In the central nervous system, direct damage of the brain cells and disturbances of neurotransmissions causes altered mental status. Cytokines such as tumor necrosis factor, interleukin 1, and interleukin 6 may activate procoagulation factors in the cells lining blood vessels, leading to endothelial damage. The damaged endothelial surface inhibits anticoagulant properties as well as increases antifibrinolysis, which may lead to intravascular clotting, the formation of blood clots in small blood vessels, and multiple organ failure.The low blood pressure seen in those with sepsis is the result of various processes, including excessive production of chemicals that dilate blood vessels such as nitric oxide, a deficiency of chemicals that constrict blood vessels such as vasopressin, and activation of ATP-sensitive potassium channels. In those with severe sepsis and septic shock, this sequence of events leads to a type of circulatory shock known as distributive shock. Diagnosis
Early diagnosis is necessary to properly manage sepsis, as the initiation of rapid therapy is key to reducing deaths from severe sepsis. Some hospitals use alerts generated from electronic health records to bring attention to potential cases as early as possible. Within the first three hours of suspected sepsis, diagnostic studies should include white blood cell counts, measuring serum lactate, and obtaining appropriate cultures before starting antibiotics, so long as this does not delay their use by more than 45 minutes. To identify the causative organism(s), at least two sets of blood cultures using bottles with media for aerobic and anaerobic organisms are necessary.
At least one should be drawn through the skin and one through each vascular access device (such as an IV catheter) that has been in place more than 48 hours. Bacteria are present in the blood in only about 30% of cases. Another possible method of detection is by polymerase chain reaction. If other sources of infection are suspected, cultures of these sources, such as urine, cerebrospinal fluid, wounds, or respiratory secretions, also should be obtained, as long as this does not delay the use of antibiotics.Within six hours, if blood pressure remains low despite initial fluid resuscitation of 30 mL/kg, or if initial lactate is ≥ four mmol/L (36 mg/dL), central venous pressure and central venous oxygen saturation should be measured. Lactate should be re-measured if the initial lactate was elevated. Evidence for point of care lactate measurement over usual methods of measurement, however, is poor.Within twelve hours, it is essential to diagnose or exclude any source of infection that would require emergent source control, such as a necrotizing soft tissue infection, an infection causing inflammation of the abdominal cavity lining, an infection of the bile duct, or an intestinal infarction. A pierced internal organ (free air on an abdominal X-ray or CT scan), an abnormal chest X-ray consistent with pneumonia (with focal opacification), or petechiae, purpura, or purpura fulminans may indicate the presence of an infection. Definitions
Previously, SIRS criteria had been used to define sepsis.