Transcript Document

Dr. Eduardo Martinez

Foie gras (pronounced /fwɑːˈɡrɑː/ in
English; French for "fat liver") is a food
product made of the liver of
a duck or goose that has been specially
fattened.
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Metabolic
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Carb metabolism
Protein and lipoprotein metabolism
Fatty acid metabolism
Biotransformation of drugs
Storage
◦ Glycogen
◦ Vitamins A, D, E, and K
◦ Iron and copper
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Immunological function s
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Synthesis of immunoglobulins
Phagocytosis by Kupffer cells
Filtration of bacteria
Degradation of endotoxins
Excretion of bilirubin and urea formation
Haematological functions
◦ Blood reservoir
◦ Haematopoiesis in the foetus
• Syndrome that leads to MOF and death
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Previously normal liver may fail within days
• High grade encephalopathy, survival is
<20%
• Early death:
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cerebral oedema, CVS collapse
• Late death:
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Sepsis , MOF
• ALF: Sd. defined by
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Encephalopathy
Coagulopathy
Jaundice
Individual with previously normal liver
• Fulminant Hepatic Failure
Potentially reversible condition
Consequence of severe liver injury
o Encephalopathy appears within 8 wks. of
initial Sx.
o Absence of pre-existing liver ds.
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• King’s classification:
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Hyperacute: encephalopathy within <7 days
 Paracetamol, ischaemic, viral, toxins
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Acute: 8-28 days
Subacute: 5-26 weeks
 Seronegative, idiopathic, drug-related
 Different etiology
 Poorer prognosis
Cause
Agent Responsible
Viral Hepatitis
Hep. A, B, D, E, CMV, HSV, seronegative hepatitis
(14-25% in UK)
Drug-related
Dose-related, e.g.paracetamol; idiosyncratic
reactions, e.g. anti-TB, statins, recreational drugs,
anticonvulsants, NSAIDs, many others
Toxins
Carbon tetrachloride, amanita phalloides
Vascular events
Iscahemic hepatitis, veno-occlusive disease,
Budd-Chiari, heatstroke
Other
Pregnancy-related liver disease, Wilson’s disease,
lymphoma, carcinoma, trauma
• Most common causes:
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Worldwide:
 Hepatotrophic viruses A-E
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UK
 Paracetamol overdose
 Seronegative or non-A-E hepatitis
 Idiosynchratic drug rxs. or Wilson’s ds.
• Identify the etiology
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Hx., examination, viral and autoimmune
profiles
• Bloods
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FBC, EUC, CMP, coags, LFTs, drug levels
• Abdo USG and CT
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Vascular pattern, ascitis, splenomegaly
• Liver Bx.
Done by transjugular route
Mays suggest specific Dx.
Watch for sample from healthy liver
>50% necrosis assoc. with poor prognosis
o Need to reverse coagulopathy before doing
it
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• Hepatic encephalopathy
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alteration in mental status and cognitive function
occurring in the presence of liver failure
• Liver failure leads to:
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portal HTN
splachnic vasodilation
Hypoalbuminaemia
Reduced plasma oncotic pressure
Leads to ascitis and organ oedema
• Decreased intravascular volume
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Kidneys try to “compensate” and retain Na+
and water making oedema worse
• Also,
• Gut-derived toxins reach the liver
Ammonia levels are often high
o Correlation between ammonia and
symptoms is poor
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• Depend on the severity, which depends
on:
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Etiology
Speed of onset of symptoms
• Non-specific
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N&V, abdo pain
• Neurological
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Confusion, agitation, coma
Grade
Level of Consciousness
Personality and Intellect
Neurologic Signs
Electroencephalogram
(EEG) Abnormalities
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Normal
Normal
None
None
Subclini
cal
Normal
Normal
Abnormalities only on psychometric testing
None
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Day/night sleep reversal,
restlessness
Forgetfulness, mild confusion, agitation,
irritability
Tremor, apraxia, incoordination, impaired
handwriting
Triphasic waves (5 Hz)
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Lethargy, slowed responses
Disorientation to time, loss of inhibition,
inappropriate behavior
Asterixis, dysarthria, ataxia, hypoactive
reflexes
Triphasic waves (5 Hz)
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Somnolence, confusion
Disorientation to place, aggressive behavior
Asterixis, muscular rigidity, Babinski signs,
hyperactive reflexes
Triphasic waves (5 Hz)
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Coma
None
Decerebration
Delta/slow wave activity
• Mortality is higher for Grade III/IV
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Mostly due to cerebral oedema
Occurs in 80% of pts. w/ALF
 Due to lack of equilibration of osmotic gradient
 30% of those have cerebellar tonsil and/or
temporal lobe herniation causing death
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We’re now better at treating cerebral
oedema
• Elevated ICP
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HTN, bradycardia, blown pupils: occur late
CTB won’t tell you
ICP monitor is best way of knowing
• CVS changes
Similar to sepsis
o Might be due to infection
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• Renal failure
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Oliguric
Poor prognosis
 Except with paracetamol overdose where it has
a good prognosis
• Impaired immunity
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Decreased complement synthesis, Kupffer
cell dysfunction, poor neutrophil adhesion
and superoxide production
• Increased susceptibility to infection
80% of pts. have bacteriologically proven
infections
o Major sepsis is contributor to death in 20%
of cases
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 Staph. aureus 70% of gram (+)
