Sepsis / Septic Shock

rd
for 3 year MBBS
Dr. Ahmad Uzair Qureshi
FCPS ( SURGERY) /
MRCS ( ENGLAND) /

MCPS ( SURGERY)
Dip Med Edu (Cardiff)

Colorectal Fellow Yonsei University, South Korea

Assistant Professor of Surgery, King Edward Medical
University, Lahore

SEPSIS
Is a systemic, harmful ( deleterious) host response to infection.

SEPSIS
Is a systemic, deleterious host response to infection.

leading to

Severe Sepsis
(acute organ dysfunction secondary to documented or suspected infection)

Severe Sepsis
(acute organ dysfunction secondary to documented or suspected infection)
Dysfunction of organ(s) distant from the site of infection

leading to

SEPTIC SHOCK
(severe sepsis plus hypoperfusion or hypotension not reversed
with fluid resuscitation).

INFECTION

INFECTION
Presence of microorganisms in a normally sterile site

INFECTION
Presence of microorganisms in a normally sterile site
Do Not confuse with colonization, which is the presence of
microorganisms on an epithelial surface

Bacteremia

Bacteremia
Cultivatable bacteria in the bloodstream
May be transient and inconsequential;

Systemic inflammatory
response syndrome (SIRS)

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Systemic inflammatory
response syndrome (SIRS)

Early Host Responses to Infection

Local Defenses: Walling Off and Killing
Invading Microbes

Early Systemic Responses:

Keeping Infection and
Inflammation Localized

Early Systemic Responses:

Keeping Infection and
Inflammation Localized
Acute-Phase Responses (Categorized According to
Possible Roles in Defense)

Anti-infective

Increases synthesis of complement factors, microbe pattern-recognition

molecules (mannose-binding lectin, LBP, CRP, CD14, others)
Sequesters iron (lactoferrin, hepcidin) and zinc (metallothionein)

Antiinflammatory

Releases anti-inflammatory neuroendocrine hormones (cortisol, ACTH,

epinephrine, -MSH)
Increases synthesis of proteins that help prevent inflammation within the
systemic compartment
Cytokine antagonists (IL-1Ra, sTNF-Rs)
Anti-inflammatory mediators (e.g., IL-4, IL-6, IL-6R, IL-10, IL-13, TGF-)
Protease inhibitors (e.g., 1-antiprotease)
Antioxidants (haptoglobin)
Reprograms circulating leukocytes (epinephrine, cortisol, PGE 2 , ? other
factors)

Procoagulant
Metabolic
Thermoregulat

Walls off infection, prevents systemic spread

Increases synthesis or release of fibrinogen, PAI-1, C4b
Decreases synthesis of protein C, antithrombin III
Preserves euglycemia, mobilizes fatty acids, amino acids
Epinephrine, cortisol, glucagon, cytokines

Inhibits microbial growth

Fever

Harmful Responses to Infection:

Severe Sepsis and Septic Shock
Hypofunction implies an inadequate level of activity, whereas
dysfunction suggests that organ performance is in some way abnormal.
Develop when normally adaptive stress responses are pushed
beyond their ability to be protective.

CONCEPTs
1.Microvascular
TWO Theories
derangement
2.Mitochondrial
dysfunction.

 An extension of the body's normal neuroendocrine responses to

stress
An exhaustion of ATP in critical organs
when the inflammatory stimulus is too strong or too prolonged .

 Cytokines circulate via the blood and induce injury to the

vascular endothelium and/or microcirculation in different
organs.
An extension of the body's normal neuroendocrine responses to
stress
An exhaustion of ATP in critical organs
when the inflammatory stimulus is too strong or too prolonged .

Septic Shock
Opportunistic commensal bacteria typically invade across
disrupted epithelia.
Hosts in whom immunosuppressive acute-phase responses are
already occurring because of illness, injury, or infection.
Host is unable to kill the bacteria because of mechanical failure
(obstructed drainage pathway), immunosuppression
(neutropenia, endogenous immunosuppression)

 These bacteria invade the bloodstream when local defenses are

unable to kill or contain them; bacteremia.
Locally-produced mediators act as trigger for severe sepsis and
septic shock
Outcome is strongly related to the patient's underlying
physiologic fitness.

