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Renal Intensive Care
Rivers, E. P. et al. CMAJ 2005;173:1054-1065
Sepsis – The “real milieu”
Sepsis
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
0
50000
100000
150000
200000
250000
deat
hs/y
ear
AIDS BreastCancer
AMI SevereSepsis
0
50
100
150
200
250
300
Cas
es/1
00,0
00
AIDS BreastCancer
SevereSepsis
Sepsis
*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
2001 2025 2050
Severe Sepsis Cases
US Population
Sep
sis
Cas
es
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;101:1644-55.
Opal SM et al. Crit Care Med. 2000;28:S81-2.
MODS
Sepsis
We don’t always know where we are on the spectrum
Infection Sepsis Severe Sepsis MODS Death
SIRS = Systemic inflammatory response syndrome
CARS = Compensatory anti-inflammatoryresponse syndrome
Hyper-inflammation
Normal
Immunoparalysis
“pro”“mixed”
“anti”
Sepsis
Extracorporeal therapies for acute renal failure
0 20 40 60 80
ARF +sepsis
ARF -sepsis
Sepsis
How to treat sepsis1.Pharmacologic
• Antibiotics• Vasopressors• Steroids• Xigris
2. Extracorporeal therapy
• Generally accepted for Sepsis+ARF• No evidence, (not accepted) for Sepsis alone• CRRT therapies
Sepsis
bacteria
earlymediator
latemediator
latemediator
anti endotoxin (polymyxin or moAb)
anti TNF antibodiesTNF soluble receptorsIL-1 receptor antagonistsBradykinin agonistsPAF receptor antagonists
Treatment Strategies
Sepsis
Infection
Systemic Inflammatory
Response
Multi-Organ Dysfunction
Eliminate infection Reduce systemic reaction
Support organs
IV fluidsVasopressors
xigris
Sepsis chain and therapeutic approch
Heart (hemodynamics)
Liver
Lungs
Kidneys
Blood and coagulation
Brain
antibiotics Steroids
Insulin (glucose control)
Antiinflammatory agents
Ventilation
CRRT
Toraymixina
Sepsis
1. External “interphase”Transfer solute from bulkThin film on outer surface of resin
2. Internal “intraphase”Solute enters pore by diffusion
3. Surface Diffusion
4. Surface Adsorptionhydrophobic bindingAffinity binding (if specific resin)
Adapted Winchester ASN 2002
Adsorption (Specific or not specific)
Sepsis
anticoagulant
CPFA
Sepsis