Dutch Intensive Care Society Acute Liver Failure · [email protected] “Liver Failure ... •...
Transcript of Dutch Intensive Care Society Acute Liver Failure · [email protected] “Liver Failure ... •...
Pulsion, Excalez MAB member
Fresenius, Ashai Kasei consultancy
“Liver Failure”
Julia WendonKings College London and Kings College Hospital
London
Disclosure of speaker’s interests
(Potential) conflict of interest
Potentially relevant company
relationships in connection with
event 1
• MAB member of Pulsion and (Excalenz) : no payment
• I have undertaken consultancy work for Fresenius and AshaiKasei
• Pulsion and Baxter supported research through provision of products
What is Liver Failure ?
• Cirrhosis
– Fibrosis, Portal hypertension
• Decompensated Liver Disease
– Ascites, varices, renal dysfucntion
• Acute on Chronic Liver Failure
– Acute event with worsening of liver and other organ function
• Acute Liver Failure
– Previously normal liver : acute, hyperacute, subacute
• Post surgical Liver failure
• Liver dysfunction / failure in critically ill patients
• Post trauma liver dysfunction / failure
Possible points of CC referral
Is this new disease
Is this a homogoenous population
What is AoCLF ?
Asian view
minor fibrosis/ fat + viral, DILI
European / USA view
varices, sepsis, paracentesis, alcohol
Sepsis
Variceal bleed
Paracentesis
Metabolic status / drugs
Alcoholic hepatitis
Surgery
Alastair J. O’Brien Intensive Care Med (2012) 38:991–1000
Definition of organ failureModified SOFA score for Cirrhosis (The SOFA-CLIF SCORE)
Organ/system 0 1 2 3 4
Liver (Bilirubin, mg/dL)
<1.2 ≥1.2 - ≤1.9 ≥2 - ≤5.9 ≥6 - <12 ≥12
Kidney (Creatinine (mg/dL)
<1.2 ≥1.2 - ≤ 1.9 ≥2 - <3.5 ≥3.5 - <5 ≥5
or use of renal-replacement therapy
Cerebral (HE grade)
No HE
1 2 3 4
Coagulation (INR) <1.1 ≥1.1 – <1.25 ≥1.25 - <1.5 ≥1.5 – <2.5 ≥2.5 or Platelets≤20x109/L
Circulation (MAP mm Hg)
≥70 <70 Dopamine ≤5or Dobutamine or Terlipressin
Dopamine >5 or E ≤ 0.1 or NE ≤ 0.1
Dopamine >15 or E > 0.1 or NE > 0.1
Lungs PaO/FiO2: or SpO2/FiO2
>400
>512
>300 - ≤400
>357 - ≤512
>200 - ≤300
>214 - ≤357
>100 - ≤200
>8 - ≤214
≤100
≤89
GASTROENTEROLOGY 2013;144:1426–1437
Acute on chronic liver failure:
Other factors and prognosis
Levesque E et al. J Hepatology 2012, n = 377
Source :
Chest : HE
Ascites
Blood
Urine
MDR organisms / infections
18% overall BUT :
4, 18 and 35 % of community, HCA,
nosocomial
Efficacy of treatment only 40% in
nosocomial sepsis
Mortality of 25% vs 12% for MDR
Multivariate analysis : predictors of mortality ignoring appropriate antiobiotic choice
diagnosis of infection, age, Bilirubin, creatinine,
Multivariate analysis : predictors of mortality considering appropriate antiobiotic choice
diagnosis of infection , appropriate antibiotic choice, age, INR
Alcoholic hepatitis
Lille score
Age
Renal
INR
Bilirubin
Albumin
Delta Bilirubin
Aliment Pharmacol Ther 2014; 39: 721–732, Burroughs
Comparison of 9 scores : no difference in AUC
3.19-0.101*(age)+0.147*(alb day 0)
+0.0165*(change in Bili)-
0.206*(renal insufficiency
{0/1:creat < or > 115 µmol/L)-0.0065
(Day 0 Bili)
Hypoxia and CLD
Common
Hydrothorax : “SBP”
Atelectasis
Sepsis
Interstitial lung disease
Intra-abdominal pressure Ascites
Hepatopulmonary syndromeO2, position
Portopulmonary hypertensionsidenafil, PGI2, bosanten
Aliment Pharmacol Ther 2015; 41: 189-198
Pro-coagulant
Protein C, S, FVIII
and ATIII
Thrombomodulin
resistant
Avoid FFP
Increase anticoagulation
The 4 fluids of lifeJournal of Hepatology 2014 vol. 60 j 1310–1324
Journal of Hepatology 2010 vol. 53 j 397–417
SBP
Endothelial markers TLR4, IL-10
Phagcytosis
Oxidative burst
Albumin for bacterial infections other than
spontaneous bacterial peritonitis in cirrhosis. A
randomized, controlled study.
• J Hepatol. 2012 Oct;57(4):759-65.
• Non SBP infections 100 patients
• Antibiotics ± albumin at diagnosis and day 3
(1.5 and 1 g/kg)
• No difference in survival at 3 mnths
• Improved creatinine and circulation markers –
no difference in HRF ( 1 vs 3)
Journal of Hepatology 2015
62 822–830
Thierry Thévenot
• Resuscitation : Airway
• Coagulation support - as per massive Tf
• Diagnostic endoscopy +
• Therapy
• Vasoactive drugs
• Endoscopic therapy
• banding and glue
• Failed drugs + OGD
• Balloon tamponade
• TIPS
Lactate
Number of endoscopies
CXR – that wasn’t seen before the OGD!
