Objectives:

• Definitions
• Pathophysiology
• Standard of care (approach & management)
Systemic Inflammatory Response Syndrome
(SIRS):

• SIRS is defined as 2 or more of the following variables:

• Fever of more than 38°C (100.4°F) or less than 36°C
(96.8°F)
• Heart rate of more than 90 beats per minute
• Respiratory rate of more than 20 breaths per minute or
arterial carbon dioxide tension (PaCO2) of less than 32
mm Hg
• Abnormal white blood cell count (>12,000/µL or <
4,000/µL or >10% immature [band] forms)
Definitions:

Sepsis— A life-threatening condition

caused by a dysregulated host response to
infection, resulting in organ dysfunction.

Septic shock— Circulatory, cellular, and

metabolic abnormalities in septic patients,
presenting as fluid-refractory hypotension
(MAP<65mmgh) requiring vasopressor therapy with
associated tissue hypoperfusion (lactate > 2mmol/L).
Pathophysiology
 SEPSIS PATHOPHYSIOLOGY

Microvascular
dysfunction
 Inflammation  Hypoperfusion/hypoxia  Organ dysfunction
Microvascular thrombosis Global tissue hypoxia
 Coagulation
Endothelial dysfunction Direct tissue damage
 Fibrinolysis
 Standard care of sepsis
•Early Identification ( Hx & examination) &
early source identification .
•Early Resuscitation
•Early inotropes
•Early appropriate Antibiotics
•Control the source

13
 FLUID RESUSCITATION
Phases of Septic Shock:
Rescue
Optimization:
Ischemia and reperfusion phase repeated assessments of
intravascular fluid status and determination for further fluid
administration
Stabilization:
Maintain intravascular volume, replace ongoing fluid losses, support
organs dysfunction, avoid iatrogenic harm with unnecessary fluid
administration
De-escalation
With this in mind, fluid resuscitation should be managed as
follows during consecutive
phases:
• Rescue: During the initial minutes to hours, fluid boluses (a 1-
to 2-L fluid bolus of crystalloid solution) are required to reverse
hypoperfusion and shock.
• Optimization: During the second phase, the benefits of giving
additional fluid to improve cardiac output and tissue perfusion
should be weighed against potential harms.
• Stabilization: During the third phase, usually 24 to 48 hours
after the onset of septic shock, an attempt should be made to
achieve a net neutral or a slightly negative fluid balance.
• De-escalation: The fourth phase, marked by shock resolution
and organ recovery, should trigger aggressive fluid removal
strategies.
Saline versus Albumin Fluid

versus
 Fluid Therapy

• Crystalloid (RL, NS) as fluid at 30 ml/kg

within 1 hour!.
• Goal is to reach target MAP (≥ 65 mm Hg )
• Albumin:
• Used in fluid refractory septic shock and if
>0.2 mcg/kg/min of Norad. is required
• Dose: 100-200ml of 20% Human Albumin
within 30-60 minutes
Central venous catheter vs. peripheral lines

Which is better in fluid Resuscitation???

Multiple wide bore cannulae (14 or16
gauge) is more effective than a central
line in fluid resuscitation in case of
shock.
 Targets in resuscitation
• Map  65 mmHg (SBP  90 mmHg)
• Urine output  0.5 ml/kg /hr
• SVO2  70%
• CVP 8-12 mmHg
• LACTATE ≤ 2.0
 
O2

ScvO2
SvO2 O2 Content

Venous Arterial

Cardiac
Output
O2 Consumption
O2 Return O2 Delivery

Capillary Beds

 Central venous oxygen saturation (ScvO2)

 Mixed venous oxygen saturation (SvO2)
 Inotropes and vasopressors

• Target MAP ≥ 65 mm Hg
• Noradrenaline : 1st Choice
• Adrenaline: when additional agent is needed.
• Vasopressin 0.03 units-0.04 units/min: added to NE with
intent of either raising MAP or decrease Norad dose
(Salvage Therapy).
• Low dose vasopressin not recommended.
• Dopamine: alternative to Norad only in selected patients,
Patients with low risk of tachycardia or absolute relative
bradycardia.
• Phenylephrine:
Not recommended except:
• NE is a/w serious arrythmias.
• Cardiac output is known to be high as BP persistently low.
• Salvage therapy when combined inotropes/vasopressor
drugs have failed.
• Dobutamine:
• Up to 20 mcg/kg/min in presence of:
• Myocardial dysfunction as suggested by elevated cardiac
filling pressures and low cardiac output
• Ongoing signs of hypoperfusion, despite achieving
adequate intravascular volume and adequate MAP.
 Steroid Therapy

