Sepsis & Septic Shock

• Sepsis is a clinical syndrome characterized by systemic inflammation due to infection.
• Whenever there is infection there is a reaction from host involving various responses.

Systemic responses to infection:

• · Fever
• · Hypothermia
• · Tachypnea
• · Tachycardia.

Sepsis DEFINITIONS

There is a continuum of severity ranging from sepsis to severe sepsis and septic shock. A systemic inflammatory response to infection, in which there is fever or hypothermia, tachycardia, tachypnea, and evidence of inadequate blood flow to internal organs

Sepsis (Septic Shock) Definition Diagnosis and Pathophysiology

Bacteremia –

• Presence of bacteria in blood.

Septicemia –

• Presence of organisms or their toxins in blood.

SIRS

• (Systemic Inflammatory Response Syndrome) Presents with 2 or more of the following:
• • Fever
• · Tachypnoea
• · Tachycardia
• · Leucocytosis
• · Leucopenia.
• Sepsis is microbial infection with SIRS.
• Severe sepsis or sepsis syndrome – Sepsis with organ dysfunction.
• Septic Shock – Sepsis with hypotension.
• Refractory septic shock – Septic shock for more than 1 hour.
• Multiple Organ Dysfunction Syndrome (MODS)­
• Dysfunction of more than 1 organ, requiring inter­vention.
• When the defence mechanism fails, there is dysfunc­tion of major organs.

The different stages are :

• Septic shock Hypotension Organ dysfunction Death.
• Sepsis is reversible but septic shock is usually not.

SIRS:

• SIRS is an inflammatory reaction to various clinical insults (e.g., severe trauma or burn) manifested by 2 or more of the following:
• Temperature >38°C or <36°C
• Heart rate >90/min
• Respiratory rate >20/min or PaCO₂ <32 mm Hg
• White blood cell (WBC) count >12,000/mm³, <4,000/mm³, or >10% immature forms (bands)
• is systemic inflammatory response syndrome.
• It may be infectious or a non-infectious syndrome. If there is infection, it is called sepsis.

Etiology :

• Genitourinary system
• Hepatobiliary tract
• Gastrointestinal tract
• Lungs
• Indwelling catheter
• Surgical wound
• Decubitus ulcer

Spread :

• By blood stream, local spread, systemic spread of signal molecules or toxins.
• Blood cultures yield bacteria or fungi in severe sepsis and septic shock. 70% are gram negative or positive bacteria.

DIAGNOSIS of Sepsis

• By blood culture.
• Microscopic examination of infected material from local site.
• Culture of micro-organisms from infected mate­rial from local site.

Differential Diagnosis Septic Shock

• Hyponatremia due to other causes, e.g., SIADH, cirrhosis, vomiting
• Abdominal pain due to other causes
• Other types of shock, e.g., septic, cardiogenic, hypovolemic, anaphylactic
• Hyperkalemia due to other causes, e.g., renal failure, rhabdomyolysis

Gram-negative bacteremia occurs in :

• Diabetes mellitus Lymphoproliferative diseases
• Cirrhosis of liver
• Burns
• Invasive procedures, devices
• Treatment with drugs which cause neutropenia.

Gram-positive bacteremia occurs in :

• Vascular catheterization Indwelling mechanical devices Burns
• IV drug use.

Fungemia occurs in :

• Immunosuppressed patients Neutropenia
• After broad-spectrum treatment.

Increased risk

• Age more than 50 years.
• Primary site pulmonary, abdominal or.
• Age extremes (very old and very young)
• Impaired host (see Associated Conditions)
• Community-acquired pneumonia
• Critically ill patients
• Indwelling catheters: Intravascular, urinary, biliary
• neuromeningeal.
• (From urinary tract or catheter there is less severe sepsis).

Sepsis PATHOPHYSIOLOGY

• In sepsis, an imbalance between pro- and anti-inflammatory mediators at the site of infection results in widespread systemic inflammation that damages distant uninvolved tissues.
• · Local spread – GIT, skin, blood
• Dysregulated nitric oxide production and activation of the coagulation system are the main contributors to maldistribution of organ blood flow.
• · Direct into blood stream (IV catheters)
• Widespread endothelial damage and microvascular dysfunction leads to maldistribution of blood flow, causing impaired tissue oxygenation and resultant organ dysfunction.
• · Low immune response (any microbe anywhere can cause septicemia)
• · Endotoxins (act as super antigens).
• The initial, overexuberant inflammatory response can progress to significant immunosuppression in the later stages of sepsis.

• Microbial signals

  • When microorganisms invade body, certain signals are recognized by the individual like : LPS ­Lipopolysachharide or endotoxins, LPS-binding pro­tein-LBP which transfers LPS to CD₁₄ on the surface of monocytes, macrophages, neutrophils. This causes release of TNF (Tumor necrosis factor) and signals amplify and spread.

• Host response

  • Involves microbial signal molecules-Ieucocytes, hu­moral mediators, vascular endothelium, cytokines, phospholipid derived mediator, coagulation factors, complement, vascular endothelium.
  • Mediator for septic shock is probably inducible nitric oxide synthase (iNOS).