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CRRT in Liver Failure
Akash DeepDirector - PICU
King’s College HospitalLondon
ChairRenal/CRRT Section
European Society of Pediatric and Neonatal Intensive Care (ESPNIC)
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Overview
• AKI and CRRT in ALF• CRRT in CLD/ AoCLF• Role of MARS and TPE in Liver failure• Anticoagulation in liver Patients
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RRT in liver patients •ALF•AoCLF •Post Liver Transplant•Metabolic disease- hyperammonaemia, primary hyperoxaluria•CRRT – standard ICU indications in patients with liver disease
pCCRT Rome 2010 5
Survival in patients treated by RRT according to diagnoses: ppCRRT Registry
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Overall survival 58%
Symons, Clin J Am Soc Nephrol, 2: 732, 2007
CRRT in ALF
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ELAD
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Bridging means identifying which patient is sufficiently lucky to survive
Why use liver support?
• Survival ?• Improved Cardiovascular Stability• Improved HE, decreased ammonia• Control fluid balance (before/after ELT)• Increase delay to ELT, bridge to ELT• Standard use in ICU setting• Conducive Environment for Either Liver
Regeneration /Liver Transplant
Hepatology 1998:27:1050-5
Controversies in RRT in Liver Failure
• Why do patients with Liver failure develop AKI?
• What is the best time to initiate RRT in patients with ALF? - Elective versus standard CRRT
• What dose of RRT is the best dose?
• Anticoagulation in CRRT for ALF
• Ideal Extracorporeal Liver Assist Device (ELAD) – excretory and synthetic function
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Mechanisms of AKI in ALF
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Multifactorial Pre-renal AKI Acute tubular necrosis due
to profound hypovolemia and hypotension
Direct drug nephrotoxicity (paracetamol, NSAIDs)
Hepatorenal syndrome Intra-abdominal
hypertension (IAH) and development of abdominal compartment syndrome
Pathogenesis of AKI in ALFArterial vasodilatation (‘’VASOPLEGIA’’)
Decreased SVR High Cardiac Output
Renal Auto-regulation becomes Pressure Dependent - Intra-renal Vasoconstriction
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Why patients with FHF die ?
• Cerebral edema/intracranial hypertension
• Sepsis – MOSF
• SIRS at presentation associated with mortality - immune modulation
Ammonia levels and its brain delivery predicts brain swelling and advanced HE
Bernal et al. Hepatology, 2007Clemmesen et al.
Jalan et al. J Hepatology; 2004 Oct;41(4):613-20
Bhatia et al. Gut. 2006 Jan;55(1):98-104.
Evidence for Ammonia
Comparison of arterial ammonia levels at admission between survivors and non‐ survivors
among acute liver failure patients
Gut. 2006 January; 55(1): 98–104
Hyponatremia potentiate ammonia effect on HE
Gines et al Hepathology 2008
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WITH 35 MLS/KG/HR - At 1 hour AC – 39 AND AT 24 HOURS – 44MLS/MIN
WITH 90 MLS/KG/HR – AT 1 HOUR – 85 AND AT 24 HOURS 105 MLS/MIN. Ammonia clearance is closely correlated with ultrafiltration rate. HF was
associated with a fall in arterial ammonia concentration
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Overall mortality was 45.4% (n = 10). Emergency liver transplantation was performed in eight children. Five patients spontaneously recovered liver function
HVHF - > 80mls/kg ultrafiltrate, Median flow of ultrafiltrate was 119 mL/kg/hr(80– 384).
After 48 hours of treatment, mean arterial pressure (p = 0.0005), grade of hepatic encephalopathy (p = 0.04), and serum creatinine
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Authors – Akash Deep, Anil Dhawan
RRT – Indications in ALF• Hepatic encephalopathy grade 3-4
• NH3 >150 µmol/litre and not getting controlled or an
absolute value >200 µmol/litre• Renal dysfunction (Oligo-anuria, Hyperkalemia, fluid
overload)• Metabolic abnormalities ( hyponatremia Na <125
meq/litre, High lactate and increasing despite optimising fluid therapy, Metabolic acidosis)
No one indication is an absolute one for initiation of RRT
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Primary outcome : Survival to hospital discharge with or without liver transplantation
Secondary outcome: arterial ammonia, lactate, percentage fluid overload, creatinine and mean arterial pressure
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Box plot of the trend in ammonia level (umol/L) by survival.
