9 th International p CRRT Conference on Pediatric

9 th International p. CRRT Conference on Pediatric Continuous Renal Replacement Therapy August 31 -September 2, 2017 Plasmapheresis With (and Without) CRRT Jordan M. Symons, MD University of Washington School of Medicine Seattle Children’s Hospital

Apheresis • “Apheresis”: Greek, “To take away or separate” • Blood perfuses extracorporeal circuit Hey!Pheresis® • Blood components separated; selected component removed • If large volume removed replacement is required • Uses include therapeutic indications or for blood component harvest

• American Society for Apheresis (AFSA) • List of indications with Fact Sheets – 87 diseases/medical conditions; 179 indications • Rigorous review – Strength of recommendation; ratings of evidence • Many modalities along with TPE evaluated – Cytaphersis, extracorporeal photopheresis, immunoadsorption, rheopheresis, etc.

ASFA Fact Sheet Format Schwartz et al. Journal of Clinical Apheresis 31: 149– 338 (2016)

Schwartz et al. Journal of Clinical Apheresis 31: 149– 338 (2016)

Therapeutic Apheresis in Critically Ill Patients • Added challenges to TPE in ICU – Critically ill patient – less stable – Already limited vascular access – More prone to complications • Hypo. Ca, low BP, blood product reactions (TRALI) • Uncertainty of TPE effects in critically ill – Theory: non-specific immunomodulation – Practice: case-reports and small studies suggest improvement; RCTs do not support

Can TPE Help our Patients who have Sepsis with Multi-Organ Failure? • Why TPE might work – Remove inflammatory and antifibrinolytic mediators – Replenish anticoagulant proteins (FFP replacement) – Reverse derangement, restore hemostasis • Category III indication (ASFA Guidelines 2016) – “Optimum role of apheresis therapy is not established” – “Decision making should be individualized” • Grade 2 B evidence • Selective endotoxin binding columns? – Some suggestion of improvement – In Europe and Asia; not in United States

Plasma Exchange: Technique

Components of Whole Blood Separation and removal of individual components may be required for therapeutic need

Pheresis. Philtre. PLUS Membrane Apheresis: Separates Components by Size Plasmafilter: Similar to CRRT hemofilter but with larger pores

Membrane Apheresis: Separates Components by Size Creatinine 113 D Urea 60 D Glucose 180 D Vancomycin ~1, 500 D Albumin ~66, 000 D Ig. G ~150, 000 D • Larger pores will allow proteins to pass through • Blood cells are restricted • Membrane system can be used for plasmapheresis, not cytapheresis

Apheresis by Centrifugation: Separates Components by Density Hey!Pheresis® • Spinning centrifuge separates blood components by density • Specific component may be selected for removal by choosing appropriate layer • Permits plasmapheresis and cytapheresis

Apheresis by Centrifugation: Separates Components by Density Blood in from patient Plasma Hey!Pheresis® WBCs, Plts RBCs Blood return

Fraction Removed from Plasma by Plasma Volume Replaced 1 -x y=e 0. 9 Remaining fraction 0. 8 0. 7 0. 6 0. 5 0. 4 0. 3 0. 2 0. 1 0. 223 (77. 7% removed) 0 0 0. 5 1 1. 5 Plasma volumes 2 2. 5 3 • Ig. G: only 45% intravascular • 1. 5 vol removes ~35% of total body Ig. G • Re-equilibration within ~2 days • Repeated session QOD often needed

Plasma Ig. G Levels Before and After Apheresis % of Original Level 120 100 80 60 40 20 0 Post 1 Post 2 Post 3 4 Treatment Day Post 5 Post 6

Pediatric Considerations • Used less often in children than adults – Diseases less common – Physicians less familiar • Technically more challenging – No pediatric devices – Circuit volume (blood prime? ) – Vascular access – Complications more frequent than adults

Tandem Apheresis and CRRT • Apheresis and CRRT simultaneously (same access) • Avoid interruption of CRRT • Avoid risks/challenges associated with CRRT restart • Need appropriate preparation, procedures, systems in place to assure safety/efficiency

Apheresis in Parallel with CRRT Return to Patient NOTE: Reduce CRRT Qb by rate of apheresis Qb From Patient

Apheresis in Parallel with CRRT Return to Patient NOTE: Likely need higher Qb for membrane From Patient

Apheresis in Series with CRRT Return to Patient NOTE: Qb is the SAME From Patient

Apheresis in Series with CRRT Return to Patient From Patient

Secondary Plasma Processing Return to Patient • Plasma regeneration • Adsorptive columns • Selective filters From Patient

Summary • Therapeutic plasmapheresis may be necessary in critically ill patients, some of whom may also require CRRT • Utility in MODS/sepsis remains unclear • Apheresis can be combined with CRRT • Newer techniques may permit plasma regeneration of more selective apheresis

Thanks for your attention!