The objectives of this study are to examine the relationship between the severity of illness, and temporal changes in the activity of endocrine, metabolic and bioenergetic pathways, and consequent immune dysfunction in critically ill patients with sepsis and multiple organ failure in the Intensive Care Unit.~This study will be undertaken using sequential blood sampling (until ICU discharge) and muscle biopsies (to a maximum of 5) in critically ill patients (a) with or (b) without sepsis plus a comparator group undergoing elective orthopaedic surgery. A variety of hormonal, cytokine, immune and mitochondrial measures wil lbe then made to assess whether any relationship exists between alterations in these different pathways, and whether eventual survivors and non-survivors can be distinguished.
The hypothesis of this study is that bioenergetic failure in human sepsis, related to endocrine, metabolic and mitochondrial dysfunction, is a major determinant of defective host immune responses, increasing disease severity and risk of death. The objectives of this study are to examine the relationship between the severity of illness, and temporal changes in the activity of endocrine, metabolic and bioenergetic pathways, and consequent immune dysfunction in critically ill patients with sepsis and multiple organ failure in the Intensive Care Unit.