To the editor: Sepsis mortality decreased over the last decades, although it remains dramatically high [1]. The implementation of guidelines such as the Surviving Sepsis Campaign (SSC) contributed to these progresses. SSC recommends to guide resuscitation on normalization of lactate levels [2]. Guiding resuscitation on lactate reduction is highly debated [3]. Anyway, normalization of lactate is associated with improved outcome [4]. We have recently shown that plasma levels of bio-adrenomedullin (bioADM), a peptide regulating vascular integrity and endothelial function, were associated with patient outcome during sepsis [5]. Interestingly, we observed that patients with elevated bio-ADM levels at admission and with low bio-ADM levels 2 days later had similar outcome to patients with persistently low bio-ADM levels. We therefore aimed to evaluate the added value of bio-ADM to lactate measurement in the AdrenOSS-1 cohort. The AdrenOSS-1 study is a prospective observational study conducted in 24 centers within 5 European countries and included 583 septic patients from June 2015 to May 2016 [5]. The primary endpoint was 28-day mortality. We evaluated the relationship between the association of initial evolution of lactate plasma levels and bio-ADM level at 24 h and outcome in patients for whom both markers were available at admission and 1 day later (“24 h”). As described previously, bio-ADM levels below or above 70 pg/mL were considered respectively as low and high [5]. In patients with high lactate levels (> 2 mmol/L) at admission (n = 328) (Table 1), lactate normalization (< 2 mmol/L) at 24 h was associated with better outcome than in patients with persistently high lactate at 24 h (28-day mortality 15.9% vs 41.9% respectively, HR 3.3 [2.0–5.3], p < 0.001) (Fig. 1). Interestingly, among patients with decreasing lactate, high and low bio-ADM levels at 24 h identified patients with substantially different outcomes (28-day mortality 7% vs 26% for low vs high bio-ADM respectively, HR 4.4 [1.6–11.7], p < 0.005) (Fig. 1). High and low bio-ADM levels at 24 h also differentiated outcome of patients with persistently elevated lactate (HR 4.5 [1.6–12.3], p < 0.005). In patients with low initial lactate (n = 234 admitted and n = 171 alive at 24 h), overall 28-day mortality was 11.2%, neither lactate nor bio-ADM added prognostic value. For all analyses, similar results were obtained, when missing 24 h data were replaced by the last available values. Accordingly, our data suggest that measurement of bio-ADM in addition to lactate may help physicians to refine risk stratification and therefore to guide resuscitation during sepsis.

中文翻译：

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除乳酸外，连续测量生物肾上腺髓质素对入住ICU的脓毒症患者预后的附加价值

致编辑：脓毒症死亡率在过去几十年中有所下降，但仍然非常高 [1]。诸如败血症幸存运动 (SSC) 等指南的实施促成了这些进展。SSC 建议指导复苏使乳酸水平正常化 [2]。关于乳酸减少的指导复苏备受争议 [3]。无论如何，乳酸的正常化与改善的结果有关 [4]。我们最近表明，生物肾上腺髓质素 (bioADM)（一种调节血管完整性和内皮功能的肽）的血浆水平与脓毒症患者的预后相关 [5]。有趣的是，我们观察到入院时生物 ADM 水平升高和 2 天后生物 ADM 水平低的患者与生物 ADM 水平持续低的患者具有相似的结果。因此，我们旨在评估生物 ADM 对 AdrenOSS-1 队列中乳酸测量的附加值。AdrenOSS-1 研究是一项前瞻性观察性研究，在 5 个欧洲国家的 24 个中心进行，包括 2015 年 6 月至 2016 年 5 月的 583 名脓毒症患者 [5]。主要终点是 28 天死亡率。我们在入院时和 1 天后（“24 小时”）评估了两种标志物都可用的患者 24 小时时乳酸血浆水平的初始演变与生物 ADM 水平之间的关系与结果之间的关系。如前所述，低于或高于 70 pg/mL 的生物 ADM 水平分别被视为低和高 [5]。在入院时乳酸水平高 (> 2 mmol/L) 的患者 (n = 328)（表 1）中，乳酸正常化（< 2 mmol/L）与 24 小时持续高乳酸的患者相比，与 24 小时持续高乳酸的患者预后相关（28 天死亡率分别为 15.9% 和 41.9%，HR 3.3 [2.0-5.3]，p < 0.001）（图 2）。 1）。有趣的是，在乳酸降低的患者中，24 小时高和低生物 ADM 水平确定了具有显着不同结果的患者（28 天死亡率分别为低和高生物 ADM 的 7% 和 26%，HR 4.4 [1.6–11.7] , p < 0.005)（图 1）。24 小时的高和低生物 ADM 水平也区分持续升高的乳酸患者的结果（HR 4.5 [1.6-12.3]，p < 0.005）。在初始乳酸低的患者（n = 234 入院，n = 171 24 小时存活）中，总体 28 天死亡率为 11.2%，乳酸和生物 ADM 均不增加预后价值。对于所有分析，获得了相似的结果，当丢失的 24 小时数据被最后可用的值替换时。因此，我们的数据表明，除了乳酸之外，测量生物 ADM 可能有助于医生完善风险分层，从而指导脓毒症期间的复苏。