…………….
RRT/ metabolic support : yes or no
Na, brain and outcome
Critical Care 2014, 18:700 Increased ITU stay and mortality
Liver International (2013)
Acute on chronic liver failure:
Prognostication based on scores
Levesque E et al. J Hepatology 2012, n =377
A
B
C
D
The American Journal of GASTROENTEROLOGY 2014 McPhail et al
• A SOFA/CLIF-SOFA score of greater than 13 on Day 1
• 90% mortality rate
• SOFA scores greater than 13 on Day 3 and 7
• 89% and 90% mortality rates respectively
• Lactate level greater than 4 mmol/L on Day 1
• 81% mortality rate
• Lactate level greater than 4 mmol/L on day 3 and 7
• 91% mortality rate and 88% mortality respectively
• The absolute SOFA score on day 3 was a better predictor of mortality than change in
score.
• Delta SOFA score changes
• Increase from day 1 : mortality 51%
• Unchanged : mortality of 42%
• Decrease after Day 1 : mortality was 28%.
Mark J. W. McPhail Clinical Gastroenterology and Hepatology 2014
The Royal Free Hospital Score: A Calibrated Prognostic Model for Patients With
Cirrhosis Admitted to Intensive Care Unit. Comparison With Current Models and CLIF-
SOFA Score
Am J Gastroenterol. 2014 Feb 4.
Burroughs AK
Incorporation of age and wbc : CLIFF C score
Jalan et al Journal of Hepatology
2014 vol. 61 j 1038–1047
Fixing specificity at 95% and estimating sensitivity (bootstrap
method)
A cut-off value of greater than 14 for CLIF-SOFA gives a sensitivity of
32% (26%– 40%)
A cut-off of greater than 12 for SOFA gives a sensitivity of 33 % (26–
39)
Suggests neither score : SOFA or CLIFF SOFA provide an accurate
indicator of futility.
Mark J. W. McPhail Clinical Gastroenterology and Hepatology 2014
Can we predict “Futility”
The right lobe is injured more commonly than the left
(>85% involve segments VI, VII, and VIII)
Deceleration injury
IVC and hepatic veins
Children at increased risk -
flexible ribs and a weaker
connective tissue framework
Grade 3 – laceration >3cm deep Grade 5 – laceration >75% of lobe
juxta-hepatic venous injury
Pseudo-aneurysms
Presentation 2 weeks post trauma
Haemodynamic collapse,
Malaena, Haematemesis
Obstructive liver function
Rare in
those managed with
embolization
Horse kick injury
Failure of stent with ongoing
high volume drain loss
Ileus - consider nasobiliary tube
33% bile leakAll managed with ERCP
Stent placed across sphincter
Bala et al. Scandinavian
Journal of Trauma, Resuscitation
And Emergency Medicine
2012, 20:20
Acute Liver Failure
Bernal et al, Lancet 2010
Bone marrow stained for T cell marker
CD3
in situ hybridization for EBV
Liver Int 2013
Coagulation
Journal of Hepatology
2012 vol. 57 780–786
Mallett et al
Larsen et al J Hepatology 2016
Bernal et al 2016
D1: INR 6.5 rising to 8.5, CK 150K, ALT 9,000 , ARF, lactate 6 - D2 INR 5, lactate 3.0, ALT 7000
Found outside club - fitting – intubated and brought to ED : Temp 41 seizure control : D0
Teams make things [email protected]
Case : 50 year old man ALD, occasional drinking but remains in full employment
Presents jaundice, oedema, SoB - ?PE Rx clexane - admitted to ward
Day 2 : CT-PA negative BUT now Confused ++, malaena developed
Intubated for OGD in theatre : no bleeding point seen
Extubated - bradycardic, intubated, CPR X 1 cycle
In recovery - annuric, acidotic, adrenaline / noradrenaline infusions
pH 7.06 pO2 8.6 pCO2 8.2 HCO3 13.6 BE-14 Fi02 0.5
Lactate 2.7 mMol/l
Na 135 K 6.8
Urea 30 (N< 7) Creatinine 587 (N < 120)
Bilirubin 100 µmol/L (5.8 mg /dl)
ALP 56 AST 244 GGT 339
WBC 16.4 Hb 12.4 Plt 73
INR 2.94 APTT 2.02
CRP 190
Child Pugh 6-8 (pre)MELD 27SOFA 17CLIFF COF ACLF 3CLIFF C 70 (91% mortality)
Swollen inflammedLeg with area of necrosis
Day 4
Free of pressorsPassing urine Fi02 0.4INR 1.6
Culture negative Rising ASO titre
Discharged to ward day 18
*Patients who fulfil these criteria may still have structural damage such as tubular
damage. Urine biomarkers will become an important element in making a more accurate
differential diagnosis between HRS and acute tubularnecrosis.
Journal of Hepatology 2015
Rare
Most have an AKI
Mark J. W. McPhailClinical Gastroenterology and Hepatology 2014