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RRT in hepatic failure

Pr Etienne Javouhey Pediatric Intensive Care Unit Hôpital Femme-Mère-Enfant University of Lyon France etienne.javouhey@chu-lyon.fr. RRT in hepatic failure. Rationale for supportive therapy. To provide an environment facilitating recovery

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RRT in hepatic failure

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

  2. Rationale for supportive therapy pCCRT Rome 2010 • 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

  3. ALF/Acute on CLF: main issues pCCRT Rome 2010 • 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

  4. Objective: removal of toxins pCCRT Rome 2010 • 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

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

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

  7. Continuous hemofiltration/diafiltration pCCRT Rome 2010 • Efficient and easy treatment of AKI • Hemodynamic stability • But caution with children weighting<10kg • 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

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

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

  10. AKI in hepatic failure: 30% pCCRT Rome 2010 • 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

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

  12. MARS: Molecular adsorbent and recirculating system pCCRT Rome 2010

  13. MARS : technical aspects pCCRT Rome 2010 • Filters : • MARS flux : 2m2 ECV = 150 ml! + lines, 600ml 20% Alb • MARSMini: 0.6m2 ECV = 56ml + lines, 500ml 20% Alb • PRISMARS • 1 kit = 1800 € • Flow Rates : • Blood flow rate: 4-10 ml/kg/min • Albumin dialysate FR = BFR • Dialysate FR : variable • UFR : 2000ml/h/1m2 73 in CVVH or in CVVHDF • Anticoagulation ? • According to coagulation factors : no anticoagulation or minimal NFH (5 U/kg/h) • Citrate? Prostacyclin?

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

  15. Hepatic encephalopathy pCCRT Rome 2010  NH3 Glutamine ↓Fischer index ratio NMDA NO Endogenous BZD Liver failure  Vm, CBF Hyperhemia, lost of autoregulation • Vm,  IP CBF Intracranial hypertension Brain ischemia, Cerebral herniation

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

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

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

  19. MARS: Tolerance and efficacy pCCRT Rome 2010

  20. Wilson disease pCCRT Rome 2010 Ferenci Liver int 2003 Hepatic Encephalopathy Elevated ICP AoCLF Cholestasis AKI Cu2+ Hemolysis Hemodynamic instability

  21. Albumin dialysis and Wilson pCCRT Rome 2010 • Mars was able to remove Copper • 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

  22. MARS/Copper removal pCCRT Rome 2010 MARS 1 MARS 2 MARS 3 MARS 4 New wilson index = 13 Javouhey. Personal data 2009

  23. Hemodynamics effect pCCRT Rome 2010 Schmidt et al. Liver Transplantation 2003: 250-7

  24. pCCRT Rome 2010 In Acute liver failure 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 In AoCLF Refractory Pruritus Strenghts Improve Quality of life Improve growth status Bridge to LT Improve survival? Limitations Cost Need for KT Javouhey et al. Pediatric transplantation 2009

  25. pCCRT Rome 2010 Conclusion: proposals CVVH + SPAD or « PRISMiniMARS » ? P<10kg ALF 10<P<30kg MiniMARS or PRISMARS P≥30kg MARS or PRISMARS MiniMARS but limitations for children < 10kg SPAD? HVHF AoCLF/RP

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