Zhihong Liu Research Institute of Nephrology Jinling Hospital Nanjing University School of Medicine, China

Size: px

Start display at page:

Download "Zhihong Liu Research Institute of Nephrology Jinling Hospital Nanjing University School of Medicine, China"

Aubrie Higgins
5 years ago
Views:

1 Combined CRRT-bilirubin Adsorption System: A Novel Support System For Management of Critical Patients with Liver Failure Zhihong Liu Research Institute of Nephrology Jinling Hospital Nanjing University School of Medicine, China

2 Liver function synthesis excretory detoxication ALS: detoxication Bio-ALS Non-Bio-ALS Hybrid ALS

3 Water-soluble toxins Ammonia, phenols, nitrogenous waste producs, amino acid, fatty acid, etc Depurative modality: CRRT/IHD Protein-bound toxins Bilirubin, bile acid, etc Depurative modality: adsorption

4 The tightest binding to protein(>99%) Hardly removed by CRRT/IHD

$on their free fractions Meyer TW, et al.$

5 Removal of protein-bound solutes by CRRT dependent on their free fractions Meyer TW, et al. KI, 2005,68

6 Molecular adsorption recycling system(mars) Fractionated plasma separation adsorption system (PROMETHEUS) Plasma separation adsorption system

7 Albumin dialysis:mars Blood circulation Albumin Dialysate circulation Dialysate circulation MARS FLUX Dilyzer diamars IE250 Adsorber (resin) diamars AC250 Adsorber (Acitivated charcoal)

8 Transmembrane movement of bilirubin Free bilirubin moves across membrane by diffusion diffusion driven by free bilirubin concentration gradient between blood and albumin dialysate free bilirubin decline in blood facilitates bound bilirubin to dissociate from albumin

9 hemodialysis Free bilirubin in blood: very low concentration Even very small amount of free bilirubin diffuses into dialysate can make the free bilirubin concentration in dialysate rise close to blood, the concentration gradient between blood/dialysate declines, and diffusion stops Albumin dialysis Using albumin as dialysate, free bilirubin diffuses into dialysate will be bound by albumin, which keep the free bilirubin concentration in dialysate persistently lower than blood and diffusion sustained Persistent diffusion of free bilirubin into dialysate will make bound bilirubin in blood dissociate from albumin

10 Great divergence for bilirubin reduction ratio between different treatment sessions Gong D, Liu Z, et al, IJAO, 2008

11 TB(umol/L Concentration gradient between blood/dialysate: function of adsorbers Nevens F, Liver Transpl, 2005,11(7) Gong D, Liu Z, et al, IJAO, 2008

12 Blood and Dialysate clearance of bilirubin Evenepoel P, et al. Blood Purif, 2003,21

13 Albumin as dialysate Binding bilirubin in dialysate to keep a much lower free bilirubin level than blood Facilitates free bilirubin in blood to diffuse Decline of free bilirubin in blood facilitates dissociation of bound bilirubin from albumin The key step for bilirubin removal is its dissociation from albumin The tightness of bilirubin binding to albumin determines its dissociation from albumin Binding to the high affinity sites will result in worse dissociation and low clearance; binding to the low affinity sites will results in better dissociation and higher clearance The adsorption capacity of albumin in dialysate and adsorber are not saturated

14 Evenepoel et al. Blood Purif 2005

15 Evenepoel et al. Blood Purif 2005

16 Evenepoel et al. Blood Purif 2005

17 Dialysis using an albumin-permeable filter Albumin diffusion process taking bilirubin across membrane Blood Blood Blood Blood Albumin concentration Gradient declines albumin diffusion reduces bilirubin across membrane declines clearance declines Dialysate Dialysate Dialysate Dialysate Loss of some albumin and adsorbers unsatured

18 Plasma separation adsorption Through plasma protein convection, bilirubin is provided directly to the adsorber For removal of protein-bound toxins Not for water-soluble toxins

19 Combined CRRT-bilirubin adsorption system: a novel ALS Al SC: 1.0 IgG SC:0.9 IgM SC: 0.7 Al SC: 0.6 IgG SC:0.2 IgM SC: <0.1 Plamsa Adsorption modalities Plasma seperation: using a plasma seprator; Plasma perfusion: through an adsorber BRS350 and returned to the patient. Combined modalities Albumin-rich plasma separation: from blood when blood passes through a fraction plasma separator EC40W; Plasma ultrafiltration: using a hemofilter AV600 with simultaneous infusion of bicarbonated-based replacement fluid via predilution route into blood; Plasma perfusion: through an adsorber BRS350 and returned to the patient.

Compared with plasma adsorption: bilirubin clearance clearance(ml/min) 40 35

20 Compared with plasma adsorption: bilirubin clearance clearance(ml/min) 组合式 Combined modality 单纯吸附 Plasma adsorption min 2h 4h 6h 8h

21 Compared with plasma adsorption: bilirubin reduction ratio Reduction ratio(%) 80 组合式 70 Combined modality 单纯吸附 60 Plasma adsorption TB DB IDB Bile 胆酸 Acid BUN SCr

Δ(%) 80 70 60 50 Plasma adsorption 单纯吸附组合式 Combined

22 Δ(%) Plasma adsorption 单纯吸附组合式 Combined modality 白蛋白 APTT PT INR Fib Albumin

SBP mmhg DBP mmhg HR BPM Before After P Combined 92.7±13.6 102.6±18.3 0.004 PSA 112.3±13.9 111.1±13.3 0.788 Combined 56.0±11.7 59.4±15.7 0.241 PSA 58.8±11.6 60.6±10.7 0.396 Combined 109.2±21.2 101.

23 SBP mmhg DBP mmhg HR BPM Before After P Combined 92.7± ± PSA 112.3± ± Combined 56.0± ± PSA 58.8± ± Combined 109.2± ± PSA 89.7± ± APACHEII Combined 21.3± ± PSA 22.7± ± MELD Combined 20.4± ±3.2 < PSA 21.4± ± Glascow Combined 12.9± ± PSA 12.8± ±

24 Able to remove water-soluble toxins (BUN,SCR) Better for removal of protein-bound toxins (bilirubin, bile acid) No loss of albumin No deterioration of coagulation function Improvement of clinical conditions

27 Summary of combined CRRT-bilirubin adsorption system Mechanism for removal of bilirubin: Combined ALS: albumin convection taking bound bilirubin across membrane, persistent process until the adsorber being satured

28 Summary of combined CRRT-bilirubin adsorption system Using a fraction plasma separator Permitting only albumin(toxins carrier) to move across membrane into the adsorber preventing other proteins to go into the adsorber,reducing protein loss and blockade of the adsorber Hemofilter being built in plasma circuit Reducing extracorporeal blood volume Reducing the risk of extracorporeal circuit clotting Reducing the required dose of anticoagulant

29 Evolution of non-bio ALS From Bilirubin dissociation /diffusion To Albumin diffusion taking bilirubin To Albumin convection taking bilirubin

Physiology of Blood Purification: Dialysis & Apheresis. Outline. Solute Removal Mechanisms in RRT

Physiology of Blood Purification: Dialysis & Apheresis Jordan M. Symons, MD University of Washington School of Medicine Seattle Children s Hospital Outline Physical principles of mass transfer Hemodialysis