Bacteraemic and endotoxic shock.

In 1924 Sanarelli recorded that endotoxins of Gram-negative organisms would damage capillary and postcapillary venular endothelium. By 1935 it was known that two spaced doses of endotoxin given to rabbits would cause renal cortical necrosis and foci of damage in many organs, the Shwartzman reaction. This is due to a combination of vasospasm and intravascular coagulation. Human equivalents of the generalised Shwartzman reaction (GSR) are being recognised with increasing frequency' because of the use of accurate coagulation indices2 and the sensitive radiofibrinogen catabolism study.3 Disseminated intravascular coagulation (DIC) has been shown to occur at the onset of many types of acute renal failure, and, by concurrent use of the Limulus assay, endotoxaemia has been found to be a frequent cause of renal failure in man.34 Whether DIC is damaging depends on (a) the fibrinolytic potential of normal renal vascular endothelium, (b) the fibrinolytic activity of the blood, reduced in postoperative and post-traumatic states, and (c) the capacity of the Kupffer cells to clear endotoxin, reduced by alcohol, anaesthetics, and shunting in liver disease. The lipid-A of endotoxin causes vasospasm and intravascular coagulation and in fact all those several factors that are known to contribute to renal shut-down.45 Lipid A is a concealed antigen on the bacterial surface but when released can insert into cell membranes so as to trigger the various pathophysiological mechanisms that together explain the GSR.6 Anti-lipid-A antitoxin antibodies are low in normal people,7 and this fact, coupled with relative inadequacy of the Kupffer cell defences in man, explains the susceptibility to the GSR. Genetic influences have not been explored. Even newer antibiotics have not reduced the mortality of Gram-negative bacteraemia much below 50%. One has to consider whether loading doses of antibiotics liberate endotoxin. Clearly, protective antibody, such as antiserum to lipid A-KDO, should be useful in many situations. The efficacy has yet to be demonstrated.8