Endotoxinaemia in the critically III patient

Abstract

Endotoxins are lipopolysaccharides (LPS) which form part of the hydrophobic outer cell membrane of Gram-negative bacteria. The saccharide chain (the O-specific serotypic chain) differs between different bacterial genera, but the terminal lipid fraction ('lipid A') has a common structure 1, and is considered to be responsible for the bioactivity of endotoxin. 2 Lipid A is not exposed when the bacterial membrane is intact, and only exerts its biological effects when LPS is released during membrane lysis. Lipid A and the polysaccharide chain are linked together by a core of oligosaccharides with a more uniform structure than that of the O-specific chain, and antibodies with clinical efficacy can be formed to this core region 3 as well as to the O-antigens. Lipid A is weakly bound to the rest of the saccharide chain, and can be released by hydrolysis. Synthetic lipid A has been shown to mediate all the clinical effects of the natural substance 4, best characterised in its extreme form as septic shock. can be produced by virtually any micro-organism either as a consequence of circulating foreign material or by the synthesis of exotoxins operating through common pathways. The clinical picture of sepsis depends not on the organism but on the capacity of the host to mount a physiological response, s Although we may not know all the details of the septic process, the clinical pattern of surgical sepsis or of a Gram-negative bacteraemia is easily understood. Much less clear is what this clinical pattern means when it occurs in patients in whom there is no obvious source of infection. Such patients are commonly those requiring respiratory support following multiple trauma, sustained haemorrhagic shock, emergency aortic aneurysm repair, or cardiogenic shock, in whom the common factor appears to be an abrupt reduction in tissue oxygen delivery. How does one explain the features of systemic sepsis and progressive organ-system failures despite excluding occult sources of active infection? There are two main theories currently under investigation: progressive Gram-negative colonisation, and the leaky gut.