Septic Shock Nonsurvivors Have Persistently Elevated Acylcarnitines Following Carnitine Supplementation

Michael A. Puskarich, Charles R. Evans, Alla Karnovsky, Arun K. Das, Alan E. Jones, Kathleen A. Stringer

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Introduction: Sepsis-induced metabolic disturbances include hyperlactatemia, disruption of glycolysis, protein catabolism, and altered fatty acid metabolism. It may also lower serum l-carnitine that supports the use of l-carnitine supplementation as a treatment to ameliorate several of these metabolic consequences. Methods: To further understand the association between l-carnitine-induced changes in serum acylcarnitines, fatty acid metabolism and survival, serum samples from (T0), 12hfollowing completion (T24) of l-carnitine (n = 16) or placebo (n = 15) administration, and 48h (T48) after enrollment from patients with septic shock enrolled in a randomized control trial were assayed for acylcarnitines, free fatty acids, and insulin. Data were analyzed comparing 1-year survivors and nonsurvivors within treatment groups. Results: Mortality was 8 of 16 (50%) and 12 of 15 (80%) at 1 year for l-carnitine and placebo-treated patients, respectively. Free carnitine, C2, C3, and C8 acylcarnitines were higher among nonsurvivors at enrollment. l-Carnitine treatment increased levels of all measured acylcarnitines; an effect that was sustained for at least 36h following completion of the infusion and was more prominent among nonsurvivors. Several fatty acids followed a similar, though less consistent pattern. Glucose, lactate, and insulin levels did not differ based on survival or treatment arm. Conclusions: In human patients with septic shock, l-Carnitine supplementation increases a broad range of acylcarnitine concentrations that persist after cessation of infusion, demonstrating both immediate and sustained effects on the serum metabolome. Nonsurvivors demonstrate a distinct metabolic response to l-carnitine compared with survivors, which may indicate preexisting or more profound metabolic derangement that constrains any beneficial response to treatment.

Original languageEnglish (US)
Pages (from-to)412-419
Number of pages8
JournalShock
Volume49
Issue number4
DOIs
StatePublished - Apr 1 2018

Bibliographical note

Funding Information:
Address reprint requests to Kathleen A. Stringer, PharmD, University of Michigan College of Pharmacy, 428 Church Street, Ann Arbor, MI 48109. E-mail: stringek@umich.edu This work was supported by a metabolomics supplement to a grant from the National Institute of General Medical Sciences (NIGMS; R01GM103799 to AEJ), R01GM111400 to KAS, K23GM113041 to MAP and R03CA211817 to AK. The Michigan Regional Comprehensive Metabolomics Research Core (MRC)2 is funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK; DK097153, DK092558). The clinical trial was supported by a grant from the American Heart Association (10POST3560001) and the Cannon Foundation (SRG10-004). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIGMS, NIDDK or the National Institutes of Health. The authors report no conflicts of interest.

Keywords

  • Free fatty acids
  • gas chromatography
  • liquid chromatography-mass spectroscopy
  • metabolomics
  • pharmacometabolomics
  • sepsis

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