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 (bio-ADM), 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).

Table 1 Clinical characteristics of septic patients admitted with a lactate level > 2 mmol/L and alive at 24 h (n = 269)
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Fig. 1
figure 1

Impact of 24 h lactate and bio-ADM values in patients with elevated lactate level at admission. The green curve in the left KM-plot illustrates data from 75 patients with 5 events, the red curve 70 patients with 18 events. The green curve in the right KM-plot illustrates data from 28 patients with 4 events, the red curve 96 patients with 48 events. Of note, differences in numbers between admission (n = 328) and 24 h (n = 269) is related to initial mortality

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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.