Transcript Fulminant Liver Failure - UBC Critical Care Medicine

Fulminant Liver Failure
Stevo’s AHD
April 3rd, 2008
Introduction
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Sue, a 28 year old previously
healthy 80 kg woman, is brought to
the emerg department with
progressive obtundation. Her ALT is
7,200 U/L, AST is 11,300 U/L, INR
is 3.6 and a total bilirubin of 5.3
mg/dL. As the ICU fellow on, you
are consulted to figure out what is
going on and how to manage her.
Take it away Dave….
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What are some of the overarching themes of
managing ALF?
How is acute liver failure defined? How is
fulminant liver failure defined?
What is the differential for the etiologies of ALF?
How would you differentiate between these
etiologies?
What is the most common cause of ALF in North
America and what it is pathophysiology? What
is the most common cause in the developing
world? Why?
What are the specific therapies for each of these
identified etiologies of ALF? Please give names,
doses and frequency.
Describe the grades of hepatic encephalopathy.
What is her grade?
Presumed agents of idiosyncratic drug
induced hepatic failure
Alcoholic hepatitis ----Pentoxifylline (400 mg PO TID), looked
at in one single centre randomized study and showed a
benefit where short-term survival was significantly better with
active therapy (25 versus 46 percent, respectively).
Norfloxacin in FHF
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A randomized trial reported significant benefits with the
oral administration of norfloxacin at 400 mg/day to 68
patients with;
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cirrhosis with ascites with a total serum protein <1.5 g/L
And impaired renal function (serum creatinine >106
micromol/L & BUN >25 mg/dL, serum sodium <130
meq/L)
Or severe liver disease (Child-Pugh score >9 points with
serum bilirubin >3 mg/dL).
Benefits include a significantly decreased one-year
probability of SBP (7 versus 61 percent) and
hepatorenal syndrome (28 versus 41 percent), and
improved survival at three months (94 versus 62
percent) and one year (60 percent versus 48 percent,
p = 0.05).
Grades of hepatic encephalopathy
Now onto NNNNNNaisan
8. Can we prognosticate at all for Sue
right now (ie lactate values vs
other values)? What is her MELD
score? What is the MELD score
anyway? What is the Child-Pugh
score?
MELD score
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It is calculated according to the
following formula:
3.8 x log (e) (bilirubin
mg/dL) + 11.2 x log (e) (INR)
+ 9.6 log (e)
(creatinine
mg/dL)
MELD score interpretation
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In interpeting the MELD Score in
hospitalized patients, the 3 month
mortality is:
40 or more - 100% mortality
30-39 - 83% mortality
20-29 - 76% mortality
10-19 - 27% mortality
<10 - 4% mortality
Child-Turcotte-Pugh score
Gordo and interventions for FHF
9. What interventions would you like to start now?
Specifically discuss the rationale and evidence
for the following;
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Lactulose
Oral non-absorbable antibiotics
Prophylactic systemic antibiotics
Agents of sedation and analgesia
Correction of coalopathy (FFP, Vitamin K,
Platelets, cryoprecipitate, aminocaproic acid,
factor VIIIa). Routine vs procedure specific
Routine albumin administration
Gastric acid suppression
Nutrition
Glycemic control
Onto Yoan and infections and ascites
10. What is her risk for infection? How
about from fungal pathogens?
She has significant ascites. With a large
right sided pleural effusion that is
making it moderately difficult to
ventilate her.
11. How do you manage her ascites?
12. What indicates SBP? How is it
managed?
Hepatic encephalopthy and crazy Yoan
Her CNS status continues to deteriorate and
now she is unresponsive to pain.
13. What etiologies should you consider
at this point? What investigations/history
do you want to get specifically?
14. What is the pathophysiology of
cerebral edema in ALF? What’s the
pathophysiology of multiple organ failure
in ALF?
15. What is the evidence for ICP
monitoring? What can be done in cases of
high ICP?
Take it away Scotto…
Things are not going so well for Sue.
A GI keener says that we should
just give up and send her to MARS.
16. What is MARS? Is there any
evidence for it? How does it work?
17. What other similar technologies
are out there for ALF?
Evidence for MARS;
•Initial Phase I trials
•Subsequent randomized trial in acute on chronic hepatic failure, which
was stopped early
•MARS registry paper and effects in encephalopathy
•Meta-analysis of 4 randomized and 2 non-randomized trials
•Evidence in hepato-renal syndrome
Scot redux
She is now going into progressive renal failure.
18. What is the pathophysiology of hepato-renal
syndrome?
