Protein carbonyl measurements show evidence of early oxidative stress in critically ill patients

Objective: To determine whether there is evidence of oxidative injury in patients who are critically ill with severe sepsis or major trauma, by measuring protein and lipid oxidation products. Design: A prospective, observational study. Setting: Critical care unit at a university teaching hospital. Patients: Twenty-two patients with severe sepsis (Acute Physiology and Chronic Health Evaluation II score 15-34) and eight patients with major trauma (Injury Severity Score 26-50), Interventions: Plasma and bronchoalveolar lavage fluid was collected regularly during the first 10 days after trauma or onset of sepsis, Both fluids were analyzed for protein carbonyl concentrations as a measure of protein oxidation and thiobarbituric acid-reactive substances as a measure of lipid peroxidation, Myeloperoxidase concentrations were measured as an index of neutrophil activation. Measurements and Main Results: Protein carbonyl concentrations were initially highly elevated compared with those in healthy adults in the plasma of both patient groups. They fell significantly within the first few days but remained above control values. Protein carbonyl concentrations were also high initially in bronchoalveolar lavage fluid and fell significantly with time. Thiobarbituric acid-reactive substances were not increased in plasma, and varied over a wide concentration range in lavage fluid. Myeloperoxidase activity reached micromolar levels in the lavage fluid when corrected for dilution, and was significantly higher in the plasma of the sepsis patients who subsequently died. There was a strong correlation between carbonyl concentrations in lavage fluid and plasma, and between protein carbonyls, thiobarbituric acid-reactive substances and myeloperoxidase in the lungs. Conclusions: Our results provide evidence of oxidation occurring early in severe sepsis and major trauma patients, with protein carbonyl measurements providing a sensitive index of this process, High protein carbonyl concentrations in plasma as well as bronchial aspirates indicate that oxidation is not restricted to the lungs. The correlation between oxidative measures and myeloperoxidase concentrations in the lung indicates that neutrophil oxidants could be responsible for the injury.