Cut-off Se Sp PPV NPV AUROCC DOR LR+ LR- Severity scores (points)
SOFA Day 1 SAPS II 9.5
68.0 59.1%
89.1% 77.8%
57.1% 60.4%
54.3% 76.9
% 90.2
%
0.74 [0.67-0.82]
0.79 [0.72-0.84] 5.1 10.9 2.7
2.1 0.5 0.2
Blood lactate (mmol/L) 2.9 74.7% 61.7% 52.7% 81.0
%
0.73 [0.65-0.81] 4.8 1.9 0.4 CRP (mg/L)
Day 1 Day 5
121.5 139.5
62.5%
87.0%
57.1%
35.0%
45.5%
43.4%
72.7
% 82.5
%
0.56 [0.47-0.65]
0.54 [0.38-0.70]
2.2 3.6
1.5 1.3
0.7 0.4
PCT (μg /L)
Day 1 Day 5
0.73 4.13
43.4%
80.0%
84.4%
57.1%
61.4%
51.6%
72.3
% 83.3
%
0.65 [0.58-0.72]
0.73 [0.60-0.86]
4.1 5.3
2.8 1.9
0.7 0.4
MR-ProADM (nmol/L) Day 1 Day 5
5.19 4.13
81.2%
84.5%
62.3%
72.7%
55.2%
63.9%
85.3
% 89.1
%
0.75 [0.67-0.85]
0.86 [0.75-0.96]
7.1 14.5
2.2 3.1
0.3 0.2
CT-ProET-1 (pmol/L) Day 1 Day 5
156.4 56.3
56.9%
58.4%
58.4%
92.9%
43.9%
82.5%
70.3
% 79.6
%
0.56 [0.46-0.65]
0.61 [0.46-0.76]
1.9 18.4
1.4 8.2
0.7 0.4
CT-ProET-1/ProADM (AU) Day 1 Day 5
38.5 30.0
80.0%
90.7%
68.8%
85.0%
59.5%
77.6%
85.7
% 94.1
%
0.82 [0.75-0.89]
0.91 [0.84-0.99]
8.8 55.3
2.6 6.0
0.3 0.1
Copeptin (pmol/L) Day 1 Day 5
85.7 37.6
62.1%
61.2%
71.4%
77.8%
55.4%
61.2%
76.7
% 77.8
%
0.67 [0.59-0.75]
0.70 [0.57-0.85]
4.1 5.5
2.2 2.7
0.5 0.5
Table S1. Clinical severity scores and blood lactate on admission, biomarkers performance at day 1 and day 5 regarding ICU survival prediction.
Se: sensibility; Sp: specificity; AUROCC: are under receiver characteristics curve; LR: likelihood ratio; DOR: diagnostic odd ratio; PPV:
positive predictive value; NPV: negative predictive value; ICU: intensive care unit; CRP: C-reactive protein; PCT: procalcitonin; MR- ProADM: mid regional proadrenomedullin; CT-ProET 1: c-terminal proendothelin 1; AU: arbitrary unit; SOFA: sequential organ failure assessment; SAPS II: simplified acute physiological score II.
HR 95 % CI p
Age 1.02 1.00-1.04 0.0447
SOFA on ICU admission 1.10 1.01-1.18 0.0309
Gender (male/female) 1.92 1.13-3.29 0.0167
Log10MR-ProADM day 1 4.06 1.04-10.39 0.0015
HR 95 % CI p
SAPS II on ICU admission 1.03 1.02-1.05 <0.0001
Gender (male/female) 2.26 1.31-3.90 0.0034
Log10MR-ProADM day 1 3.58 1.72-7.48 0.0007
HR 95 % CI p
Gender (male/female) 2.00 1.17-3.43 0.0117
Age 1.02 1.01-1.04 0.0310
SOFA on ICU admission 1.10 1.01-1.19 0.0226
CT-ProET-1/MR-ProADM day 1 0.98 0.96-0.99 0.0070
HR 95 % CI p
Gender (male/female) 2.34 1.35-4.05 0.0024
SAPS II on ICU admission 1.03 1.02-1.05 <0.0001
CT-ProET-1/MR-ProADM day 1 0.98 0.97-0.99 0.0094
Table S2. Independent predictors of death in the ICU.
ICU: intensive care unit; MR-ProADM: mid regional proadrenomedullin; CT-ProET-1: c-terminal proendothelin 1; SOFA: sequential organ failure assessment; SAPS II: simplified acute physiological score II; HR: hazard ratio; CI: confidence interval.
Cut-off Se Sp PPV NPV AUROCC DOR LR+ LR-
Blood lactate (mmol/L) 2.9 74.7% 61.7% 73.2% 63.6
%
0.68 [0.55-0.82] 4.8 1.9 0.4
CRP (mg/L) 97.8 46.7% 64.3% 64.7% 46.3
% 0.51 [0.37-0.64] 1.6 1.3 0.8
PCT (μg /L) 0.72 46.7% 88.1% 84.6% 54.2
%
0.65 [0.52-0.79] 6.5 3.9 0.6 MR-ProADM (nmol/L) 2.45 56.7% 90.5% 89.3% 59.9
%
0.77 [0.66-0.89] 12.5 6.0 0.5 CT-ProET-1 (pmol/L) 170.7 73.3% 61.9% 72.9% 62.4
%
0.65 [0.52-0.68] 4.5 1.4 0.4 CT-ProET-1/ProADM (AU) 40.5 90.0% 64.3% 77.9% 82.1
%
0.81 [0.71-0.91] 16.2 2.5 0.2 Copeptin (pmol/L) 109.2 79.3% 68.3% 77.9% 70.2
% 0.72 [0.59-0.85] 8.3 2.5 0.3
Table S3. Blood lactate and biomarkers performance at day 1 regarding organ failure prediction on day 5 (i.e., SOFA score ≥ 4 points).
Se: sensibility; Sp: specificity; AUROCC: are under receiver characteristics curve; LR: likelihood ratio; DOR: diagnostic odd ratio; PPV:
positive predictive value; NPV: negative predictive value; ICU: intensive care unit; CRP: C-reactive protein; PCT: procalcitonin; MR- ProADM: mid regional proadrenomedullin; CT-ProET 1: c-terminal proendothelin 1; AU: arbitrary unit; SOFA: sequential organ failure assessment.
Rho p
MR-ProADM +0.41 <0.0001
CT-ProET-1 +0.17 0.0234
CT-ProET-1/MR-ProADM -0.45 <0.0001
Copeptin +0.39 <0.0001
PCT +0.21 0.0054
CRP +0.10 0.1767
Table S4. Correlations between biomarkers levels on Day-1 and fluid balance as assessed through fluid input minus fluid output calculation from ICU admission to Day-5 according to Spearman test.
D: Day; ICU: intensive care unit; MR-ProADM: mid regional proadrenomedullin; CT-ProET-1: c-terminal proendothelin 1.
