Superior accuracy of mid-regional proadrenomedullin for mortality prediction in sepsis with varying levels of illness severity.
Superior accuracy of mid-regional proadrenomedullin for mortality prediction in sepsis with varying levels of illness severity.
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DOI：
10.1186/s13613-017-0238-9
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发表时间：
2017-12
影响因子：
8.1
通讯作者：
Charles PE
中科院分区：
文献类型：
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作者：
Andaluz-Ojeda D;Nguyen HB;Meunier-Beillard N;Cicuéndez R;Quenot JP;Calvo D;Dargent A;Zarca E;Andrés C;Nogales L;Eiros JM;Tamayo E;Gandía F;Bermejo-Martín JF;Charles PE
近年来，新型脓毒症生物标志物的使用有所增加。然而，他们的预后价值方面的疾病严重程度尚未探讨。在这项工作中，我们研究了中部区域肾上腺髓质素原（MR-proADM）在预测不同程度的器官衰竭脓毒症患者的死亡率的能力，与降钙素原，C-反应蛋白和乳酸相比。这是一项双中心前瞻性观察队列研究，入组入住ICU的严重脓毒症或脓毒性休克患者。在入院的前12小时内测量血浆生物标志物。通过考克斯回归分析和Kaplan-Meier曲线评估生物标志物与28天死亡率之间的关联。根据序贯器官衰竭评估（SOFA）评分将患者分为三组。通过受试者工作特征曲线下面积（AUROC）分析确定死亡率生物标志物的准确性。共入组326例严重脓毒症（21.7%）或脓毒性休克（79.3%）患者，28天死亡率为31.0%。在多变量分析中，仅MR-proADM和乳酸盐与死亡率相关：风险比为8.5 vs 3.4（p < 0.001）。在整个队列的分析中，MR-proADM显示了28天时死亡率预测的最佳AUROC（AUROC [95% CI] 0.79 [0.74-0.84]）（p < 0.001）。当患者按器官衰竭程度分层时，MR-proADM是预测所有严重程度组死亡率的唯一生物标志物（SOFA ≤ 6、SOFA = 7-12和SOFA ≥ 13），AUROC [95% CI]分别为0.75 [0.61-0.88]、0.74 [0.66-0.83]和0.73 [0.59-0.86]（p < 0.05）。所有MR-proADM浓度≤0.88 nmol/L的患者均存活长达28天。在SOFA ≤ 6的患者中，将MR-proADM添加到SOFA评分中增加了SOFA识别非幸存者的能力，AUROC [95% CI]分别为0.70 [0.58-0.82]和0.77 [0.66-0.88]（两者均为p < 0.05）。脓毒症的预后生物标志物的性能受到疾病严重程度的高度影响。MR-proADM预测死亡率的准确性不受器官衰竭程度的影响。因此，它是早期识别中度疾病严重程度但有死亡风险的脓毒症患者的良好候选药物。本文的在线版本（doi：10.1186/s13613-017-0238-9）包含补充材料，可供授权用户使用。
The use of novel sepsis biomarkers has increased in recent years. However, their prognostic value with respect to illness severity has not been explored. In this work, we examined the ability of mid-regional proadrenomedullin (MR-proADM) in predicting mortality in sepsis patients with different degrees of organ failure, compared to that of procalcitonin, C-reactive protein and lactate. This was a two-centre prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to the ICU. Plasma biomarkers were measured during the first 12 h of admission. The association between biomarkers and 28-day mortality was assessed by Cox regression analysis and Kaplan–Meier curves. Patients were divided into three groups as evaluated by the Sequential Organ Failure Assessment (SOFA) score. The accuracy of the biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. A total of 326 patients with severe sepsis (21.7%) or septic shock (79.3%) were enrolled with a 28-day mortality rate of 31.0%. Only MR-proADM and lactate were associated with mortality in the multivariate analysis: hazard ratio 8.5 versus 3.4 (p < 0.001). MR-proADM showed the best AUROC for mortality prediction at 28 days in the analysis over the entire cohort (AUROC [95% CI] 0.79 [0.74–0.84]) (p < 0.001). When patients were stratified by the degree of organ failure, MR-proADM was the only biomarker to predict mortality in all severity groups (SOFA ≤ 6, SOFA = 7–12, and SOFA ≥ 13), AUROC [95% CI] of 0.75 [0.61–0.88], 0.74 [0.66–0.83] and 0.73 [0.59–0.86], respectively (p < 0.05). All patients with MR-proADM concentrations ≤0.88 nmol/L survived up to 28 days. In patients with SOFA ≤ 6, the addition of MR-proADM to the SOFA score increased the ability of SOFA to identify non-survivors, AUROC [95% CI] 0.70 [0.58–0.82] and 0.77 [0.66–0.88], respectively (p < 0.05 for both). The performance of prognostic biomarkers in sepsis is highly influenced by disease severity. MR-proADM accuracy to predict mortality is not affected by the degree of organ failure. Thus, it is a good candidate in the early identification of sepsis patients with moderate disease severity but at risk of mortality. The online version of this article (doi:10.1186/s13613-017-0238-9) contains supplementary material, which is available to authorized users.