Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study
Increased Plasma Acetylcarnitine in Sepsis Is Associated With Multiple Organ Dysfunction and Mortality: A Multicenter Cohort Study
复制标题
脓毒症中血浆乙酰肉碱升高与多器官功能障碍和死亡率相关：一项多中心队列研究
DOI：
10.1097/ccm.0000000000003517
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发表时间：
2019-02-01
影响因子：
8.8
通讯作者：
Yu, Chong-Jen
中科院分区：
文献类型：
--
作者：
Chung, Kuei-Pin;Chen, Guan-Yuan;Yu, Chong-Jen
目的：最近对脓毒症的代谢组学研究表明，循环中的酰肉碱增加与较差的存活率有关。然而，目前尚不清楚血浆肉碱和酰肉碱是否能反映脓毒症的严重程度，而特定的酰肉碱在预后评估中的作用还需要进一步证实。本研究旨在澄清这些问题。设计：前瞻性多中心队列研究，采用衍生和验证队列设计。地点：在台湾的两个医疗中心和三个地区医院的ICU。患者：纳入败血症和急性器官功能障碍患者。分别在2010年10月至2012年3月和2013年1月至2014年11月招募衍生(n=90)和验证队列(n=120)。干预：入院后立即采集血浆样本，用超高效液相色谱-质谱仪测定肉碱和酰肉碱水平。测量和主要结果：在衍生队列中，血浆中短链酰肉碱水平升高与肝胆功能障碍、肾功能障碍、血小板减少和高乳酸血症显著相关。然而，乙酰卡尼汀是唯一与各种血浆细胞因子浓度显著相关的乙酰卡尼汀，也与血培养阳性和28天死亡风险相关。血浆乙酰肉碱与多器官功能障碍的严重程度、血培养阳性和28天死亡率之间的关系在验证队列中得到证实。与血浆乙酰卡尼汀<6,000 ng/mL的患者相比，血乙酰卡尼汀水平高的患者28天死亡率显著增加(52.6%比13.9%；风险比5.293；95%CI，2.340-11.975；P<；0.001，COX比例风险模型)。结论：我们证实血浆乙酰卡尼汀可以反映脓毒症患者器官功能障碍、炎症和感染的严重程度，并可作为预测死亡率的生物标志物。
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.