Septic Shock

Dr. dr. Hori Hariyanto, SpAn, KIC, KMN

Outline
1. Shock review
2. Septic shock
Shock Review
What is shock?
 Is a physiologic state characterized by a
significant reduction of systemic tissue
perfusion, resulting in decreased oxygen
delivery to the tissues
 Imbalance between oxygen delivery and
oxygen consumption.
Prolonged oxygen deprivation leads to

Cellular hypoxia
Cell membrane ion pump dysfunction
Intracellular edema
Leakage of intracellular contents into the extracellular space
Inadequate regulation of intracellular pH
Systemic hypoxia
Alterations in the serum pH
Endothelial dysfunction
Inflammatory and anti-inflammatory cascades
Organ dysfunction and damage
Death
Physiology
Perfusion depend on 3 components of
circulatory system
 Pump (Heart)
 Fluid (Blood)
 Container (Blood vessels)
 Type of shock
CARDIOGENIC SHOCK
OBSTRUCTIVE SHOCK*

HEART

VESSEL BLOOD

DISTRIBUTIVE SHOCK* HYPOVOLEMIC SHOCK

*Obstructive shock: Cardiac tamponade, Tension pneumothorax or Massive PE

*Distributive shock: Sepsis
 Differential
Diagnosis
Type of shock HR JVP Peripheries
Cardiogenic  or  or  Cold

Hypovolemic   Cold

Distributive   Warm

Obstructive   Cold

 OXYGEN DELIVERY SYSTEM

Uptake1

2
Diffusion2
CaO2
ScvO2
SvO2

CvO2 TISSUES DaO2 SaO2

Delivery3
Extraction4
Oxygen delivery
 DO2 : CO x CaO2
Normal values suggests that the heart & lungs are working efficient
to provide oxygen to the tissues
< 400 ml/mnt is bad sign
 Arterial Oxygen Content (CaO2)
CaO2 = (1.34 x Hgb x SaO2) + (PaO2 x 0.0031)
If low, check hemoglobin or pulmonary gas exchange
 Oxygen extraction ratio (O2ER)
O2ER = (CaO2 - CvO2)/ CaO2 (0.2 to 0.3)
SUPPLY DEPENDENT O2
CONSUMPTION
Critical DO2 Values

INCREASED METABOLIC STATE

OXYGEN CONSUMPTION (VO2)

NORMAL PHYSIOLOGIC STATE

400 800 1200

OXYGEN DELIVERY (DO2)

Physiology
Tissue perfusion is determined by Mean Arterial
Pressure (MAP)

MAP = CO x SVR

Heart Rate Stroke Volume

Preload Afterload Contractility

Stages of shock
Pre-shock/Compensated shock
 Defense mechanisms are successful in maintaining
perfusion
 Neurohormonal mechanisms help maintain CO & BP
 Baroreceptor reflexes, Catecholamines, RAAS/ADH
 Tachycardia, peripheral vasoconstriction
Stages of shock
Uncompensated shock/End-organ dysfunction
 Defense mechanisms begin to fail
 Presentation
• Hypotension
• Prolonged Cap refill
• Marked increase in heart rate
• Agitation, restlessness, confusion
• Dyspnea, diaphoresis, metabolic acidosis, oliguria, and cool
clammy skin
Septic Shock
Why should we care?
1. High mortality 20-90%
2. Early on the effects of O2 deprivation on
the cell are REVERSIBLE
3. Early intervention reduces mortality
4. Early diagnosis is essential, as the
prognosis depend on severity and
duration
 Comparison With Other Major Diseases
Incidence of Severe Sepsis Mortality
250 of Severe Sepsis

Deaths/Year
300 200
250
Cases/100,000

200
150

150
100
100

50 50
0 AIDS* Colon Breast CHF† Severe AIDS* Breast AMI† Severe
Cancer§ Sepsis‡ Cancer§ Sepsis‡
†
National Center for Health Statistics, 2001. §American Cancer Society, 2001.
0
*American Heart Association. 2000. ‡Angus DC et al. Crit Care Med. 2001;29(7):1303-1310.
 The Continuum (old definition)

