SYSTEMIC INFLAMMATORY

RESPON SYNDROM

SYAHARA
 SYSTEMIC INFLAMMATORY
RESPON SYNDROM
“SYAHARA”

 In medicine, systemic inflammatory

response syndrome (SIRS) is an
inflammatory state of the whole body (the
"system") without a proven source of
infection.
 It is a serious medical condition.
 SIRS
Background: In 1992, the American College of
Chest Physicians (ACCP) and the Society of
Critical Care Medicine (SCCM) introduced
definitions for:
 systemic inflammatory response syndrome
(SIRS)
 sepsis, severe sepsis, septic shock
 and multiple organ dysfunction syndrome
(MODS).
The idea behind defining SIRS was to define a
clinical response to a nonspecific insult of either
infectious or noninfectious origin
 Bacteremia is the presence of bacteria within the blood
stream, but this condition does not always lead to SIRS or
sepsis.

 Sepsis is the systemic response to infection and is defined

as the presence of SIRS in addition to a documented or
presumed infection. SEPSIS = SIRS + PROOF OF
INFECTION

 Severe sepsis meets the aforementioned criteria and is

associated with
- organ dysfunction
- hypoperfusion
- hypotension.
Sepsis-induced hypotension is defined as “the presence of
a systolic blood pressure of less than 90 mm Hg or a
reduction of more than 40 mm Hg from baseline in the
absence of other causes of hypotension.”
 Septic shock if they have :
- persistent hypotension and perfusion
abnormalities despite adequate fluid
resuscitation.

 MODS is the presence of altered organ function

in acutely ill patients such that homeostasis
cannot be maintained without intervention.
It usually involves two or more organ systems .
 Multiple organ dysfunction
syndrome (MODS)
 is altered organ function in an acutely ill
patient requiring medical intervention to
maintain homeostasis.
 It usually involves two or more organ
systems
 Aetiology
 The condition usually results from :
-infection
-injury (accident, surgery)
-hypoperfusion and hypermetabolism.
 The primary cause triggers an uncontrolled inflammatory
response.
 In operative and non-operative patients sepsis is the most
common cause. Sepsis may result in septic shock.
 In the absence of infection a sepsis-like disorder is termed
systemic inflammatory response syndrome (SIRS).
 Both SIRS and sepsis could ultimately progress to
multiple organ dysfunction syndrome.
 However, in one-third of the patients no primary focus can
be found.
 Pathophysiology
 A definite explanation has not been found.
Local and systemic responses are initiated
by tissue damage.
 Respiratory failure is common in the first 72
hours after the original insult.
 Following this one might see hepatic failure
(5-7 days).
 gastrointestinal bleeding (10-15 days).
 and renal failure (11-17 days).
 Gut hypothesis
 Due to splanchnic hypoperfusion and the
subsequent mucosal ischaemia there are
structural changes and alterations in cellular
function. This results in increased gut permeability,
changed immune function of the gut and increased
translocation of bacteria.
 Hepatic dysfunction leads to toxins escaping into
the systemic circulation and activating an immune
response. This results in tissue injury and organ
dysfunction
 Endotoxin macrophage theory
 Gram negative infections in MODS patients are
relatively common, hence endotoxins have been
advanced as principal mediator in this disorder.
 It is thought that following the initial event
cytokines are produced and released. The pro-
inflammatory mediators are: tumor necrosis factor-
α (TNF-α), interleukin-1, interleukin-6,
thromboxane A2, prostacyclin, platelet activating
factor, and nitric oxide
 Tissue hypoxia-microvascular
hypothesis
 As a result of macro- and microvascular
changes insufficient supply of oxygen
occurs.
 Hypoxemia causes organ dysfuntion and
cell death.
 Diagnosis
 The European Society of Intensive Care
organized a consensus meeting in 1994 to
create the "Sepsis-Related Organ Failure
Assessment (SOFA)" score to describe and
quantitate the degree of organ dysfunction
in six organ systems.
 Using similar physiologic variables the
Multiple Organ Dysfunction Score was
developed
 Four clinical phases have been suggested:
 Stage 1
The patient has increased volume requirements and mild respiratory
alkalosis which is accompanied by oliguria, hyperglycemia and
increased insulin requirements.

 Stage 2
The patient is tachypneic, hypocapnic and hypoxemic. Moderate liver
dysfunction and possible hematologic abnormalities.

 Stage 3
The patient develops shock with azotemia and acid-base disturbances.
Significant coagulation abnormalities.

