Download Septicemia and Systemic Inflammatory Response Syndrome (SIRS)

Septicemia and Systemic
Inflammatory Response
Syndrome (SIRS)
Epidemiology
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The most common cause of mortality in the
intensive care unit is septic shock . Even with the
best treatment mortality ranges from 15% in
patients with sepsis to 40-60% in patients with
septic shock.
Septic shock develops in about 40% of sepsis
patients.
Around 750,000 cases of sepsis are diagnosed
per year and around 31% of those diagnosed die.
The annual health care cost from caring for
patients with sepsis is $5-10 billion.
Factors contribute to the
increasing incidence of sepsis:
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Widespread us of corticosteroid and immunosuppressive therapies for
organ transplants and inflammatory diseases.
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Aggressive cancer chemotherapy and radiation therapy.
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Longer lives of patients predisposed to sepsis, the elderly, diabetics,
cancer patients, patients with major organ failure, and with
granulocytopenia.
Increased use of invasive devices such as surgical protheses, inhalation
equipment, and intravenous catheters and urinary catheters.
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Neonates are more likely to develop sepsis.
Indiscriminate use of antimicrobial drugs that create conditions of
overgrowth, colonization, and subsequent infection by aggressive,
antimicrobial-resistant organisms.
Microorganisms 1
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Although septic shock can be caused by viruses and fungi,
most is due to bacterial infections.
Common gram-negative bacteria causing septic shock
include opportunistic normal flora of the intestines such as
Escherichia coli, Klebsiella species, Enterobacter species,
and Proteus species.
Another opportunistic gram-negative causing septic shock
is Pseudomonas aeruginosa.
The most common obligate anaerobe to cause sepsis is
Bacteroides fragilis. Approximately 45% of the cases of
septicemia are due to gram-negative bacteria.
Microorganisms 2
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Common gram-positive bacteria causing septic
shock include Staphylococcus aureus,
Streptococcus pneumoniae, Enterococcus species
that are normal flora of the intestines, and
Streptococcus pyogenes.
The most common cause of neonatal sepsis is
Group B Streptococcus (GBS). Approximately
45% of the cases of septicemia are due to grampositive bacteria.
Approximately 10% of the cases of septicemia
are due to fungi, mainly the yeast Candida.
The sources for sepsis are
infections elsewhere in the body.
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lung infections: Streptococcus pneumoniae, Haemophilus
influenzae, Legionella species, Chlamydia pneumoniae.
wound, soft tissue infections: Streptococcus pyogenes,
Staphylococcus aureus, Clostridium species, Pseudomonas
aeruginosa, anaerobes, coagulase-negative Staphylococcus
species.
urinary tract infections: Escherichia coli, Klebsiella species,
Enterobacter species, Proteus species, Enterococcus
species.
central nervous system: Streptococcus pneumoniae,
Neisseria meningitidis, Listeria monocytogenes,
Escherichia coli, Haemophilus influenzae, Pseudomonas
aeruginosa, Klebsiella species, Staphylococcus species.
Pathogenesis
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In order to protect against infection, one of the things the body
must initially do is detect the presence of microorganisms. The
body does this by recognizing molecules unique to
microorganisms that are not associated with human cells. These
unique molecules are called pathogen-associated molecular
patterns.
Molecules unique to bacterial cell walls, such as peptidoglycan
monomers, teichoic acids, LPS, mycolic acid, formyl peptides, and
mannose, bind to pattern-recognition receptors on a variety of
defense cells of the body causing them to synthesize and secrete
a variety of proteins called cytokines.
These cytokines can, in turn promote innate immune defenses
such as inflammation, phagocytosis, activation of the complement
pathways, and activation of the coagulation pathway.
Pathogenesis
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Cytokines are intercellular regulatory proteins produced by one cell that
subsequently bind to other cells in the area and influence their activity in
some manner.
Cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1
(IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are known as
proinflammatory cytokines because they promote inflammation.
Some cytokines, such as IL-8, are also known as chemokines. They
promote an inflammatory response by enabling white blood cells to leave
the blood vessels and enter the surrounding tissue, by chemotactically
attracting these white blood cells to the infection site, and by triggering
neutrophils to release killing agents for extracellular killing.
In addition to promoting an inflammatory response, these same cytokines
activate the complement pathways as well as the coagulation pathway.
Pathogenesis
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Inflammation is the first response to infection and injury and is critical to
body defense. Basically, the inflammatory response is an attempt by the
body to restore and maintain homeostasis after injury. Most of the body
defense elements are located in the blood, and inflammation is the means
by which body defense cells and defense chemicals leave the blood and
enter the tissue around an injured or infected site.
The release of proinflammatory cytokines eventually leads to vasodilation
of blood vessels.
Vasodilation is a reversible opening of the junctional zones between
endothelial cells of the blood vessels and results in increased blood vessel
permeability. This enables plasma, the liquid portion of the blood, to enter
the surrounding tissue. The plasma contains defense chemicals such as
antibody molecules, complement proteins, lysozyme, and defensins.
Increased capillary permeability also enables white blood cells to squeeze
out of the blood vessels and enter the tissue. As can be seen,
inflammation is necessary part of body defense.
Excessive or prolonged inflammation can, however, cause harm.
Pathogenesis
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At moderate levels, inflammation,
products of the complement pathways,
and products of the coagulation pathway
are essential to body defense.
However, these same processes and
products when excessive, can cause
considerble harm to the body.
