Patho-Physiology and

ICU Management of
Septic Shock

Dr.T.R.ChandraShekar
Director critical
care,
K.R.Hospital,
Bengaluru
 Case Scenario
 35 year old male patient brought to ICU
with 3 day old perforation, Posted for
emergency Lapratomy
 Has chills with fever
 Tachypneic- RR 40/mt, has respiratory
Is he in septic shock ?
distress,
 Tense abdomen, bilateral crepts,
Can we administer anaesthesia right now ?
 Spo2
Do youon 89%
want on room
to stabilise air.
him before surgery ?
 Pulse 130/mt well felt, BP 80/60 mm Hg,
Restless,
 Investigations
 WBC – 19,000 T.B 3.5, Enzymes
 Shock definition
 Shock is defined as a life-threatening,
generalized maldistribution of blood flow
resulting in failure to deliver and/or utilize
adequate amounts of oxygen, leading to
tissue dysoxia.
 Hypotension [SBP < 90 mmHg, SBP
decrease of 40 mmHg from baseline, or
mean arterial pressure (MAP) < 65
mmHg], while commonly present, should
not be required to define shock. Shock
requires evidence of inadequate tissue
perfusion on physical examination.
 Sepsis: Defining a Disease Continuum

Severe SEPTIC
Infection SIRS Sepsis SHOCK
Sepsis
Inflammatory
response to SIRS with a presumed or
microorganisms or confirmed infectious process
invasion of normally
A clinical
sterile tissuesresponse arising from a nonspecific
insult, including ≥ 2 of the following:
•Temperature ≥38oC or ≤36oC
•HR ≥90 beats/min
•Respirations ≥20/min
•WBC count ≥12,000/mm3 or
≤4,000/mm3 or >10% immature neutrophils

SIRS
Systemic Inflammatory Response Syndrome
Infection/ SEPTIC
SIRS Sepsis Severe
Trauma Sepsis Shock

Sepsis with ≥ 1 sign of organ

failure
Cardiovascular ( hypotension) HYPOTENSION
Lungs: (ARDS): despite adequate
Kidneys fluid
Liver resuscitation/Requiri
Digestive ng Vasopressors or
Brain - confusion Inotropes
Relationship Of Infection, SIRS,
Sepsis Severe Sepsis and Septic
Shock

SEPSIS PANCREATITIS

SEVERE
SEPSIS

SIRS BURNS
INFECTION SEPTIC
Bacteria SHOCK
Fungus
Parasites
TRAUMA
Virus
OTHER
 Definitions

DO WE REQUIRE TO CHANGE THE

DEFINITION?

MODS
SIRS Sepsi Severe Septic
Infection s Sepsis Shock
 2001 Sepsis Definitions
Conference
 Current definitions will remain
unchanged
 However, will accept the uncertainty of
definitions
 SIRS expanded
Expanded tosigns
list of SIRS signsandand symptoms
symptoms

Although none of these is specific of sepsis,

the unexplained presence of several in
combination should raise suspicion of sepsis
 Expanded signs of SIRS
General inflammatory Hemodynamic
General signs & symptoms
reaction alterations

Altered WBC count Arterial hypotension

Rigor– fever Increased CRP, Tachycardia
Tachypnea Altered skin perfusion
Decreased U.O
ositive fluid balance – edema
PCT concentrations
Hyperlactatemia –

Signs of organ dysfunction

Hypoxemia
Coagulation abnormalities
Altered mental status
 Case Scenario
 35 year old male patient brought to ICU
with 3 day old perforation, Posted for
emergency Lapratomy
 Has chills with fever
 Tachypneic- RR 40/mt, has respiratory
distress, Severe SEPSIS
 Tense abdomen, bilateral crepts,
 Spo2 on 89% on room air.
 Pulse 130/mt well felt, BP 80/60 mm Hg,
Restless,
 Investigations
 WBC – 19,000 T.B 3.5, Enzymes
 Pathogenesis of shock
Infectious trigger

