Systemic hemodynamic abnormalities and vasopressor therapy in sepsis and septic shock.
Septic shock, a distributive form of shock, is a common and lethal disease characterized by tachycardia, hypotension, normal or elevated cardiac index, and decreased systemic vascular resistance (SVR). For 2 to 4 days after onset of shock, the left ventricular ejection fraction (LVEF) is depressed; with adequate volume replacement, the left ventricle dilates and cardiac output (CO) is maintained or increased. In survivors, these abnormalities reverse to normal within 7 to 10 days. The myocardial depression found in patients with septic shock is not associated with global myocardial ischemia. In our animal model of sepsis, myocardial depression is not associated with impaired myocardial high-energy stores, or abnormal myocardial oxygen utilization. However, septic animals have histopathologic evidence of coronary nonocclusive microvascular damage and myocyte injury. The majority of human deaths caused by septic shock are related to the peripheral vascular dysfunction and multiorgan system failure that occurs over time. The pathophysiology of this disease is complex. Clinical and experimental evidence support the notion that myocardial depression, peripheral vascular abnormalities, and multiorgan dysfunction result from the combined effect of exogenous and endogenous mediators (eg, endotoxin, cytokines, and nitric oxide) released during septic shock. Although conventional therapy with fluids, vasopressors, and antibiotics is effective, the disease still has a high mortality rate. Studies investigating the effects of bacterial toxins and potentially harmful host mediators offer the greatest hope in finding new ways to eradicate this highly lethal disease.
Quezado
Z M
ZM
Critical Care Medicine Department, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD 20892.
Natanson
C
C
D000818:Animals; D001424:Bacterial Infections / Q000188:drug therapy / Q000503:physiopathology; D004285:Dogs; D004731:Endotoxins / Q000502:physiology; D005440:Fluid Therapy; D006439:Hemodynamics; D006801:Humans; D007378:Interleukins / Q000502:physiology; D009102:Multiple Organ Failure / Q000209:etiology; D012772:Shock, Septic / Q000188:drug therapy / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000627:therapeutic use*
D004731:Endotoxins; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents