Cerebral Edema in ALF
Acute liver failure is defined as:
- Acute liver injury
- Hepatic encephalopathy
- 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"
Four grades:
- 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
Physiology
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")
- Ammonia, produced by gut flora, usu broken down by liver; this bypasses liver an enters systemic circulation, diffuses across BBB
- 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
- 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
- Classic S&S: pupillary dilation, preogressive worsening HE, progressive loss of DTR
- 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
- Physical Exam, Hx:
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
- CRRT
- Mortality benefit - "Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Cardoso FS et al. Hepatology 2017
- 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
- Hypertonic saline
- No consistent data regarding mortality; hard to dose of mannitol already given
- Hyperventilation
- Temporarily effective - use as bridge to other therapies
- Hypothermia
- 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
Attribution
“Bass Rider", "Refraction", "Rubber Robot", "Prism Tone", "The Window", "Skippy" and "Feeding Pigeons" by Podington Bear is licensed under CC BY-NC 3.0 / Song has been decreased in length from original form
"Confused and Angry Muttering" by RoivasUGO is licensed under CC BY 3.0 / Song has been decreased in length from original form