Sepsis and Septic Shock

SEPSIS AND SEPTIC SHOCK

Bacteremia is the presence of viable bacteria circulating in the blood. When signs and symptoms result, further terms are used to delineate the progression of potential consequences that may occur. Both Gram-negative and Gram-positive organisms can produce the same findings, as well as fungi, protozoa, and even some viruses.

Sepsis is the suspicion (or proof) of infection and evidence of a systemic response toit (eg, tachycardia, tachypnea, hyperthermia, or hypothermia). The sepsis syndrome in-cludes findings of sepsis plus evidence of altered organ perfusion. These can include re-duction in urine output, mental status changes, systemic acidosis, and hypoxemia. If the process remains uncontrolled, there is subsequent progression to septic shock (develop-ment of hypotension); refractory septic shock (hypotension not responsive to standard fluid and pharmacologic treatment); and multiorgan failure, including major target or-gans such as the kidneys, lungs, and liver, and disseminated intravascular coagulation. Mortality is exceedingly high when patients develop refractory septic shock or multiorgan failure.

The initial events in the sepsis syndrome appear to be vasodilatation with resultant de-creased peripheral resistance and increased cardiac output. The patient is flushed and febrile. Capillary leakage and reduced blood volume follow, leading to a whole series of events identical to those seen in shock resulting from blood loss. These manifestations in-clude vasoconstriction, reflex capillary dilatation, and local anoxic damage. Once this stage is reached, the patient may develop hypotension and hypothermia, and acidosis, hy-poglycemia, and coagulation defects ensue with failure of highly perfused organs such as the lungs, kidneys, heart, brain, and liver.

The mechanisms involved in development of septic shock have been studied exten-sively in experimental animals. Most of the features seen in humans can be produced with the lipopolysaccharide endotoxin of the Gram-negative cell wall, although there is some variation between animal species and with different preparations. The various events that occur are complex. They include (1) release of vasoactive substances such as histamine, serotonin, noradrenaline, and plasma kinins, which may cause arterial hypotension di-rectly and facilitate coagulation abnormalities; (2) disturbances in temperature regulation, which may be due to direct central nervous system effects or, in the case of the early febrile response, mediated by interleukin 1 (IL-1) and tumor necrosis factor (TNF) re-leased from macrophages; (3) complement activation and release of other inflammatory cytokines by macrophages (eg, IL-2, IL-6, IL-8, and interferon-gamma); (4) direct effects on vascular endothelial cell function and integrity; (5) depression of cardiac muscle con-tractility by TNF, myocardial depressant factor, and other less well-defined serum factors; and (6) impairment of the protein C anticoagulation pathway, resulting in disseminated intravascular coagulation. The resultant alterations in blood flow and capillary permeabil-ity lead to progressive organ dysfunction.

Early recognition of the problem is critical, and management obviously requires considerably more than antimicrobial therapy. Other primary therapeutic measures in-clude maintenance of adequate tissue perfusion through careful fluid and electrolyte management and the use of vasoactive amines. There is also evidence that protein C replacement may ameliorate the coagulopathy.