Increased Plasma Acetylcarnitine in Sepsis Is Associated with Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study
Journal
Critical Care Medicine
Journal Volume
47
Journal Issue
2
Pages
210-218
Date Issued
2019
Author(s)
Chuang T.-Y.
Huang Y.-T.
Chang H.-T.
Liu W.-L.
Chen Y.-J.
Huang M.-T.
Abstract
Objectives: Recent metabolomic studies of sepsis showed that increased circulatory acylcarnitines were associated with worse survival. However, it is unknown whether plasma carnitine and acylcarnitines can reflect the severity of sepsis, and the role of specific acylcarnitines in prognostic assessment need further confirmation. This study aimed to clarify these questions. Design: Prospective multicenter cohort studies with derivation and validation cohort design. Setting: ICUs at two medical centers and three regional hospitals in Taiwan. Patients: Patients with sepsis and acute organ dysfunction were enrolled. Recruitment of the derivation (n = 90) and validation cohorts (n = 120) occurred from October 2010 through March 2012 and January 2013 through November 2014, respectively. Interventions: Plasma samples were collected immediately after admission, and the levels of carnitine and acylcarnitines were measured by ultra-high performance liquid chromatography-mass spectrometry. Measurements and Main Results: In the derivation cohort, increased plasma levels of short- and medium-chain acylcarnitines were significantly associated with hepatobiliary dysfunction, renal dysfunction, thrombocytopenia, and hyperlactatemia. However, acetylcarnitine is the only acylcarnitine significantly correlating with various plasma cytokine concentrations and also associated with blood culture positivity and 28-day mortality risk. The association between plasma acetylcarnitine and multiple organ dysfunction severity, blood culture positivity, and 28-day mortality, was confirmed in the validation cohort. Patients with high plasma acetylcarnitine (? 6,000 ng/mL) had significantly increased 28-day mortality compared with those with plasma acetylcarnitine less than 6,000 ng/mL (52.6% vs 13.9%; hazard ratio, 5.293; 95% CI, 2.340-11.975; p < 0.001 by Cox proportional hazard model). Conclusions: We confirm that plasma acetylcarnitine can reflect the severity of organ dysfunction, inflammation, and infection in sepsis and can serve as a prognostic biomarker for mortality prediction. ? 2018 American Heart Association, Inc.
SDGs
Other Subjects
acetylcarnitine; carnitine; cytokine; hexanoylcarnitine; interleukin 10; interleukin 6; interleukin 8; octanoylcarnitine; tumor necrosis factor; unclassified drug; acetylcarnitine; biological marker; carnitine; acute kidney failure; adult respiratory distress syndrome; aged; amino acid blood level; arterial oxygen tension; Article; artificial ventilation; blood culture; cohort analysis; female; hepatobiliary disease; human; hyperlactatemia; kidney failure; major clinical study; male; mass spectrometry; mortality; multiple organ failure; partial pressure; pneumonia; priority journal; prospective study; sepsis; septic shock; Sequential Organ Failure Assessment Score; Taiwan; thrombocytopenia; ultra performance liquid chromatography; urosepsis; Youden index; blood; clinical trial; complication; epidemiology; mortality; multicenter study; multiple organ failure; proportional hazards model; sepsis; Acetylcarnitine; Aged; Biomarkers; Carnitine; Female; Humans; Male; Multiple Organ Failure; Proportional Hazards Models; Prospective Studies; Sepsis; Taiwan
Type
journal article