SEPTIC SHOCK

10th Leading Cause Of Death.

Annual Cost = Approximately 16.7 Billion $.

Reasons For Standardizing
Terminology Related To
Sepsis.

In 1992, A Joint Committee Of The American

College Of Chest Physicians & The Society Of
Critical Care Medicine Standardized The
Terminology Related To Sepsis For Several
Reason.
Reasons For Standardizing
Terminology Related To
Sepsis.
A. Widespread Confusion With The Use Of
These Terms.

B. The Need To Provide A Flexible Classification

Scheme For Patient Identification.

C. Identification Of An Earlier Therapeutic

Intervention, And

D. Standardization Of Research Protocols.

 Advantages Of
Terminology.
The Criteria For The New Terms Provide Specific Physiologic
Variables That Can Be Used To Categorize A Patient As
Having;

1. Bacteremia.

2. Systemic Inflammatory Response Syndrome. [SIRS]

3. Sepsis.

4. Severe Sepsis.

5. Septic Shock.

6. Multiple Organ Dysfunction Syndrome. [MODS]

. Suggesting An Important Continuum Of Progressive

Physiologic Decline.
 Advantages Of
Terminology.

Introduction Of The Term SIRS Reflects The

Knowledge That A Physiological Similar
Systemic Inflammatory Response Can Be
Seen Even In The Absence Of Identifiable
Infection.
Classification Of
Sepsis
More Recently, The Classification Of Sepsis
Was Modified To Include;

1. Severe Sepsis.

2. Septic Shock.

3. Refractory Septic Shock.

DEFINITIONS.
SYSTEMIC INFLAMMAORY
RESPONSE SYNDROME.

Systemic Inflammatory Response To A Variety

Of Clinical Insults, Which Can Be Infectious Or
Non-Infectious.

The Response Is Manifested By Two Or More

Of The Following Conditions.
Following Conditions.
1. Temperature > 38C or < 36C.

2. Heart rate > 90 beats / min.

3. Respiration Rate > 20/min or Pa CO2 < 32 Torr.

4. WBC > 12,000 Cells/mm2, <4000 Cells / mm3 or >10% Immature [Band]
Forms.

5. Positive Fluid Imbalance [>20ml/kg Over 24h]

6. Arterial Hypotension Cl > 3.5 L /min

7. Arterial Hypoxemia, Acute Oliguria.

8. Creatinine Increase > 0.5 mg/dl, Coagulation Abnormalities.

9. Platelets < 100,000 mcL.

10.Bilirubin > 4 mg/dl.

BACTEREMIA.

Presence Of Viable Bacteria In The Blood

Stream.
INFECTION.

Inflammatory Response To Invasion Of

Normally Sterile Host Tissue By The Micro-
Organism.
SEPSIS.

SIRS Secondary to infection.

SEVERE SEPSIS.

Sepsis Associated With

A. One Or More Organ Dysfunction,

B. Hypoperfusion,Or

C. Hypotension.
SEPTIC SHOCK

Sepsis With Persistent Hypotension Despite

Fluid Resuscitation Along With The Presence
Of Perfusion Abnormalities.
REFRACTORY SEPTIC
SHOCK.

Persistant Septic Shock, Requiring Dopamine

> 15Mcg/Kg/Min To Maintain Mean Arterial
Blood Pressure.
MULTIPLE ORGAN
DYSFUNCTION SYNDROME.

Presence Of Altered Organ Function Requiring

Intervention To Maintain Homeostasis.

[ Progression From Sepsis To MODS Can Occur

In The Absence Of An Intervening Period Of
Septic Shock.]
PATHOPHYSIOLOGY
Sepsis Occurs Due To Complex Interactions
Between The

1. Invading Pathogen,

2. Host Immune System &

3. Inflammatory Responses.
 SIRS Occurs Due To The Imbalance Between The Control Of
The Anti-Inflammatory Mediators Over The Pro-
Inflammatory Mediators.

Pro-Inflammatory Mediators Are Involved In The

Eradication Of The Micro-Organism.

Anti-Inflammatory Mediators Exert A Control On The Pro-

Inflammatory Mediators.

Inflammatory Responses Causes Damage To The Specific

Tissue.

SIRS The Progresses To Sepsis To Severe Sepsis To Septic

Shock To MODS.
COMPLICATIONS OF
SEVERE SEPSIS.
The Majority Of Patients With Severe Sepsis
Have Dysfunction Of 2 Organs, And The The 3
Most Frequent Organ Dysfunction Are,

1. Respiratory.

2. Circulatory &

3. Renal.
COMPLICATIONS OF
SEPSIS.

Shock Is The Most Ominous Complication

Associated With Sepsis, And Mortality Occurs
In Approximately Half Of The Patients With
Septic Shock.

