AN INTRODUCTION TO EXTRACORPOREAL BLOOD PURIFICATION IN CRITICAL ILLNESS. Proceedings of Singapore Healthcare Volume 21 Number

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1 AN INTRODUCTION TO EXTRACORPOREAL BLOOD PURIFICATION IN CRITICAL ILLNESS Proceedings of Singapore Healthcare Volume 21 Number 本檔僅供內部教學使用檔案內所使用之照片之版權仍屬於原期刊公開使用時, 須獲得原期刊之同意授權

2 Mechanisms of Extracorporeal Blood Purification Diffusion Convection Adsorption

3 SOLUTE FACTORS AFFECTING EXTRACORPOREAL BLOOD PURIFICATION Molecular Weight Low molecular weight solutes (less than 500 Daltons) reach equilibrium rapidly in diffusive transport Protein Binding and Volume of Distribution Highly protein-bound solutes or those with large volumes of distribution are generally not dialysable. Haemoperfusion or albumin dialysis.

4 SYSTEM FACTORS AFFECTING EXTRACORPOREAL BLOOD PURIFICATION Vascular Catheter adequate blood flow rates to achieve the target solute clearance minimal complications such as infections and thrombosis Membrane The mass transfer area coefficient K OA The ultrafiltration coefficient K UF Anticoagulation Systemic anticoagulation with unfractionated heparin Regional citrate anticoagulation

5 TYPES OF EXTRACORPOREAL BLOOD PURIFICATION THERAPIES USED IN CRITICALLY ILL PATIENTS 1. Continuous Venovenous Haemofiltration(CVVHF) 2. Continuous Venovenous Haemodialysis(CVVHD) 3. Continuous Venovenous Haemodialfiltration (CVVHDF) 4. Standard Intermittent Haemodialysis (HD) 5. Sustained Low Efficiency Dialysis (SLED) 6. Intermittent Haemodialfiltration (HDF) 7. High Volume Haemofiltration (HVHF) 8. Haemoperfusion or Haemoadsorption 9. Selective Plasmapheresis Techniques

6 CVVHF, CVVHD, CVVHDF

7 HD, SLED, HDF HD Blood flow rates range from ml/min dialysate flow rates are typically ml/min diffusive transport of small solutes SLED blood and dialysate flow rates are slower, less haemodynamic fluctuation. HDF diffusive and convective solute transport mechanisms increase removal of middle molecules

8 High Volume Haemofiltration (HVHF) a variant of CVVH with larger therapy volumes of up to ml/kg/h for 24 hours each day. Intermittent pulse HVHF is defined as brief, very-high-volume treatment at ml/kg/h for four to eight hours

9 Haemoperfusion or Haemoadsorption Whole blood is circulated through thin, porous membranes containing sorbents.

10 Selective Plasmapheresis Techniques A: separation of plasma from blood by centrifugation or plasma filtration using membranes with pore diameters of 0.20 B: Separated plasma is circulated through sorbent columns and then returned to blood within the extracorporeal circuit where it passes through a

11 Selective Plasmapheresis Techniques C: Coupled Plasma Filtration Immunoadsorption (CPFIA) similar to CPFA sorbent used are beads with immobilised antigens or specific monoclonal antibodies. Ex: Protein A (a 42 kdalton protein derived from Staphyloccocus aureas) which adsorbs immunoglobulin.

12 Renal Replacement Therapy (RRT) In Acute Kidney Injury (AKI) AKI in critically ill patients is associated with high mortality of up to 60% Dialysis Modalities: intermittent (IRRT) and continuous (CRRT) Dialysis Intensity Dialysis Initiation

13 Dialysis Intensity Acute Renal Failure Trial Network study SLED or intermittent haemodialysis 6 sessions per week or pre-dilution CVVHDF with effluent flow rate 35 ml/kg/h SLED or intermittent HD 3 sessions per week or predilution CVVHDF with effluent flow rate 20 ml/kg/h no difference in 60-day mortality rates The Australian and New Zealand Intensive Care Society Clinical Trials Group effluent flow rate 40 ml/kg/h compared to effluent flow rate 25 ml/kg/h no difference in outcomes

14 Dialysis Initiation

15 Dialysis Initiation

16 BLOOD PURIFICATION IN SEPSIS Clearance of harmful cytokines involved in the SIRS CVVH: inadequate in removing significant numbers of tumour necrosis factor alpha (TNFalpha) or interleukins compared to endogenous clearance High cut-off haemofilter membranes, highvolume haemofiltration (HVHF), haemoperfusion and CPFA

