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


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.
Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS; Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS.
Michael A
MA
Puskarich
Department of Emergency Medicine, University of Indiana School of Medicine, Indianapolis, IN.
Jeffrey A
JA
Kline
Department of Emergency Medicine, Carolinas Medical Center, Charlotte, NC.
John A
JA
Watts
Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS.
Kristin
K
Shirey
Department of Biochemistry, University of Mississippi Medical Center, Jackson, MS.
Jonathan
J
Hosler
Department of Emergency Medicine, University of Mississippi Medical Center, Jackson, MS. Electronic address: aejones@umc.edu.
Alan E
AE
Jones
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D009102:Multiple Organ Failure / Q000503:physiopathology*; D009840:Oligomycins / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011446:Prospective Studies; D012119:Respiration / Q000187:drug effects; D012772:Shock, Septic / Q000401:mortality / Q000503:physiopathology*
D009840:Oligomycins; D019344:Lactic Acid; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D010100:Oxygen
Lactate; Metabolism; Oxygen consumption; Pyruvate; Sepsis