatic Failure

Definition - Altered mental status with coagulopathy

in setting of acute liver disease. Hepatic

encephalopathy occurring within 8 weeks of

onset of illness.

- Hyperacute 28 days


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Etiology

Viral hepatitis Hepatitis A

Hepatitis B

Hepatitis C Hepatitis D - coinfects

with Hep B

Hepatitis E

Hepatitis non A-G

CMV, HSV

Toxins

Carbon tetrachloride

Phosphorus

Amanita phalloides(antidote penicillin andsilybin)

Industrial cleaningsolvents


4/27

Etiology

Drugs

Acetaminophen

Acetaminophen in Tx

doses with alcohol Idiosyncratic reaction -

halothane,sulfonamides,phenytoin, and others.

Vascular

Heart failure -centrolobular necrosis

Sinusoidal obstructionsecondary tometastatic disease

Budd Chiari

Veno-occlusive disease


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Clinical Presentation

Typically - nonspecific symptoms, nausea, malaise,

jaundice, altered mental status, coma all over a few

days.

Mental status changes often start with agitation,delusions, irritability before progressing to lethargy,

stupor, and coma.


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Clinical Presentation

Laboratory

Transaminases usually high (>1000)

Bilirubin usually mixed hyperbilirubinemia

Ammonia usually elevated

Coagulopathy with prolonged PT, PTT, decreased

factors

DIC

Respiratory alkalosis

Metabolic acidosis, increased lactate


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Hepatic Encephalopathy

Etiology uncertain.

Suggested mechanisms:

Depressed neural energy metabolism

Decreased hepatic clearance of neuro toxic

substances


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Grading System

Grade 0 - Normal

Grade I - Altered spatial orientation, sleep patterns, andaffect

Grade II - Drowsy but arousable, slurred speech,confusion, and asterixis

Grade III - Stuporous but responsive to painful stimuli

Grade IV - Unresponsive, with or without decorticate ordecerebrate posturing


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Cerebral Edema

Etiology uncertain - Correlated with degree of

encephalopathy. Occurs in 50 - 85% of patients with late

grade 3 to grade 4 encephalopathy.

Evidence of altered blood brain barrier Impaired cellular Na+K+ -ATP pump resulting in glial cell

edema

Inappropriate cerebral vasodilatation


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Cerebral Edema

Signs of increased ICP (may not be present until late)

Increased muscle tone

Increased DTRs

Dilated sluggish pupils

Hyperventilation

Cushing reflex (very late)


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Coagulopathy

Decreased production of liver clotting factors (all butfactor VIII), fibrinogen, ATIII, thrombocytopenia (splenicsequestration, DIC, other)

PT/PTT prolonged


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Metabolic Considerations

Hypoglycemia - decreased hepatic glycogen stores,

impaired gluconeogenesis results in hyperinsulin state

and insulin resistance. There is impaired glucose

homeostasis and hypoglycemia.

glucagon, insulin secondary to decreased hepaticclearance, leads to decreased insulin/glucagon ratio,

which favors catabolism.

Aromatic amino acids are increased, probably because

of decreased hepatic clearance.


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Hemodynamic Effects

Increased cardiac output

Decreased systemic vascular resistance

Decreased oxygen extraction ratio and decreased

consumption despite increased delivery Oxygen consumption often becomes supply

dependent.

Lactic acidosis secondary to anaerobic metabolismensues.

Lactic acidosis has been shown to herald a poorprognosis.


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Renal Effects

Renal failure common

Prerenal azotemia

Acute tubular necrosis

Hepatorenal syndrome


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Respiratory Effects

Respiratory failure can occur by several mechanisms: Neurogenic pulmonary edema

Fluid overload because of hyperaldosterone

and increased ADH with conservation of salt

and water ARDS secondary to sepsis or MSOF

Also, some have suggested capillary leak

affecting pulmonary and CNS vasculature


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Infectious Disease Issues

Impaired host defenses

Defective opsonic activity

Impaired PMN function

Impaired cell and humoral immunity

Decrease clearance of enteric organisms by hepaticRES

Ascites - good culture medium

Invasive lines, ETT, etc

Organisms:

Predominantly gram positive (strep andstaph), gram negatives also occur. 30% have fungal

infection.


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Treatment


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Protect airway - Most patients with grade III to IV

should be intubated.

Avoid precipitants:

Excessive protein load - particularly in form of GIbleed

Infection

Electrolyte abnormalities

Respiratory alkalosis


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Prevent hypotension

Lactulose - although not shown to work well in

FHF and felt to be less effective than in chronic liver

disease. Branch chain amino acids - theoretically appealing

but studies are mixed results - most authors feel

they are not helpful.


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Beware and intervene for cerebral edema

ICP monitoring - somewhat controversial because

studies have not shown altered outcome and risk is

significant because of coagulopathy.

Consider ICP monitoring if

Grade 3 - 4 with posturing

PT corrected to < 20, platelets corrected

Patient is listed for transplant and felt to be a candidate for

transplant


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Mannitol - shown to be effective in improving outcome Hyperventilation - probably useful for acute spikes in ICP.

Has not been shown to be effective in hepatic failure.

Concerns about effect on cerebral perfusion warrant

consideration.

Elevation of head - effect on CPP? Keep head midline,

perhaps 20 - 30 degrees of elevation.

Pentobarbital coma, hypothermia - unproven, occasionally

may be indicated.

Steroids - no good, may worsen outcome


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Coagulopathy

Avoid bleeding

GI prophylaxis

Avoid nasal intubation

Beware with surgical procedures, line placement, etc.

FFP - Not shown to be effective in changing bleeding risk.Most authors discourage routine attempts at normalizing PT.

Use for active bleeding and procedures.

Maintain platelet count >50K, or 100K if bleeding


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Infectious Disease Issues

Prophylactic antibioticshave not been shown to

change outcome and most authors recommend

meticulous surveillance and aggressive

intervention with antibiotics when infectionsuspected.


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Therapy

Tried but failed

Insulin and glucagon to stimulate regeneration

Prostaglandin E

Corticosteroids

Hemofiltration

Charcoal hemoperfusion

Plasma exchange

Liver transplantation - best results. Greater than 60% oneyear survival in adult patients with acute liver failure. Only 10%of patients are deemed candidates and successfully supporteduntil transplantation.


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Kings College Criteria

For Acetaminophen poisoning

pH < 7.3 (irrespective grade of encephalopathy)

orPT > 100 seconds (INR >6.5)and serum creatinine >

3.4 in patients with grade III or IV encephalopathy All other etiologies

PT > 100 seconds (irrespective of grade of encephalopathy)

OR any 3 of the following

Age < 10 years or > 40

Liver failure caused by non-A, non-B hepatitis, halothane, oridiosyncratic drug rxn (Seronegative hepatitis)

Jaundice for > 10 days prior to encephalopathy

PT > 50 seconds,INR >3.5

Serum bilirubin > 17.5


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Contraindications

Uncontrolled sepsis

Multi-organ system failure

Irreversible brain damage

By neurologic exam

Imaging studies

Sustained ICP > 50, or

CPP < 40 for 1 - 2 hours


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Therapy

ELAD (extracorporeal liver assistdevice) - most acute liver failure isthought to be recoverable if patientsurvives long enough. Most patientseither die or have regeneration andnormal liver function. Goal would beto:

Support patient whileawaiting recovery - thusavoiding transplant and itsrisks - short and long term

Stabilize patient whileawaiting transplant

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58738096 Fulminant Hepatic Failure