Sepsis and Septic Shock

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 Introduction
Sepsis, a syndrome of physiologic, pathologic, and
biochemical abnormalities induced by infection.
Sepsis is the primary cause of death from infection,
especially if not recognized and treated promptly.
Sepsis is a syndrome shaped by pathogen factors and
host factors (eg, sex, race and, age, comorbidities,
environment) with characteristics that evolve over time.
What differentiates sepsis from infection:
Their is an aberrant or dysregulated host response and
The presence of organ dysfunction.

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 Bacteremia:
Presence of bacteria in blood, as evidenced by positive
blood cultures.
 Septicemia: Presence of microbes or their toxins in
blood
 Systemic inflammatory response syndrome (SIRS):
Two or more of the following conditions:
1. Fever (oral temperature >38°C) or hypothermia
(<36°C);
2. Tachypnea (>20 breaths/min);
3. Tachycardia (heart rate >90 beats/min);
4. Leukocytosis (>12,000/L), leucopenia (<4,000/L), or
>10% bands;
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Note; SIRS may be a non-infectious etiology.
Sepsis:
SIRS that has a proven or suspected microbial etiology
 Severe sepsis (similar to "sepsis syndrome") Sepsis with one
or more signs of organ dysfunction—for example
 Cardiovascular: Arterial systolic blood pressure < 90
mmHg or mean arterial pressure < 70 mmHg that responds
to administration of intravenous fluid
 Renal: Urine output <0.5 mL/kg per hour for 1 h despite
adequate fluid resuscitation.
 Hematologic: Platelet count <80,000/L or 50% decrease in
platelet count from highest value recorded over previous 3
days

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 Septic shock
• Sepsis with hypotension (arterial blood pressure <90
mmHg systolic, or 40 mmHg less than patient's normal
blood pressure) for at least 1 h or need for
vasopressors to MAP ≥65 mm Hg and having a serum
lactate level >2 mmol/L (18 mg/dL) despite adequate
volume resuscitation
 Refractory septic shock
• Septic shock that lasts for >1 h and does not respond to
fluid or vasopressor administration.

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 Multiple-organ dysfunction syndrome (MODS)
o Dysfunction of more than one organ, requiring
intervention to maintain homeostasis
Focus of infection >Sepsis>sever sepsis>septic shock>>
refractory shock >> organ failure

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 Pathophysiology
Loss of balance between proinflammatory mediators that
contribute to eradication of invading microorganisms and
anti-inflammatory that control their response.
The inflammatory response leads to damage to host tissue
and the anti-inflammatory response causes to inhibit -
proinfilamatory mediators.
Once the balance to control the local inflammatory
process to eradicate the invading pathogens is lost, SIRS
occurs, converting the infection to sepsis, severe sepsis,
or septic shock.

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 etiology
The most common etiologic pathogens are:-
Gram-positive bacteria (52% of patients)- the most
common
Staphylococcus aureus,
Streptococcus pneumoniae,
coagulase-negative staphylococci, and
Enterococcus species
Gram-negative bacteria (37.6%)- the most common
Escherichia coli (8% to 30%),
Klebsiella species (8% to 23%), and
Pseudomonas aeruginosa (7% to 18%)
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Polymicrobial infections (4.7%),
Anaerobes (1.0%)
Fungi (4.6%)
patients with gram-negative bacteremia develop clinical
sepsis, and also more likely to produce septic shock in
comparison to gram-positive organisms, 50% versus
25%, respectively.
Specifically, P. aeruginosa sepsis has been associated in
a higher mortality rate
The sites of infections that most frequently led to sepsis
were:
respiratory tract (39% to 50%),
11 intraabdominal space (8% to 16%), and
Complications of sepsis and sepsis syndrome includes:
Disseminated intravascular coagulaphaty /DIC/
sepsis alone, the incidence was 16% in comparison to
38% in septic shock.
DIC occurs in up to 50% of patients with gram-
negative sepsis
Acute renal failure
Acute respiratory failure due to Acute respiratory
distress syndrome/ARDS
Other organ failure.
Mortality rates increase stepwise according to disease
severity.
In one study, the mortality rate of SIRS, sepsis, severe
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sepsis, and septic shock was 7, 16, 20, and 46%.
 Sign and symptoms

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 Treatment
The primary goals of therapy
Timely diagnosis and identification of pathogen;
rapid elimination of the source of infection medically
and/or surgically;
early initiation of aggressive antimicrobial therapy;
Interruption of pathogenic sequence leading to septic
shock;
Avoidance of organ failure.

