Therapeutic Plasma Exchange for hyperbilirubinemia in two newborns during

Extra Corporeal Membrane Oxygenation

Linda Koster-Kamphuis, pediatric nephrologist

Nijmegen, The Netherlands

Neonatal hyperbilirubinemiaBackground

• Bilirubin product of heme catabolism

Heme oxygenase (HO)

• Heme Carbon monoxide (CO) + Biliverdin

Biliverdin reductase

• Biliverdin Bilirubin

Neonatal hyperbilirubinemiaBackground

Bilirubin + Albumin complex Liver

Hepatocyte:

Conjugation of bilirubin with glucuronic acid (UGT)

Conjugated bilirubin is excreted in bile.

Neonatal hyperbilirubinemiaBackground

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”

Neonatal hyperbilirubinemiaBackground

Normal physiologic alterations result in mild unconjugated bilirubinemia in nearly all newborns

• Higher bilirubin production

• Decreased bilirubin clearance

• Increase in enterohepatic circulation of bilirubin

Neonatal hyperbilirubinemiaBackground

Bilirubin Neurotoxicity

Acute bilirubin encephalopathy 

Kernicterus

Neonatal hyperbilirubinemiaBackground

Treatment

Phototherapy

Improving breastfeeding or supplementing with formula

Pharmacologic agents (Phenobarbital, Ursodeoxycholic

acid)

Exchange transfusion

Neonatal hyperbilirubinemiaBackground

Exchange transfusion

Bloodvolume 80-90 ml/kg

Exchange volume 160-180 ml/kg (2 x bloodvolume)

Around 50% reduction in serum bilirubin value

Neonatal hyperbilirubinemiaPatients

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

Neonatal hyperbilirubinemiaPatients

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

Neonatal hyperbilirubinemiaPatients

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?

Neonatal hyperbilirubinemiaPatients

Therapeutic Plasma Exchange (TPE)?

Neonatal hyperbilirubinemiaTPE

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

Neonatal hyperbilirubinemiaPatients

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

Neonatal hyperbilirubinemiaPatients

Pt 1 Pt 2

Bilirubin umol/l (mg/dl) 408 (23,9) 399 (23,3)

Albumin gr/l 30 29

Exchange transfusion volume (ml)

600 600

Bilirubin umol/l (mg/dl) 308 (18) 260 (15,2)

Bilirubin umol/l (mg/dl) 333 (19,5) 293 (17,1)

TPE volume (ml) 500 250

TPE plasmavolume exchange

1.1 0.55

Bilirubin umol/l (mg/dl) 198 (11,6) 209 (12,2)

Neonatal hyperbilirubinemiaWhat 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?

Neonatal hyperbilirubinemiaWhat 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????

UMC St Radboud