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Systemic Inflammatory Response

Syndrome

A Summary
Definition
• SIRS is simply a severe systemic response
to a critical incidence.
• The response is characterized by
disseminated intravascular immune
activation, with consequent capillary and
vascular dysfunction often resulting in
hypotension, progressive major organ
dysfunction and death.
Definition
• Some authors say “It is really septic shock
or septicemia renamed in recognition of the
varying etiologies.”
• Whereas others believe septicemia and
septic shock are merely the late stages and a
consequence of the response.
Definition
• Paterson and Webster (J.R. Coll. Surg. Edinb., June
2000.) proposed the following definitions:
2 or more of:
•Temp. >38°C or <36°C
SIRS •HR >90 bpm
•RR > 20 cpm or PaCO2 < 4.3 kPa
•WBCs >12 x 109/lit OR < 4 x 109/lit OR > 10% immature forms

Sepsis SIRS due to infection


Sepsis with evidence of organ hypoperfusion (eg. Oliguria, Lactic
Severe acidosis, confusion, etc…..)

Sepsis
Severe sepsis with sys. BP < 90mmHg despite adequate fluid
Septic resuscitation or the requirement for vasopressors/inotropes to
Shock maintain BP
Other Definitions
• MOD:
– Presence of altered organ function in an
acutely ill patient such that homeostasis cannot
be maintained without intervention
• MOF:
– Like MOD, but with no improvement with any
intervention
What Happens in Burn?
Pathophysiology of SIRS

• 2 theories are proposed


– LPS (LipoPolySaccharide of Cell Membrane)
– LPC (Lipid-Protein Complex)
Pathophysiology of SIRS

LPS
• Bacterial translocation
from the gut
– Septicaemia
– Toximea
• Burn Wound Infection
Pathophysiology of SIRS

LPC
• Is formed of polymerized aggregates of
lipids & proteins of the cell membranes
from the burned skin
• It is formed under the burn eschar and is
continuously absorbed into circulation
• LPC acts as a potent antigen triggering an
inflammatory reaction similar to that
triggered by LPS
Pathophysiology of SIRS

LPC
LPC As a toxin
+
Heat Shock Proteins

Penetrates Parenchyma
Affects blood elements Inflammatory Response
Of all Organs

•Anemia Gradual
•↑ or ↓ platelet count SIRS Mitochondrial
•Immune dysfunction
destruction

MOD & MOF Late Death of Burn


Immune Dysfunction
Pathophysiology of SIRS

• The antigen-antibody reaction stimulates


multiple interacting systems such as:
– Complement Cascade
– Cytokine cascades
– Arachidonic Acid Metabolites
– Cell Mediated Immunity
– Humoral Immune Mechanisms
– Clotting Cascade
Pathophysiology of SIRS

Cytokines
• Are Intercellular signaling proteins or
messengers
• More than 30 recognized
• Act through binding to specific receptors on
the target cells triggering other cascades or
its own cascade
Pathophysiology of SIRS
Pathophysiology of SIRS

TNF-α
• The earliest and most potent mediator in SIRS
• It activates neutrophils, causing the production
of Interleukin-1(IL-1), Interleukin-6 (INL-6),
and Interleukin -8 (INL-8).
• It stimulates platelet activating factors and
prostaglandin, and promotes leukocyte or
vessel cell wall adhesion.
Pathophysiology of SIRS
Pathophysiology of SIRS

IL-1
• During an inflammatory response, it facilitates the
movement of WBCs toward the injury, ischemia, or
infected area
• It stimulates the release of arachidonic acid from
phospholipids in the plasma membranes, leading to fever,
hypotension, and decrease systemic vascular resistance.
• IL-1 also leads to muscle protein breakdown
• IL-1 works with other cellular immunity components to
produce IL-2, which decreases blood pressure, systemic
vascular resistance, and left ventricular ejection fraction.
• IL-2 may also increase left ventricular end diastolic
volume, cardiac output, and heart rate
Pathophysiology of SIRS

IL-6
• Is a key messenger that can either trigger
the rest of the cascade or its arrest
• Stimulates the release of acute phase
reactors
• Its serum levels are consistent with the
gravity of the immune reaction
Nitric Oxide
• Nitric oxide is synthesised by inducible
nitric oxide synthase (iNOS) in the vascular
endothelium and smooth muscle in response
to pro-inflammatory cytokines
• NO is the vasoactive mediator responsible
for the fall in systemic vascular resistance
underlying the hypotension in the late
stages of SIRS and septic shock
Pathophysiology of SIRS

Arachidonic Acid Cascade

• Thromboxane A2
– Is a potent vasoconstrictor and platelet
aggregator
– Leads to tissue ischemia from hypoperfusion.
• Leukotrienes leads to
– ↑Capillary endothelial permeability
– Bronchoconstriction
– Activation of neutrophils
Pathophysiology of SIRS

The Complement Cascade

• Controls the inflammatory process


– Chemotaxis
– Opsonization
– Promotion of phagocytosis
Pathophysiology of SIRS

Clotting Cascade
• Fibrin is formed due to the injury of the
vascular endothelium
• Chemical mediators stimulate the release of
Hageman Factor and Thromboplastin
• These form clots at the site of the injury,
attempting to stabilize the site
• Fibrinolysis is activated by the coagulation
cascade, leading to mediator induced (DIC).
Pathophysiology of SIRS