Infection SIRS Sepsis Severe Sepsis Septic Shock

Microorganism  Systemic SIRS with a Sepsis with Refractory

invading Inflammatory presumed organ hypotension
sterile tissue Resonse or confirmed failure/hypoperfusion
Syndrome, with 2 infectious
of the following: process
 T >38oC or
<36oC
 HR >90
beats/min
 RR >20/min
 WBC
>12,000/mm3 or
<4,000/mm3 or
>10% bands
Definition (new)
Sepsis: (Sepsis in place of “Severe Sepsis”)
 Life-threatening organ dysfunction caused by a
dysregulated host response to infection
 Organ dysfunction: SOFA ≥ 2
 Bedside: quick SOFA (at least 2 clinical criteria)
 Respiratroy rate ≥ 22 x/m
 Altered mentation (GCS ≤ 13)
 Systolic blood pressure ≤ 100 mmHg

JAMA.2016;315(8):801-810
Definition (new)
 Septic shock is a subset of sepsis in which
underlying circulatory and cellular/metabolic
abnormalities are profound enough to substantially
increase mortality
 Persisting hypotension requiring vasopressors to
maintain MAP ≥ 65 mmHg and having a serum
lactate level > 2mmol/L (18 mg/dL) despite
adequate volume resuscitation

JAMA.2016;315(8):801-810
Sequential Organ Failure Assessment Score

JAMA.2016;315(8):801-810
Dysregulated host response leads to..
Definition

OLD NEW
DEFINITION DEFINITION

ORGAN
INFLAMMATION
DYSFUNCTION

JAMA.2016;315(8):801-810
Sepsis algorytm
 Management of Sepsis-Septic Shock

Initial
Diagnosis Fluid Therapy
Resuscitation

Antibiotic Source
Vasopressors Control
Therapy

Blood Product Glucose

Corticosteroid
Administration Control

Bicarbonate Sepsis Guidelines

Therapy 2016
 Management of Sepsis-Septic Shock

1 EARLY 3
Save lives
2

Hemodynamic Infection
Recognition restoration control
• q SOFA • Fluids • Antibiotics
• Vasopressors • Source control
Initial
Resuscitation
Surviving Sepsis Campaign Bundles
TO BE COMPLETED WITHIN 3 HOURS:
1. Measure lactate level
2. Obtain blood cultures prior to administration of
antibiotics
3. Administer broad spectrum antibiotics
4. Administer 30 mL/kg crystalloid for hypotension or
lactate ≥4 mmol/L
Surviving Sepsis Campaign Bundles
TO BE COMPLETED WITHIN 6 HOURS:
1. Apply vasopressors (for hypotension that does not
respond to initial fluid resuscitation) to maintain a
MAP ≥65 mmHg
2. In the event of persistent arterial hypotension
despite volume resuscitation (septic shock) or initial
lactate ≥4 mmol/L :
 Measure CVP
 Measure ScvO2

3. Remeasure lactate if initial lactate was elevated

 FLUID
THERAPY
Fluid Therapy
 Crystalloids are the fluid of choice for initial
resuscitation and subsequent intravascular volume
replacement in patients with sepsis and septic shock
(strong recommendation, moderate quality of evidence)

