Systemic Inflammatory Response Syndrome

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Systemic Inflammatory Response
Syndrome
A Summary
By
Professor Dr. Mohamed El
Rouby

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:
SIRS
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 OR < 4 x 109/lit OR > 10% immature
Sepsis SIRS due to infection
Severe
Sepsis
Sepsis with evidence of organ hypoperfusion (eg. Oliguria,
Septic
Severe sepsis with sys. BP < 90mmHg despite adequate
requirement for vasopressors/inotropes to 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)

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

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

LPC
LPC
Affects blood elements Inflammatory Response
Penetrates Parenchyma
Of all Organs
Gradual
Mitochondrial
destruction
Late Death of Burn
As a toxin
+
Heat Shock Proteins
SIRS
MOD & MOF
•Anemia
•↑ or ↓ platelet count
•Immune dysfunction

Immune Dysfunction

• 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

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

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.

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

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

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

The Complement Cascade
• Controls the inflammatory process
– Chemotaxis
– Opsonization
– Promotion of phagocytosis

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).

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

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

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

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

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
Stages

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

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

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

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

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

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

• GIT
– Impaired motility
– ⇑ SGPT & SGOT
– Hyperbilirubinemia
– Hepatic necrosis
– Hypoprothrombine
mia
– Hypoglycemia
• Blood
– ⇑ or ⇓ WBCs
– ⇑ PT and PTT
– ⇑ or ⇓ Platelets
– Anemia
Clinical Picture

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

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
Treatment

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

Systemic Inflammatory Response Syndrome

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