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Therapeutic priorities —
Early initiation of supportive care to correct physiologic
abnormalities, such as hypoxemia and hypotension.
Distinguishing sepsis from SIRS
because, if an infection exists, it must be identified and
treated as soon as possible.
Early management —
stabilization of their airway and breathing.
Next, perfusion to the peripheral tissues should be
restored

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 1. Stabilize respiration —
 Supplemental oxygen should be supplied to all
patients with sepsis and oxygenation should be
monitored continuously with pulse oximetry.
 Intubation and mechanical ventilation may be
required to support the increased work of breathing that
typically accompanies sepsis, or for airway protection
since encephalopathy and a depressed level of
consciousness frequently complicate sepsis .

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2. Restore perfusion —
This is followed respiratory status stabilization,
The adequacy of perfusion should be assessed
(hypotension, cool, vasoconstricted skin)
Early restoration of perfusion is necessary to prevent or
limit multiple organ dysfunction.
Hypo perfusion results from loss of plasma volume into
the interstitial space, decreased vascular tone, and
myocardial depression.
In ~50% of septic patients who initially present with
hypotension, fluids alone will reverse hypotension and
restore hemodynamic stability.
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The goal of fluid therapy is
to maximize cardiac output
ultimately restore tissue perfusion.
Fluid administration should be titrated to clinical
endpoints such as heart rate, urine output, blood
pressure, and mental status

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Intravenous fluids
Rapid, large volume infusions of IV fluids are
indicated as initial therapy for severe sepsis or septic
shock
Volume status, tissue perfusion, blood pressure,
and the presence or absence of pulmonary edema
must be assessed before and after each bolus.
Thus, while the early, aggressive fluid therapy is
appropriate in severe sepsis and septic shock, fluids
may be unhelpful or harmful when the circulation is
no longer fluid-responsive.

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Isotonic crystalloids, such as 0.9% sodium chloride
(normal saline) or lactated Ringer
Commonly used for fluid resuscitation.
10 L of crystalloid solution during the first 24-hour
period required for patient in septic shock.
Colloids e.g. 5% albumin, naturally occurring plasma
protein and 6% hetastarch, a synthetic colloid
formulation.
Colloids produce less peripheral edema than
crystalloid, but there is no significant clinical impact
The Saline versus Albumin Fluid Evaluation (SAFE) trial
found no difference in the 28-day mortality rate in
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critically ill patients (21.1% with saline vs. 20.9% with
albumin)
During the first 6 hrs of resuscitation, the goals of initial
resuscitation of sepsis-induced hypo perfusion should
include all of the following as a part of a treatment
protocol:
1. CVP 8–12 mm Hg
2. MAP ≥ 65 mm Hg
3. Urine output ≥ 0.5 mL ・ kg ・ hr
4. Superior vena cava oxygenation saturation (Scvo2)
or mixed venous oxygen saturation (Svo 70% or
65%, respectively)