19. How can you differentiate hepato-renal
syndrome from other causes of renal failure
commonly found in the ICU? What are the
diagnostic criteria for hepatorenal failure?
20. What treatment options are there for hepatorenal syndrome? What are the prognostic
implications of hepato-renal syndrome?
Pathophysiology of HRS
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splanchnic vasodilation, possibly due to nitric
oxide (pathogenesis of ascites), leads to
reduced GFR, reduced Na+ excretion.
increase in the ratio of vasoconstrictor
thromboxanes to vasodilator prostaglandins
may lead to renal ischemia.
Other potential, although unproven,
mediating factors in the renal
vasoconstriction include endotoxemia (due,
at least in part, to lack of hepatic removal),
endothelin, the release of false
neurotransmitters, and increased renal
sympathetic tone (induced in part by an
hepatorenal reflex that is activated by
elevated hepatic sinusoidal pressure)
Diagnostic criteria for HRS
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Chronic or acute hepatic disease with advanced hepatic failure
and portal hypertension
A plasma creatinine concentration above 133 µmol/L that
progresses over days to weeks. As noted above, the rise in
plasma creatinine with reductions in glomerular filtration rate
may be minimized by the marked reduction in creatinine
production.
The absence of any other apparent cause for the renal
disease, including shock, ongoing bacterial infection, current or
recent treatment with nephrotoxic drugs, and the absence of
ultrasonographic evidence of obstruction or parenchymal renal
disease. It is particularly important to exclude spontaneous
bacterial peritonitis, which is complicated by acute renal failure
that may be reversible in 30 to 40 percent of patients.
Urine red cell excretion of less than 50 cells per high power field
(when no urinary catheter is in place) and protein excretion less
than 500 mg/day.
Lack of improvement in renal function after volume
expansion with intravenous albumin (1 g/kg of body weight per
day up to 100 g/day) for at least two days and withdrawal of
diuretics.
Treatment:
Prevention:
 SBP – dose of IV albumin (1.5 g/kg) at time of diagnosis, and
another dose on third day of abx may reduce mortality.
 Alcoholic hepatitis – pentoxifylline may improve survival.
 Severe liver disease with cirrhosis and impaired renal function
– norfloxacin.
Active treatment:
 Correct underlying hepatic disease – eg. abstinence from
EtOH in cirrhosis, or tx with lamivudine in Hep B.
 Liver transplant
 Midodrine and octreotide titrated to increase MAP by 15
mmHg – reduces endogenous vasodilator release, and causes
systemic vasoconstriction. Multiple studies show survival
benefit.
 IV albumin at approximately 50 g/day for three or more days.
Pentoxifylline
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is a tri-substituted xanthine unlike
theophylline, is a hemorrheologic agent,
i.e. an agent that affects blood viscosity.
It’s used commonly for claudication
sympotoms.
In one four-week study, 101 patients with
severe alcoholic hepatitis were randomly
assigned to pentoxifylline (400 mg orally
three times daily) or placebo. Short-term
survival was significantly better with
active therapy (25 versus 46 percent,
respectively).
Naisans baaack..
You successfully initiate CVVHD. Your
annoying GI keener suggests
talking to the transplant team?
21. What are the indications for
liver transplant in ALF? What are
the contra-indications?
Transplant criteria
The critical criteria include;
a) age >18 yrs
b) a life expectancy without a liver transplant of <7
days
c) onset of hepatic encephalopathy within 8 wks of
the first symptoms of liver disease
d) the absence of preexisting liver disease
e) residence in an intensive care unit
f) at least one of the following:
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Ventilator dependence,
Requiring renal replacement therapy,
An INR >2.0.
Transplant contra-indications
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Active drug or alcohol abuse,
Active suicidal ideation, or history of a previous
suicide attempt
Specific exclusion criteria for liver transplantation
have not been formally established, although it is
generally agreed that active sepsis and
extrahepatic malignancy are absolute
contraindications. Still controversial are conditions
such as HIV infection in the absence of acquired
immunodeficiency syndrome, large-size
hepatocellular cancer (>5 cm), or
cholangiocarcinoma
Liver transplant (con’t)
Sue goes onto transplantation and
successfully undergoes orthotropic liver
transplantation.
22. What are the complications that you
can expect in the post op liver transplant
patient?
23. What are some of the overarching
themes of management of the fresh posttransplant liver?
24. Is there any evidence for using
albumin as the resuscitation fluid post
liver transplant?
Post op liver transplant complications
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Primary Nonfunction
Intra-abdominal Bleeding
Vascular Thrombosis
Biliary Leak
Infections
Acute Rejection