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Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality

A Multicenter Cohort Study

Chung, Kuei-Pin, MD1,2; Chen, Guan-Yuan, PhD3,4; Chuang, Tzu-Yi, MD5,6; Huang, Yen-Tsung, MD, PhD7; Chang, Hou-Tai, MD, PhD8–10; Chen, Yen-Fu, MD1,11; Liu, Wei-Lun, MD12,13; Chen, Yi-Jung, MS6; Hsu, Chia-Lin, MD6; Huang, Miao-Tzu, MD, PhD14,15; Kuo, Ching-Hua, PhD3,4,16; Yu, Chong-Jen, MD, PhD6,17

doi: 10.1097/CCM.0000000000003517
Clinical Investigations

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.

1Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.

2Department of Laboratory Medicine, National Taiwan University Hospital and National Taiwan University Cancer Center, Taipei, Taiwan.

3School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan.

4The Metabolomics Core Laboratory, Centers of Genomic Medicine and Precision Medicine, National Taiwan University, Taipei, Taiwan.

5Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan.

6Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.

7Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.

8Department of Critical Care Medicine, Far Eastern Memorial Hospital, New Taipei, Taiwan.

9Department of Industrial Engineering and Management, Yuan Ze University, Taoyuan, Taiwan.

10Institute of Health Policy and Management, National Taiwan University, Taipei, Taiwan.

11Department of Internal Medicine, National Taiwan University Hospital Yun-Lin Branch, Yun-Lin, Taiwan.

12School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei, Taiwan.

13Department of Emergency & Critical Care Medicine, Fu Jen Catholic University Hospital, New Taipei, Taiwan.

14Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan.

15Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan.

16Department of Pharmacy, National Taiwan University Hospital, Taipei, Taiwan.

17Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan.

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Supported, in part, by the National Science Council (No. 100-2321-B-002-019), Excellent Translational Medicine Research Projects of National Taiwan University College of Medicine and National Taiwan University Hospital (No. 102C101-42), National Taiwan University Hospital (No. 105-S-3080), and Taoyuan General Hospital, Department of Health and Welfare (PTH10326, North 101–15).

Drs. G.-Y. Chen and M.-T. Huang disclosed government work. Dr. M.-T. Huang received support for article research from the National Science Council, Taiwan. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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