Impact of duration of critical illness on cholesterol availability in relation to outcome

Critical illness is any acute life-threatening condition for which the body requires intensive mechanical or pharmacological support to prevent imminent death. Most patients only require a couple of days of intensive care, but 5-10% of patients remain dependent on life support for a prolonged period of time. These patients are susceptible for the development of multiple organ failure, secondary infections, the development of ICU acquired weakness and suppressed adrenal function. Further identification and understanding of those pathways involved in the delayed recovery or development of complications is clearly needed to improve clinical outcome. One of the hallmarks of critical illness is an immediate and sustained decrease in circulating cholesterol. Although the severity of the hypocholesterolemia is closely associated with worse outcome, its pathophysiology is not clear. We aim to clarify the mechanisms behind the hypocholesterolemia as we hypothesize that these change over time. Furthermore, we hypothesize that the persistently low cholesterol availability has detrimental functional consequences specifically for skeletal muscle and for the adrenal cortex. We will test our hypotheses in 4 animal studies and 3 human clinical studies.