Sepsis

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SEPSIS

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-Sepsis is the inflammatory immune response of the host to infection (bacterial, viral, fungal, parasitic) which may lead to a systemic inflammatory reaction and eventually organ dysfunction and/or failure.
-The sepsis syndrome is a continuum of clinical events with increasing severity and mortality
-Sepsis is the systemic inflammatory response syndrome (SIRS) resulting from infection.
-SIRS is a reference for a range of clinical symptoms that result from a systemic activation of the innate immune response, regardless of the cause
-Severe sepsis arises when sepsis occurs in combination with problems in one or more of the vital organs, such as the heart, kidneys, lungs, or liver.
-Multiple organ dysfunction syndrome (MODS) is characterized by the presence of altered function of two or more organs in an acutely ill patient, such that homeostasis cannot be maintained without intervention.
-Septic shock: occurs when sepsis is complicated by low blood pressure that does not respond to standard treatment (fluid administration, use of vasopressors) and leads to problems in one or more of the vital organs as described above
-is a complex and generalized process that Involves all organ systems
-Is initiated by an infection
-Bacteria may be introduced either through the pulmonary system, urinary tract, or GI system, through wounds, or through invasive devices

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Pathophysiology
Cytokine response

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-In sepsis, cytokines are released from WBC and other cells in response to an infection to protect from additional injury and to begin the healing process
-cytokines are proteins that regulate numerous functions of the inflammatory response
-Cytokines account for the s/s seen early in the infective process
-They promote vasodilation and hypotension, increased capillary permeability, fever, and decreased myocardial contractility

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Pathophysiology
Coagulation

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-Bacteria and neutrophils continue to stimulate the release of inflammatory mediators such as endotoxin, interleukin, tumor necrosis factor, and tissue factor
-tissue factor stimulates a procoagulant state and formation of fibrin clots.
-normally this procoagulant state is counter regulated by mediators of anticoagulation and or fibrinolysis such as thrombin activated fibrinolysis inhibitor, plasminogen activator inhibitor
-The end result is the formation of microcirculatory clots that inhibit perfusion to cells and tissues
-this process is believed to to be pivotal to the progression from sepsis to SIRS, MODS, and death
-In sepsis, the intravascular coagulation and thrombolytic responses are out of balance

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Perfusion imbalance

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-There is hypoperfusion of vital organs and tissue ischemia
-inflammatory mediators such as Cytokines and bacterial endotoxins produce vasodilation and increase capillary permeability
-This results in low SVR and inadequate volume in the arterial tree
-Preload is not optimal because of venous dilation, further limiting the ability of the heart to produce a CO adequate to maintain the BP
-Increased capillary permeability causes tissue edema
-activation of the coagulation cascade by inflammatory mediators may cause microthrombi to form in multiple small vessels, which obstruct blood flow to structures distal to the thrombi
-net effects are unequal perfusion of various capillary beds with inadequate or poor blood flow in many tissues, resulting in regions of tissue hypoxia and concomitant organ damage.
-Inability of the circulatory system to meet cellular demands causes cells to resort to anaerobic metabolism for energy production
-lactic acid, the end product of anaerobic metabolism is measured clinically to evaluate the effectiveness of end organ tissue perfusion

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Myocardial alterations

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-Evidence of depressed myocardial performance in the form of decreased ventricular ejection fraction and impaired contractility
-The heart demonstrates impaired contractility and ventricular performance
-Early in septic shock, it is believed that the heart is hyperdynamic, with high CO and low SVR
-however evidence indicates that even at this stage, the heart is performing less than optimally
-Later, as circulating cardiac depressants increase, the heart becomes hypodynamic, with low CO and increased SVR
-CO=stroke volume x HR
-stroke volume = preload, contractility, and afterload