17 BLOOD PURIFICATION IN SEPSIS HVHF improve cardiac output in animal studies Joannes-Boyau et al treated 24 septic shock patients with high volume CVVH (ultrafiltration rates ranged from 40 ml/kg/h to 60 ml/kg/h) for 96 hours significant improvement in blood pressures and corresponding reduction in norepinephrine doses. Improvement in these patients observed mortality compared to their predicted 28-day mortality. Same observation in other study

18 BLOOD PURIFICATION IN SEPSIS Large-scale studies are lacking Acute Dialysis Quality Initiative (ADQI) suggests that HVHF may be used in catecholamine-resistant septic shock by clinicians familiar with HVHF therapies Polymyxin B: haemoperfusion, as sorbents remove endotoxins by chemo-adsorption EUPHAS (Early Use of Polymyxin B Haemoperfusion in Abdominal Sepsis) improvement in haemodynamics decreased mortality at 28 days

19 BLOOD PURIFICATION IN SEPSIS Plasma exchange Evaluated in a single-centre study of patients with high APACHE III scores plasmapheresis group received the first treatment within six hours of diagnosis and a second treatment within 24 hours if there was no clinical improvement lower 28-day mortality this difference was diminished after multiple logistic regression.

20 BLOOD PURIFICATION IN SEPSIS CPFA few publications in septic patients but a pilot study demonstrated improved haemodynamics new generation of membranes Ex: oxiris (Gambro, Lund, Sweden) Endotoxin adsorption

21 BLOOD PURIFICATION IN HEPATIC FAILURE support liver detoxification and bridge patients with ALF or acute-on-chronic liver failure (AoCLF) to either recovery or orthotropic liver transplantation Single pass albumin dialysis(similar to CVVHDF) Blood flows through a standard albuminimpermeable high-flux dialyser Countercurrent to an albumin-containing dialysate Protein-bound molecules that are small

22 Molecular Adsorbent Recirculating System(MARS) Spent albumin dialysate is regenerated in a secondary circuit consisting of charcoal and an anion exchanger resin in series to remove albumin-bound solutes by adsorption.

23 MARS therapy Improved hepatic encephalopathy and renal function Inadequate evidence for survival benefit compared with standard medical therapy Meta-analysis by Khuroo et al, MARS treatment did not reduce mortality significantly compared with standard medical treatment RELIEF trial(to date): did not demonstrate a statistically significant beneficial effect of MARS on 28-day survival for patients with AoCLF

24 Fractionated plasma separation and adsorption (FPSA) Prometheus (Fresenius Medical Care, Bad Homburg, Germany) Albumin-permeable filter is used to separate albumin-rich plasma which then enters a secondary circuit and passed through a resin adsorption column and an anion exchanger HELIOS trial in 145 patients with AoCLF reported no statistical difference in 90-day survival between Prometheus and standard medical therapy sub-group analysis found improved survival in patients with hepatorenal syndrome type I or MELD score >30 treated with Prometheus

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26 Blood purification in humoral-mediated disease Removing plasma-borne humoral disease mediators Immunoglobulins and circulating immune complexes (CIC) acute and chronic inflammatory demyelinating polyneuropathy anti-glomerular basement membrane (anti-gbm) disease thrombotic thrombocytopenic purpura-haemolytic uremic syndrome (TTP-HUS)

27 Blood purification in humoralmediated disease CPFIA with Immusorba columns (Asahi Medical, Tokyo, Japan) and Prosorba columns (Cypress Bioscence, San Diego, USA) autoimmune neurological diseases: Gullain-Barré syndrome rheumatologic diseases: systemic lupus erythematosus and rheumatoid arthritis haematological diseases: autoimmune thrombocytopenic purpura small case series or uncontrolled comparative studies

28 Blood purification in humoralmediated disease Kidney transplantation Donor-specific anti-hla antibodies or ABOincompatibility is associated with high graft loss rates from antibody-mediated rejection Part of desensitisation protocols: Therapeutic apheresis with either plasma exchange or CPFIA with Protein A adsorption columns Remove donor-specific antibodies to permit highimmunologic risk transplants, including ABOincompatible transplants

29 Blood Purification in Toxicology standard haemodialysis was limited to removal of low molecular weight, water-soluble drugs: lithium and methanol Intoxication with protein-bound drugs such as theophylline, phenobarbitone and carbamazepine generally required treatment with activated charcoal haemoperfusion(expensive) More haemodialysis, less haemoperfusion now: High flux membranes

30 Conclusion