ringe single pass

Continuous Veno-Venous `Single Pass Albumin Haemodiafiltration (SPAD) in Acute Liver Failure (ALF) in Childhood H. I. G. Ringe, V.Varnholt, M. Zimmering*,W. Luck**, I.. M.Sauer ***

Pediatric Interdisciplinary Intensive Care Unit * Department of Pediatric Nephrology, ** Department Pediatric Gastroenterology,*** Department of Experimental Transplant Surgery

Charit Campus Virchow BerlinGermany

Albumin dialysis membrane50 K Da

Continuous Veno- Venous Single Pass Albumin Haemodiafiltration ( SPAD)

Albumin 20% . 70 ml/h

Roler pump 1

Filtrate pump

Substitute 400ml/h

Highfluxfilter

Waste 800ml/h

Substitute 330ml/h

Roler pump 2

Substitute pump

Blood pump

SubstituteAlbumin 20%Roler pumpSubsitute pump Blood pump

Tabelle1

PatientSexAge yearsBody weight KgDiagnosis

Df318ALF, pyrrolizidine alkaloid like intoxication, aplastic anaemia

Bf724Amanita poisoning

Rm1258ALF unknown origin

Hf516post re- LTX failure of the donated organ unsuitable for Re-Transplantation

m1152Valproate intoxication, hepatitis A, kidney failure, LTX failure, haemodialysis

Km1260Streptococcal -A -septicaemia, CPR, MOF, haemodialysis, HFO

M1+2m622M . Wilson crisis, kidney failure, haemolysis

Ff1461ALF unknown origin

Indication for SPAD and LTX

PatientINR >4Bilirubin >20 mg/dlOthersEncephalopathy grade (1-4)DyesyesNH33 ByesnoNH33-4 Ryesyes - 2-3 Hnoyes2nd LTx unsuitable for re-LTX1-2noyesCVVH for hepato-renal-failure3-4 KyesnoMOF CVVH elemination of endotoxin and TNF- etc intubated sedated paralizedM1+23,6 + >4yesNH3, Wilson crisis haemolysis, M2 post -tx hepatorenal failure1-2F2,5yesNH3 1

GoalsReduction of toxinsLaboratory results: bilirubin, bile-acid, NH3 Encephalopathy scoreBlood pressure stabilisation

Recovery of liver function :Laboratory results: fibrinogen, PTZCytokines ?

Side effectsPlatelet count Cytokines (IL2-Receptor, IL6, IL 8, IL 10, TNF-, LPS BP)Clinical data

Diagramm1

21.55206105

148754

111779

mg/dl mol/l

mean bilirubin mg/dl

mean bile acid mol/l

mean NH3 mol/l

Bilirubin, bile acid and NH3 mean serum levels pre, 12 and 24 hours post SPAD

Tabelle1

01224 hours

mean bilirubin mg/dl221411

mean bile acid mol/l2068717

mean NH3 mol/l1055479

Tabelle1

mean bilirubin mg/dl

mean bile acid mol/l

mean NH3 mol/l

Bilirubin and bile acid mean serum levels pre, 12 and 24 hours post SPAD

Tabelle2

Tabelle3

Diagramm2

67597471696288825769

76599268646786836969

109568262497271967472

106608469576987978684

110598445526381949681

88589661566485957777

90568964667084977777

935810065655978958878

605597655959871059965

905599626156841099084

985510562426183908783

99539660526481938881

101599558486576998376

10655101675976771008477

105549268707176647871

104569871626770578970

112599468586669655966

103579171777977816777

101549566727081926572

D

K

H

R

B

M1

M2

F

Median

Hours before and during SPAD

MAPmm Hg

MAP during SPAD

Tabelle1

Demirci 15.9.Kretzer 27.7.03hummel 29.11.02nsal 30.10.00Remmers Florian 20.6.200271707989-10