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Pulmonary alterations

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-Inflammatory mediators and activated neutrophils cause capillary leak into the pulmonary interstitium, resulting in interstitial edema, areas of poor pulmonary perfusion (shunting), pulmonary hypertension, and inc resp workload
-the pulmonary alterations may culminate in ARDS, which is frequently associated with septic shock
-As fluid collects in the interstitium, pulmonary compliance is reduced, gas exchange is impaired, and hypoxemia occurs
-Secondary pneumonia may develop
-Capillary permeability refers to the movement of blood plasma in and out of the capillaries.
-Normally, a balance exists between the amount of plasma entering the tissues from the capillaries and the amount re-entering the circulatory system from the tissues.
-When the tissue is damaged as a result of infection or injury, the lining of the small blood vessels becomes leaky, thereby increasing permeability.
-The balance shifts, allowing more fluid to enter the tissues.

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Hematological alterations

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-bacteria or their toxins cause activation of the complement cascade
-Sepsis involves a global inflammatory response
-complement causes mast cells to release histamine, which further stimulates vasodilation and increased capillary permeability
-these actions further contribute to the circulatory alterations in volume distribution and the development of interstitial edema
-platelet abnormalities also occur because endotoxin indirectly causes platelet aggregation and subsequent release of more vasoactive substances
-Circulating platelet aggregates have been identified in the microvasculature of septic pt
-These cause obstruction to blood flow and compromised cellular metabolism
-overtime clotting factors are depleted and a coagulopathy results, with the potential of progressing to DIC

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Metabolic alterations

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-cells are progessively unable to use glucose, protein, and fat as energy sources
-hyperglycemia that is resistant to insulin therapy is a frequent finding in early shock
-eventually all glycogen energy stores are depleted, cells lack ATP and cellular pumps fail, progressing to tissue and organ death
-Excessive catecholamine release stimulates gluconeogenesis and insulin resistance
-In response to lack of effect of insulin, proteins break down, as shown by high BUN and urinary nitrogen excretion
-The net effect of these metabolic derangements is that cells become energy starved

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Assessment

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-the pt is edematous yet intravascularly depleted and areas of microthrombi and vasoconstriction obstruct perfusion
-as fluid replacement occurs, the leaking capillary beds shift the fluid interstitially, requiring more fluid resuscitation, which may further exacerbate interstitial edema
-because of the inappropriate systemic activation of the coagulation system, clotting factors are depleted, and spontaneous bleeding may occur
-CO may be unusually high, but it is insufficient to maintain adequate perfusion due to circulating myocardial depressant factors
-compensatory mechanisms such as activation of the SNS continue to inc CO
-however inflammatory mediators prevent necessary vasoconstriction, and the SVR remains inappropriately low, thereby perpetuating the hypoperfusion crisis

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Infection treatment

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-identification of the infecting organism and use of appropriate antibiotic treatment are of utmost importance
-before the causal orgaism has been identified, empiric broad spectrum antibiotic therapy is initiated, usually with multiple antibiotics with coverage against gram neg and gram pos basteria and anaerobes
-however, once the infectious organism has been isolated, antibiotic therapy should be changes so specific antibiotics that are effective against that organism are used to try to minimize development of antibiotic resistance

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Restoration of intravascular volume

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-Adequate volume replacement is important for reversing hypotension
-Pt may require several liters or more of fluid because of mediator induced vasodilation and capillary leak
-A downward trend in the markers of metabolic acidosis is a good indicator of improvement in tissue perfusion

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Maintenance of adequate CO

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-In the early phase of septic shock, CO may be normal or elevated, but it is not adequate to maintain tissue oxygenation and perfusion because of decreased SVR and peripheral vasodilation
-Maintenance of CO is an essential therapeutic goal
-If adequate volume replacement does not improve tissue perfusion, vasoactive drugs are administered to support circulation
-Low dose dopamine, which increases SVR and improves renal and mesenteric blood flow
-Vasoconstricting drugs frequently used include levophed and epi and neosynephrine

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Maintenance of adequate ventilation and oxygenation

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-Because of the ARDS like picture, PEEP frequently is necessary to aid oxygenation