CPFA - Coupled Plasma Filtration Adsorption La risposta mirata alla SEPSI Marco POZZATO Struttura Complessa di Nefrologia e Dialisi (Direttore: Dr. F. Quarello) Ospedale S. Giovanni Bosco - Torino

Casi di sepsi NEJM 348:1546 (2003)

Sorbent ‘80s ‘90s Dialysate Recycling Poisoning treatment Ultrafiltrate regeneration Hemodiafiltration Coupled plasma filtration-adsorption Plasma filtrate Sorbent ‘90s ‘80s “Coated” “Uncoated” implicated in many activities directed at assessing the potential advantages of sorbents in the clinical application both in acute and chronic patients. In the ‘80, sorbents such as biomedical charcoal, resins such as XAD 7, have been used in dialysate regeneration and in the treatment of poisoning. Nevertheless, a number of untoward effects have been described and are well known to occur when sorbents of these kinds are used in direct contact with blood such as thrombocytopenia, hemolysis and coagulation. The use of the sorbents was often limited to coated sorbents that, in the direct contact with blood would limit the bioincompatibility due to charcoal or other synthetic sorbents. Only in the ‘90, we could clinically apply hemodialytic techniques that could enable us to use uncoated charcoal and resins in both chronic (hemodiafiltration) and acute (coupled filtration-adsorption) treatments

SORBENTI granuli, sfere o piccoli cilindri diametri variabili da pochi µm a circa 1 cm con superfici variabili da 300 a 1200 m2/g dimensioni dei pori come macropori (50 nm), mesopori (2-50 nm), micropori (<2 nm) geometrie differenti al fine di rendere l’adsorbimento da parzialmente a molto selettivo

Tipi di sorbenti nella pratica clinica Trattamento Non Selettivi Charcoal coated / uncoated. Uncharged resins (Amberlite XAD-7) Hydrophobic resins Powdered sorbent Hemoperfusion Hemodiafiltration Coupled plasma filtration adsorption (CPFA) Hemodiadsorption Selettivi Microphere-based detoxification system Engineered matrices: Polymyxin-B Engineered matrices: Polyethyleneimine Regenerative push-pull pheresis Polystyrene-derivative fibers Macroporous cellulosic beads

Inquadramento SIRS, SEPSI, MOF INFEZIONE SIRS SEPSI SEPSI GRAVE MOF SHOCK SETTICO

Inquadramento SIRS, SEPSI, MOF Temperatura corporea > 38°C o <36°C Frequenza cardiaca > 90 bpm Frequenza respiratoria > 20 Leucocitosi >12000 Leucopenia <4000 Mutamenti omeostasi

Inquadramento SIRS, SEPSI, MOF Infiammazione sistemica Alterazioni della coagulazione Fibrinolisi Disfunzione endoteliale Trombosi microvascolare

Inquadramento SIRS, SEPSI, MOF Alterazione coscienza Confusione mentale e/o psicosi Ipotensione (PAS <90) Tachicardia (FC >100) PaO2 < 70 SaO2 < 90% PaO2/FiO2 < 300 Aumento CVP e PAOP Oliguria, anuria, aumento ritentivi Indice di shock: FC/PAS <0.9

MULTIPLE ORGAN DISFUNCTION ipoperfusione Infezione / Trauma SIRS SEPSI SEPSI GRAVE SHOCK SETTICO MULTIPLE ORGAN DISFUNCTION

Volume 345:1368-1377 November 8, 2001 Number 19 Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D., Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson, Ph.D., Michael Tomlanovich, M.D., for the Early Goal-Directed Therapy Collaborative Group

SEPSI: DEA flow-chart

Sepsi: Protocollo di Trattamento Precoce

Sepsi: Mortalità

Sepsi: Organi e Apparati interessati

Sepsi: danno d’organo

Epidemiologia dell’IRA 5-7% di tutti i pazienti ospedalizzati 40-50% necessitano di dialisi 40-90% di mortalità nei soggetti sottoposti a trattamento dialitico Himmelfarb J. J Am Soc Nephrol 1998;9:257-66

Insufficienza Renale Acuta Trattato di NEFROLOGIA (1995). A. Vercellone, G. Piccoli, GP. Segoloni, P. Stratta Insufficienza Renale Acuta PRE-RENALE PARENCHIMALE POST-RENALE necrosi tubulare acuta patologia vascolare nefrite interstiziale acuta GN acuta The Lancet vol. 365, January 29, 2005, p. 417-430

RIFLE Criteria for Acute Renal Dysfunction GFR Criteria* Urine Output Criteria Increased Cr x 1.5 or GFR decrease > 25% UO < .5 ml/kg/h x 6 hr High Sensitivity Risk Increased Cr x 2 or GFR decrease > 50% UO < .5 ml/kg/h x 12 hr Injury Increased Cr x 3 or GFR dec >75% or Cr 4 mg/dl (Acute rise of 0.5 mg/dl) UO < .3 ml/kg/h x 24 hr or Anuria x 12 hrs High Specificity Failure Loss Persistent ARF** = complete loss of renal function > 4 weeks End Stage Renal Disease (>3 months) ESRD

IRA: incidenza nella sepsi SEPSI SEVERA 23% SHOCK SETTICO 51% Rangel-Frausto JAMA 1995; 273:117-23

Richard S. Hotchkiss et Irene E. Karl N Engl J Med 348;2 www.nejm.org january 9, 2003 Individual response is determined by many factors as the organism virulence, size of the inoculum, patients coexisting conditions, polymorphysm in genes for cytokines. The lack of an acute phase response in patients with sepsis is associated with high mortality and may reflect the immunosuppressive prevalent phase of sepsis. Richard S. Hotchkiss et Irene E. Karl

N° di organi interessati MORTALITÀ Mortalità % N° di organi interessati Chertow GM. et al, Arch Int Med 1995

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