Evidence that cellular dysoxia is an important initiating mechanism for multiple organ failure comes from studies of patients at risk or in the early stages of critical illness, which demonstrate that interventions which increase systemic oxygen supply (mainly fluid resuscitation and inotropic agents) also increase subsequent survival rates (Boyd §L§1 1993). However, the same techniques do not seem to exert a beneficial effect later in the development of the syndrome, particularly in association with sepsis, even though measures such as base deficit, hyperlactatemia, and tonometry suggest the presence of a tissue oxygen debt. Part of the reason for this is that there are substantial differences in flow distribution and intermediary metabolism between patients presenting in low flow states (e.g. hypovolemia, trauma, cardiac failure) and those with the higher flow states associated with sepsis.
In non-septic patients (the 'ebb phase' of incipient multiple organ failure) oxygen consumption remains stable, despite marked reductions in oxygen delivery, until a critical point is reached below which oxygen consumption becomes dependent on supply, and a tissue oxygen debt accumulates. However, septic patients appear to demonstrate supply dependency over a wide range of values of oxygen delivery, with consumption continuing to increase despite large increases in supply. While this may be explained in part by mathematical coupling and by the thermogenic effect of inotropic agents, it is also likely to be a real effect caused by an increase in metabolic rate, disordered intermediary metabolism, flow maldistribution, increased nitric oxide production with impaired vasoregulation and increased vascular permeability, and a prolonged diffusion distance from red cell to tissues in the septic state.
These two patient populations are evidently very different. However, at some point in the development of multiple organ failure the 'ebb phase' gives way to the later 'flow phase' of the systemic inflammatory response syndrome. How this progression occurs has been the subject of detailed research, much of which has focused on the gut and splanchnic region.
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