Patient R58727247-960

55757668-8

54708067-7

50608071-6

-561609075

-4645810285

-3686310172

-262609184

DKHRBM1M2FMedianMittelwertMedian

-1675974716962888257697472.5

0765992686467868369697775.5

11095682624972719674727271.5

21066084695769879786847776.5

31105984455263819496817072

4885896615664859577777674.5

5905689646670849777777877

69358100656559789588787771.5

76055976559598710599657976

89055996261568410990847973

99855105624261839087837472.5

10995396605264819388817472.5

111015995584865769983767470.5

12106551016759767710084778076.5

131055492687071766478717470.5

141045698716267705789707168.5

151125994685866696559667067

161035791717779778167777978

171015495667270819265727976.5

vor CVVAHD725974716874

nach CVVAHD995694646374

-1

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

Tabelle2

Tabelle3

* = FFP 6 hourly

Diagramm5

332132205115134176168397175

181791877212315882177175

1121061805915215985116157

175105195923636364036

1999848814848484048

2506060606060606060

1517272727272727272

1719696969696969696

170108108108108108108108108

192120120120120120120120120

187132132132132132132132132

SPAD ceased

H

D*

R*

K

B

M1*

M2*

F

SPAD duration hours

Fibrinogen mg/dl

Fibrinogen during SPAD

Tabelle1

Patient HPatient DPatient Patient RPatient KPatient BM1M2

0613752193212168397

1260205015292082177

2446204612382185116

366122432340

4874161640

6080

7260

9660

10861

12065

13260

Tabelle1

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

Patient H

Patient D

Patient

Patient R

Patient K

Patient B

Zeit

Quick %

Quick vor und nach CVVAHD

Tabelle2

HD*R*KBM1*M2*F

0332132205115134176168397175

12181791877212315882177175

241121061805915215985116157

361751051959240

48199988140

60250

72151

96171

108170

120192

132187

Tabelle2

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

H

D*

R*

K

B

Stunden

Fibrinogen mg/dl

Fibrinogen vor und nach CVVAHD

Tabelle3

Patient HPatient DPatient Patient RPatient KPatient B

093220378383425

1283100356036214

243530304850171

3647293144

48383486

603678134

722178128

9633108133

1083969142

1206970156

1323462150

1444177189

1563995161

16856102

Tabelle3

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

Patient H

Patient D

Patient

Patient R

Patient K

Patient B

Zeit

Thrombozyten /nl

Thrombozyten vor und nach CVVAHD

*=FFP 6 hourly

Diagramm2

613752193212293134

602050152920191829

462046123821221926

612243233636361336

74164816484848748

806060606060606060

607272727272727272

609696969696969696

61108108108108108108108108

65120120120120120120120120

60132132132132132132132132

SPAD ceased

H

D*

R*

K

B

M1*

M2*

F

SPAD duration hours

PTZ %

Pro-thrombine time (PTZ ) under SPAD

Tabelle1

HD*R*KBM1*M2*F

0613752193212293134

12602050152920191829

24462046123821221926

366122432313

487416167

6080

7260

9660

10861

12065

13260

Tabelle1

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

H

D*

R*

K

B

Zeit

Quick %


Tabelle2


0332132205115134176

121817918772123158

2411210618059152159

3617510519592

481999881

60250

72151

96171

108170

120192

132187

Tabelle2

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

Patient H

Patient D

Patient

Patient R

Patient K

Patient B

Zeit

Fibrinogen mg/dl


Tabelle3


093220378383425

1283100356036214

243530304850171

3647293144

48383486

603678134

722178128

9633108133

1083969142

1206970156

1323462150

1444177189

1563995161

16856102

Tabelle3

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

Patient H

Patient D

Patient

Patient R

Patient K

Patient B

Zeit

Thrombozyten /nl


SPADceased 425

Diagramm6

932203783834256337144

83100356036214361596

35302448501711618101

472936443636361436

383448864848482448

366060606060606060

217272727272727272

339696969696969696

39108108108108108108108108

69120120120120120120120120

74132132132132132132132132

* = FFP 6 hourly

H

D*

R*

K

B

M1*

M2*

F

SPAD duration hours

Platelets /nl

Platelets under SPAD

Tabelle1

Patient HPatient D*Patient Patient R*Patient KPatient B

0613752193212

12602050152920

24462046123821

3661224323

48741616

6080

7260

9660

10861

12065

13260

Tabelle1

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

Patient H

Patient D*

Patient

Patient R*

Patient K

Patient B

Zeit

Quick %


Tabelle2

HD*R*KB

0332132205115134176

121817918772123158

2411210618059152159

3617510519592

481999881

60250

72151

96171

108170

120192

132187

Tabelle2

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

H

D*

R*

K

B

Stunden

Fibrinogen mg/dl


Tabelle3

HD*R*KBM1*M2*F

0932203783834256337144

1283100356036214361596

24353048501711618101

3647294414

4838348624

6036

7221

9633

10839

12069

13274

Tabelle3

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

000000

H

D*

R*

K

B

Zeit

Thrombozyten /nl


Patient DPatient BFollow up in auxiliary transplantation

Tabelle1

PatientHepatic Encephalopathy Grade pre/post SPADLength of SPADSPAD bridgeOutcome