Interaction with human cells- macrophages

Monocytes, Neutrophils, Endothelial cells

Cytokines & inflammatory mediator cascade

Cardiac dysfunction, Microemboli, Microvasular injury

increased Nitric oxide- Vasoplegia

Microcirculatory Mitochondrial dysfunction

Toll receptors
 Toll receptors (TLR)
 Key mediators of the innate immune
system
 Expressed on macrophage, dendritic
cells, neutrophils, endothelial cells
and mucosal epithelial cells
 TLR are transmembrane proteins
with the ability to promote signaling
pathways downstream, triggering
cytokine release and neutrophil
activation and stimulating
 Toll receptors
Pathogen-associated molecular patterns (PAMPs)

Host factors
Immunosuppressed Chronic Health Issues –
Extremes of age Diabetes, Liver Failure, Heart
Malnutrition Disease,
Alcohol, Drug Abuse
Corticosteroids, Chemotherapy
Malignancy Multiple invasive procedures
HIV/AIDS or invasive lines
 INFECTION/MICROBIAL TRIGGER

PRO INFLAMMATORY ANTI-INFLAMATORY

Promotes-Inflammation
Inhibits- Inflammation
Coagulation
Inhibits-Anti-coagulants, MONOCYTE DERIVED Coagulation
Fibrinilysis.
CYTOKINES Immunosupression
IL-1; TNF IL-6; IL-8
Anti-Inflammatories:
IL-1ra; IL-4; IL-10

SIRS S CARS

Systemic Inflammatory Compensatory Anti- Inflammatory

Response Syndrome Response Syndrome
 SIRS
Infection

Immune Response

Sepsis

Uncontrolled Dysregulated
Pro-inflammatory anti-inflammatory
Mechanisms Mechanisms

MODS/MOF

Crit Care Med 2000, 28(4):N105-N113 with modification

 Why some patients do well
Genetic others die ?
predisposition Infection Host factors
HLA class III Delayed
Wh
genes TNF a gene Wh therapy
Toxins
promoter y? y?
Sepsis ExcessivHost Inadequate Overwhelmi
defenses ng infection
Unregulat
eed

Death
MODS Adequate
Coordinated
Survival Death
Infection
control
Survival
 Role of Nitric Oxide
Macrophag
L – arginine es
Endotheli Smooth
um muscle
Endotheliu
m
eNOS iNOS
nNOS

Neurone
s

NO Vasoplegia-
Hypotension
 Coagulation in Sepsis

Endothelium
COAGULATION CASCADE
Fibrinolysi
Coagulation s
Inflammatio PAI-1
Factor VIIIa
Tissue Factor n
Bacterial, IL-6
viral, fungal IL-1
or parasitic TNFα Factor Va
infection/end Suppressed
otoxin Monocyte fibrinolysis

TAFI
Inflammatory Response THROMBIN
Bacterial, Fibrin clot
viral, fungal Fibrin
or parasitic Neutrophil
infection/end
otoxin Micro-emboli
Tissue Factor
IL-6

Inflammatory Thrombotic Fibrinolytic

Response Response Response
to Infection to Infection to Infection

Bernard GR, et al. New Engl J Med, 2001;344:699-709.

CARDIOVASCULAR FAILURE
Vasodilatation (nitric oxide release)
Hypovolemia
Myocardial dysfunction
Cell metabolism alteration
Decrease vascular resistance

Tachycardia, Hypotension, Hypoperfusion

 Final pathway in sepsis
Vasoplegia , Cardiac dysfunction, Capillary le
Hypovolemia,Maldistribution Microemboli

Microcirculatory Mitochondrial Dysfunction syndrom

(MMDS)

Cell death-Organ injury –MODS- Death

Sepsis is a disease of the microcirculation

 Why the microcirculation is important in shock.