 Against using hydroxyethyl starches (HESs) for

intravascular volume replacement in patients with sepsis or
septic shock (strong recommendation, high quality of evidence)
Fluid Therapy
 Using Albumin in addition to crystalloids for
initial resuscitation and subsequent intravascular
volume replacement in patients with sepsis and
septic shock when patients need more crystalloids
(weak recommendation, low quality of evidence).
Diagnosis
Diagnosis
 Cultures BEFORE antimicrobial therapy
 One from percutaneous and from each vascular access
 Aerobe and anaerobe
 Invasive candidiasis is in differential diagnosis as cause
of infection
 Imaging studies to confirm a potential source of
infection
Antimicrobial Therapy
Antimicrobial Therapy
 Administration of IV anti-microbials must be
initiated as soon as possible after recognition
and within 1 hour for both sepsis and septic
shock (strong recommendation, moderate quality of
evidence).
Antimicrobial Therapy
 Antimicrobial treatment duration of 7–10 days is
adequate for most serious infections associated
with sepsis and septic shock (weak recommendation,
low quality of evidence)
Antimicrobial Therapy
 Measurement of procalcitonin levels can be
used to support shortening the duration of
antimicrobial therapy in sepsis patients (weak
recommendation, low quality of evidence).
 Procalcitoninlevels can be used to support the
discontinuation of empiric antibiotics in patients
who initially appeared to have sepsis, but
subsequently have limited clinical evidence of
infection (weak recommendation, low quality of
evidence).
Antimicrobial Therapy
 Guidelines suggest empiric combination
therapy (using at least two antibiotics of
different antimicrobial for the initial
management of septic shock (weak
recommendation, low quality of evidence)
Source
Control
Source Control
 A specific anatomic diagnosis of infection
requiring emergent source control be identified or
excluded as rapidly as possible in patients with
sepsis or septic shock, and that any required
source control intervention be implemented as
soon as medically and logistically practical after
the diagnosis is made (best practice statements)
Source Control
 Prompt removal of intravascular access devices
that are a possible source of sepsis or septic shock
after other vascular access has been established
(best practice statements)
Corticosteroids
Corticosteroids
 Guidelines are Against using IV hydrocortisone
to treat septic shock patients if adequate fluid
resuscitation and vasopressor therapy are able to
restore hemodynamic stability.
 If this is not achievable, IV hydrocortisone at
a dose of 200 mg per day
Vasopressors
Vasopressors
 Norepinephrine as the first choice (strong
recommendation, moderate quality of evidence)
 Adding either vasopressin (up to 0.03 U/min)
(weak recommendation, moderate quality of evidence) or
 Epinephrine (weak recommendation, low quality of
evidence)
Vasopressors
 Using dopamine as an alternative vasopressor
agent to norepinephrine only in highly selected
patients (patient with low risk of arrhythmias) (weak
recommendation, low quality of evidence)

 Against using low-dose dopamine for renal

(strong recommendation, high quality of evidence)
Vasopressors
 Using dobutamine in patients who show
evidence of persistent hypoperfusion despite
adequate fluid loading and the use of vasopressor
agents (weak recommendation, low quality of evidence)
Glucose Control
Glucose Control
 A protocolized approach to blood glucose
management in ICU patients with severe sepsis
commencing insulin dosing when 2 consecutive
blood glucose levels are >180 mg/dL
 Target an upper blood glucose ≤180 mg/dL
rather than an upper target blood glucose ≤ 110
mg/dL (strong recommendation, high quality of evidence)
Glucose Control
 Blood glucose values be monitored every 1–2 hrs
until glucose values and insulin infusion rates are
stable and then every 4 hrs thereafter in patients
receiving insulin infusions
Blood Product
Administration
Blood product
 RBC transfusion occur only when hemoglobin
concentration decreases to < 7.0 g/ dL in adults
in the absence of extenuating circumstances, such
as myocardial ischemia, severe hypoxemia, or
acute hemorrhage (strong recommendation, high quality
of evidence)
Blood product
Prophylactic platelet transfusion
 When counts are <10,000/mm 3 in the absence of
apparent bleeding and
 When counts are <20,000/mm 3 if the patient has
a significant risk of bleeding.
 Higher platelet counts (≥50,000/mm 3 ) are advised
for active bleeding, surgery, or invasive procedures
(weak recommendation, very low quality of evidence)
Blood product
 Against the use of fresh frozen plasma frozen
plasma to correct clotting abnormalities in the
absence of bleeding or planned invasive
procedures (weak recommendation, very low quality of
evidence)
Bicarbonate Therapy
Bicarbonate Therapy
 Against the use of sodium bicarbonate
therapy to improve hemodynamics or to reduce
vasopressor requirements in patients with
hypoperfusion-induced lactic acidemia with pH ≥
7.15 (weak recommendation, moderate quality of
evidence)
Fluid management in sepsis
Outline
Current controversies fluid therapy in sepsis
1. Volume
2. Type of fluid
3. Management of fluid
Why should we give fluids in sepsis?

Capillary
Vasoplegia
leak

SEPTIC SHOCK
Vasodilatory
shock
Distributive
shock

No volume loss !!!

