Research description

Mitochondrial Derangement and Lactate Metabolism in Skeletal Muscle of Septic ICU Patients

Septic shock remains a critical condition with high mortality and consumption of Intensive care unit (ICU) resources worldwide, despite advances in recent years . Early identification and timely treatment are essential for survival, but correct diagnosis is often difficult and can delay potentially lifesaving treatment.

Studies have proven that changes in plasma lactate levels in septic patients correlate to poor outcome, and are therefore used for initiation and evaluation of treatment. Furthermore, an inability to lower an initially (even minimally) increased level correlates stronger to poor outcome than absolute values suggesting that absolute lactate values should be interpreted with caution. However, the inability to lower lactate could be the result of either an ongoing high production or a compromised clearance/utilization. Although animal studies suggest that the inability to clear lactate is stronger related to increased mortality, the human clinical data is not clear on this point.  By quantifying lactate production and utilization in patients, using isotopically labeled lactate, and relate those to patients absolute lactate levels, clinical outcome, age and sex we will elucidate what is causing high lactate levels and how this is related to clinical outcome. We will also investigate if a bed-side clearance test, by giving patients a bolus of lactate, is of clinical value. We also aim to investigate if increased plasma levels of lactate correlate to the mitochondrial derrangement seen in sepsis. Hopefully the increased knowledge will enable us to better diagnose and risk-stratify patients to allocate potentially lifesaving treatment at the right time to the right patient!