 It is where oxygen exchange

takes place.
 It plays a central role in the
immune system.
 During sepsis and shock it the
first to go and last to recover.

ue of the microcirculation = resuscitation end-point

 TIME
is

TISSUE
Oxygen Don’t Go
Where the Blood Won’t Flow!
From these two statements three things are obvious
arly therapy before mitochondria gets damage
Macro circulation should be optimised first.
Micro circulation optimisation to prevent
Mitochondrial injury is the target
Resuscitation end points
Macro circulation Micro circulation

CVP 8–12 mm Hg Lactate < 2 mmol/L

(MAP) >=65 mm Hg SCVO2 > 70%
Urine output >=to 0.5
mL/kg/hr
SCVO2(superior vena
cava) >=70% or SVO2
>= 65%,
Tissue hypoperfusion
can persist despite
normal vital sign.
Normal Lactate and SCVO2
despite MMDS
 No extraction of oxygen-
mitochondrial damage
 Shunting of blood away from
microcirculation
 Although ScvO2 tracked SvO2, it is
tended to 7 ± 4 % higher
Management of Sepsis the
bottom line is

 Blood to be oxygenated
 Have Adequate pressure
 Deliver this blood into
microcirculation early before
Mitochondria are damaged
 DO2 –oxygen delivery
with adequate pressure

Arterial oxygen content X Cardiac out

put
HR Preload
Pacing Fluids
SaO2/Pao2 x Hb% Isoproterenol

MV/
oxygen Blood
therapy transfusi Contractility Afterload
on Inotropes
PEEP Vasodialators
 Oxygen to mitochondria
 Patient may have defective oxygen
extraction or oxygen may not reach
the cells due to micro emboli or
shunting of blood.
 Defective extraction may be due to
Mitochondrial injury.
 Shunting of blood
O2
a v
lactate Micro-Emboli
CO2
Maldistribution
 MMDS- Prevention
 Optimize Macro-circulation.
 rhAPC- Prevents coagulation
enhances fibrinolysis.
 Vasodilators

Microcirculation Monitoring at bedside is difficult

Therapeutically Not much can be done at MM leve
Except early and protocol based treatment
 War on Sepsis
Surviving Sepsis Campaign- Phase II
25% reduction in sepsis mortality within 5 years
- by 2009

Society of Critical Care Medicine, European Society of Intensive

Care
Medicine, International Sepsis Forum + Institute of Healthcare
Even with the ‘best’ parameters it
is not always easy to make the
right decision.………
 EGDT
Obtain two or more BCs
One or more BCs should be percutaneous
One BC from each vascular access
Suspected infection
device in place more than equal to 48 hrs
Blood cultures
Culture other sites as clinically indicated.
Other diagnostic/imaging as indicated

SBP< 90 even after

20-30ml/kg fluid or
Lactate > 4mmol/l

Appropriate Empirical
Host factors/ local antibiogram/ suspected site
Antibiotics with in 1 hr/
Combination antibiotics/ right dose
source control
Always look at you

Antibiotics

local organisms
and resistance
patterns

Early antibiotic therapy

Right dose
 Case Scenario
 35 year old male patient brought to ICU
with 3 day old perforation, Posted for
emergency Lapratomy
 Has chills with fever
3l of oxygen RBM, Two BC
 Tachypneic- RR 40/mt, has respiratory
Inj Meoropenem 500mg tid+ Inj Metrogyl 100 ml tid
distress,
 Tense abdomen, bilateral crepts,
 Spo2 on 89% on room air.
 Pulse 130/mt well felt, BP 80/60 mm Hg,
Restless,
 Investigations
 WBC – 19,000 T.B 3.5, Enzymes
 Suspected infection
Blood cultures
SBP< 90 even after
20-30ml/kg fluid or
Lactate > 4mmol/l
Appropriate Empirical
Antibiotics with in 1 hr/
source control

CVP < 8 Fluids NS, RL/

Colloid
8-12
Decrease < 60-90
Oxygen
MAP Vasopressors
consumption >60- Noradrenaline/dopamine
90mmHg

