Cerebral Edema in ALF

Acute liver failure is defined as:

  1. Acute liver injury

  2. Hepatic encephalopathy

  3. Impaired synthetic function (typically INR>1.5)

In someone who previously had a normal, healthy functioning liver.

Hepatic Encephalopathy - West Haven Criteria

asterixis, aka flapping tremor

asterixis, aka flapping tremor

"Catch all term for neurologic dysfunction that occur because of shunting of toxins (chiefly ammonia) from the portal circulation into the systemic circulation, crossing the blood brain barrier"

Four grades:

  1. Grade 1: changes in behavior, no change in level of conciousness

  2. Grade 2: disorientation, drowsiness, asterixis

  3. Grade 3: significant confusion, incoherent speech, sleeping but awaken to voice

  4. Grade 4: comatose; unresponsive to pain, decorticate or decerebrate positioning

Causes of ALF

In the US - acetaminophen. In other countries - viral hepatitis.

Relatively uncommon - ~2000 cases/year in US but have high rates of morbidity and mortality with leading causes of death being multi-organ failure 2/2 sepsis and cerebral herniation due to cerebral edema


The skull is a rigid container that holds blood, brain parenchyma and CSF. Cerebral edema is an increase in the amount of interstitial fluid in the brain parenchyma; because the volume of the cranium is fixed, even small increases in this brain water can lead to big changes in ICP = badness.

  • CPP (cerebral perfusion pressure) = MAP - ICP

  • Goal CPP >60; reflects the pressure the systemic circulation needs to overcome to enter cerebral circulation and perfuse the brain

Three mechanisms for cerebral edema in ALF:

  1. Cytotoxic edema related to ammonia (and ultimately osmotically active breakdown product, glutamine)

    1. Ammonia, produced by gut flora, usu broken down by liver; this bypasses liver an enters systemic circulation, diffuses across BBB

      1. Astrocytes in brain detoxify ammonia to glutamine; breaking down this ammonia is a good thing but glutamine is osmotically active and draws water into astrocytes, making them swell. Ultimately also paves the way for additional ammonia to be shunted into astrocytes ("Trojan Horse Hypothesis")

  2. Vasogenic edema - Breakdown and eventual "leakiness" of BBB

  3. Impaired cerebral autoregulation


Recognizing Cerebral Edema

  • Which patients are at high risk of developing cerebral edema?

    • Hyperacute liver failure (<7 days, such as acetaminophen)

    • Patients <35 yo

    • Grade 3-4 hepatic encephalopathy**

      • Risk increases to about 35% at grade III

    • Arterial ammonia>200

      • 55% of patients developed clinically significant ICP in study done at King's College in 2007

    • Sepsis

    • Those requiring pressors/CRRT

  • How can we diagnose elevated ICP?

    • Physical Exam, Hx:

      • Classic S&S: pupillary dilation, preogressive worsening HE, progressive loss of DTR

        • Use end of stethescope to check DTR

      • Cushings Reflex: hypertension, bradycardia, cheyne-stokes respirations

    • Invasive methods:

      • Epidural/subdural/parenchymal/intraventricular catheters

      • High risk of bleeding; no demonstrated clinical benefit among patients w/ALF in literature

      • Should you do it?

        • Currently US ALF study group (ALFSG) recommends placement of invasive ICP monitors in patients with grade 3-4 HE

        • King's College Hospital (one of major liver transplation centers in UK) recommends we monitor ICP in patietns with S&S, evidence of evolving cerebral edema = clinical judgement

        • Will likely be institution specific

    • Optic nerve POCUS

      • >5 mm is c/w elevated ICP; sensitivity ~80%, specificity ~90%

    • Overall should meet with your hepatology team and come up with a plan for evaluating patients for cerebral edema vs low threshold to transfer patients w/ALF to transplant center

Management of Cerebral Edema in ALF

  • Transfer ALF + grade II HE and above to ICU

  • Likely intubaated grade III/VI:

    • Propofol to reduce CBF

    • HOB >30 deg

    • Minimize painful stimuli

    • Early vascath

Advanced strategies in conjunction w/transplant team



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