Bradykinin
• The activation of the Hageman Factor
stimulates the release of bradykinin
• Bradykinin creates vasodilatation and
capillary leakage, therefore volume
depletion.
Pathophysiology of SIRS

Myocardial Depressant Factor

• Myocardial depressant factor is a serum


protein released by the hypoperfused and
ischemic cells of the pancreas
• It decreases the velocity of contractions of
myocardial cells, leading to decreased right
and left ventricular ejection fractions
Pathophysiology of SIRS

Beta Endorphins
• Beta endorphins are released, by the pituitary
and hypothalamus, in response to
hypoperfusion
• They cause peripheral vasodilatation, and
decrease cardiac contractility
Pathophysiology of SIRS

Stages of SIRS
• 4 stages according to the gravity of the situation
Pathophysiology of SIRS
Stages

SIRS 1
• Release of proinflammatory mediators
– These mediators create a web of reactions
designed to limit new damage and ameliorate
whatever damage has already occurred
Pathophysiology of SIRS
Stages

SIRS 2
• Pro-inflammatory and anti-inflammatory
mediators appear in the systemic
circulation
– Pro-inflammatory mediators recruit
neutrophils, lymphocytes, platelets, and
coagulation factors
Pathophysiology of SIRS
Stages

SIRS 3
• Massive Systemic Inflammation
– Progressive endothelial dysfunction occurs
increasing microvascular permeability
– Vessels lose tone and profound vasodilatation
occurs resulting in severe shock
Pathophysiology of SIRS
Stages

SIRS 4
• Most patients do not make it this far --but
if they do--
– A compensatory anti-inflammatory response
occurs trying to suppress inflammation
Clinical Picture
• The typical 2 or more of:
– Temp. >38°C or <36°C
– HR >90 bpm
– RR > 20 cpm or PaCO2 < 4.3 kPa
– WBCs
• >12 x 109/lit
• < 4 x 109/lit
• > 10% immature forms
• Symptoms & Signs of each organ sequels
Clinical Picture

Organ Manifestations
• Cardiovascular
– Skin warm and flushed
– Widened pulse pressure
– Cardiac output is ⇑ but SVR is ⇓
– Eventually C.O. declines exacerbating
hypoperfusion
Clinical Picture

Organ Manifestations
• Pulmonary
– Hypoxemia may be masked by
hyperventilation
– Respiratory alkalosis
– Pulmonary edema
– Respiratory failure
– Bronchoconstriction
– ARDS
Clinical Picture

Organ Manifestations
• CNS • Renal
– Altered mental status – Oliguria:    < 500 ml/day
– Confusion – Metabolic Acidosis
– Irritability
– Agitation
– Disorientation
– Lethargy
– Seizures
– Coma
Clinical Picture

Organ Manifestations
• GIT • Blood
– Impaired motility – ⇑ or ⇓ WBCs
– ⇑ SGPT & SGOT – ⇑ PT and PTT
– Hyperbilirubinemia – ⇑ or ⇓ Platelets
– Hepatic necrosis – Anemia
– Hypoprothrombinemia
– Hypoglycemia
Investigations
• Cytokines assay (IL-6, IL-8 & TNF)
• Blood Culture
• Burn eschar biopsy with culture & sensitivity
• Serum Procalcitonin
– The only lab test that differentiates
• SIRS (0.5 -2 ng/dl) from
• Sepsis (>2 & <10 ng/dl) from
• MOD (>10 and often >100ng/dl)
Treatment
= Elimination of triggering factor (LPC &
LPS)
• LPS
– Antibiotics according to C&S
– Gut decontamination
• LPC through
• Prompt early surgical eschar excision
• Chemical elimination eg. Cerium Nitrate
Treatment
• Supportive
• Medical
• Surgical
Treatment

Supportive Therapy
• Volume replacement
• +ve inotropes & vasopressors
• Ventilation (Pressure support or PEEP)
• Nutritional Support
– Iso-Osmotic Feedings
– TPN
– PPN
– Immune Modulatory Foods such as Arginine,
Glutamine & fish oils
Treatment

Medical
• Potent anti-oxidants
– Methylene Blue given IV
– Acetyl Cysteine
– Vitamin C
• Immune Modulators
– Ibuprofen (proved of limited value)
– Centoxin: an Ab to endotoxins
– NOSI (nitric oxide synthetase inhibtor) very much
accepted
– IL-6 blockers Experimental
Surgical Excision
• Best option = Early excision + coverage
• Best performed within the 1st 72 hours and
after resuscitation
• Is the only way to break the circle
Surgical Excision
• ⇓⇓ incidence of burn wound colonization

Barret et al, 2003


Prognosis
• Death in 60% of cases of late stages &
shock in patients with no previous history
of medical conditions
• Death rate is higher if MOD develops & is
dependant on no. of organs affected
– 3 organs 85%
– 4 organs 95%
– 5 organs 99%
Thank You

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