D3 / 251 hoursyes -auxilary LTX successful, SAA BMT 6 month later, GVHD died

B3-4 / 2-318 hoursyes ++auxillary LTX, own liver recovered, alive

R2-3 / 136 hoursyes +LTX, alive

H1-2 / 024 hours continuous 3 days 4-11 hours /dyes/ no Re-LTXOrgan recovered, alive

3-4 / 3-42 hoursnoBioreactor, Re- LTX,aspergillus septicaemia, died

Kintubated sedated paralized35 hoursyes -treatment withdrawal, brain death

M1+21-2/1-215/42 hoursYes -/ Yes-LTX and Re-LTX , Aspergillus septicaemia, brain haemorrhage, died

F1 / 020 hoursyes +successfully bridged to LTX , alive

Diagramm1

17.72.40254296

7.268.113.8pg/ml ml/min/1,73 M1848

24064pg/ml ml/min/1,73 D128

Serum 0 hours

Serum 12 hours

Serum 24 hours

Urine

SPAD

IL 6 serum levels pg/ml during 24 hour SPAD and urine and SPAD clearance ml/min/1,73 m2(n=3)

0

Tabelle1

IL 6 pg/ml pg/ hSerum 0 hoursSerum 12 hoursSerum 24 hoursUrineSPADUrine IL 6 / hourCAVVH IL 6 / hourUrine pg/mlDialysate pg/mlUrine pg/kg/hSPAD pg/kg/h

pg/ml ml/min/1,73 F17.72.42,4254296530623< 2 - 6,1< 2 - 3,88.810.3

pg/ml ml/min/1,73 M17.268.113.8848.03,2-10,2246.0

pg/ml ml/min/1,73 D24.00.064.0128.03320.0184.0

IL 6 mean16.323.538.9254.0424.08.8146.8

Tabelle1

Serum 0 hours

Serum 12 hours

Serum 24 hours

Urine

SPAD

IL 6 serum levels pg/ml during 24 hour SPAD and urine and SPAD clearance ml/min/1,73m2

0

Tabelle2

IL 6 mean levels pg/ml during 24 hour SPAD and mean urine and dialysate extraction in pg/kg/hour

Tabelle3

Diagramm1

4818.525.50 12 24h 6 12 24 h 6 12 24 h Patient F152525673.63.73

7.257.91100 12 24h 6 12 24 h Patient M14151392322313930 12 24h 6 12 24 h Patient M10 12 24h 6 12 24 h Patient M10 12 24h 6 12 24 h Patient M1

ml/min 1.73 pg/kg/min pg/ml

Clearance

Clearance

Serum pg/ml

Serum pg/ml

Serum pg/ml

SPAD pg/kg/min

SPAD pg/kg/min

SPAD pg/kg/min

SPAD Clearance ml/min 1.73m2

Urine pg/kg/min

Urine pg/kg/min

Urine pg/kg/min

Serum IL-8 pg/ml during 24 hour SPAD and urine plus SPAD extraction g/kg/min and SPAD clearance ml/min 1,73m2 (n=2)

Tabelle1

IL 8Serum pg/mlSerum pg/mlSerum pg/mlSPAD pg/kg/minSPAD pg/kg/minSPAD pg/kg/minSPAD Clearance ml/min 1.73m2Urine pg/kg/minUrine pg/kg/minUrine pg/kg/minUrine pg/mlDialysate pg/mlSPAD IL 8 pg/kg/Min

0 12 24h 6 12 24 h 6 12 24 h Patient F4819261525256744319,9-16228,9-5318

0 12 24h 6 12 24 h Patient M1758110415139232231393549-42551194

IL 8Serum pg/mlSerum pg/mlSerum pg/mln.a.SPAD pg/kg/minSPAD pg/kg/minSPAD pg/kg/minn.a.Urine pg/kg/minUrine pg/kg/minUrine pg/kg/minUrine pg/mlDialysate pg/mlSPAD IL 8 pg/kg/Min

0 12 24h 6 12 24 h 6 12 24 h Patient F48192615252544319,9-16228,9-5318

0 12 24h 6 12 24 h Patient M175811041513923223549-42551194

Tabelle1

0000000000

0000000000

Serum pg/ml

Serum pg/ml

Serum pg/ml

SPAD pg/kg/min

SPAD pg/kg/min

SPAD pg/kg/min

SPAD Clearance ml/min 1.73m2

Urine pg/kg/min

Urine pg/kg/min

Urine pg/kg/min

pg/kg/min pg/ml

Serum IL 8 levels pg/ml and urine and dialysate extraction pg/kg/min 0,12 and 24 hours after SPAD (n=2)

