Sepsis/Septic shock

Introduction

• When bacteria is not effectively cleared by host defenses, a systemic inflammatory response is activated →sepsis

SIRS(systemic inflammatory response system)- cardinal signs are fever or hyothermia, leukocytosis or leukopenia, tachypnea,and tachycardia

• If SIRS is accompanied by an infections it is termed SEPSIS

Severe sepsis- when sepsis is associated with dysfunction of organs distant from the sight of infection

Septic shock- when hypotension cannot be corrected by infusing fluids

Introduction

Harrisons 17th ed.

Etiology

• Sepsis may developed as a complication of localized community-aquired infections or may follow colonization and local mucous invasion by virulent pathogens

• Children 3mos-3years of age are at risk for occult bactermia, which occasionally progresses to sepsis

Pathogenesis

• SIRS related to sepsis results from tissue damage following the host response to bacterial products

• When bacterial cell wall components are released onto the bloodstream, cytokines are activated, and these in turn can lead to further physiologic derangements

Pathogenesis

Alone or in combination, bacterial products and proinflammatory cytokines trigger physiologic responses to inhibit microbial invaders:

1. Activation of the complement system2. Activation of Hageman factor (factor XII), which then

initiates the coagulation cascade3. Aderenocorticotropic hormones and B-endorphin

release4. Stimulation of polymorphonuclear neutrophils5. Stimulation of the kallikrein-kinin system

Pahogenesis

• TNF and other inflammatory mediators increase vascular permeability, producing diffuse capillary leakage, reduced vascular tone, and at microcirculatory level an imbalance between perfusion and increased tissue metabolic needs

Shock- is a disruption in circulatory function leading to poor perfusion and inadequate delivery of oxygen and other nutrients to tissues

Pathogensis

• Shock is not diagnosed by a decrease in blood pressure because compensatory mechanisms work to maintain the BP(↑HR and peripheral vasoconstriction)

• Hypotension→ compensatory mechanisms are failing→ cardiorespiratory arrest

Pathogensis

Early phase of sepsis:• ↓systemic vascular resistance• ↓preload → tachycardia, widened pulse

pressure, ↑CO• Patients are usually warm and have

rebounding pulses w/ brisk capillary refill

Pathogenesis

Late phases of septic shock:• Cool extremities• Poor peripheral pulses• ↓BP (myocardial dysfunction)• ↓CO• As tissue O2 consumption exceeds O2

delivery, the tissue hypoxia leads to lactic acidosis

Clinical manifestations

• Fever• Shaking chills• Hyperventilation• Tachycardia• Hypothermia• Cutaneous lesions• Changes in mental status (confusion, agitation,

anxiety, excitation, lethargy, obtundation, or coma)

Diagnosis

• Microbial confirmation if an infectious agent: blood culture, gram stain

• a CBC, platelet count, PT and aPTT, fibrinogne level and D-dimer, arterial blood gas, renal and hepatic profiles, and ionized calcium should me obtained

Lab findings

• Metabolic acidosis• Thrombocytopenia • Prolonged PT and aPTT• Elevated fibrin split products• Anemia• Decrease PaO2 and increasePaCO2• Alteration in morphology and # of neutrophilsNeutropenia sign of overwhelming sepsis

Treatment

• Broad-spectrum bactericidal synergistic antimicrobial agents should be given to a patient in septic shock

For community acquired and nosocomial sepsis: 3rd generations cephalosporins (ceftriaxone, cefotaxime)

For fungal infections: amphotericin B

Prevention

• Immunization with conjugate H. influenzae and S. pneumoniae vaccine is recommended for all infants