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

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).