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3. Vasopressors —
IV vasopressors are useful in patients who
Remain hypotensive despite adequate fluid
resuscitation or
Who develop cardiogenic pulmonary edema.
In severe septic shock, there is no definitive evidence of
the superiority of one vasopressor over another.
We prefer to use norepinephrine and dopamine in most
patients.
However, we find phenylephrine (a pure alpha-adrenergic
agonist) to be useful when tachycardia or arrhythmias
preclude the use of agents with beta-adrenergic activity.
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Agents commonly considered includes:
Dopamine, Dobutamine, Norepinephrine – more
preferable in many aspects, Phenylephrine,
Epinephrine
Norepinephrine
potent α-adrenergic agent with less pronounced β-
adrenergic activity
more potent agent than dopamine in refractory
septic shock
resulted in greater increases in arterial blood pressure
in comparison to dopamine
dopamine was associated with a higher risk of death
and more frequently associated with arrhythmias
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 Dopamine it exhibits dose dependent pharmacologic
effects.
Doses >5 mcg/kg/min increase MAP and cardiac
output, primarily stimulation of β-adrenergic receptors.
At higher doses, α- adrenergic effects predominate,
resulting in arterial vasoconstriction.
Because of combined vasopressor and inotropic
effects, dopamine is more useful in patients with
hypotension and compromised systolic function.

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Additional therapies —
 Inotropic therapy —
For pts who have myocardial dysfunction, a trial of
inotropic therapy is warranted.
 Dobutamine is the usual inotropic agent.
At low doses, dobutamine may cause the blood
pressure to decrease because it can dilate the
systemic arteries.
However, as the dose is increased, blood pressure
usually rises because cardiac output increases out of
proportion to the fall in vascular resistance.
 Red blood cell transfusions —
Cautious approach to transfusion in critically ill patients
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 Antimicrobial therapy
Aggressive, early antimicrobial therapy because of high
incidence of complications and mortality.
Early administration of broad-spectrum antibiotics was
independently associated with lower hospital mortality in
patients with severe sepsis
All patients should be treated initially with parenteral
antibiotics for optimal drug concentrations within the
first hour of recognition of severe sepsis after appropriate
cultures have been taken.
Empiric therapy for an immunocompromised patient
should be broad enough to cover likely pathogens and
penetrate adequately into the presumed infection site
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The selection of an empiric regimen should be based on
the suspected site of infection,
the most likely pathogens,
acquisition of the organism from the community or
hospital,
the patient’s immune status,
the antibiotic susceptibility and resistance profile for
the institution
For example:
In the nonneutropenic patient with a UTI, ceftriaxone
and fluoroquinolones are generally recommended.
When there is increased risk of P. aeruginosa in sepsis
or hospital-acquired infections, an antipseudomonal
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antibiotic, such as ceftazidime, is recommended
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 If Pseudomonas is an unlikely pathogen
 Combining vancomycin with one of the following:
Cephalosporin, 3rd or 4th generation (eg, ceftriaxone
or cefotaxime) or
Beta-lactam/beta-lactamase inhibitor
(eg, piperacillin-tazobactam, ticarcillin-clavulanate,
or
Carbapenem (eg, imipenem or meropenem)

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 If Pseudomonas is a possible pathogen, combining
vancomycin with two of the following
Antipseudomonal cephalosporin (ceftazidime,
cefepime ), or
Antipseudomonal carbapenem (eg,
imipenem, meropenem),
Antipseudomonal beta-lactam/beta-lactamase inhibitor
(eg, piperacillin-tazobactam, ticarcillin-clavulanate
piperacillin), or
Fluoroquinolone with good anti-pseudomonal activity
(eg, ciprofloxacin), or
Aminoglycoside (eg, gentamicin, amikacin), or
Monobactam (eg, aztreonam)
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Combination therapy
does not appear to be more effective than monotherapy
in reducing organ failure or mortality.
However, the greatest benefit of combination therapy
appeared to be in patients with Pseudomonas or
multidrug-resistant gram-negative bacteremia and in
neutropenic patients with severe sepsis or septic shock.

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Other Evidence-based Treatment Recommendations for
Sepsis and Septic Shock

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 Duration of Therapy

In the normal host with sepsis, 7 to 10 days

 fungal infections can require 10 to14 days.
 “step-down” from parenteral to oral antibiotics can be
considered for patients.
hemodynamically stable,
has been afebrile for 48 to 72 hours,
has a normalizing white blood cell (WBC) count
able to take oral medications
Treatment can continue considerably longer if:
the infection is persistent.
In a neutropenic patient,
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 Thanks

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