Department of Clinical Medicine, Anaesthesiology and Intensive Care, Lund University, 22185, Lund, Sweden.
Department of Intensive and Perioperative Care, Skåne University Hospital, 20502, Malmö, Sweden.
Crit Care. 2020 Nov 4;24(1):636. doi: 10.1186/s13054-020-03351-1.
Biomarkers can be of help to understand critical illness and to identify and stratify sepsis. Adrenomedullin is a vasoactive hormone, with reported prognostic and potentially therapeutic value in sepsis. The primary aim of this study was to investigate the association of circulating bioactive adrenomedullin (bio-ADM) levels at intensive care unit (ICU) admission with mortality in sepsis patients and in a general ICU population. Secondary aims included the association of bio-ADM with organ failure and the ability of bio-ADM to identify sepsis.
In this retrospective observational study, adult patients admitted to one of four ICUs during 2016 had admission bio-ADM levels analysed. Age-adjusted odds ratios (OR) with 95% CI for log-2 transformed bio-ADM, and Youden's index derived cut-offs were calculated. The primary outcome was 30-day mortality, and secondary outcomes included the need for organ support and the ability to identify sepsis.
Bio-ADM in 1867 consecutive patients were analysed; 632 patients fulfilled the sepsis-3 criteria of whom 267 had septic shock. The median bio-ADM in the entire ICU population was 40 pg/mL, 74 pg/mL in sepsis patients, 107 pg/mL in septic shock and 29 pg/mL in non-septic patients. The association of elevated bio-ADM and mortality in sepsis patients and the ICU population resulted in ORs of 1.23 (95% CI 1.07-1.41) and 1.22 (95% CI 1.12-1.32), respectively. The association with mortality remained after additional adjustment for lactate in sepsis patients. Elevated bio-ADM was associated with an increased need for dialysis with ORs of 2.28 (95% CI 2.01-2.59) and 1.97 (95% CI 1.64-2.36) for the ICU population and sepsis patients, respectively, and with increased need of vasopressors, OR 1.33 (95% CI 1.23-1.42) (95% CI 1.17-1.50) for both populations. Sepsis was identified with an OR of 1.78 (95% CI 1.64-1.94) for bio-ADM, after additional adjustment for severity of disease. A bio-ADM cut-off of 70 pg/mL differentiated between survivors and non-survivors in sepsis, but a Youden's index derived threshold of 108 pg/mL performed better.
Admission bio-ADM is associated with 30-day mortality and organ failure in sepsis patients as well as in a general ICU population. Bio-ADM may be a morbidity-independent sepsis biomarker.
生物标志物有助于了解危重病，并识别和分层脓毒症。肾上腺髓质素是一种血管活性激素，在脓毒症中具有预后和潜在的治疗价值。本研究的主要目的是探讨入院时循环生物活性肾上腺髓质素（bio-ADM）水平与脓毒症患者和一般 ICU 人群死亡率之间的关系。次要目的包括生物活性 ADM 与器官衰竭的关系，以及生物活性 ADM 识别脓毒症的能力。
在这项回顾性观察性研究中，分析了 2016 年期间入住四个 ICU 之一的成年患者的入院时生物活性 ADM 水平。计算了经年龄调整的对数 2 转换的生物活性 ADM 的优势比（OR）及其 95%置信区间，以及 Youden 指数得出的截断值。主要结局是 30 天死亡率，次要结局包括器官支持的需要和识别脓毒症的能力。
分析了 1867 例连续患者的生物活性 ADM；632 例符合脓毒症-3 标准，其中 267 例患有感染性休克。整个 ICU 人群的中位生物活性 ADM 为 40pg/ml，脓毒症患者为 74pg/ml，感染性休克患者为 107pg/ml，非脓毒症患者为 29pg/ml。在脓毒症患者和 ICU 人群中，升高的生物活性 ADM 与死亡率的相关性导致 OR 分别为 1.23（95%CI 1.07-1.41）和 1.22（95%CI 1.12-1.32）。在脓毒症患者中，在进一步调整乳酸后，与死亡率的相关性仍然存在。升高的生物活性 ADM 与需要透析的相关性增加，OR 分别为 2.28（95%CI 2.01-2.59）和 1.97（95%CI 1.64-2.36），用于 ICU 人群和脓毒症患者，以及与血管加压素需求增加的相关性，OR 为 1.33（95%CI 1.23-1.42）（95%CI 1.17-1.50），用于两个人群。生物活性 ADM 对脓毒症的识别 OR 为 1.78（95%CI 1.64-1.94），在进一步调整疾病严重程度后。生物活性 ADM 的截断值为 70pg/ml 可区分脓毒症患者的存活者和非存活者，但经 Youden 指数得出的 108pg/ml 截断值效果更好。
入院时的生物活性 ADM 与脓毒症患者和一般 ICU 人群的 30 天死亡率和器官衰竭有关。生物活性 ADM 可能是一种与发病率无关的脓毒症生物标志物。