1. Controversy in fluid volume
Is there danger in the water?
Fluids
 Double-edge sword
 Fluids are drugs
• Indications and contra indications
• Dosing
• Timing
• Type of fluid
 Fluid imbalance leads to
MOF and Death
Hypervolemia
Hypovolemia Fluid overload
Easily
Hypoperfusion Hardly
Tissue Edema
Recognized Recognized
Mortality

MOF
Compensation MOF
Compensation
mechanism mechanism
“YES”
DEATH “NONE”
DEATH
Normovolemia

Volume Status
FEAST Trial (Fluid Expansion As Supportive Therapy)
 Multi center RCT: To investigate early resuscitation with a
saline/albumin bolus as compared with no bolus (control)
 Population: 3141 children with severe febril illness and
impaired perfusion
 Intervention: IV bolus 20-40 ml/Kg NaCl 0.9% or albumin 5%
 Control: No Bolus
 Primary outcome: Mortality at 48 hour and 4 weeks
 Mortality at 48 hours

Bolus
Mortality

No bolus

Time/hour Fluid Exp a nsio n As a Sup p o rtive The ra p y

 Mortality at 4 weeks

Bolus

No bolus
Mortality

Time/day
Fluid Exp a nsio n As a Sup p o rtive The ra p y
 Daily fluid balance in AKI and Cumulative fluid balance in AKI and non-
non-AKI in the first 3 days of ICU AKI in the first 3 days of ICU stay
stay

Wang et al. Critical Care (2015) 19:371

 Cumulative
Fluid overloadfluid was
balance
aninindependent
AKI survivors andrisk
non-survivors
factor forin the
the first 3 days of ICU stay
incidence of AKI and increased the severity of AKI

Wang et al. Critical Care (2015) 19:371

 Association between progressive increases in
volume-related weight gain (VRWG) and mortality

3% mortality per 1% increase fluid overload

ASAIO Journal. 56(4):333-337, July/August 2010
Positive fluid balance is associated with
increased mortality in septic shock
 Pathological sequelae of fluid overload in
organ systems

Not
Sinking
Swimming

Prowle, J. R. et al. Nat. Rev.

Nephrol. 6, 107–115 (2010)
Paracelsus (1493-1541)
“All Things are poison and
nothing is without poison, only
the dose makes a thing not a
poison”

The dose makes the poison 

“Sola dosis facit venerum” Father of toxicology
2. Controversy in choice of fluid
Ideal resuscitation fluid
1. Predictable and sustained increase in intravascular
volume
2. Chemical composition as close as possible to that of
extracellular fluid
3. Metabolized and completely excreted without
accumulation in tissues
4. Does not produce adverse metabolic or systemic effects
5. Cost-effective in terms of improving patient outcomes
 Choice of Fluids
Fluids

Crystalloids Colloids

Buffered Unbuffered Gellatin HES Albumin Dextran

Crystalloids vs Colloids
• Colloids vs crystalloids: No significant difference in 28-day mortality
(CRISTAL trial 2013)
• HES vs Saline: No mortality difference, Increased AKI and CRRT use with HES
(CHEST study 2012)
• Albumin 4% vs Saline: No significant difference in 28-day mortality (SAFE
study 2004)
• Albumin 20% + Saline vs Saline: No significant difference in 28-day mortality
(ALBIOS trial 2014)
 Crystalloid

Buffered Unbuffered

Normal saline (unbuffered)

• Iatrogenic hyperchloremic metabolic acidosis
• Increased risk of acute kidney injury (AKI) and renal
replacement therapy (RRT)
• Saline vs Plasmalyte 148: No difference in incidence of AKI, RRT
and mortality, low volume ≤ 2 L (SPLIT trial, JAMA 2015)

Recommendations (SSC guidelines)

Crystalloids as the initial choice for fluid resuscitation in
sepsis and against used of HES
3. Controversy in fluid management
1. The Surviving Sepsis Campaign Guidelines only
focus on the initial resuscitation
2. Limited information beyond “resuscitated sepsis”
3. Limited information on the assessment of volume
overload or when and how to perform de-
escalation/de-resuscitation
4. Fluid loading is a common practice in ICU
 Sepsis Continuum
Three Hit Model and Fluid management
• Persistent capillary
Acute • AKI, ARDS leakage (CLI ↑)
Inflammatory • Acute Bowel • Increasing MOF
insult Injury • Tissue edema ↑
• CNS failure
Vascular
dysfunction
1st Hit • Coagulopathy
• UID
2nd Hit Unresolved shock 3rd Hit DEATH
Multi Organ GIPS
Septic Global Increased
Shock Dysfunction Permeability
Syndrome

