1. Renal Intensive Care

2. Rivers, E. P. et al. CMAJ 2005;173:1054-1065 Sepsis – The “ real milieu ” Sepsis

3. Severe sepsis Comparison with other major diseases & Economic Aspect Cost of care for traditional (Farmacologic) treatment of septic patient €26.373 Sepsis costs Today €17.4 billion in USA €7.6 billion in Europe † National Center for Health Statistics, 2001. § American Cancer Society, 2001. *American Heart Association. 2000. ‡ Angus DC et al. Crit Care Med. 2001 Sepsis

4. *Angus DC. Crit Care Med. 2001 Severe Sepsis An increasing problem Year 200,000 400,000 600,000 800,000 1,000,000 1,200,000 1,400,000 1,600,000 1,800,000 200120252050 Severe Sepsis Cases US Population Sepsis Cases Sepsis

5. The Lungs –Hospital acquired infection –Pneumonia The Abdomen –Appendicitis –bowel problems –gallbladder –peritonitis The Urinary Tract –Urinary catheter –Diabetic patients UTI The Skin –Wounds –Skin inflammation –Catheter infection Common Sources of Infection Sepsis

6. Sepsis: A Complex Disease The inflammatory changes of sepsis are tightly linked to disturbed hemostasis. Adapted from: Bone RC et al. Chest. 1992;101:1644-55. Opal SM et al. Crit Care Med. 2000;28:S81-2. MODS Sepsis

7. We don ’ t always know where we are on the spectrum InfectionSepsis Severe SepsisMODS Death SIRS = Systemic inflammatory response syndrome CARS = Compensatory anti-inflammatory response syndrome Hyper-inflammation Normal Immunoparalysis “pro” “mixed” “anti” Sepsis

8. Extracorporeal therapies for acute renal failure Sepsis

9. How to treat sepsis 1.Pharmacologic Antibiotics Vasopressors Steroids XigrisXigris 2. Extracorporeal therapy Generally accepted for Sepsis+ARF No evidence, (not accepted) for Sepsis alone CRRT therapies Sepsis

10.  mortality by 6-17% Launched US Q4 2001 Europe Q4 2002 Worldwide sales 2003 $160.4 million U.S. $109.2 million Sales outside the U.S. $51.2 million Growth Q1 2004 US Q4 20% Outside 81% Cost/therapy $6800 Reduces inflammation and coagulation Sepsis

11. bacteria early mediator late mediator late mediator anti endotoxin (polymyxin or moAb)anti TNF antibodies TNF soluble receptors IL-1 receptor antagonists Bradykinin agonists PAF receptor antagonists Treatment Strategies Sepsis

12. Infection Systemic Inflammatory Response Multi-Organ Dysfunction Eliminate infection Reduce systemic reaction Support organs IV fluids Vasopressors xigris Sepsis chain and therapeutic approch Heart (hemodynamics) Liver Lungs Kidneys Blood and coagulation Brain antibioticsSteroids Insulin (glucose control) Antiinflammatory agents Ventilation CRRT Toraymixina Sepsis

13. 1.External “interphase” Transfer solute from bulk Thin film on outer surface of resin 2.Internal “intraphase” Solute enters pore by diffusion 3.Surface Diffusion 4.Surface Adsorption hydrophobic binding Affinity binding (if specific resin) Adapted Winchester ASN 2002 Adsorption (Specific or not specific) Sepsis

14. anticoagulant CPFA Sepsis