• Lars W Andersen, Xiaowen Liu, Sophia Montissol, Mathias J Holmberg, Christopher Sulmonte, Julia L Balkema, Michael N Cocchi, Raúl J Gazmuri, Kathrine M Berg, Maureen Chase, and Michael W Donnino.
• *Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts †Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark ‡Research Center for Emergency Medicine, Aarhus University Hospital, Aarhus, Denmark §Department of Anesthesia Critical Care, Division of Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts ¶Resuscitation Institute at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois ||Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
• Shock. 2016 May 1; 45 (5): 512-7.

PurposeCytochrome c is an essential component of the electron transport chain, and circulating cytochrome c might be an indicator of mitochondrial injury. The objective of this study was to determine whether cytochrome c levels are elevated in septic patients, whether there is an association between cytochrome c levels and lactate/inflammatory markers, and whether elevated levels of cytochrome c are associated with poor outcomes.MethodsThis was a single-center, prospective, observational, pilot study within a randomized, placebo-controlled trial. We enrolled adult patients in septic shock and with an elevated lactate (>3 mmol/L). Blood was collected at enrollment and at 12 and 24  h thereafter. Cytochrome c was measured in plasma using an electrochemiluminescence immunoassay.ResultsWe included 77 patients. Plasma cytochrome c levels were significantly higher in septic patients than in healthy controls (0.70  ng/mL [quartiles: 0.06, 1.99] vs. 0.19  ng/mL [quartiles: 0.03, 1.32], P = 0.008). Cytochrome c levels at enrollment were positively correlated with lactate levels (r(s) = 0.40, P < 0.001) but not with inflammatory markers. Patients who died before hospital discharge had significantly higher cytochrome c levels than survivors (0.99  ng/mL [quartiles: 0.36, 4.09] vs. 0.58  ng/mL [quartiles: 0.03, 1.64], P = 0.01). When analyzed over time, the difference between survivors and nonsurvivors remained significant (P < 0.001).ConclusionsCytochrome c levels are higher in septic patients than in controls. In unadjusted analysis, septic nonsurvivors had higher cytochrome c levels than survivors.

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