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In the name of GOD
Sepsis and related Syndromes
Dr.M.Farahbakhsh
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Important steps in microbial
pathogenesis
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Encounter
Attachment to host cells
Local or general spread in the body (invasion)
Cell and tissue damage
Evasion of host defenses
Shedding from the body
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Non-immunologic host defenses
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Endogenous infections
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Note:
Asymptomatic contaminations and normal
endogenous flora waits for a SUITABLE
situation for invasion.
e.g: Staphylococcus aureus in skin that invades soft
tissues after an abrasion.
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Exogenous infections
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Exogenous infections
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Exogenous infections occur after a direct
contamination from microbial populations in
the environment:
▪ in air, soil and water,
▪ in live animals,
▪ in other people with infections, and
▪ in healthy people who are carriers.
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in air, soil, food and water
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Clostridium tetani and Bacillus anthracis
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Staphylococcus aureus, Clostridium perfringens and
Clostridium botulinum, may be present in our food
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in live animals
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the so-called zoonoses — include brucellosis,
rabies
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in other people with infections
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human-to-human transmission include the
common cold, AIDS, Tuberculosis and …
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in healthy people who are carriers
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people recovering from typhoid fever may retain
Salmonella typhi in the gallbladder
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GENERAL SIGNS, SYMPTOMS AND
CONSEQUENCES OF THE HOST
RESPONSE TO INFECTION
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The classic peripheral signs and symptoms of
inflammation (rubor, calor, dolor, tumor and functio
laesa — redness, heat, pain, swelling and loss of
function) commonly go hand in hand with general
systemic signs and symptoms such as fever, chills,
myalgias, headache and anorexia
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Infection, Toxins,
Inflammatory
mediators, Immune
reactions
Fever
Heat saving
Heat production
Monocytes,
Macrophages,
Endothelial cells, …
Heat saving
Heat production
Pyrogenic cytochines
IL-1, IL-6, TNF
PGE2 from
Hypothalamus
Endothelium
C AMP
Temperature
set point
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‫انسان سه دشمن دارد‪:‬‬
‫تب‪ ،‬قحطی و جنگ؛‬
‫از این سه مهم ترین و آزارنده ترین“ تب ” است‪.‬‬
‫ویلیام اسلر‬
Definition
H
D
E
E
L
Bacteremia Septicemia Sepsis
Sever sepsis Septic shock
A
T
T
H
H
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Definition
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Bacteremia is defined as growth of bacteria
in blood cultures.
Almost always Asymptomatic!
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Definition
H
D
E
E
L
Bacteremia Septicemia Sepsis
Sever sepsis Septic shock
A
T
T
H
H
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Definition
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Septicemia is presence of microbes or their
toxins in blood.
Fever!
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Definition
H
D
E
E
L
Bacteremia Septicemia Sepsis
Sever sepsis Septic shock
A
T
T
H
H
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Definition
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(1)
(2)
(3)
(4)
Sepsis is defined by presence of at least two of four signs of
the systemic inflammatory response syndrome (SIRS); with
infectious etiology:
fever (>38° C) or hypothermia (<36° C);
tachycardia (>90 beats per minute);
tachypnea (>24 breaths per minute), hypocapnia (partial
pressure of carbon dioxide <32 mm Hg), or the need for
mechanical ventilatory assistance; and
leukocytosis (>12,000 cells/mm3), leukopenia (<4000
cells/mm3), or a left shift (>10% immature band cells) in the
white cell differential and suspected or proven infection.
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Definition
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SIRS may be seen in non-infectious
conditions.
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Definition
H
D
E
E
L
Bacteremia Septicemia Sepsis
Sever sepsis Septic shock
A
T
T
H
H
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Definition
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Severe sepsis is sepsis in addition to
dysfunction of `(e.g. hypoxemia, oliguria,
lactic acidosis, thrombocytopenia,
decreased consciousness).
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Definition
H
D
E
E
L
Bacteremia Septicemia Sepsis
Sever sepsis Septic shock
A
T
T
H
H
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Definition
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Septic shock is defined as severe sepsis in
addition to hypotension (systolic blood
pressure <90 mm Hg or a decrease of >40
mm Hg from baseline) despite adequate
fluid resuscitation.
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Definition
H
D
E
E
L
Bacteremia Septicemia Sepsis
Sever sepsis Septic shock
A
T
T
H
H
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Definition
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At the bedside, the clinician identifies shock by
linking the clinical impression, synthesized
from the patient's history of present illness,
age, underlying health status, and general
appearance, to quantitative data, including vital
signs, blood chemistry, urine output, and direct
measurements of oxygenation.
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Definition
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In the laboratory, the scientist defines the
metabolic effect of shock quantitatively, by
examining the mechanisms by which shock
alters mitochondrial energy transfer, evokes the
production of toxic chemicals, and reduces
their removal.
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Epidemiology
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Approximately 750,000 cases of severe sepsis or
septic shock occur every year in the United States.
Contributing factor in more than >200,000 deaths/year
Sepsis causes as many deaths as acute myocardial
infarction, and
septic shock and its complications are the most
common causes of death in noncoronary intensive
care units.
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Epidemiology
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The frequency of septic shock is increasing !
Why?
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Epidemiology
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Septic shock may be caused by gram-positive
or gram-negative bacteria(70%), fungi, and,
very rarely, protozoa or rickettsiae.
gram-positive bacteria, especially methicillinresistant Staphylococcus aureus, vancomycinresistant enterococci, penicillin-resistant
Streptococcus pneumoniae, and resistant gramnegative bacilli.
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Epidemiology
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The common sites of infection causing septic shock
are:
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pneumonia,
peritonitis,
pyelonephritis,
abscess (especially intra-abdominal),
primary bacteremia,
cholangitis,
cellulitis, necrotizing fasciitis, and
meningitis.
