一氧化氮抑制剂的变化与重症患者的死亡率:一项队列研究。

IF 5.7 1区 医学 Q1 CRITICAL CARE MEDICINE
Karoline Myglegård Mortensen, Theis Skovsgaard Itenov, Jakob Stensballe, Thore Hillig, Claus Antonio Juel Jensen, Martin Schønemann-Lund, Morten Heiberg Bestle
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引用次数: 0

摘要

背景:重症患者大循环和微循环之间的最佳平衡对于确保最佳器官灌注至关重要。一氧化氮(NO)是血管止血和张力的调节剂。一氧化氮的供应受不对称二甲基精氨酸(ADMA)、对称二甲基精氨酸(SDMA)以及一氧化氮底物精氨酸和高精氨酸供应的控制。我们研究了重症监护病房(ICU)入院后第 1-5 天 ADMA、SDMA、精氨酸和高精氨酸血浆浓度的变化,以及第 1-3 天浓度变化与 30 天全因死亡率之间的关系:方法:对哥本哈根大学医院重症监护室(北西兰)的成年重症患者进行单中心队列研究。在第 1-5 天测量 ADMA、SDMA、精氨酸和高精氨酸(NO-生物标志物)。首先,我们用线性混合模型确定了 1-5 天内 NO 生物标志物的变化,随后确定了 1-3 天内 NO 生物标志物的变化与 30 天内全因死亡率的关系。事后,我们分析了入院时血浆浓度与 30 天全因死亡率之间的关联:在 577 名患者中,共有 567 人获得了 1-5 天的血浆样本。血浆中 ADMA 和精氨酸的浓度在第 1-5 天有所增加。SDMA 浓度从第 1-2 天开始上升,随后从第 2-5 天开始下降。高精氨酸的浓度在第 1-3 天没有变化,但在第 3-5 天略有增加。共有 512 名患者在入住重症监护室 3 天后存活。在这些患者中,在多变量分析中,ADMA 浓度从第 1-3 天开始每天增加 2 倍与死亡率降低有关(HR 0.45;95% CI 0.21-0.98;P = 0.046)。SDMA、精氨酸或同精氨酸的增加与死亡率无关。我们发现,入院时ADMA或SDMA浓度增加两倍与死亡率有关(HR分别为1.78;95% CI 1.24-2.57;p = 0.0025,HR分别为1.41;95% CI 1.05-1.90;p = 0.024):第1-3天ADMA浓度的升高与死亡率成反比,但与入院时ADMA或SDMA浓度高的情况不同。我们建议将入院时的 ADMA 和 SDMA 浓度作为 ICU 患者死亡率的预测指标或潜在的治疗目标,这是未来研究的重点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Changes in nitric oxide inhibitors and mortality in critically ill patients: a cohort study.

Changes in nitric oxide inhibitors and mortality in critically ill patients: a cohort study.

Background: Optimal balance between macro- and microcirculation in critically ill patients is crucial for ensuring optimal organ perfusion. Nitric oxide (NO) is a regulator of vascular hemostasis and tone. The availability of NO is controlled by asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the availability of the NO substrates arginine and homoarginine. We investigated the changes in plasma concentrations of ADMA, SDMA, arginine, and homoarginine days 1-5 of intensive care unit (ICU) admission and the association between the change in concentration days 1-3 and 30-day all-cause mortality.

Methods: Single-center cohort study of adult critically ill patients from the ICU at Copenhagen University Hospital - North Zealand. ADMA, SDMA, arginine, and homoarginine (NO-biomarkers) were measured on days 1-5. Initially, we determined the changes in NO-biomarkers days 1-5 with linear mixed models, and subsequently how the changes in NO-biomarkers days 1-3 were associated with 30-day all-cause mortality. Post-hoc we analyzed the association between plasma concentration at admission and 30-day all-cause mortality.

Results: In total 567 out of 577 patients had plasma samples from days 1-5. Plasma concentrations of ADMA and arginine increased from days 1-5. SDMA concentrations increased from days 1-2, followed by a decrease from days 2-5. Concentrations of homoarginine did not change from days 1-3 but slightly increased from days 3-5. In total 512 patients were alive 3 days after ICU admission. Among these patients, a daily twofold increase in ADMA concentration from days 1-3 was associated with decreased mortality in multivariate analysis (HR 0.45; 95% CI 0.21-0.98; p = 0.046). An increase in SDMA, arginine, or homoarginine was not associated with mortality. Post-hoc we found that a twofold increase in ADMA or SDMA concentrations at admission was associated with mortality (HR 1.78; 95% CI 1.24-2.57; p = 0.0025, and HR 1.41; 95% CI 1.05-1.90; p = 0.024, respectively).

Conclusions: Increasing ADMA concentrations on days 1-3 are inversely associated with mortality, however not with the same strength as high ADMA or SDMA concentrations at admission. We suggest that admission concentrations are the focus of future research on ADMA and SDMA as predictors of mortality or potential therapeutical targets in ICU patients.

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来源期刊
Annals of Intensive Care
Annals of Intensive Care CRITICAL CARE MEDICINE-
CiteScore
14.20
自引率
3.70%
发文量
107
审稿时长
13 weeks
期刊介绍: Annals of Intensive Care is an online peer-reviewed journal that publishes high-quality review articles and original research papers in the field of intensive care medicine. It targets critical care providers including attending physicians, fellows, residents, nurses, and physiotherapists, who aim to enhance their knowledge and provide optimal care for their patients. The journal's articles are included in various prestigious databases such as CAS, Current contents, DOAJ, Embase, Journal Citation Reports/Science Edition, OCLC, PubMed, PubMed Central, Science Citation Index Expanded, SCOPUS, and Summon by Serial Solutions.
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