Kaplein Meier 60 day survival curves according to age- CRRT pts
< 1 year and > 1 year
<1 gray>=1 black
P=0.0095
Y = probability of survivalX = time in days
Kaplan Meier Curve for CRRT pts no transplant; shows improved survival with CRRT severity adjusted by PELD
Non CRRT dotted CRRT solid
p=0.002
Y = probability of survivalX = time in days
Since transplantation interferes with the natural progression of PALF; analysed pts didn’t undergo transplant; Severity adjusted for case mix with PELD
Kaplan Meier Curve for Survival of PELD Adjusted PALF on CRRT – Severity by PELD Score;
<2011 dotted >= 2011 solid
P= 0.4 (not)
Y = probability of survivalX = time in days
HV-CVVH in Pediatric FHF
• Reduces ELT requirement ?
• Improved hemodynamic, renal and neurological function
• Allows a prolonged delay to ELT ?
Continuous vv hemofiltration and plasma exchange in infantile ALF - NCCH, Tokyo, Japan
Ide and coll. PCCM Accepted
17 infants, 88% survival
Modalities
• CRRT – CVVH, CVVHD, CVVHDF – no evidence which is better
• TPE – Therapeutic Plasma Exchange • MARS• SPAD – Single Pass Albumin Dialysis
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MARS
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36Courtesy – Fin Larsen
37Courtesy – Fin Larsen
38Ideal ELAD – Tackles synthetic and excretory dysfunction
Courtesy – Fin Larsen
SUMMARYNo Evidence for RRT in Liver patientsShould we undertake CRRT in ALF
• Yes - and review : population data vs individual care
Why ? –Neuro-protection, metabolic disarray, bridge for recovery or transplant
When
• Earlier - need new markers
Mode
• CRRT – unstable, TPE coming in fashion !!
Access sites
• Internal Jugular
Dose
• No evidence in Paediatrics
•High – gaining popularity
Anticoagulation - YES
•PGI2 and /or low dose heparin
RRT in CLD / AoCLF• Mainstay of supportive therapy for patients who
deteriorate despite aggressive resuscitation• Volume overload, intractable metabolic acidosis, and
hyperkalemia• Delay in RRT – MORTALITY > 90%• High risk in hepatic encephalopathy, hypotension, and
coagulopathy• Serves as bridge to transplant• If RRT > 8 weeks before LT - ???? Combined Liver-
Kidney Transplantation
Anticoagulation
Anticoagulation in RRT in liver patients
– is it different ?
Should CRRT circuits in patients with hepatic failure be anti-coagulated?
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Background :Coagulopathy & Liver Disease
• No Anticoagulation
• Low dose Heparin
• Prostacyclin
• Citrate ???
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HEPARIN
PROSTACYCLIN
CVVHD + regional citrate in liver failure Observational study Schultheiss C et al Crit Care 2012
• Accumulation in citrate correlated with an increase in Ca tot/Caion
– Critical ratio of 2.5 exceeded 10 times (of 273) in 7 of 43 runs; • Seen at 12 hours(3), 24 hours (6) and 1 at 72 hours
• Equalization of acid base was possible
• Standard lab values did not correlate with citrate accumulation ratio > 2.5
• Lactate > 3.5 mmol/L or prothrombin ratio < 26% – Predict ratio Catot/Caion > 2.5
Sensitivity 86% for both
Specificity of 86% for lactate and 92% for prothrombin
Schultheiss C et al Crit Care 2012 16:R162
Decreased citrate clearance in cirrhosis 340 ml/min Vs 710 ml/min in normals
Krammer et al 2003
29 fold increase in citrate
? Option of CVVHD vs CVVHF the former allowing lower blood flow and greater clearance of citrate
CRRT in Liver Disease• Different from non-liver ICU patientsIndicationsTiming?Dose – Role of HVHFRole of TPE – is there a role in combining
TPE with CRRT ??AnticoagulationMain Role – Bridge to LT or spontaneous
recovery46
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