 Stage 4
The patient is vasopressor dependent and oliguric or anuric.
Ischemic colitis and lactic acidosis follow.
 Management

 At present there is no agent that can reverse the

established organ failure.
 Therapy therefore is limited to supportive care, i.e.
- Safeguarding hemodynamics and respiration.
- Maintaining adequate tissue oxygenation is a
principal target.
- Starting enteral nutrition within 36 hours of
admission to an Intensive care unit has
reduced infectious complications
 Prognosis
 Mortality varies from 30% to 100%.
 The chance of survival is diminished as the
number of organs involved increases.
 Since the 1980s the mortality rate has not
changed
 SIRS is defined as 2 or more of the following
variables:
 Fever of more than 38°C or less than 36°C
 Heart rate of more than 90 beats per minute
 Respiratory rate of more than 20 breaths per minute or
BLOOD GAS PaCO2 level of less than 32 mm Hg
 Abnormal white blood cell count
(>12,000/mL or <4,000/mL or the presence of greater
than 10% immature neutrophils. )
 SIRS is nonspecific and can be
caused by
 Ischemia
 Inflammation
 Trauma
 Infection
 or a combination of several insults.
SIRS is not always related to infection.
Infection is defined as “a microbial phenomenon
characterized by an inflammatory response to
the microorganisms or the invasion of normally
sterile tissue by those organisms.”
 Pathophysiology: SIRS
 SIRS, independent of the etiology, has the same
pathophysiologic properties, with minor differences
in inciting cascades. Many consider the
syndrome a self-defense mechanism.
 Inflammation is the body's response to nonspecific
insults that arise from :
- chemical
- traumatic
- infectious stimuli.
 The inflammatory cascade is a complex process
that involves:
- humoral and cellular responses
- complement,
- and cytokine cascades.
 SIRS as the following 3-stage process:
 Stage I:
Local cytokine is produced with the goal of inciting an
inflammatory response, thereby promoting :
-wound repair
-and recruitment of the reticular endothelial system.

 Stage II:
Small quantities of local cytokines are released into
circulation to improve the local response.
This leads to growth factor stimulation and the recruitment of
macrophages and platelets.
This acute phase response is typically well controlled by a
decrease in the proinflammatory mediators and by the
release of endogenous antagonists. The goal is
homeostasis.
 Stage III:

If homeostasis is not restored, a significant systemic

reaction occurs.

The cytokine release “ leads to destruction rather

than protection “
A consequence of this is the activation of numerous
humoral cascades and the activation of the
reticular endothelial system and subsequent loss
of circulatory integrity.
This leads to end-organ dysfunction.
The following is a partial list of the noninfectious causes of SIRS:

