Substrate utilization in sepsis and multiple organ failure

Abstract

Sepsis and multiple organ failure are characterized by an excessive release of inflammatory mediators and a marked stimulation of stress hormones. These in turn have profound effects on energy and substrate metabolism: energy expenditure is generally increased, and increased lipolysis and fat oxidation are observed. Net protein breakdown occurs and leads to accelerated wasting. Most of these effects can be produced in healthy humans by administration of bacterial endotoxin or by tumor necrosis factor-alpha. Hyperlactatemia is a hallmark of sepsis and critical illness, and its severity is related to mortality. An increased lactate production, possibly secondary to activation of Na-K adenosine 5'-triphosphatase and to muscle mitochondrial dysfunction, is involved. Lactate production by immune cells and wound tissue may also play a role. Long-chain, n-3 polyunsaturated fatty acids have anti-inflammatory effects that may be beneficial in sepsis. They also decrease the stimulation of stress hormones induced by bacterial endotoxin, possibly through an effect exerted at the level of the central nervous sytem. Their use in patients with sepsis does not lead to adverse metabolic effects.