SIRS (Systemic Inflammatory Response Syndrome)

Adrian P. Ireland
Surgery, Final Med, SIRS – p.1/47
SIRS
Players (Molecules, Cells)
Definition
Final common pathway of many insults
High Mortality
Definition - ACCP/SCCM (1992)
Variable Abnormality
More than 38 Centigrade
less than 4.3 kPa
More than 12
Critical Care Med 20:864-75, 1992 Surgery, Final Med, SIRS – p.4/47
More definitions
Infection - Sepsis
invasion of normally sterile tissue by microbes
Sepsis
Surgery, Final Med, SIRS – p.6/47
Severe Sepsis - Septic Shock
hypotension
resuscitation
Causes of SIRS
Mortality in SIRS/Sepsis
Stepwise
Why is it important
Advances in care of surgical patient are not sufficent to
date
Advances in Care of Surgical patient
Pre op preparation; Rapid Transportation, Parmedical
Care, ATLS vs Scoop and Run
Better Surgery; Minimally Invasive, Damage Control,
Planned re-op, Volume and Outcome data
Better Anaesthesia
Markers
Surgery, Final Med, SIRS – p.11/47
Modulation of SIRS?
Review of the Basics
Cellular response to stress
Organism response to stress
Cellular response to stress
Heak Shock
Organism response to stress
Surgery, Final Med, SIRS – p.15/47
Role of the Leucocyte
Leucocyte-Endothelial Interactions
Rolling - P-selectin
Rolling
a
b
c
leucocyte
endothelium
Adherence
a
b
c
Integrins
Beta2 - Integrins
Transmigration
Integrin to VCAM-1 binding
Leucoctye extends pseudopodia and migrates into
interstitium
Role of the Leucocyte - Reactive Oxygen Species
Leucocyte endothelial interactions
Reactive Oxygen Species
Reactive Oxygen Species
Reactive Oxygen Species - How they damage
Paritally empty outer shell (reactive++)
DNA nicking


Reactive Oxygen Specis - Leucocyte
Myeloperoxidase stored in granules
Role of the Leucocyte - Release of Active Agents
Leucocyte endothelial interactions
Reactive Oxygen Species
Leucocyte - Active Agents
intestitial matrix, transmigration)
Organism response to stress - Inflammatory Mediators
Special cells
Surgery, Final Med, SIRS – p.31/47
Inflammatory Mediators - PAF


Inflammatory Mediators - LTB4
Special cells
Surgery, Final Med, SIRS – p.34/47
Cytokines - Pro Inflammatory - IL-1
Cytokines - Pro Inflammatory - IL-2
NK cells
Cytokines - Anti Inflammatory - IL-10
Cytokines - Mixed Effect
Final Common Pathway
P and E−selectin,ICAM−1 and 2, VCAM−1
PG−I2, NO
SIRS - Clinical Stages
2. Spill over of cytokines into the circulation, but balance
maintained
Monitoring SIRS
Sepsis Markers
Treatment of SIRS
SIRS and enteral feeding
Surgery, Final Med, SIRS – p.43/47
Glutamine
Enterocytes need glutamine
Role of additional glutamine is probably beneficial but small
Surgery, Final Med, SIRS – p.44/47
Activated Protein C - What it does
Thrombomodulin
Thrombin +
Recombinant human activated protein C Drotrecogin
alfa
Group Mortality (28 d)
Int Care Med 29(6):894–903, Jun 2003
Surgery, Final Med, SIRS – p.46/47
Thanks

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SIRS
Definition
Modulation of SIRS?
Reactive Oxygen Species
Reactive Oxygen Specis - Parenchymal cells
Reactive Oxygen Specis - Leucocyte
Leucocyte - Active Agents
Inflammatory Mediators - PAF
Inflammatory Mediators - LTB4
Cytokines - Pro Inflammatory - IL-1
Cytokines - Pro Inflammatory - IL-2
Cytokines - Anti Inflammatory - IL-10
Activated Protein C - PROWESS RCT
Thanks