 E. Coli most common gram (-)
 C. albicans in 30% of pts.
• Pts. need HDU/ICU
• Need CVC and continuous IBP
monitoring and IDC
• Baseline ABG and lactate
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Lactate >3mmo/L after adequate resus has
same sensi. and speci. for death as The
King’s College Hospital criteria
• Early indicators of prognosis in fulminant
hepatic failure.
 O'Grady JG, Alexander GJ, Hayllar KM, Williams R.
 Gastroenterology. 1989 Aug;97(2):439-45.
• King’s Collage Hospital Criteria
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Originally devised as prognostic criteria to predict
patient survival without liver transplant
Now used as selection criteria for potential liver
transplant recipients
• Patients with paracetamol
toxicity
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pH <7.3 (7.25 if given NAC)
Or
all three of the following:
Prothrombin time >100s
Serum creatinine level >300
μmol/l
Grade III or
IVencephalopathy
• Other patients
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Prothrombin time >100
seconds or
Three of the following
variables:
Age <10 yr or >40 yr
Jaundice >7 days before
encephalopathy
PT > 50s
Bilirubin > 300mmol/L
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Positive predictive value for ICU death without
transplantation of 0.98
Negative predictive value of 0.82
• Intensive care of patients with acute
liver failure: recommendations of the
U.S. Acute Liver Failure Study
Group.
 Stravitz RT, Kramer AH, Davern T, Shaikh AO,
Caldwell SH et al.
 Critical Care Medicine 2007; 35: 2498-508
• Adult U.S. Acute Liver Failure Study
Group
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Data from
 23 liver transplant centers
 >1,110 pts.
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In 2005 convened to
 review literature on management
 Care of pts. w/high ICPs
 Compare practices of different centers
• Admit to hospital and HDU/ICU
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When evidence of ALF
 E.g.: INR>1.5
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D/W:
 Physician
 Intensivist
 Nearest transplant center
 Regarding best time to refer
• Etiology-specific treatment
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Studies only for paracetamol overdose
NAC regardless of time of overdose
 IV if Grade I encephalopathy
 Hypotension
 Any other reason PO NAC is not tolerated
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HELLP or acute fatty liver of pregnancy
 Tx. Is immediate delivery
• NAC
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150mg/kg IV in 200ml NS over 15-60mins
50mg/kg IV over 4hrs
100mg/kg IV over 16hrs
 Total dose: 300mg/kg over 20hrs
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Infusion recommended until there is
evidence of improved hepatic function
rather than time or paracetamol levels
• Hepatic encephalopathy and
hyperammonaemia
• Infections
• Sedation and analgesia
• Bleeding diathesis
• Nutrition
• Seizures
• Circulatory dysfunction
• Standard treatment:
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Lactulose
 Watch for:
 Abdo distension
 Oesophageal varices will need a scope
 Avoid intravascular depletion
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Non-absorbable ATBs
 Neomycin not recommended by ALFSG
because of nephrotoxicity
• Infection is one of main causes of death in
ALF
• Most common sites:
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Lung
Urinary tract
Blood
• Most common M.O.
