Early alterations in platelet mitochondrial function are associated with survival and organ failure in patients with septic shock.

INTRODUCTION: The objective of the study is to determine if changes in platelet mitochondrial function in patients with sepsis are present early after presentation and the association of these changes with clinical outcomes and systemic metabolic function. MATERIALS AND METHODS: This is a prospective observational cohort study of a convenience sample of patients with severe sepsis. Mitochondrial function of intact, nonpermeabilized platelets suspended in their own plasma was estimated using high-resolution respirometry. Unstimulated basal respiration, oligomycin-induced state 4, and maximal respiratory rate after serial titrations of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone were measured. Organ failure was estimated using Sequential Organ Failure Assessment score, and patients were followed up until 28 days to determine survival. Lactate levels were measured in all patients, and a subset of patients had lactate/pyruvate (L/P) ratios measured. RESULTS: Twenty-eight patients were enrolled, 21 of whom survived. Initial Sequential Organ Failure Assessment score and lactate levels were 8.5 (interquartile range [IQR], 6-10) and 2.3 (IQR, 1.2-3.5) respectively, whereas the median L/P ratio was 23.4 (IQR, 15.2-38). Basal and maximal respiratory rates were significantly higher among nonsurvivors compared to survivors (P = .02 and P = .04), whereas oligomycin-induced state 4 respiration was not statistically different between groups (P = .15). We found a significant association between maximal respiration and organ failure (P = .03) and both basal and maximal rates with initial lactate level (P = .04, P = .02), but not with L/P ratio. CONCLUSIONS: Differences in platelet mitochondrial function between survivors and nonsurvivors are present very early in the hospital course and are associated with organ failure and lactate.