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Pathophysiology
Gram-negative bacteria traditionally have been the most commonly implicated microorganisms in septic shock. However, there is also an increased incidence of gram-positive bacterial infections, and gram-positive bacteria currently account for 50% of cases of septic shock (Smith & McInnis, 2007). Other infectious agents, such as viruses and fungi, also can cause septic shock. However, it is estimated that 20% to 30% of patients with severe sepsis may never have an identifiable site of infection (King, 2007). When microorganisms invade body tissues, patients exhibit an immune response. This immune response provokes the activation of biochemical cytokines and mediators associated with an inflammatory response and produces a complex cascade of physiologic events that leads to poor tissue perfusion. Increased capillary permeability, which leads to fluid seeping from the capillaries, and vasodilation are two such effects that interrupt the ability of the body to provide adequate perfusion, oxygen, and nutrients to the tissues and cells. In addition, proinflammatory and anti-inflammatory cytokines released during the inflammatory response activate the coagulation system, which begins to form clots whether or not bleeding is present. The imbalance of the inflammatory response and the clotting and fibrinolysis cascades are considered critical elements of the devastating physiologic progression that occurs in patients with severe sepsis. Sepsis is an evolving process, with neither clearly definable clinical signs and symptoms nor predictable progression. Initial physiologic changes are subtle. In the early stage of septic shock, BP may remain within normal limits, or the patient may be hypotensive but responsive to fluids. The heart rate increases, progressing to tachycardia. Hyperthermia and fever, with warm, flushed skin and bounding pulses, is evident. The respiratory rate is elevated. Urinary output may remain at normal levels or decrease. GI status may be compromised, as evidenced by nausea, vomiting, diarrhea, or decreased bowel sounds. Signs of hypermetabolism include increased serum glucose and insulin resistance. Subtle changes in mental status, such as confusion or agitation, may be present. The lactate level is elevated because of the maldistribution of blood. Inflammatory markers such as white blood cell counts and C-reactive protein are also elevated (King, 2007). As sepsis progresses, tissues become less perfused and acidotic, compensation begins to fail, and the patient begins to show signs of organ dysfunction. The cardiovascular system also begins to fail, the BP does not respond to fluid resusci-tation and vasoactive agents, and signs of end-organ damage are evident (eg, renal failure, pulmonary failure, hepatic failure). As sepsis progresses to septic shock, the BP drops, and the skin becomes cool, pale, and mottled. Temperature may be normal or below normal. Heart and respiratory rates remain rapid. Urine production ceases, and multiple organ dysfunction progressing to death occurs. Systemic inflammatory response syndrome (SIRS) presents clinically like sepsis and is part of the initial continuum of sepsis. The physiologic presentation of SIRS is similar to sepsis, except there is no identifiable source of infection (Dellinger, et al., 2008; King, 2007). SIRS stimulates an overwhelming inflammatory immunologic and hormonal response similar to that seen in septic patients. Any overwhelming insult stimulates SIRS and may progress to sepsis. Therefore, despite an absence of infection, antibiotic agents may still be administered because of the possibility of unrecognized infection. Additional therapies directed to support patients with SIRS are similar to those for sepsis. If the inflammatory process progresses, septic shock may develop.