FLUID RESUSCITATION FLUID RESTRICTIVE FLUID REMOVAL/DE-ESCALATION

• Fluid bolus • Zero fluid balance • Negative fluid balance
• Fluid challenges • Diuretic, RRT

• Different stages of septic shock different in fluid management

• “One size does not fit all”
Annals of Intensive Care 2012, 2(Suppl 1):S1
 Four phases fluid management in sepsis
R O S E
RESUSCITATION OPTIMIZATION STABILIZATION EVACUATION

Principles Life saving Organ rescue Organ support Organ recovery

Phenotype Shock Unstable Stable Recovering

Goals Correct shock Optimize and Zero/negative Fluid evacuation

maintain perfusion balance

Fluid Fluid bolus Titrate and fluid Minimal infusion Oral intake, avoid
challenges If oral inadequate Unnecessary iv
fluids
Time Minutes Hours Days Days to weeks

Br J Anaesth. 2014 Nov;113(5):740-7

N Engl J Med 2013;369:1726-34
 Volume status at different stages of
resuscitation
EAFM Fluid LCFM LGFR
Challenges
Volume Status

RESUSCITATION OPTIMIZATION STABILIZATION EVACUATION

EAFM: Early Adequate Fluid Management

LCFM: Late Conservative Fluid Management Br J Anaesth. 2014 Nov;113(5):740-7
LGFR: Late Goal Fluid Removal/De-escalation N Engl J Med 2013;369:1726-34
Fluid Challenge
The Frank-Starling & Marik-Phillips Curves

Marik-Phillips curve

Extra Vascular Lung Water

Large increase in EVLW
Sepsis Small increase in CO
Stroke volume

Fluid unresponsive

EVLW
Frank-Starling curve

Small increase in EVLW

Large increase in CO
Fluid responsive

Preload Marik et al . Br J Anaesth 2014; 112: 620–2

 Monitoring fluid management in sepsis
RESUSCITATION OPTIMIZATION STABILIZATION EVACUATION

Minimum monitoring
Blood Pressure SBP MAP MAP MAP
Heart Rate + + + +
Capillary Refill + + + +
Lactat + + + +
Urine Output - + + +
Fluid Balance - + + +
Optimum monitoring
CVP - ±/? - -
ScvO2 - + - -
Fluid Challenge - + - -
Cardiac Output - + - -
(PPV,SPV,SVV) Br J Anaesth. 2014 Nov;113(5):740-7
N Engl J Med 2013;369:1726-34
Predictive value of techniques used to
determine fluid responsiveness

Marik et al. Annals of Intensive Care 2011, 1:1

Central Venous Pressure ?
 CVP = RAP = RVEDP = RVEDV = LVEDV = LV stroke vol =
Cardiac Output

CVP = Cardiac Output ??

 Veins are 30 times more compliant than the arteries
 CVP can accurately predict fluid responsiveness is only 56%
(No better than flipping a coin !!!)
 Fluid redistribution occur 30-60 minutes after fluid challenge
Anesthesiology 2008; 108:735–48
Crit Care Med 2013; 41:1774–1781
The goals of hemodynamic stabilization
1. Adequate MAP without vasopressors
2. Preserved mental status
3. Normal skin perfusion
4. Urine output ≥ 0.5 cc/Kg/hour
5. Lactate levels normal/decreasing
 Summary
1. Fluid therapy should be tailored to the specific indications
“One size does not fit all”
2. Aggressive IV fluid in septic shock carries risk “The dose
makes the poison”
3. Positive fluid balance is associated with increased mortality
“Sinking, not swimming”
4. Early adequate resuscitation followed by a restrictive fluid
strategy is associated with better outcomes “ROSE”
5. Early use of norepinephrine improve outcome and avoid
fluid overload “Early safe lives”
THANK
YOU