Transcript Fulminant hepatitis - British Society of Gastroenterology

Liver failure
Hyper - acute liver failure
Acute liver failure
Greatest risk of cerebral
oedema, CVS failure
Greatest chance of
spontaneous survival
Sub - acute liver failure
Lowest risk of cerebral
oedema/ encephalopathy
Easily confused with CLD
Ascites
Lowest chance of
spontaneous survival
Principle Causes of Acute Liver Failure
Cause
Agent responsible
Viral
Drug related
Hepatitis A, B, D E, others
Idiosyncratic and dose related
Toxins
Carbon tetrachloride, Phosphorous
Amanita phalloides
Ischemic hepatitis, Budd-Chiari, VOD, heat
shock liver
Pregnancy related, Wilson disease, lymphoma
Vascular events
Other
No previous liver disease
Various definitions
Jaundice or symptoms to encephalopthy
•
Decompensated chronic liver disease
– Decompensation with sepsis
· Bacterial peritonitis : Rx as “peritonitis”
· Bacteraemia, chest, urine
– Variceal bleed : frequently septic, endoscopic skills ± TIPS
– Encephalopathy
– Hepatorenal failure
– Alcoholic hepatitis : steroids, pentoxifylline, feed, delta bilirubin
Differential with ALF :
History
Pattern of LFT’s
Imaging : ultrasound, CT scan
Biopsy : vary rarely indicated
•
Liver trauma
Multi system disease
Coagulopathy
· INR important prognostic indicator in established ALF
· Platelet dysfunction DIC - rare
Metabolic
· Insulin resistance : Clarke et al Hepatology
· Hyperlactataemia :Bernal et al Lancet 2002 : useful to track
· Liver net producer of lactate Murphy et al Crit Care Med 2001
· P04, Mg, Na, glucose, K, pH
· High incidence of pancreatitis
Nutrition
· Frequent poor recent oral intake ± vomiting
· No evidence for protein restriction in either acute or CLD
· Gastric prophylaxis
· Increased metabolic requirements Walsh et al CCM
2000;28(3):649-54
Renal failure
• Common 45% of all cases
• Multifactorial - frequently pre renal, ATN rather than
HRS
• Role of intra-abdominal pressure
• Specific associations with viral disease, alcohol,
auto-immune
• CRRT or slow haemodialysis is ideal
• Anticoagulation
– epoprostenol, heparin, regional anticoagulation,
citrate
Infection : ALF
•
Impaired innate and cellular immunity
•
Bacterial infection 335 of 887 patients (550 episodes)
•
Severe sepsis 58% mortality
•
Septic shock 98% mortality
•
Fungal infection 99 of 887 : 11% : 64% mortality
•
•
Rolando et al Hepatology 2000 32:734, 31(4):872
Components of SIRS associated with encephalopathy
•
Rolando et al Hepatology 2000;32:734-9, Vaquero et al Gastroenterology
2003;125:755-64, Shawcross D et al J Hepatol inpress
•
Cultures +++
•
Antibiotics : broad initially - 5/7 course
•
No benefit to routine prophylaxis or Selective gut decontamination
•
Antifungals
Rolando et al Semin Liver Dis 1996;16:389-402, Rolando et al Liver Trans
Surg 1996;2:8-13
Vasopressors in ALF
•
What mean arterial pressure ?
– Clinical examination ….invasive
– Determined by JV saturation and ICP : autoregulating or not ?
•
Which drug?
