Platelet Bioenergetics and Associations With Delirium and Coma in Patients With Sepsis: A Prospective Cohort Study

Abstract

BackgroundAcute brain dysfunction during sepsis, which manifests as delirium or coma, is common and associated with multiple adverse outcomes including longer periods of mechanical ventilation, prolonged hospital stays, and increased mortality. Delirium and coma during sepsis may be manifestations of alteration in systemic metabolism. Since access to brain mitochondrial is a limiting factor, measurement of peripheral platelet bioenergetics offers a potential opportunity to understand metabolic changes associated with acute brain dysfunction during sepsis. Research QuestionAre altered platelet mitochondrial bioenergetics associated with acute brain dysfunction during sepsis? Study Design and MethodsWe assessed participants with critical illness in the ICU for the presence of delirium or coma via validated assessment measures. Blood samples were collected and processed to isolate and measure platelet mitochondrial oxygen consumption. We used Seahorse extracellular flux to directly measure baseline, proton leak, maximal oxygen consumption rate, and extracellular acidification rate. We calculated ATP-linked, spare respiratory capacity, and non-mitochondrial oxygen consumption rate from the measured values. ResultsMaximal oxygen consumption was highest in patients with coma, as was spare respiratory capacity and ECAR in unadjusted analysis. After adjusting for age, sedation, modified Sequential Organ Failure Assessment (SOFA) without the neurological component, and pre-existing cognitive function, increased spare respiratory capacity remained associated with coma. Delirium was not associated with any platelet mitochondrial bioenergetics. InterpretationIn this single-center, exploratory, prospective cohort study, we found increased platelet mitochondrial spare respiratory capacity was associated with coma in patients with sepsis. Future studies powered to determine any relationship between delirium and mitochondrial respiration bioenergetics are needed.