Acute liver failure is defined as:
Acute liver injury
Impaired synthetic function (typically INR>1.5)
In someone who previously had a normal, healthy functioning liver.
Hepatic Encephalopathy - West Haven Criteria
"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"
Grade 1: changes in behavior, no change in level of conciousness
Grade 2: disorientation, drowsiness, asterixis
Grade 3: significant confusion, incoherent speech, sleeping but awaken to voice
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:
Cytotoxic edema related to ammonia (and ultimately osmotically active breakdown product, glutamine)
Ammonia, produced by gut flora, usu broken down by liver; this bypasses liver an enters systemic circulation, diffuses across BBB
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")
Vasogenic edema - Breakdown and eventual "leakiness" of BBB
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
55% of patients developed clinically significant ICP in study done at King's College in 2007
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
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
>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
Advanced strategies in conjunction w/transplant team
For our team, ALF + elevated ammonia = CRRT
Mannitol = draw water out of astrocytes
Limited benefit if anuric (no osmotic diuresis)
Very small studies demonstarted survivial benefit; not consistent across literature
No consistent data regarding mortality; hard to dose of mannitol already given
Temporarily effective - use as bridge to other therapies
Janet et al - mortality benefit although selection bias, sicker patients were cooled
Glucocorticoids DO NOT WORK IN THIS COHORT = increased risk of infection, no benefit
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