– Determine fluid responsiveness initially
·
Whatever you can get your hands on
– In sepsis and MOF epinephrine may be detrimental
·
increases splannchnic V02 : glucose turnover Meier Hellman et al 1997
Crit care Med
– Phenylephrine : decreased flow with decrease in spl V02 Reinelt
Crit Care Med 1999,27:325
– Norepinephrine as first choice
– Vasopressin may be potentially detrimental : cerebral
complications and potential splanchnic ischaemia
Results stratified according to blood pressure on day of SST
Harry et al Hepatology 2002
–57% of patients have abnormal synacthen response
–hypotension associated with lower baseline and increment (p<0.05)
1500
NS
P<0.01
P
<0.05
1000
500
Marik 2005 CCM 53;1254
• LDL cholesterol did separate groups
– 8.2±7.6 vs 28.4±14
• Mortality 39% vs 56%
• 75% of those on pressors had abnormal
response
0
Baseline
Increment
Peak
* P<0.001
mortality associated with lower baseline and
increment (p<0.05)
–correlates with APACHE III and SAPS
–No correlate with other parameters other than cholesterol
Encephalopathy
Portal Systemic Encephalopathy
Portal systemic shunt
– spontaneous collateral
– Surgical
– TIPPS
Not at risk of cerebral oedema
Precipitating factors
– Sepsis
· SBP Rx fluids ++
HE of Acute Liver Failure
Hepatocellular failure
Rapid onset
Cerebral oedema
· Albumin
· Avoid renal failure
– CNS active drugs
– Electrolyte abnormalities
Myoinositol levels not reduced
– Diuretics - over use
Cytotoxic and vasogenic
– Gastrointestinal bleeding
Hepatic encephalopathy in CLD
•
Not a cause of death ……. Providing the airway is managed
• Treat precipitating cause : sepsis screen, fluids…….
•
•
•
•
•
Association of SIRS with encephalopathy
Feed - std protein, high calorie, fibre content ideally vegetable based
Lactulose and enemas - cleaning or acidification
– Als-Nielson BMJ 2004 ; 328: 1064
Non-absorbable antibiotics
Decreasing ammonia therapies
– (i) ornithine and (ii) benzoate
•
Benzodiazepine antagonists - no efficacy Pomiers-Layrargues
Hepatology 1989 10;969
•
Sedation - real risk in ward environment
– Yes, they are a menace : up all night, climbing into the wrong bed,
shouting
Incidence of cerebral
oedema
Reviewed 229 patients
Grade III/IV coma
1999-2002
Incidence
Hyperacute : 24%
Acute : 23%
Subacute : 9%
Progressive neuropsychiatric syndrome,
progressive neural inhibition
Occurs in both acute and chronic liver disease
Clinical state may change very rapidly
NH4
Neurosteroids
Inflammatory response
Shawcross Lancet 365 2005
Larsen Neurochem International 2004 (44)
Increased ammonia in cerebral deaths :
splanchnic ammonia production Larsen et
al Hepatology 1998
NH4 cut off 124 .pH, cerebral oedema +
NH4 predict outcome Bhatia V Gut 2005
Partial pressure NH4 correlates with level
of encephalopathy Kramer Hepatology
2000:21
CBF variable : loss of autoregulation to
pressure
Terlipressin in ALF Shawcross et al;
Hepatology 2004;39(2):464-70
N=14
Jalan et al Gastroenterology
o
2004;27:1338 Cooled to 32-33 C
ICP
CBF
CPP
CI
PRE
45 (25-49)
103 (25-134)
45 (37-56)
9.8 (7-13)
POST n=7
16 (13-17) *
44 (24 -75) *
70 (60-78) *
5.1 (4.3-6.1) *
•Arterial NH4 343 (109 - 490) to 259 (100-453
•Uptake 2.6 ( 0.6-6.3) to -0.3 (-3.1 - 1.4)
Reduced risk of intracranial
hypertension (p<0.05)
Reduction in ICP in treatment group
(p<0.005)
Murphy et al Hepatology 2004;39(2):464-70
• Agitation and airway management
– Grade III : Intubate ventilate and sedate with opiate and propofol
– Control ventilation - avoid alkalosis
• Position - 10 to 20 degrees head up
• Insert reverse jugular line: JV sat 55 to 80%
• Tight control of glucose, K, pH, Na (145-150 mmol/L) Murphy et al Hepatology
2004;39(2):464-70
• Ammonia : early CRRT
• MAP >65 : frequently not autoregulating - need to measure ICP
• Treat “ICP” - pupillary abnormalities
