Cytochrome C levels in severe sepsis and septic shock

Abstract

Cytochrome C levels in severe sepsis and septic shock Lars Wiuff Andersen, Maureen Chase, Katherine M. Berg, Jeejabai Radhakrishnan, Raul J. Gazmuri, Xiaowen Liu, Michael Cocchi, Michael Donnino Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA Resuscitation Institute at Rosalind Franklin University of Medicine and Science, North Chicago, IL, USA Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, MA, USA Background/Purpose: Cytochrome C is an essential component of the electron transport chain loosely bound to the inner mitochondrial membrane. Plasma cytochrome C may be a marker of mitochondrial injury. Methods: We included patients as part of a randomized trial of ubiquinol (reduced form of coenzyme Q10) in patients with severe sepsis or septic shock (NCT01948063). The results of the trial have been reported elsewhere, and no difference was found in cytochrome C levels or other outcomes between the groups. Blood was drawn at enrollment and 12 and 24 hours later. We used repeatedmeasures analysis to compare cytochrome C levels between survivors and nonsurvivors. Cytochrome C levels were log transformed before analysis, and a level of 4 ng/mL was imputed for those with undetectable levels. Results: Thirty-eight patients were enrolled. The median age was 65 years (quartiles: 52, 73), and 18 (47%) were female. Eighteen (47%) received mechanical ventilation at time of enrollment, 24 (63%) received vasopressor support, and 6 (16%) died before hospital discharge. Plasma cytochrome C levels were detectable in 25 (66%) of the patients at the time of enrollment. Cytochrome C levels were higher in patients who died before hospital discharge as compared to hospital survivors (P = .02; Fig. 1). Conclusions: Plasma cytochrome C levels are detectable in approximately 2/3 of severely septic patients. In this preliminary study, we found that patients who died had higher cytochrome C levels as compared to survivors. Cytochrome C might hold promise as a marker of mitochondrial injury or as a prognostic marker in septic patients.