RRT in hepatic failure Pr Etienne Javouhey Pediatric

RRT in hepatic failure Pr Etienne Javouhey Pediatric Intensive Care Unit Hôpital Femme-Mère-Enfant University of Lyon France etienne. javouhey@chu-lyon. fr p. CCRT Rome 2010 1

Rationale for supportive therapy To provide an environment facilitating recovery To prolong the window of opportunity for LT : “Bridge to LT” To allow waiting for the native liver recovery (Bridge to recovery) Liver transplantation is required most of the time 2 p. CCRT Rome 2010

ALF/Acute on CLF: main issues Acute kidney injury Hepatorenal syndrome (20 -30%) Acute tubular necrosis AKI following liver tranplantation Hepatic encephalopathy Intracranial Hypertension Cerebral ischemia Hypotension and fluid management Bilirubin level Multi-Organ Failure 3 p. CCRT Rome 2010

Objective: removal of toxins Endogenous: Inborn Error Metabolism (urea cycle disorder, leucinosis…) Cu, Fe: Wilson disease, neonatal Hemochromatosis Exogenous: medication intoxications, mushrooms or herbs intoxications Removal of inflammatory mediators Sepsis/SIRS MOF Majority of toxins in LF are water insoluble and albumin bound 4 p. CCRT Rome 2010

Survival in patients treated by RRT according to diagnoses: pp. CRRT Registry Symons, Clin J Am Soc Nephrol, 2: 732, 2007 p. CCRT Rome 2010 5

RRT modalities in LF Continuous Albumin dialysis Hemofiltration • MARS or Hemodiafiltration Davenport et al. Seminars in Dialysis 2009; 22: 169 • SPAD: single pass albumin dialysis • Prometheus: plasmafiltration and albumin dialysis Plasmafiltration with high flux hemodiafiltration Inoue et al. Transplantation Proceedings 2009; 41: 259 p. CCRT Rome 2010 6

Continuous hemofiltration/diafiltration Efficient and easy treatment of AKI Hemodynamic stability But caution with children weighting<10 kg Improvement of hepatic encephalopathy No RCT, no evidence No removal of bile acids, bilirubin, albumin bound substances Davenport et al. Nephrol Dial transplant 1990, 5: 192 7 p. CCRT Rome 2010

CVVH in ALF : anticoagulation Predilution UFR = 2, 35 -2, 7 l/h Agarwal etal J of Hepatol 2009 51: 504 p. CCRT Rome 2010 8

Complications of CRRT Santiago et al Crit Care 2009 Madrid: 178 patients mainly heart diseases 55, 7%; 19, 5% sepsis Catheter (7, 5%): more frequent in infants < 1 an, and < 10 kg 10% haemorrhage 30% Hypotension after starting the procedure 9 p. CCRT Rome 2010

AKI in hepatic failure: 30% MELD scoring system Hepatorenal failure Related to the etiology of AKI: Wilson disease, mathylmalonic acidemia; acetaminophen poisoning Objective: control volemia, improve RSVI and MAP Avoid fluid overload and electrolytes imbalance 10 p. CCRT Rome 2010

Hepatorenal syndrome Mitzner et al. Liver Transplantation 2000; 6: 277 -286 11 p. CCRT Rome 2010

MARS: Molecular adsorbent and recirculating system 12 p. CCRT Rome 2010

MARS : technical aspects Filters : Flow Rates : MARS flux : 2 m 2 ECV = 150 ml! + lines, 600 ml 20% Alb MARSMini: 0. 6 m 2 ECV = 56 ml + lines, 500 ml 20% Alb PRISMARS 1 kit = 1800 € Blood flow rate: 4 -10 ml/kg/min Albumin dialysate FR = BFR Dialysate FR : variable UFR : 2000 ml/h/1 m 2 73 in CVVH or in CVVHDF Anticoagulation ? According to coagulation factors : no anticoagulation or minimal NFH (5 U/kg/h) Citrate? Prostacyclin? 13 p. CCRT Rome 2010

Ao. CLF Heemann et al Hepatology 2002; 36: 949 -958 Survival rates Survival 1 MARS (n=12) 0, 6 Control (n=12) 0, 2 p<0, 05 0 5 10 15 p. CCRT Rome 2010 20 25 30 35 Days 14

Hepatic encephalopathy Liver failure NH 3 Glutamine ↓Fischer index ratio NMDA NO Endogenous BZD Hyperhemia, lost of autoregulation Intracranial hypertension Vm, CBF Vm, IP CBF Brain ischemia, Cerebral herniation 15 p. CCRT Rome 2010

Hepatic encephalopathy Improvement with Mars : 64% Improvement with SMT : 38% p 0, 04 Hassanein et al. Hepatology 2007; 46: 1853 16 p. CCRT Rome 2010

MARS in ALF: neurological effect ALF n=22, 16 medical, 6 surgery 7/22 (32% 16 -53) improvement wo LT (12% in France) 17 p. CCRT Rome 2010

Lyon, 2000 -2009 : 12 children/88 sessions (personal data) 18 p. CCRT Rome 2010

MARS: Tolerance and efficacy 19 p. CCRT Rome 2010

Wilson disease Ferenci Liver int 2003 Hepatic Encephalopathy Elevated ICP Ao. CLF Cholestasis Cu 2+ AKI Hemolysis Hemodynamic instability 20 p. CCRT Rome 2010

Albumin dialysis and Wilson Mars was able to remove Copper found in ultrafiltrate Copper increased within albumin circuit during session Serum copper decreased after Mars session Albumin is not detoxified in Cu: same levels in the circuit Mars improved renal function Mars improved hepatic encephalopathy Clinically: GCS, EEG data Increases Fischer index Decreases ammonia and glutamin levels Mars decreased bilirubin level Sen et al Liver Transplant 2002 Chiu et al Liver Transplant 2008 21 p. CCRT Rome 2010

MARS/Copper removal MARS 1 MARS 2 New wilson index = 13 MARS 4 Javouhey. Personal data 200922 p. CCRT Rome 2010

Hemodynamics effect HR MARS (n=8) -20% CONTROL (n=5) Unchanged p 0. 0001 MAP +20% Unchanged <0. 001 SVRI +46% +6% 0. 004 Schmidt et al. Liver Transplantation 2003: 250 -7 23 p. CCRT Rome 2010

In Ao. CLF In Acute liver failure Refractory Pruritus Strenghts May improve encephalopathy May stabilise fluid balance Bridge to LT Limitations Hemodynamic tolerance Risk of bleeding: 20% reduction of platelets Need for adapted materials Strenghts Improve Quality of life Improve growth status Bridge to LT Improve survival? Limitations Cost Need for KT Javouhey et al. Pediatric transplantation 200924 p. CCRT Rome 2010

Conclusion: proposals P<10 kg ALF CVVH + SPAD or « PRISMini. MARS » ? 10<P<30 kg Mini. MARS or PRISMARS P≥ 30 kg Ao. CLF/RP MARS or PRISMARS Mini. MARS but limitations for children < 10 kg SPAD? HVHF 25 p. CCRT Rome 2010