Cytopathic hypoxia. Mitochondrial dysfunction as mechanism contributing to organ dysfunction in sepsis

Several lines of evidence support the notion that cellular energetics are deranged in sepsis, not on the basis of inadequate tissue perfusion, but rather on the basis of impaired mitochondrial respiration and/or coupling; that is, organ dysfunction in sepsis may occur on the basis of cytopathic hypoxia. If this concept is correct, then the therapeutic implications are enormous. Efforts to improve outcome in patients with sepsis by monitoring and manipulating cardiac output, systemic Do2, and regional blood flow are doomed to failure. Instead, the focus should be on developing pharmacologic strategies to restore normal mitochondrial function and cellular energetics.