Gram (+) cocci: Staph aureus
Gram (-) rods: E. coli
o Fungi: candida
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• Empirical ATBs are recommended by ALFSG
when:
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Surveillance cultures reveal significant isolates
Advanced stage (III/IV) encephalopathy
Refractory hypotension
SIRS
• 3rd gen. Cephalosporin or Timentin,
Vancomycin, Fluconazole
• Agitation contributes to raised ICP
• Propofol vs. Benzos
Both increase GABA neurotransmission, therefore
may exacerbate encephalopathy
o Propofol decreases ICP and wears off quickly
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• Opioids
Shorter acting are preferable
o When there is concommitant ARF, avoid morphine
or pethidine due to metabolite accumulation
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• Pts. with ALF are by definition coagulopathic
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Low plts. and fibrinogen, Vit. K deficient
Spontaneous bleeding is rare
• Very difficult to obtain complete correction
• ALFSG recommends aiming for:
INR 1.5
o Plts. 50,000
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• Prophylactic FFP not recommended
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Obscures the trend of PT as prognostic marker
• Cryo recommended when fibrinogen low
• When FFP fails to correct PT/INR, then
recombinant factor VIIa can be given
Should be given before planned procedures
o Avoid in patients with risk of thrombotic
complication
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 MI, DVTs, etc.
• UGI bleeding
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reduced by H2 antagonists or PPIs
• TEDS and Scuds
• ALF is a catabolic state
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Negative nitrogen balance
Immunodeficiency
• Enteral nutrition when possible
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Hi-cal
Avoid free water and hypo-osmolarity
• TPN when:
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Specific contraindication for enteral feeds
• Nonconvulsive seizure activity is common
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Prophylactic antiepileptics not recommended
EEG when:
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Grade II/IV encephalopathy
Sudden neuro deterioration
Myoclonus
To titrate use of barbiturates
• Tx.
Phenytoin
o Propofol, midaz, barbiturates
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• Correct hypovolaemia before starting
vasopressors
• Pressors needed for hypotension and low
CPP
Norad is first line, can give high dose dopamine
Adrenaline may compromise HBF
o Vasopressin not recommended because directly
causes cerebral vasodilation and high ICPs
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• Medium doses of steroid may improve
pressor response
• Raised ICP due to cerebral oedema is
one of major causes of M&M
• CTB for Grade III/IV
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To rule out anything else, i.e. bleed
• ICP monitor
Grade III/IV encephalopathy
To optimize CPP
o Not routine
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• Aim for
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ICP<25mmHg
CPP 50-80
• General recommendations
Keep it quiet , minimize chest physio and
ETT suctioning, head at 30o
o Don’t treat spontaneous hyperventilation,
keep PaCO2 35-40mmHg, treat fever
aggressively with physical measures
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• Specific management
Manitol: first line therapy
Hypertonic Saline
Induced hypothermia
Barbiturate coma
o Indomethacin: 25mg IV over 1min.
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• When to intubate:
Respiratory failure
o Airway protection in advanced
encephalopathy
o Agitation
o Imminent ICP monitor placement
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• Pts. w/ALF often develop ALI/ARDS
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Follow ARDSNet protocol
Avoid high PEEP
 Use the minimum needed
• Indicated for:
Renal failure
Fluid overload
Metabolic derangements
o Need to create space for IV colloids, i.e.
FFP
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• CRRT preferred over IRRT
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HD instability common
• Use citrate over heparin
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Monitor ionized calcium
• Use bicarb buffer over lactate or citrate
buffer
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Liver won’t be able to convert them to
HCO3-
• Avoid hyponatraemia
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May exacerbate cerebral oedema
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Orthotopic liver transplant is the definitive
treatment for patients who meet the criteria
◦ or·tho·top·ic (ôrth-tpk)adj.In the normal or usual
position
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1 yr. and 5 yr . survival of patients
undergoing OLT for ALF is about 20% lower
than elective cases for cirrhotic patients
Auxiliary liver transplantation is and
alternative
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Absolute contraindications
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Overwhelming sepsis
Refractory hypotension
AIDS
Uncontrolled raised ICP with likely permanent
damange
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MARS: molecular absorption and recirculation
system
◦ Adaptation of haemodialysis
◦ Blood is dialysed against 20% albumin
 Shown to improve encephalopathy, renal function and
haemodynamic parameters
◦ The efficacy of this technique has not yet been
studied