1. Therapeutic Plasma Exchange for hyperbilirubinemia in two newborns during Extra Corporeal Membrane Oxygenation Linda Koster-Kamphuis, pediatric nephrologist Nijmegen, The Netherlands

2. Neonatal hyperbilirubinemia Background Bilirubin product of heme catabolism Heme oxygenase (HO) Heme Carbon monoxide (CO) + Biliverdin Biliverdin reductase BiliverdinBilirubin

3. Neonatal hyperbilirubinemia Background Bilirubin + Albumin complexLiver Hepatocyte: Conjugation of bilirubin with glucuronic acid (UGT) Conjugated bilirubin is excreted in bile.

4. Neonatal hyperbilirubinemia Background Conjugated bilirubin with bile excreted in digestive tract Reduced to urobilin (in adults) Deconjugation of conjugated bilirubin (in infants) Unconjugated bilirubin reabsorbed into the circulation “enterohepatic circulation of bilirubin”

5. Neonatal hyperbilirubinemia Background Normal physiologic alterations result in mild unconjugated bilirubinemia in nearly all newborns Higher bilirubin production Decreased bilirubin clearance Increase in enterohepatic circulation of bilirubin

6. Neonatal hyperbilirubinemia Background Bilirubin Neurotoxicity Acute bilirubin encephalopathy Kernicterus

7. Neonatal hyperbilirubinemia Background Treatment Phototherapy Improving breastfeeding or supplementing with formula Pharmacologic agents (Phenobarbital, Ursodeoxycholic acid) Exchange transfusion

8. Neonatal hyperbilirubinemia Background Exchange transfusion Bloodvolume 80-90 ml/kg Exchange volume 160-180 ml/kg (2 x bloodvolume) Around 50% reduction in serum bilirubin value

10. Neonatal hyperbilirubinemia Patients R.K. born at term, PROM, 3640 gr Early onset GBS infection with severe sepsis, pneumoniae with pulmonary hypertension -> ECMO Severe hyperbilirubinemia due to hemolysis caused by ECMO treatment in combination with severe sepsis Normal serum Albumin at the time of maximum bilirubin value Failure of intensive phototherapy

12. Neonatal hyperbilirubinemia Patients S.R. 34 5 / 7 wks, 3400 gr, omphalocele ruptured Surgery on day one, bilateral pneumothorax Pulmonary hypertension -> ECMO Severe hyperbilirubinemia due to hemolysis caused by ECMO treatment in combination with sepsis Normal serum Albumin at the time of maximum bilirubin value Failure of intensive phototherapy

13. Neonatal hyperbilirubinemia Patients Both patients were treated with exchange transfusion while on ECMO Decrease in bilirubin value (not 50%, but less) Rapidly increasing afterwards What to do? Repeat exchange transfusion? Or?

14. Neonatal hyperbilirubinemia Patients Therapeutic Plasma Exchange (TPE)?

15. Neonatal hyperbilirubinemia TPE Some early reports in the mideighties about plasmapheresis in newborns Some reports in the nineties about treatment of hyperbilirubinemia of the newborn by plasmapheresis Several recent reports on the efficacy of plasmapheresis for hyperbilirubinemia Little or no reports found on plasmapheresis in combination with ECMO as a treatment option for hyperbilirubinemia

17. Neonatal hyperbilirubinemia Patients Both our patients were treated with TPE while on ECMO. Fresh frozen plasma was used as replacement fluid In both patients TPE was effective in lowering serum bilirubin In both patients one TPE treatment session was sufficient Phototherapy was continued during and after TPE No serious side effects of the TPE were seen

19. Neonatal hyperbilirubinemia Patients Pt 1Pt 2 Bilirubin umol/l (mg/dl)408 (23,9)399 (23,3) Albumin gr/l3029 Exchange transfusion volume (ml) 600 Bilirubin umol/l (mg/dl)308 (18)260 (15,2) Bilirubin umol/l (mg/dl)333 (19,5)293 (17,1) TPE volume (ml)500250 TPE plasmavolume exchange 1.10.55 Bilirubin umol/l (mg/dl)198 (11,6)209 (12,2)

20. Neonatal hyperbilirubinemia What did we learn Take the bloodvolume of the ECMO system into account when calculating exchange transfusion volume and plasma volume to exchange for TPE In our patients the chosen exchange transfusion volume was to low (volume calculated based on ml/kg and forgotten to calculate the blood in the ECMO system) Would exchange transfusion with adequate blood volume have been enough?

21. Neonatal hyperbilirubinemia What did we learn In patiënt two the chosen plasma volume for the TPE was to low, but treatment was still effective Is removal of bilirubin the only thing that happened during TPE or was there something more done with TPE that prevented increase of bilirubin after treatment????

23. UMC St Radboud