Tabelle2

Tabelle3

Diagramm1

142212611318

66.485950.26.3

Serum 0 hours

Serum 12 hours

Serum 24 hours

Urine

Dialysate

Serum PCT and PTH pg/ml during 24 hour SPAD and their urine and SPAD extraction pg/kg/hour

Tabelle1

Pre12 hours24 hours

TNF alpha pg/ml24.413.717.3

IL 2 IU/ml281131282667

IL 6 pg/ml17.72.41

IL 8 pg/ml4818.525.5

IL 10 pg/ml4644.656

LPS b P g/ml9.776.1

Pre12 hours24 hours

IL 2 IU/ml281131282667

IL 8 post Haemolysis pg/ml11921916

Serum 0 hoursSerum 12 hoursSerum 24 hoursUrineDialysateUrin /hourDialysat/ hour

PCT pg/ml pg/kg/min1422126113184732466256

PTH pg/ml pg/kg/in66.485950.26.378322983

PCT pg/ml6625647324

PTH pg/ml22983783

Tabelle1

000

000

000

000

000

000

Pre

12 hours

24 hours

Plasma cytokines pre and post CAVVH

Tabelle2

Tabelle3

Diagramm2

24.413.717.3225

28113128266720

17.72.41254296

Serum 0 hours

Serum 12 hours

Serum 24 hours

Urine

SPAD

TNF alpha, IL2-Receptor and IL 6 serum levels during SPAD and urine- and SPAD-clearance ml/min/1,73 m2

Tabelle1

Serum 0 hoursSerum 12 hoursSerum 24 hoursUrineSPADUrine cytokine / hourCAVVH cytokine/ hour12 hours24 hoursUrineSPAD

TNF-a pg/ml ml/min/KO24.413.717.322519642094513.717.315.8

IL 2 R IU/ml ml/min /KO2811312826672< 80000209588< 800003128266758< 80000

IL 6 pg/ml ml/min/KO17.72.412542965306232.4111

IL 8 pg/ml4818.525.52041167122517000618.525.52041167

IL 10 pg/ml4644.656< 90017< 900100144.656< 90017

LPS b P g/ml9.776.11.51290.771376.11.512

12 hours24 hours

31282667

1916

PCT pg/ml473246625647324662564732466256

PTH pg/ml783229837832298378322983

Tabelle1

24.413.717.3252

28113128266702

17.72.41296254

4818.525.51167204

4644.656170

9.776.1121.5

Serum 0 hours

Serum 12 hours

Serum 24 hours

SPAD

Urine

Cytokine Serum Levels during CAVVH and Hourly Extration via Urine and CAVVH

Tabelle2

Tabelle3

48192605446455600.39.776171360102030405060IL 8 pg/ml ml/min KOIL 10 pg/ml ml/min KOLPS b P g/ml ml/min KOCytokine serum levels during SPAD and urine- and SPAD-clearance ml/min 1,73m2Serum 0 hoursSerum 12 hoursSerum 24 hoursUrine SPAD

Costs: SPAD versus MARSSPADMA R S

HA 20%

2-4 L/d

235- 470 Euro

Filter

1 Filter

43 Euro

Bag production

2 Bags

20 Euro

Substitute solution

9-18 L/d

21- 42 Euro

SPAD

Sum/d

338 574 Euro

MARS system

8 hours effective

2 Adsorbers

1 Filter

1840 Euro

HA 20%

600 ml

70 Euro

MARS

Sum / d

1910 Euro

Conclusion

SPAD :- lowers effectively bilirubin, bile acids und ammonium in ALF

- reduces hepatic encephalopathy

- is well tolerated in case of SPAD System pre-filling even in a catecholamine dependant patient

- stabilizes children prior to LTX and is helpful for bridging to transplantation.

ConclusionSide effectsAllergic reaction to human albuminThrombocytopenia (HIT)

Unclear Whether SPAD can replace liver function until liver recovery appearsRole of cytokine reduction / stimulation

Definition of criteria to distinguish between those who recover or not is needed (Cytokines, Coagulation, HE ?)

SPAD is easy to set up and cheaper than MARS

ringe single pass

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