Septic Shock Nonsurvivors Have Persistently Elevated Acylcarnitines Following Carnitine Supplementation.

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), 12 hfollowing completion (T24) of L-carnitine (n = 16) or placebo (n = 15) administration, and 48 h (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 36 h 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.

• Authors: Michael A Puskarich, Charles R Evans, Alla Karnovsky, Arun K Das, Alan E Jones, Kathleen A Stringer
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 49 Issue 4 Pg. 412-419 (04 2018) ISSN: 1540-0514 [Electronic] United States
• PMID: 29384504 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Fatty Acids
• Insulin
• acylcarnitine
• Carnitine

Topics

• Aged
• Carnitine (analogs & derivatives, blood, therapeutic use)
• Fatty Acids (metabolism)
• Female
• Humans
• Insulin (blood)
• Magnetic Resonance Spectroscopy
• Male
• Middle Aged
• Shock, Septic (blood, drug therapy)