(3) host defense systems activated – modulate host responses
(4) mediators released
(5) shock and multiorgan failure – provide intensive care support
– Microorganisms in a normally sterile site; subclinical or symptomatic.
– Bacteria present in bloodstream; may be transient.
– Same as bacteremia but greater severity.
– Clinical evidence of infection plus systemic response to infection (fever/hypothermia >38oC or <36oC, tachycardia >90, tachypnea >20, leukocytosis/leukopenia >12 x 109/L or <4 x 109/L or 10% immature forms).
syndrome – Sepsis (due to infection) plus altered organ perfusion (hypoxemia, oliguria, altered mentation).
– Same as sepsis syndrome plus hypotension and organ hypoperfusion.
– Sepsis with hypotension despite adequate fluid resuscitation. Patients on vasopressors may not be hypotensive at the time hypoperfusion abnormalities are evident.
Refractory septic shock
– Shock lasting more than 1 hour unresponsive to fluid administration or vasopressors.
Systemic inflammatory response syndrome
(SIRS) – Wide variety of insults (infectious and noninfectious) that initiate profound systemic responses. Sepsis syndrome is a subset of SIRS.
The incidence of sepsis and associated deaths have increased dramatically in the USA in the last 20 years.
The highest rates for hospital-acquired blood stream infections were seen in oncology patients, burn/trauma victims, and in high-risk nurseries.
It has been estimated that hospital-acquired bloodstream infections are associated with 7.4 extra days of hospitalization and $4,000 of extra hospital charges per occurrence.
Most common sepsis bugs
: Staph, strep, E. coli, Enterobacter, Pseudomonas. Fungi are increasingly observed.
Why has sepsis been on the rise?
More and more complex and immunocompromised patients, AIDS, more intense chemotherapy regimens, aging population, aggressive employment of invasive procedures and surgery.
Factors influencing survival in the setting of bacteremia
: severity of underlying disease, timely initiation of appropriate antimicrobial therapy, the pathogen, the extremes of age, site of infection (respiratory > abdominal > urinary), nosocomial acquisition, magnitude of bacteremia, polymicrobial infection and development of end-organ complication (ARDS, anuria, DIC, coma, etc.).
When there is evidence of dysfx in 2 or more systems, the diagnosis of multiorgan system failure can be made. Mortality rises in proportion to the number of organ systems involved and is near 100% when 4 or more systems are involved.
Pathogenesis and Clinical Management
Sepsis is caused by either gram negative (LPS endotoxin) or gram positive (cell wall products like teichoic acid and peptidoglycan) bugs.
(1) Endotoxin induces marcophages to produce a number of proinflammatory cytokines including TNF-
a , IL-1, IL-6, IL-8, g -interferon and G-CSF. Each of these cytokines exerts multiple effects related directly or indirectly to the development of sepsis, affects its own production and that of other mediators, and in some cases, acts synergistically with one or more of the cytokines. These marcophage -associated cytokines can also stimulate B, T, NK, and bone marrow cells. Mediators released from macrophages can stimulate T-cells to generate IL 2, 4 and 10, and GM-CSF.
(2) Endotoxin stimulates membrane phospholipid metabolism leading to the generation of platelet activating factor and other bioactive metabolites of arachidonic acid, including prostaglandins and leukotrienes. These compounds, in turn, exert a variety of synergistic and antagonistic effects on vascular endothelium, smooth muscle, platelets, and leukocytes and contribute to or modulate pathophysiologic events associated with septic shock.
(3) Endotoxin may also serve as a cofactor to prime granulocytes to produce toxic oxidative radicals.
(4) Endotoxin induces the production of
b -endorphins (which have been implicated in the pathogenesis of sepsis), as well as counter-regulatory hormones such as cortisol, glucagon and catecholamines which may oppose many of the shock-producing actions of endorphins and other mediators.
– Signs and Symptoms Suggesting Bacterial Infection as the Cause of the Sepsis Syndrome
Fever, chills (note: elderly/debilitated patients may not develop fever)
Hyperventilation – early clue to systemic infectious process
Hypothermia – poor prognosticator
Mental status changes – could be associated to hypoglycemia
Hypotension – Shock is observed most often with gram-negative bacilli
End organ failure: lung, kidney, liver, heart, DIC
– Cellulitis, diffuse erythroderma (toxin producers like staph and strep).
– Ecthyma gangrenosum (round/oval 1-5 cm lesions with a halo of erythema and usually a vesicular to necrotic central area, pathognomonic of Pseudomonas), petechia/hemorrhagic skin lesions (Neisseria).
The above findings should prompt blood cultures and initiation of antibiotics.
History: underlying diseases, previous infections, previous antimicrobial therapy, travel, diet, environmental exposure, contact with infectious agents, known drug toxicities/allergies, etc.
: focused on discovering clues to infection and localizing sites.
: Specimens for microbiologic evaluation need to be obtained (blood cultures from bacteremic patients will yield the organism 89% - 99% of the time). However, identification of patients with the sepsis syndrome does not require positive blood cultures or the presence of hypotension.
: CT scans, CSF exam
The key to management of sepsis is the early recognition of the systemic response and initiation of therapy before hypotension and complications ensue.
Patients with sepsis syndrome, especially if hypotensive, are probably best managed in intensive care units.
The essential therapies of the sepsis syndrome and septic shock include: wide spectrum antibiotics, adequate fluid administration, oxygen and vasopressors.