Abnormalities of vascular reactivity in the sepsis syndrome.

Iultiple organ failure (MOF) denotes a clinical syndrome that is characterized by a process of dysfunction and ultimately failure of vital organs. Commonly found in association with infection in critically ill patients,’ it has supplanted refractory hypoxemia as the major cause of late mortality in patients with the adult respiratory distress syndrome (ARDS).2 Although ARDS is often an initial manifestation of MOF, dysfunction of the circulatory, hepatic, renal, and other organ systems may follow if the underlying processes responsible for this syndrome of progressive organ dysfunction are not identified and adequately managed. Many lines of evidence point to the likelihood of significant disturbances in the regulation of tissue oxygen delivery (Qo2) in the sepsis syndrome. Paradoxically, such alterations in tissue Qo,, during sepsis complicate a process that is typically characterized by increased tissue needs for O . For example, Bihari et aI proposed that a “covert” 02 debt characterized some critically ill patients. Rashkin et al correlated death with the presence of a low systemic Qo2 and elevated arterial lactate concentrations in patients with sepsis. Shoemaker et aI demonstrated that maintaining a “supranormal” systemic Qo2 differentiated the survivors of a critical illness from the nonsurvivors. On the basis of these, as well as other, data, some investigators have proposed that in sepsis, dysregulation of the cirulatory processes governing tissue 0 availability leads to diffuse organ dysfunction due to ischemia. 1 When the functional reserve of specific organs is exceeded by this process of diffuse ischemic injury, biochemical and then clinical MOF ensues. In the sepsis syndrome, abnormalities that could signfficantly destabilize the appropriate matching of tissue Qot to tissue 02 needs have been demonstrated within the 3 levels of the circulation. For example, at the central level, an inability to maximally augment systemic Qo2 will complicate a reduction in arterial 09 saturation secondary to a sepsisinduced pulmonary microcirculatory lesion, (eg, ARDS or depression in myocardial performance). The latter may arise for a number of reasons in the sepsis syndrome, including the effects of a circulating myocardial depressant factor, ventricular interference consequent on pulmonary hypertension, and myocardial edema. At the regional levels of the circulation, the distribution of flow (Q) between organs is significantly altered during sepsis.89 Within the microcircu-