– Acute mesenteric ischemia

– Autoimmune disorders
– Burns
– Chemical aspiration
– Cirrhosis
– Dehydration
– Drug reaction
– Electrical injuries
– Erythema multiforme
– Hemorrhagic shock
– Medication side effect (eg, theophylline)
– Myocardial infarction
– Pancreatitis
– Substance abuse (stimulants such as cocaine and amphetamines)
– Surgical procedures
– Toxic epidermal necrolysis
– Transfusion reactions
– Upper gastrointestinal bleeding
– Vasculitis
The following is partial list of the infectious causes of SIRS:
 Bacterial sepsis
 Burn wound infections
 Candidiasis
 Cellulitis
 Cholecystitis
 Community-acquired pneumonia
 Diabetic foot infection
 Erysipelas
 Infective endocarditis
 Influenza
 Intraabdominal infections (eg, diverticulitis, appendicitis)
 Gas gangrene
 Meningitis
 Nosocomial pneumonia
 Pseudomembranous colitis
 Pyelonephritis
 Septic arthritis
 Toxic shock syndrome
 Urinary tract infections (both male and female)
 TREATMENT
Medical Care:
 Treatment should then be focused based on
possible inciting causes of systemic inflammatory
response syndrome (SIRS; eg, appropriate
treatment of acute myocardial infarction differs
from the treatment of community-acquired
pneumonia or pancreatitis).
Empiric antibiotics are not indicated for all patients with SIRS.
Indications for antibiotic therapy include:
(1) suspected or diagnosed infectious etiology (eg, urinary
tract infection [UTI], pneumonia, cellulitis),
(2) hemodynamic instability,
(3) neutropenia (or other immunocompromised states), and
(4) asplenia (due to the potential for overwhelming
postsplenectomy infection [OPSI]).
When feasible, culture data should always be obtained prior
to initiating antibiotic therapy.
Empiric antibiotic therapy should be guided by available
practice guidelines and knowledge of the local antibiogram,
as well as the patient's risk factors for resistant pathogens
and allergies.
Once a bacteriologic diagnosis is obtained, narrowing the
antibiotic spectrum to the most appropriate therapy is critical.
Because of increasing bacterial resistance, broad-spectrum
antibiotics should be initiated when an infectious cause for
SIRS is a concern but no specific infection is diagnosed.
With the increasing prevalence of methicillin-resistant
Staphylococcus aureus (MRSA) in the community,
vancomycin or another anti-MRSA therapy should be
considered.
Gram-negative coverage with either cefepime or a quinolone
is reasonable.
Recent exposure to antibiotics must be considered when
choosing empiric regimens because recent antibiotic therapy
increases the risk for resistant pathogens.
Care must be made not to use an antibiotic to which the
patient is allergic. This may be a second hit and lead to
worsening SIRS.
Because of the high prevalence of patients with penicillin
allergy, a quinolone or aztreonam is reasonable alternatives
for gram-negative coverage.
Antiviral therapy has no role in SIRS.
Empiric antifungal therapy (fluconazole or an
echinocandin) can be considered in patients who
have already been treated with antibiotics, patients
who are neutropenic, patients who are receiving
total parenteral nutrition (TPN), or patients who
have central venous access in place.
Although empiric antibiotics may be reasonable in
many situations, the key is to stop antibiotics when
infection is ruled out or narrow the antibiotic
spectrum once a pathogen is found.
Proper culture data must be obtained prior to any
antibiotic therapy. Antibiotics prior to culturing a
patient may be a cause of sterile sepsis.
 TNF-a and IL-1 receptor antagonists,
antibradykinin, platelet-activating factor
receptor antagonists, and anticoagulants
(antithrombin III) have been studied without
showing statistically significant benefits in
SIRS (with variable results for sepsis and
septic shock). These medications have no
role in treating patients who meet criteria for
SIRS only.
 Drotrecogin alfa, a recombinant form of APC, warrants further
comment. APC reduces microvascular dysfunction by reducing
inflammation and coagulation and increasing fibrinolysis.
– The Patients in the Recombinant Human Activated Protein-C Worldwide
Evaluation in Severe Sepsis (PROWESS) study demonstrated its ability to
reduce 28-day all-cause mortality following severe sepsis. Further studies
have demonstrated that it is best used in patients with gram-negative
septic shock. In the PROWESS study, no clinical benefit was found in
patients with acute physiology and chronic health evaluation (APACHE)
scores of less than 25, and further studies have demonstrated worse
outcomes in patients with lower APACHE scores.
– Therefore, APC has no role in most SIRS cases unless the clinical
presentation is consistent with septic shock. APC has strict inclusion and
exclusion criteria that must be considered in all patients prior to initiating
therapy. The greatest benefit of APC has been demonstrated when this
medication is initiated early in the inflammatory cascade.
Steroids for sepsis and septic shock have been
extensively studied, but no SIRS-specific
studies have been performed to date.
The initial research in sepsis and septic
shock showed a trend toward worse
outcomes when treating with high doses of
steroids (methylprednisolone sodium
succinate 30 mg/kg every 6 h for 4 doses)
compared with placebo.
However, research into low-dose steroids
(200-300 mg of hydrocortisone for 5-7 d)
improved survival and the reversal of shock
in vasopressor-dependent patients.
As mentioned above, the inflammatory mediators
and receptors associated with infectious insults
(ie, septic shock) are the same as those of
noninfectious insults (ie, trauma, inflammatory
conditions, ischemia).
Therefore, in patients with severe or progressive
SIRS, even without an obvious infectious insult,
low steroids could be considered.
Current data do not support using ACTH
stimulation testing to determine patients who
should receive steroid therapy.
Patients receiving steroids require careful
monitoring for hyperglycemia.
Hyperglycemia
A common laboratory finding in SIRS, even in individuals
without diabetes, has numerous deleterious systemic
effects.
An increase of counterregulatory hormones, namely
cortisol and epinephrine, and relative hypoinsulinemia lead
to increased hepatic glucose production, increased
peripheral insulin resistance, and increased circulating free
fatty acids. This has direct inhibitory action on the immune
system. Oxidative stress and endothelial cell dysfunction,
along with proinflammatory cytokines (IL-6, IL-18, TNF-a)
and other secondary mediators (NF-kB) have all been
implicated as causes of cellular injury, tissue damage, and
organ dysfunction in patients with hyperglycemia.
Intensive control of blood glucose levels has been
shown to diminish in-hospital morbidity and mortality in both
the surgical and medical intensive care setting.
Various trials have shown that glycemic control with
insulin improves patient outcomes (including renal function
and acute renal failure), reduces the need for red blood cell
transfusions, reduces the number of days in the ICU, lowers
the incidence of critical-illness polyneuropathy, and
decreases the need for prolonged mechanical ventilation.
Van den Berghe et al (2006) reported a reduction of in-
hospital mortality rates with intensive insulin therapy
(maintenance of blood glucose at 80-110 mg/dL) by 34%.
The greatest reduction in mortality involved deaths due to
multiple-organ failure with a proven septic focus.
Supplemental oxygen:
Should be provided to any patient that demonstrates an
increased oxygen requirement or decreased oxygen
availability.
Oxygen can be provided via nasal canula or mask, or, in
certain situations, ventilator support may be required to
maximize oxygen delivery. Supplying supraphysiologic
oxygen has shown mixed results in a multitude of studies.
Providing too much oxygen in a patient with severe chronic
obstructive pulmonary disease (COPD) should be avoided
because it can depress their respiratory drive.
Patients who do not respond to increased oxygen supply
have a poor prognosis.
Patients with associated respiratory failure who require
mechanical ventilation should be treated with low tidal
volume mechanical ventilation (6 mL/kg).
Consultations:
Consultations vary depending on the admitting
physician's training and the cause of SIRS (ie, cardiology
consultation for acute myocardial infarction or
gastroenterology for acute GI bleeding).
Patients with potential surgical issues should undergo a
surgical evaluation, often in the emergency room, early in
the course of illness.
Consider consultation with an intensivist, if one is
available. If organ dysfunction develops, the intensivist or
a consultant specialist in that organ system should be
involved.
Early consultation with an expert in infectious diseases is
particularly helpful for patients who are
immunocompromised, regardless of the cause (eg, HIV,
AIDS, malignancy, solid organ transplantation).
They can also provide guidance in situations in which
patients are not responding to standard antibiotic
therapy, have multiple drug allergies, or are infected with
multidrug-resistant organisms or when a diagnosis is still
uncertain.
Diet:
Enteral feedings with arginine and omega-3 fatty acids
have been shown to be beneficial (decreased infectious
complications, hospital days, and duration of mechanical
ventilation) in critically ill patients.
The ability to feed a patient and the route of nutrition vary
based on the etiology of SIRS.