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Pathobiology
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Initially, septic shock activates inflammation,
thereby leading to enhanced coagulation,
activated platelets, increased neutrophils and
mononuclear cells, and diminished fibrinolysis
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Pathobiology
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After several days, a compensatory antiinflammatory response with
immunosuppression may contribute to death.
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Pathobiology
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Several pathways amplify one another
inflammation
coagulation
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Pathobiology
Widespread endothelial injury is an important
feature of septic shock; an injured endothelium
is more permeable, so fluid flux of protein-rich
edema fluid into tissues such as the lung
increases.
Injured endothelial cells release nitric oxide, a
potent vasodilator that is a key mediator of
septic shock
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Pathobiology
Septic shock also injures epithelial cells of the lung
and intestine.
Intestinal epithelial injury increases intestinal
permeability, and this leads to translocation of
intestinal bacteria and endotoxin, which further
augment the inflammatory phenotype of septic
shock.
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Pathobiology
1.
Innate immune response
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TNF-α and interleukin-6 (IL-6)
Cytokines upregulate adhesion molecules of
neutrophils and endothelial cells, and neutrophil
activation leads to bacterial killing
Injury to endothelial cells
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Pathobiology
2. Adaptive Immunity Adds Specificity and
Amplification of the Immune Response
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Microorganisms stimulate specific humoral and
cell-mediated adaptive immune responses that
amplify innate immunity
B cells release immunoglobulins that bind to
microorganisms and thereby facilitate delivery of
microorganisms to natural killer cells and
neutrophils.
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Pathobiology
3. Coagulation Response to Infection
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Septic shock activates coagulation system
Fibrinogen
fibrin
which is bound to platelets to form microvascular
thrombi.
Microvascular thrombi further amplify endothelial
injury by release of mediators and by tissue
hypoxia because of obstruction to blood flow.
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Pathobiology
4. Tissue hypoxia
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Upregulation of Erithropoitin that is protective for
Brain and other tissues
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Pathobiology
5. Late septic shock and immunosuppression
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Genetic: Death from infectious diseases appears to
be heritable!
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Sepsis is a polygenic disease with an environmental
insult (infection)
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Pathobiology
6. Cardiovascular dysfunction
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Sinus tachycardia
Decreased blood pressure
Distributive shock and Functional hypovolemia
Vasodilatation and Microvascular vasoconstriction
Hypovolemia
Decreased ventricular contractility
Coronary ischemia
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Clinical Manifestations
1.Primary source of sepsis and it’s presentations:
Lung: Cough, Sputum, Fever, Chest pain,…
Urinary: Disuria, Frequency, Flank pain, Tenderness
…
2.Secondary manifestations:
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Acute Lung Injury
Renal Dysfunction
Gastrointestinal Tract Injury
Hepatic Dysfunction
Immune Dysfunction
Cutaneous Manifestations
Coagulopathy
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Diagnosis
Vital signs
WBC
ABG, lactate levels
Source evaluation
Lung, Urinary tract, Peritonitis
Intravascular devices and I.V
Skin and Soft tissues
Surgical sites
CNS
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Diagnosis
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Appropriate cultures and Gram stains
Positive blood culture in 40-70% of septic shock and 20-40% of sever sepsis cases.
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CXRay
Abdominal sonography and CTscan
Cardiac output
Renal, Hepatic and Coagulation tests
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Differential Diagnosis
Acute pancreatitis
Acute respiratory distress syndrome
Aspiration pneumonitis
Multiple trauma
Recent major surgery
Anaphylactic shock
Spinal shock
Acute adrenal insufficiency
Acute hepatic failure
Other causes of shock
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Treatment
1.Respiratory therapy
2.Circulatory therapy
3.Erythrocytes and Erythropoietin
4.Drugs
Antibiotics
Corticosteroids
Recombinant Human Activated Protein C
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Treatment
1.Respiratory therapy
O2 for all patients
Mechanical ventilation (TV = 6ml/kg)
Sedation with daily interruption
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Treatment
2.Circulatory therapy
Goals
Increasing BP
Increasing blood flow
Increasing arterial oxygen saturation
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Treatment
2.Circulatory therapy
Central venous oxygen saturation > 70%
CVP = 8-12 cmH2O
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Albumin (5 mL/kg) or Normal Saline (20 mL/kg)
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Treatment
2.Circulatory therapy
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Dopamine, infused at 5-15μg/kg/min, or
Norepinephrine , infused at 0.1-1μg/kg/min
Packed red cells (if CV saturation <70%) to maintain
Hct > 30%
Dobutamine (2.5-20 μg/kg/minute) if CVP, arterial
pressure, and hematocrit are optimized yet
the central venous oxygen saturation
remains less than 70%
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Treatment
3.Erythrocytes and Erythropoietin
Hematocrite = 30%
In patients with M.I or U.A
Recombinant Erithropoietine
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4. Drugs
Antibiotics
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Treatment
4.Drugs
Corticosteroids are not recommended for all!!
May be useful in patients who have serum Cortisol
levels 9 μg/dL or less after a 250-μg
corticotropin stimulation test
Hydrocortisone 50mg IV QID + Fludrocortisone
50 μg/day P.O
For 7 days
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Treatment
Recombinant Human Activated Protein C
For high risk patients but not post surgery
Activated protein C infusion (24 μg/kg/hour
for 96 hours) decreases mortality, improves
organ dysfunction, and decreases
biomarkers of inflammation and
coagulation in severe sepsis and septic
shock
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Prognosis
28 days mortality in septic shock is 40 – 70 % and
20-35% in sever sepsis.
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