Renal Intensive Care

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

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

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

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

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

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

Extracorporeal therapies for acute renal failure Sepsis

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

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

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

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

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

anticoagulant CPFA Sepsis