SCVO2 < 30 HCt-Packed cells

SCVO2< 70%
< Inotrope
70% Dobutamine
Goal achieved
SCVO2 >70%
 Fluid Therapy: Fluid
Challenge
 Fluid challenge in patients with
suspected hypovolemia may be given

 500 - 1000 mL of crystalloids over 30

mins
 300 - 500 mL of colloids over 30 mins

 Repeat based on response and tolerance

 Input is typically greater than output due

to venodilation and capillary leak
 Most patients require continuing
Grade E
aggressive
Dellinger, fluid
et. al. Crit Care Med 2004, 32: 858-873. resuscitation during the
 Suspected infection
Blood cultures
SBP< 90 even after
20-30ml/kg fluid or
Lactate > 4mmol/l
Appropriate Empirical
Antibiotics with in 1 hr/
source control

CVP < 8 Fluids NS, RL/

Colloid
8-12
Decrease < 60-90
Oxygen
MAP Vasopressors
consumption >60- Noradrenaline/dopamine
90mmHg

SCVO2 < 30 HCt-Packed cells

SCVO2< 70%
< Inotrope
70% Dobutamine
Goal achieved
SCVO2 >70%
 Vasopressors
 MAP >=65 mm Hg.
 Noradrenaline or dopamine as the first
choice
 Adrenaline/ Vasopressin be the first
chosen alternative agent in septic shock
that is poorly responsive to
norepinephrine or dopamine.
 Low-dose dopamine not be used for renal
protection.
 Arterial catheter placed
 Inotropic Therapy
 Dobutamine -myocardial dysfunction
 Suspected infection
Blood cultures
SBP< 90 even after
20-30ml/kg fluid or
Lactate > 4mmol/l
Appropriate Empirical
Antibiotics with in 1 hr/
source control

CVP < 8 Fluids NS, RL/

Colloid
8-12
Decrease < 60-90
Oxygen
MAP Vasopressors
consumption >60- Noradrenaline/dopamine
90mmHg

SCVO2 < 30 HCt-Packed cells

SCVO2< 70%
< Inotrope
70% Dobutamine
Goal achieved
SCVO2 >70%
 Case Scenario
 35 year old male patient brought to ICU
with 3 day old perforation, Posted for
emergency Lapratomy
 Has chills 1-2with
litrs fever
NS/ RL still hypotensive
 Tachypneic- RR 40/mt, and
Add noradrenaline hasadrenaline
respiratory
distress,
BP 130/70 mmHg, lactate 3 mmol/l, SCVO2 68%
 CVP 8 cmsbilateral
Tense abdomen, H20/ UO 1ml/kg/mt
crepts,
If he continues to improve for first 6 hrs
 Spo2 onplan
I may 89% on room
to administer air. for his surgery.
anesthesia
 Pulse 130/mt well felt, BP 80/60 mm Hg,
Restless,
 Investigations
 WBC – 19,000 T.B 3.5, Enzymes
EGDT
 Steroids
 Treat patients who still require
vasopressors despite fluid
replacement with hydrocortisone
200-300 mg/day, for 7 days in three
or four divided doses or by
continuous infusion.
 ACTH stimulation test is not
recommended.
 Steroid therapy may be weaned once
vasopressors are no longer required.
 Supportive care
 Deep vein thrombosis
prophylaxis.
 Stress ulcer prophylaxis.
 Glucose control.
 Maintain a Plateau pressure of
less than equal to 30 cmH2O and
low tidal volume 4-6 ml/kg of
Predicted body weight for
mechanically ventilated patients
.
 Conclusions
 Sepsis is a disease of
microcirculation.
 Oxygen Don’t Go
Where the Blood Won’t Flow-
Optimise the Macrocirculation
first.
 Monitoring microcirculation at
bedside is difficult- Lactate/
SCVO2 are most important
parameters to be monitored,
validated by studies.
 Treatment –SS guidelines
Thank you