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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

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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

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