Hypocholesterolemia in surgical trauma, sepsis, other acute conditions and critical illness

It is rather paradoxical, in a world so heavily concerned with the implications of hypercholesterolemia, that also hypocholesterolemia represents an important issue. This is the case in some categories of subjects, including surgical and critically ill patients. Original observations of hypocholesterolemia in severe illness date back to the beginning of last century, however the topic and its relationship with abnormal circulating lipoprotein patterns, have been addressed systematically only in recent decades. It has been found that hypocholesterolemia characterizes post-traumatic states and critical illness as a common manifestation of acute phase response. In various conditions there is a variable contribution of different factors in decreasing plasma cholesterol through a decrease in lipoprotein concentration. These include for instance increased need for cholesterol for new cell synthesis and reparative processes, hemodilution from blood loss, hepatic dysfunction and the cholesterol-lowering effect of inflammatory mediators. Thus severity of hypocholesterolemia may reflect the cumulative impact of multiple “adverse” factors: this explains how degree of hypocholesterolemia may become a cumulative index of severity of illness, with important prognostic implications. It must be specified, however, that in the presence of cholestasis the decrease in cholesterol related to the other factors may be moderated. Furthermore, with regard to outcome, it is the persistence of severe hypocholesterolemia that has the worst prognostic implications. Finally, with regard to therapeutic implications, it is not yet clear whether hypocholesterolemia just passively reflects adverse events, or it does actively contribute to worsening of the disease. Modern lines of research address the possibility that cholesterol be a conditionally essential substrate in critical illness, and also address substitution therapy with exogenous fat in sepsis, where hypocholesterolemia and hypolipoproteinemia may impair endotoxin binding and neutralization.