 Pathogenic microbes/virus that can survive and multiply in

previously healthy humans.
the microbes/viruses may enter the bloodstream, infect vascular
endothelial cells and/or blood cells, and release toxins.
The circulating microbes may provoke both shock and
profound coagulopathy that not uncommonly results in
hemorrhage and/or arterial thrombosis

DIAGNOSTIC CRITERIA

Initial Resuscitation and

Infection
Issues
A. Initial Resuscitation (Goals during the first 6 hrs of
resuscitation)
1. Hypotension persisting after initial fluid challenge or blood
lactate concentration 4 mmol/L
a) Central venous pressure 812 mm Hg
b) Mean arterial pressure (MAP) 65 mm Hg
c) Urine output 0.5 mL/kg/hr
d) Central venous (superior vena cava) or mixed venous oxygen saturation
70% or 65%, respectively

B. Diagnosis
Cultures as clinically appropriate before antimicrobial therapy if no
significant delay (> 45 mins) in the start of antimicrobial(s)
At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be
obtained before antimicrobial therapy
Imaging studies performed promptly to confirm a potential source of
infection (UG).

C. Antimicrobial Therapy
Administration of effective intravenous antimicrobials within the
first hour of recognition of septic shock and severe
sepsis without septic shock as the goal of therapy.
Initial empiric anti-infective therapy of one or more drugs that
have activity against all likely pathogens
Antimicrobial regimen should be reassessed daily for potential
deescalation.
Use of low procalcitonin levels in the discontinuation of empiric
antibiotics
Combination empirical therapy for neutropenic respiratory failure
and septic shock,

TO BE COMPLETED WITHIN 3 HOURS OF TIME OF

PRESENTATION*:
1. Measure lactate level
2. Obtain blood cultures prior to administration of antibiotics
3. Administer broad spectrum antibiotics
4. Administer 30ml/kg crystalloid for hypotension or lactate
4mmol/L

TO BE COMPLETED WITHIN 6 HOURS OF TIME OF

PRESENTATION:
5. Apply vasopressors (for hypotension that does not respond to
initial fluid resuscitation) to maintain a mean arterial pressure
(MAP) 65mmHg
6. In the event of persistent hypotension after initial fluid
administration (MAP < 65 mm Hg) or if initial lactate was 4
mmol/L, re-assess volume status and tissue perfusion 7. Remeasure lactate if initial lactate elevated.

Fluid Therapy of Severe Sepsis

Crystalloids as the initial fluid of choice
Against the use of hydroxyethyl starches
Albumin when substantial amounts of crystalloids (grade 2C).
Initial fluid challenge a minimum of 30 mL/kg of crystalloids (a portion of
this may be albumin equivalent).
Fluid challenge technique be applied
Change in pulse pressure,
Stroke volume variation)
Arterial pressure, Heart rate

Vasopressors
Vasopressor therapy initially to target a mean arterial pressure (MAP) of 65 mm Hg
Norepinephrine as the first choice vasopressor.
Epinephrine (added to and potentially substituted for norepinephrine) when an additional
agent is needed to maintain adequate blood pressure (grade 2B).
Vasopressin 0.03 units/minute can be added to norepinephrine (NE) with intent of either
raising MAP or decreasing NE dosage .
Low dose vasopressin is not recommended as the single initial vasopressor for treatment of
sepsis-induced hypotension and vasopressin doses higher than 0.03-0.04 units/minute
should be reserved for salvage therapy (failure to achieve adequate MAP with other
vasopressor agents) .
Dopamine as an alternative vasopressor agent to norepinephrine only in highly selected
patients (eg. patients with low risk of tachyarrhythmias and absolute or relative
bradycardia).

Hemodynamic Support and Adjunctive Therapy

Inotropic Therapy
Corticosteroids
Blood Product Administration.
Immunoglobulins
Mechanical Ventilation of Sepsis-Induced ARDS
Sedation, Analgesia, and Neuromuscular Blockade in Sepsis
Glucose Control
Renal Replacement Therapy
Bicarbonate Therapy
Deep Vein ThrombosisProphylaxis
Nutrition

For any queries

+923144001410
or
ahmeduzairq@gmail.com