Severe hypocholesterolemia in surgical patients, sepsis, and critical illness
Section snippets
Background
Although hypocholesterolemia is anecdotally considered a marker of malnutrition, other factors become prominent causes of hypocholesterolemia after surgery and trauma, in sepsis, and in other critical illnesses. Because there is synergism of clinically adverse components in decreasing cholesterol, hypocholesterolemia often becomes a cumulative marker of severity of illness and poor prognosis. At the same time, the multifactoriality of changes and the undefined thresholds of risk limit the
Methods
The review was based on relevant data from the literature, describing most of the involved aspects together with controversial issues, and on locally performed patient measurements. These were derived from a prospectively collected data bank including 1313 laboratory measurements obtained in 190 patients (108 males, 82 females) undergoing resective surgery of the liver (89 patients), stomach, colon, or pancreas and other abdominal procedures (61 patients), and/or with major complications or
Multifactoriality of hypocholesterolemia
Plasma cholesterol behaves as a negative acute phase reactant. It decreases after surgery and trauma, in sepsis, in liver dysfunction, and after acute hemorrhage; the main mechanisms involved include the cholesterol-lowering effect of inflammatory mediators, impaired cholesterol synthesis, and hemodilution from blood loss [2], [4], [5], [6], [7], [8], [9], [10]. The dynamics of these decreases are complex; however, the effect is cumulative, so that the degree of hypocholesterolemia may
The effect of cholestasis
Cholestasis is peculiar among the commonest “adverse” factors altering cholesterol because it is associated with an increase in cholesterol (rather than contributing to its decrease) or, more often, with moderation of the decrease related to other factors [7], [14], [16]. This is likely related to the stimulated release of cholesterol-rich lipoprotein-X from the liver and/or the impaired cholesterol excretion in bile and explains why critically ill patients with cholestasis may fail to show
Correlation with changes in plasma proteins
Although it appears peculiar for a fat substance, cholesterol maintains a relatively strong direct relationship with albumin and several other plasma proteins. Fig. 2 shows it for albumin over a large distribution of observations, ranging from the normal condition to extreme preterminal illness. In the normal condition, the main factor supporting the correlation should be the nutritional state. In postoperative and/or critically ill conditions, the underlying factors are various combinations of
Correlation with outcomes
Transiently severe hypocholesterolemia is not necessarily relevant. It is severe persistent hypocholesterolemia, which is associated with death, whereas increasing cholesterol (unless related to cholestasis) is associated with recovery [2], [7], [8], [9], [10], [12], [15], [20]. Again, the absence of precise thresholds of abnormality and the multifactoriality of hypocholesterolemia limit the definition of exact landmarks of risk. In a previous assessment in patients with sepsis and organ
Hypocholesterolemia and triglyceride levels in trauma and sepsis
Plasma triglycerides generally tend to follow a pattern similar to that of cholesterol, although not strictly related to it. In the locally collected data bank, triglycerides were obtained in almost half of the cases and were directly correlated with cholesterol, although with an r2 of only 0.25 (P < .0001). One factor was that cholestasis, if present, affected cholesterol more than triglycerides. Remarkably, however, within this variability, severe hypocholesterolemia became sometimes
The impact of nutrition (parenteral nutrition)
Although it may appear counterintuitive, the nutritional state has little to do with hypocholesterolemia after surgery and trauma, in sepsis, and in critical illness because other driving factors prevail. Furthermore, the mechanisms by which the infusion of nutrients can modify cholesterol are not so obvious. For instance, some increase in cholesterol related to the infusion of fat emulsions depends on the release of cholesterol from cell membranes, in exchange with the components of the
Conclusion
After surgery and trauma, in sepsis, and in critical illness, 2 very simple measurements such as cholesterol and triglycerides often become markers of severity of disease and, therefore, helpful adjunctive clinical tools. Obviously, cholesterol and triglyceride levels do not only reflect their concentrations but also altered lipoprotein patterns with modified lipoprotein compositions, and the issue is far too complex and still too poorly understood to be reduced to simple concepts. A better
Acknowledgment
This work was supported by a contribution from the Catholic University School of Medicine and the Italian Ministry for University and Scientific Research (D.1 Funds).
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