• NOT recommended to treat septic shock if fluids or

vasopressors can maintain MAP (Hemodynamic
stability).
• If this is not achievable, Inj. Hydrocortisone 200
mg/day.
 Other Supportive Therapy

1. Infection Prevention:
• Limited patient contact
• Hand washing
• Prevent Ventilator associated pneumonia
• Propped Up position
• Chlorhexidine mouth wash

2. Blood Products:
• Once tissue hypoperfusion has resolved
• RBC transfusion only if Hb <7 g/dl
• NOT to use erythropoietin, antithrombin
• FFP not to be used to correct lab clotting abnormalities in absence of bleeding or
planned invasive procedure.
• Administer platelets prophylactically if:
• Platelets < 10,000/uL in absence of apparent bleeding
• Platelets < 20,000/uL if risk of bleeding
• Platelets < 50,000/uL if active bleeding, surgery
• No use of Selenium or Immunoglobulins
3. Mechanical Ventilation of Sepsis induced ARDS:

• Target TV 6 ml/kg predicted body weight

• Head end of bed 30-45 ° elevated
• Plateau pressures initial upper limit goal in passively inflated lung ≤ 30
cm water
• Apply PEEP
• For Severe Hypoxemia: use recruitment maneuvers
• Prone Positioning: PaO2/FiO2 ratio ≤ 100 mm Hg
• In absence of specific indications (bronchospasm) DO NOT use beta-2
agonists in sepsis induced ARDS.
• Avoid NMBAs as possible but a short course(<48 hr) can be used in
early sepsis induced ARDS and a PaO2/FiO2 ratio ≤ 150 mm Hg
• 4. Glucose Control:
• If 2 consecutive blood glucose levels are >180 mg/dl, commence
insulin dosing
• Target: ≤ 180 mg/dl
• Glucose monitoring every 1-2 hours until glucose values and insulin
rates are stable and then every 4 hours thereafter.

• 5. Bicarbonate:
• NOT to be used if pH ≥ 7.15
• Used after calculating deficit
• Shouldn't be corrected rapidly
• 6. DVT Prophylaxis:
• Daily LMWH (Inj. Enoxaparin 40 mg SC OD)
• If CrCl < 30 ml/min, use Dalteparin or another form of LMWH
that has low degree of renal metabolism.
• Graduated compression stockings or intermittent compression
devices

• 7. Stress Ulcer Prophylaxis:

• H2 Histamine blocker
• Proton Pump Inhibitors
• 8. Nutrition:
• • Oral or enteral feeding as tolerated within the first 48 hours
of diagnosis.
• Low dose feeding (up to 500 calories/day) in 1st week,
advancing only as tolerated.
• • Use IV glucose and enteral nutrition rather than TPN alone in
first 7 days.
 Antibiotics

* Early within (1) HR (Hit hard Hit fast’ with a high dose
of broad-spectrum antibiotic).
* Appropriate spectrum
* Duration :
Empiric combination therapy should not be administered
for >3-5 days de-escalation to appropriate single therapy.
Duration of therapy: 7-10 days (longer for slower
response).
 Biomarkers
C-reactive protein and erythrocyte sedimentation rate :
have been used in the past, but with limited success.
Procalcitonin:
has emerged as a method to help detect bacterial infections early
and to guide de-escalation or discontinuation of antibiotics.
Procalcitonin-guided de-escalation of antibiotics reduces
duration of antibiotic exposure, with a trend toward decreased
mortality.
Galactomannan and beta-D-glucan:
can be used to detect infections with fungi, specially Aspergillus.
Beta-d-glucan is more sensitive for invasive Aspergillus, while
galactomannan is more specific.
Cytokines such as interleukins (eg, IL- 6, IL-8, IL-10),
tumor necrosis factor alpha, acute-phase proteins, and
receptor molecules:
are currently being studied to determine their utility in sepsis care.
The limited sensitivity and specificity of single biomarkers may be
overcome by using a combination of biomarkers, which is a
current focus of research.
For now, the decision to initiate, escalate, and de-escalate therapy
should be based on clinical assessment, with procalcitonin or
other biomarkers used as an adjunct to other clinical factors.
 Source Control

 Early Identification of the Source

 4 D’s
 Team Work
 Communication