Activity:
Because of the causative illness, many patients are bed-
bound.
Therefore, deep venous thrombosis (DVT) and GI stress
ulcer prophylaxis should be considered to help prevent
complications.
Patients who are otherwise clinically stable and without
contraindications to mobility should be permitted to do
activity as tolerated.
 MEDICATION
No drugs of choice exist for this entity. Medication
prescriptions target specific diagnoses, preexisting
comorbidities, and prophylaxis regimens for
complications. No pharmacologic agents have
been demonstrated to improve the systemic
inflammatory response syndrome (SIRS) outcome.
Should be considered in patients who meet criteria
for SIRS.
 Broad-spectrum antibiotics
 Insulin therapy (in patients with hyperglycemia),
 Steroids
 Complications:
Complications vary based on underlying etiology.
Routine prophylaxis including :
 deep vein thrombosis (DVT) ----Lovenox
 stress ulcer prophylaxis should be initiated when
clinically indicated.
 Long-term antibiotics, when clinically indicated,
should be as narrow spectrum as possible to limit
potential for superinfection (suggested by a new
fever, change in white blood cell count, or clinical
deterioration).
 Unnecessary vascular catheters and Foley
catheters should be removed as soon as possible.
Other potential complications include the following:

•Respiratory failure, acute respiratory distress syndrome

(ARDS), and nosocomial pneumonia
•Renal failure
•GI bleeding and stress gastritis
•Anemia
•DVT
•Intravenous catheter–related bacteremia
•Electrolyte abnormalities
•Hyperglycemia
•Disseminated intravesicular coagulation (DIC)
Patient Education:

Education should ideally target the patient's

family.
Family members need to understand the fluid
nature of immune responsiveness and that
SIRS is a potential harbinger of other more
dire syndromes.
 Medical/Legal Pitfalls:

 Failure to consider a diagnosis beyond

systemic inflammatory response syndrome
(SIRS) is a pitfall. The clinical evaluation
should focus on a potential cause of SIRS.
 Special Concerns:

 Pregnant patients require intensive evaluation

because of the presence of 2 patients, as well as
the propensity of uncontrolled inflammation to lead
to preterm labor.
 Patients at the extremes of age, patients with
immunosuppression, and patients with diabetes
may present with sepsis or other complications of
infection without meeting SIRS criteria.