Severe Hypotension Occurs To Be Caused.

Severe
Complications.
Septic Shock Is Associated With Several
Complications Including,

1. Disseminated Intravascular Coagulation.

2. Acute Respiratory Distress Syndrome, &

3. Multiple Organ Failure.

Disseminated
Intravascular
Coagulation.
It Is The Inappropriate Activation Of The
Clotting Cascade That Causes Formation Of
Micro Thrombi, Resulting In

A. Consumption Of Coagulation Factors,

B. Organ Dysfunction &

C. Bleeding.
Incidence Of DIC

The Incidence Of DIC Increases As The

Severity Of Sepsis Increases.

In Sepsis Alone, The Incidence Was 16% In

Comparison To 38% In Septic Shock.
Complications Of DIC
Vary & Depend On The Target Organ Affected And The Severity Of
The Coagulopathy.

DIC Can Produce,

1. Acute Renal Failure.

2. Hemorrhagic Necrosis Of The GI Mucosa.

3. Liver Failure.

4. Acute Pancreatitis,

5. ARDS, &

6. Pulmonary Failure.
 Furthermore, As The Procoagulant State
Appears To Be The Key In The Pathogenesis Of
MODS.

MODS Often Co-Exist In Sepsis.

Acute Respiratory
Distress Syndrome.
Pulmonary Dysfunction Usually Precedes
Dysfunction In Other Organs, & It Can Even
Initiate The Development Of SIRS With
Resultant MODS.

The End Result Is

1. Loss Of Functional Alveolar Volume.

2. Impaired Pulmonary Compliance &

3. Profound Hypoxemia.
Hemodynamic
Effects.
The Hallmark Of The Hemodynamic Effect Of
Sepsis Is The Hyper Dynamic State
Characterized By High Cardiac Output & An
Abnormally Low Systemic Vascular
Resistance. [SVR].

TNF- Alpha & Endotoxin Directly Depress

Cardiovascular Function.

Persistent Hypotension Raises Concern For

The Balance Of O2 Delivery To The Tissues &
O2 Consumption By The Tissues.
Acute Renal Failure.

Early Acute Kidney Injury Occurs In 42% To

64% Of Adult Patients With Sepsis & Septic
Shock.

Adequate Renal Perfusion & A Trial Of Loop

Diuretics Should Be Initiated Promptly In
Oliguric Or Anuric Patients With MODS.
CLINICAL
PRESENTATION
The Initial Clinical Presentation Can Be
Referred To As Signs & Symptoms Of Early
Sepsis, Defined As The First 6 Hours.

Progression Of Uncontrolled Sepsis Leads To

Clinical Evidence Of Organ System Dysfunction
As Represented By The Signs & Symptoms
Attributed To Late Sepsis.
EARLY SEPSIS LATE SEPSIS
Fever/Hypothermia Lactic Acidosis
Rigors, Chills Oliguria
Tachycardia Leukopenia
Tachypnea DIC
Nausea,Vomiting M.D
Hyperglycemia Pulmonary Edema
Myalgias Hypertension
Lethargy, Malaise Hypoglycemia
Proteinuria Azotemia
Hypoxia Thrombocytopenia
Leucocytosis A.R.D.S
Hyperbilirubinemia Coma
PROGNOSIS
As The Patient Progresses From SIRS To Sepsis To
Severe Sepsis To Septic Shock, Mortality Increases In
A Stepwise Fashion.

Mortality Rates Are Higher For Patients With

1. Advanced Age.

2. Pre-Existing Disease.

3. Including COPD.

4. Neoplasm & HIV Disease.

 In One Analysis Of Cases, Mortality Increased
With Age, From 10% In Children To 38.4% In
Those 85 Years Or Older.

ICU Admission Was Required In 51.1% Of

Patients With Severe Sepsis, Of Those Patients
Mortality Was Reported In 34.1%.
 Mortality From Severe Sepsis & MODS Is Most
Closely Related To The Number Of
Dysfunctioning Organs.

As The Number Of Failing Organs Increased

From 2 To 5, Mortality Increased From 54% To
100%.

Duration Of Organ Dysfunction Can Also

Affect The Overall Mortality Rate.
 Mortality Related To
Number Of Failing
Organs.
0 & 1(Mortality Rate)

1 & 2 (Mortality Rate)

2 & 3 (Mortality Rate)

3 & 4 (Mortality Rate)

4 & 5 (Mortality Rate)

0 25 50 75 100 125
REFERENCE.

Pharmacotherapy 8th Edition.A

Pathophysiologic Approach.

By, Joseph T. Dipiro, Robert, Gaery, Matzke,

Barbara, & Michael Posey.
THANK YOU

Presented By;

Shrikanth Nambanath.

Fourth Year Pharm.D

Al-Shifa College Of Pharmacy.