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Systemic Inflammatory Response
Syndrome (SIRS):
The Shock Cascade
Systemic Inflammatory
Response Syndrome (SIRS):
During a severe systemic infection, an
excessive inflammatory response
triggered by overproduction of
cytokines such as TNF-alpha, IL-1, IL6, IL-8, and PAF often occurs.
This leads to the following sequence of
cytokine-induced events:
Blood vessels dilate
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During a severe systemic infection, an excessive
inflammatory response triggered by overproduction
of cytokines such as TNF-alpha, IL-1, IL-6, IL-8, and
PAF often occurs. This leads to the following sequence of
cytokine-induced events:
Blood vessels dilate and phagocytic WBCs called
neutrophils adhere to capillary walls in massive
amounts.
Chemokines such as IL-8 activate neutrophils causing them
to release proteases and toxic oxygen radicals while
still in the blood vessels. These are the same toxic
chemicals neutrophils use to kill microbes, but now they are
dumped onto the vascular endothelial cells to which the
neutrophils have adhered. This results in damage to the
capillary walls and leakage of blood.
Prolonged vasodilation
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Prolonged vasodilation and increased capillary permeability causes plasma to
leave the bloodstream and enter the tissue. Prolonged vasodilation also leads to
decreased vascular resistance that, in turn, results in a drop in blood pressure
(hypotension) and reduced perfusion of blood through tissues and organs.
Damage to the capillaries and prolonged vasodilation result in blood and
plasma leaving the bloodstream and entering the tissue. This can lead to a
decreased volume of circulating blood (hypovolemia)
Activation of the blood coagulation pathway and concurrent downregulation of anticoagulation mechanisms cause clots to form within the
blood vessels throughout the body. This is called disseminated intravascular
coagulation (DIC). This further limits the perfusion of blood and oxygen through
tissues and organs.
Damage to the capillaries and prolonged vasodilation result in blood and
plasma leaving the bloodstream and entering the tissue. This can lead to a
decreased volume of circulating blood (hypovolemia)
Disseminated intravascular
coagulation
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Activation of the blood coagulation
pathway and concurrent downregulation of anticoagulation
mechanisms cause clots to form within
the blood vessels throughout the
body. This is called disseminated
intravascular coagulation (DIC). This
further limits the perfusion of blood and
oxygen through tissues and organs.
Acute respiratory distress
syndrome (ARDS)
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The increased capillary
permeability and injury to
capillaries in the alveoli of the
lungs results in acute
inflammation, pulmonary edema,
and loss of gas exchange. This is
called acute respiratory distress
syndrome (ARDS).
Liver, kidney, bowel
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Reduced perfusion and capillary
damage in the liver results in
impaired liver function and a
failure to maintain normal blood
glucose levels. Reduced
perfusion also leads to kidney
and bowel injury.
Heart failure
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The combination of hypotension,
hypovolemia, DIC, loss of perfusion,
and ARDS, leads to acidosis and
decreased cardiac output. Cytokineinduced overproduction of nitric
oxide (NO) by cardiac muscle cells
leads to heart failure.
MSOF and Death
Collectively, this cascade of events
results in irreversible septic
shock, multiple system organ
failure (MSOF), and death
Symptoms
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Symptoms of sepsis are usually
nonspecific and include fever, chills,
and constitutional symptoms of
fatigue, malaise, anxiety, or
confusion. These symptoms are not
limited to infection and may be seen
in a variety of noninfectious
inflammatory conditions.
Symptoms
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1. temperature > 38°C or < 36°C
2. heart rate > 90 beats/minute
3. respiration > 20/min or PaCO2 < 32mm Hg
4. leukocyte count > 12,000/mm3, < 4,000/mm3
or > 10% immature (band) cells.
Definitions
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Sepsis was defined as the systemic host response to
infection with SIRS plus a documented infection.
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Severe sepsis was defined as sepsis plus end-organ
dysfunction or hypoperfusion.
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Septic shock was defined as sepsis with hypotension,
despite fluid resuscitation, and evidence of inadequate
tissue perfusion.
While SIRS, sepsis, and septic shock commonly are
associated with bacterial infection, bacteremia may not be
present.
MORTALITY
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The mortality rate in SIRS has been
reported to be about 7%, that in
sepsis is about 16-20%, and that in
septic shock is about 45%
TREATMENT
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The drugs used depends on the source of the sepsis
1. Community acquired pneumonia a 2 drug regimen is usually utilized. Usually a third
(ceftriaxone) or fourth (cefepime) generation cephalosporin is given with an aminoglycoside
(usually gentamicin).
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2. Nosocomial pneumonia: Cefipime or Imipenem-cilastatin and an aminoglycoside.
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3. Abdominal infection: Imipenem-cilastatin or Pipercillin-tazobactam and aminoglycoside.
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4. Nosocomial abdominal infection: Imipenem-cilastatin and aminoglycoside or Pipercillintazobactam and Amphotericin B.
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5. Skin/soft tissue: Vancomycin and Imipenem-cilastatin or Piperacillin-tazobactam
6. Nosocomial skin/soft tissue: Vancomycin and Cefipime
7. Urinary tract infection: Ciprofloxacin and aminoglycoside
8. Nosocomial urinary tract infection: Vancomycin and Cefipime
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9. CNS infection: Vancomycin and third generation cephalosporin or Meropenem
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10. Nosocomial CNS infection: Meropenem and Vancomycin