– Mannitol 150 ml 20% (osmolarity < 320) or hypertonic NaCl (30%) : 20 ml
Indomethacin 0.5 mg/kg
• Hyperventilation - only for ICP in association with high JV satn
• ICP trigger:– JV saturation, ammonia >150, pressors, fever, hyperacute and acute, pupilllary
abnormalities
• Temperature - avoid fever : hypothermia should not be undertaken routinely
Currently available…
Phase III study with BAL Demetriou et al Ann Surg 2004;239 660-670
MARS Therapy
Mitzner et al Liver Transpl 2000;6:277-286, Heemann et al Hepatology 2002;36:949-58
24 patients with CLD and ‘acute liver injury’
• MARS group: reduced bile acids, bilirubin, encephalopathy
• Controls: biochemistry static, worsening
encephalopathy
– MARS 11/12 , SMT 6/12 (P<0.05)
– 6 mnth survival 6/12 MARS vs 4/11
Coagulopathy and
MARS treatment in CLD
Doria et al Clinical transplantation 2004;18:365
Single Pass Albumin Dialysis (SPAD)
Clearance of bilirubin, bile acids, NH4 : improved
Sauer Hepatology 2004;39:1048
MARS
Nathan et al Liver Transplant 2004;10:1109 Lai W et al Int Care Med 2005
• 18 patients with alcohol related AoCLD randomized to MARS or SMT over 7 days
• Significant improvement in encephalopathy
• No change in renal function or creatinine
• No change in ammonia or cytokine levels (TNF, IL-6, IL-10, IL-8), MDA, MELD fell
in both groups
10 patients with ALF grade III/IV coma Treated 8 hours on 2 consecutive days
Increase SVRI on first Rx 1114±196 to 1432±245, changes not significant by end
of second Rx
No change in ICP 14.5 (7-25) to 14 (3-25)
MARS+ SMT vs. SMT Acute on Chronic Liver Disease n=70
Significant improvements in encephalopathy grade
No differences in survival
Hassanein et al AASLD 2004
Outcome of CLD in ITU
143 patients :observational study,
Wehler et al Hepatology 2001;34:255-261
Apache III>90, pressors,
Clinical jaundice > 92% 1month
Mortality vs 11% in those with < 3
criteria
420 patients
Gildea Chest 2004;126:1598
30 patients with HRF
8/30 30 day survival (median 21)
Ventilated survival 0/15
Non-ventilated survival 8/15
No difference INR/alb/pressors
J Gastroenterology and Hepatology
Witzke et al 2004 19;1369
Accuracy of ICU scoring systems
Child Pugh 0.72
MELD
0.72
APACHE II 0.78
SOFA
0.80
Graphical representation of LITU mortality and the
Sequential Organ Failure Assessment System.
100
90
80
70
60
Mortality
50
(Percent)
40
30
20
10
0
1
2
3
4
5
No. of organ failure
PSE+CVS+RENAL failure =
98% Mortality
SOFA score cut off : 13
363 patients with
CLD admitted to LITU
6
Guidelines for referral
Paracetamol
Arterial pH < 7.30 or HC03 < 18
INR > 3.0 day 2 or > 4.0 thereafter
oliguria and/or elevated creatinine
altered conscious level
hypoglycaemia
Non-Paracetamol
pH < 7.30 or or HC03 < 18
INR >1.8
oliguria/renal failure
encephalopathy
hypoglycaemia
shrinking liver size
Children - coagulopathy
Budd Chiari
Pregnancy related
< 1000 ml need OLT
Na < 130 mmol/L
Bilirubin > 300 µmol/l
Paracetamol
pH < 7.30
all 3 of the following
within 24 hrs
PT > 100 INR > 6.5
Creatinine > 300 µmol/l
grade 3 - 4 encephalopathy
Low P04 : good prognosis
Alpha feta protein
Lactate : 4 hrs > 3.5 OR 43 p<0.001
Lactate : 12 hrs > 3.5 OR 63 p<0.001
Children - coagulopathy INR > 4.5
Budd Chiari : renal failure + HE
Non-Paracetamol
pH<7.3
INR > 6.5
Liver volume
any 3 of :
seronegative hepatitis or
drug related / halothane
Bilirubin > 300 µmol/l
INR > 3.5
Age < 10 yrs or > 40 yrs
J - E > 7 days
MELD > 30
Encephalopathy +
Factor V < 20% or
< 30% if > 30 yrs of age
The future:
Increasing liver disease
alcohol, HCV, NAFLD
HCC
Treatment changing
Innovative treatment options
liver support systems - further
Controlled trials required
Transplantation is a real option
Early discussion
Assume fluid deplete: time is tissue
Infection is common
Agitation=HE
Close observation
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