Sepsis
- causative pathogens
- clinical manifesations
- diagnosis
- management
- consequences and course
- pathogenesis
- resources and references
Sepsis is the systemic response to infection, and is a common cause of death in hospitalized patients. Rates of sepsis have increased dramatically. It is now the 13th most common cause of death in the US, with approximately 600,000 cases per year. Disease of increasing severity includes:
- bacteremia: bacteria in bloodstrea; may be asymptomatic or transient
- sepsis syndrome: SIRS - altered organ perfusion, leading to hypoexia, decreased urine output, or altered mental status, or elevated lactate levels
- septic shock: hypotension, despite IV fluids
Causative Pathogens
The most commonly identified bloodstream pathogens include
- staphylococci
- Streptococci
- E coli
- Enterobacter
- Pseudomonas aeruginosa
Fungal causes are less likely but increasing in frequency.
Clinical Manifestations
Signs and symptoms of sepsis are non-specific. They include:
- tachypnea and respiratory alkalosis (early sign)
- fever, chills
- hypothermia (poor prognosis)
- tachycardia
- hypotension
- mental status changes or delirium
- leukocytosis
- leukopenia (common in overwhelming bacteremia, severe viral infections, alcoholics, elderly)
- end-organ failure
Fever does not alsways occur, especially in the elderly and those with renal or liver failure.
Some organisms, especially gram-negatives, can cause ecthyma gangrenosum.
Diagnosis
Assess underlying diseases, previous infections and antimicrobial therapy, and symptoms of local infection.
Inquire into travel, occupational exposure, or encounters with infectious sources.
Two or three sets of blood cultures have a sensitivity of 89% and 99%, respectively, in people with bacteremia.
Management
Early recognition and initiation of treatment is of paramount importance. Patients are best served in the ICU, especially if hypotensive.
Tissue perfusion can be maintained using crystalloid fluid recusitation, transfusion to kepp hematocrit >30%, and use of inotropes if necessary.
Antibiotics should be based on pathogen identified, local resistance patterns, and potential sites of infection. Early, broad-spectrum emperic therapy is necessary.
Glucose maintenance between 80-100 mg/dl can prevent death.
Activated protein C (drotrecogin-alpha) can reduce risk of mortality, but does increase risk of bleeding.
Consequences and Course
Sepsis is more likely to be fatal with the following risk factors:
- severe disease
- delayed onset of treatment
- dangerous pathogen
- nosocomial infection
- organ failure (ARDS, anuria, DIC, bowel ischemia, coma)
Pathogenesis of Sepsis
Sepis is caused by the body's response to pathogenic material. Bacterial LPS is a common trigger for the inflammatory response. Other bacterial agents include teichoic acid and peptidoglycan. However, sepsis can also occur with viral, fungal, rickettsial, mycobacterial, or parasitic infections.
Pathogenic materials are taken up by macrophages, who respond by producing large amounts of pro-inflammatory cytokines such as TNF, IL-1, IL-6, IL-8, and G-CSF. Cytokines have multiple actions, inducing systemic response as well as stimulating T cells, B cells, and NK cells.
Coagulation can be induced by pro-inflammatory cytokines, tissue factor release, both through intrinsic and extrinsic pathways. Anticoagulants including proteins C and S, antithrombin III, and TFPI also become depleted, further inducing blot clot. Endotoxin stimulates membrane phospholipid production of platelet-activating factor (PAF), prostaglandins, and leukotrienes.
Resulting widespread microvascular thrombosis can act with disseminated intravascular coagulation to induce ischemia and mulitple organ failure.
Hormones such as cortisol, glucagon, and epinephrine can also be produced in response to endotoxin.