encephalopathy are controversial and probably not helpful in acute liver failure. • Lactulose[r]
(1)Acute Liver Failure (ALF) Overview
• Many causes of ALF
• The primary cause of death in ALF is CNS disease (intracranial hypertension, brain herniation)
• Limited definitive treatments:
– N-acetylcysteine (NAC) in acetaminophen overdose
(2)Previously healthy
(3)61 yr old woman
• Four days of progressive confusion and fatigue • Presented to an outside hospital
• Labs:
– Glucose 24
– AST 11,500
– ALT 12,000
– Tbili 6.1 (direct 3.8)
(4)• CT abd: Thickened GB wall, non-dilated bile ducts, no stones; all else negative
• Presentation interpreted as acute cholecystitis
• Next day: cholecystectomy
(5)Fulminant Hepatic Failure (Acute Liver Failure)
Defined by characteristics: Severe acute liver injury
2 Hepatic encephalopathy Elevated PT/INR (≥ 1.5 )
In a patient without cirrhosis or pre-existing liver disease (< 26 weeks)
Hyper-acute: < days Acute: 7-21 days
(6)Causes
• #1 USA/West: acetaminophen toxicity
– suicide attempt or unintentional overdose
(7)Other Causes
• Other viruses
– herpes simplex – Cytomegalovirus – Zoster
• Other drugs
– Antibiotics/anti-TB – NSAIDs
– Anti-seizure
– Herbal supplements
• Amanita (mushroom)
• Autoimmune hepatitis
• Vascular
– Budd Chiari
– Ischemia/shock states – Veno-occlusive disease
(complication of graft vs host disease after bone marrow transplant)
– Pregnancy
• HELLP
• Fatty liver
(8)This patient
• Hepatitis A serology (IgM) positive, suggesting acute infection
• Uncommon in US, vaccine for those at-risk (travel to endemic areas)
• Transmitted by the oral-fecal route
– well water, restaurant food, shellfish
• Usually self-limited; acute liver failure in
(9)Presentation
Mayo Day #1 (HD #4)
• Transferred intubated on propofol
• BP 150/80, HR 80, T 36.6C
• Exam: scattered ecchymoses
• Labs: INR 7.7, plt 160, glu corrected, creat 0.7
(10)That evening
• Unresponsive off propofol
• Hypertensive (SBP 180-200)
• Extensor posturing?
• Pupils equal, sluggish
(11)Outcomes
• The most common cause of death in acute liver failure:
– CNS catastrophe related to vasogenic cerebral edema and intracranial hypertension→uncal herniation
• Prognosis/spontaneous recovery factors:
– Is the cause reversible? (APAP—N-acetylcysteine)
(12)Encephalopathy
Grade I: mild confusion, slurred speech, sleep disturb
Grade II: lethargy, moderate confusion Cerebral edema: rare
Grade III: Marked confusion, incoherent speech, sleepy but arousable
Cerebral edema: 30%
Grade IV: coma, unresponsive, posturing
(13)• Management
– Typical agents used for chronic hepatic
encephalopathy are controversial and probably not helpful in acute liver failure
• Lactulose
• Rifaximin
• Neomycin
(14)High intracerebral pressure (ICP) compromises cerebral perfusion
pressure (CPP)
CPP=MAP-ICP
MAP= mean arterial pressure
(15)Intracranial pressure monitors
• Penetrate dura
• Arachnoid memb intact
• 4% risk of hemorrhage
• Bolt is screwed into skull
(16)Methods to decrease ICP:
– HOB elevated 30 degrees to promote venous flow
– Hyperventilate to PaCO2 low 30’s
– Mannitol IV push—watch Na and serum osm, particularly if also in renal failure
– Deeper sedation; barbiturate coma
– Unlike in ICP due to brain tumors, corticosteroids (dexamethasone) NOT proven
(17)(18)General Measures
• Proximity to a liver transplant center • ICU setting if encephalopathy ≥ grade II • Hemodynamics
– CPP 50-60
– MAP 65-75
(19)Infection
• These patients are at increased risk • Surveillance in all patients
– Culture sputum, blood, urine, ascites
• Prophylactic antibiotics are controversial
– We give them if infection is proven or if the patient is deteriorating
(20)Bleeding Risk in ALF
• The PT/INR is prognostic (MELD) but is not a reliable indicator to trend the bleeding risk in ALF
(21)Management of Bleeding
• Prevention
– Vitamin K should be given
– Otherwise, prevention is controversial (unless an invasive procedure is planned)
– No role to empirically correct PT/INR in a non-bleeding patient
• Fresh frozen plasma/cryoprecipitate
(22)Factor concentrates
• Recombinant factor VIIa
– Small studies in cirrhosis; effect on bleeding prevention unclear
– Since it’s activated, some (small) risk of
hypercoagulability and clotting complications
• Prothrombin complex concentrates (inactivated)
– Bebulin-3 Factors II, IX, X
– K-centra—4 factors
(23)N-acetylcysteine
• For acetaminophen toxicity
• Might be useful in other drug-related toxicity
(24)(25)• Hepatitis B or Herpes simplex
– Antivirals (nucleos(t)ide analogues, acyclovir)
• Mushroom poisoning
– Activated charcoal binds to amatoxin
• Budd-Chiari
– Restore hepatic drainage: TIPS (transjugular
(26)• Wilson’s Disease
– Plasma exchange to remove copper
– No role for chelation therapy
• Autoimmune hepatitis
(27)Prognosis
• Degree of Encephalopathy
– Grade IV < 20% survival
• Age
– Best age 10-40
• Cause of the liver failure
(28)MELD-Na
(29)Mayo Day #2
• ICP monitor placed at 10:00 (INR 1.6 after bebulin; increased to 5.4 later that day)
• Initial ICP: mm Hg (normal > 15)
– Goal CPP = MAP – ICP of 60 mm Hg
• ICP varied from to 30 throughout day
(30)• Extubated POD #
• Slowly regains cognitive function