Introduction
Methods
Study design
Collection of patient data
Sample collection
Bio-ADM measurement
Statistical analyses
Results
Patient characteristics | All | Bio-ADM < 70 pg/ml at admission | Bio-ADM > 70 pg/ml at admission | p Value* | No. |
---|---|---|---|---|---|
Epidemiological data | n = 583 | n = 257 | n = 326 | ||
Bio-ADM at admission (pg/ml) | 80.5 [41.5–148.0] | 36.9 [27.1–51.0] | 136.7 [97.6–241.0] | < 0.0001 | |
Age (years) | 66 [55–76] | 64 [53–75] | 67 [58–76] | 0.0052 | |
Male sex (n, %) | 364 (62.4) | 171 (66.5) | 193 (59.2) | 0.0837 | |
Body mass index (kg/m2) | 25.7 [22.9–30.1] | 25.0 [22.3–28.4] | 26.7 [23.2–31.6] | 0.0013 | |
Septic shock at admission | 293 (50.3) | 84 (32.7) | 209 (64.1) | < 0.0001 | |
Type of ICU admission | < 0.0001 | ||||
Medical | 473 (81.1) | 230 (89.5) | 243 (74.5) | ||
Surgical - emergency procedure | 93 (16) | 21 (8.2) | 72 (22.1) | ||
Surgical - elective procedure | 17 (2.9) | 6 (2.3) | 11 (3.4) | ||
Origin of sepsis | < 0.0001 | ||||
Lung | 218 (37.4) | 129 (50.2) | 89 (27.3) | ||
Bloodstream | 90 (15.4) | 31 (12.1) | 59 (18.1) | ||
Urinary tract | 62 (10.6) | 10 (3.9) | 52 (16) | ||
Catheter | 29 (5) | 9 (3.5) | 20 (6.1) | ||
Peritonitis | 31 (5.3) | 12 (4.7) | 19 (5.8) | ||
Endocarditis | 31 (5.3) | 12 (4.7) | 19 (5.8) | ||
Bile duct infection | 8 (1.4) | 2 (0.8) | 6 (1.8) | ||
CNS | 4 (0.7) | 4 (1.6) | 0 (0) | ||
Skin and soft tissue | 10 (1.7) | 9 (3.5) | 1 (0.3) | ||
Gynecologic | 2 (0.3) | 1 (0.4) | 1 (0.3) | ||
Other | 98 (16.8) | 38 (14.8) | 60 (18.4) | ||
Medical historya | |||||
Any cardiac comorbidity | 400 (68.6) | 147 (57.2) | 253 (77.6) | < 0.0001 | |
Chronic heart failure | 60 (10.3) | 19 (7.4) | 41 (12.6) | 0.0544 | |
Hypertension | 293 (50.3) | 105 (40.9) | 188 (57.7) | < 0.0001 | |
Diabetes mellitus | 160 (27.4) | 57 (22.2) | 103 (31.6) | 0.0150 | |
Any noncardiac comorbidity | 414 (71) | 167 (65) | 247 (75.8) | 0.0058 | |
Chronic renal disease | 76 (13.0) | 19 (7.4) | 57 (17.5) | 0.0004 | |
Active/recent malignant tumors | 124 (21.3) | 34 (13.2) | 90 (27.6) | < 0.0001 | |
Smoking (active) | 117 (20.1) | 63 (24.5) | 54 (16.6) | 0.0302 | |
COPD | 89 (15.3) | 37 (14.4) | 52 (16.0) | 0.6421 | |
Any chronic medication | 371 (63.6) | 138 (53.7) | 233 (71.5) | < 0.0001 | |
Immunosuppressive therapy | 46 (7.9) | 11 (4.3) | 35 (10.7) | 0.0066 | |
Physiological values at admission | |||||
Temperature (°C) | 37.2 [36.4–38.2] | 37.4 [36.6–38.2] | 37.1 [36.2–38.1] | 0.0034 | |
Mean blood pressure (mmHg) | 75 [64–90] | 81 [69–95] | 72 [60–85] | < 0.0001 | |
Heart rate (beats/min) | 104 [90–119] | 100 [86–116] | 105 [94–121] | 0.0013 | |
Central venous pressure (mmHg) | 8 [5–13] | 8 [5–13] | 10 [6–14] | 0.2419 | |
Glasgow Coma Scale score | 15 [14–15] | 15 [14–15] | 15 [14–15] | 0.8161 | |
Fluid balance (ml) | 1928 [592–3552] | 1425 [500–2699] | 2311 [764–4202] | < 0.0001 | |
Urine output for 24 h (ml) | 1000 [450–1900] | 1276 [650–2050] | 800 [300–1650] | < 0.0001 | |
PaO2/FiO2 | 228 [137–340] | 233.5 [140–360] | 223 [137–337] | 0.4995 | |
Laboratory values at admission | |||||
Lactate (mmol/L) | 1.4 [1.0–2.2] | 1.1 [0.8–1.6] | 1.8 [1.2–2.7] | < 0.0001 | n = 562 |
Arterial pH | 7.38 [7.3–7.44] | 7.42 [7.36–7.46] | 7.36 [7.27–7.42] | < 0.0001 | |
Bilirubin (μmol/L) | 11 [6–19] | 10 [6.5–17] | 12 [6–21] | 0.1360 | |
Platelets (109/L) | 190 [121–275] | 196 [136–279] | 181 [104–271] | 0.0583 | |
Creatinine (mg/dl) | 1.4 [0.9–2.2] | 1 [0.7–1.4] | 1.8 [1.2–2.9] | < 0.0001 | |
BUN or urea (mg/dl) | 61 [37–107] | 44 [28–69] | 80 [50–127] | < 0.0001 | |
Hematocrit (%) | 34 [29–38] | 35 [30–38] | 34 [29–38] | 0.1010 | |
White blood cell count (per mm3) | 12,525 [7200–18,585] | 13,000 [8475–18,075] | 12,025 [5942–19,025] | 0.0547 | |
Troponin T, maximum on day 1 | 42 [18–158] | 29 [14–124] | 55 [25–176] | 0.0230 | n = 153 |
Troponin I, maximum on day 1 | 69 [20–246] | 40 [11–228] | 99 [40–289] | 0.0049 | n = 186 |
PCT, maximum on day 1 (ng/ml) | 11.4 [1.9–49.8] | 3.9 [0.9–19.5] | 24 [6–84] | < 0.0001 | n = 330 |
PCT, central laboratory (ng/ml) | 10.2 [2.3–34.3] | 3.7 [0.8–13.0] | 18.2 [6.0–52.7] | < 0.0001 | n = 583 |
BNP, maximum on day 1 | 257 [102–723] | 187 [61–388] | 473 [147–1154] | 0.0004 | n = 131 |
NT-proBNP, maximum on day 1 | 4382 [1525–11,565] | 2170 [497–6633] | 6116 [2816–15,431] | 0.0001 | n = 117 |
Organ support at admission | |||||
Mechanical ventilation | 0.0739 | ||||
Invasive | 219 (37.6) | 85 (33.1) | 134 (41.1) | ||
Noninvasive | 131 (22.5) | 67 (26.1) | 64 (19.6) | ||
None | 233 (40.0) | 105 (40.9) | 128 (39.3) | ||
Renal replacement therapy | 49 (8.4) | 8 (3.1) | 41 (12.6) | 0.0001 | |
Vasopressors/inotropes at admission | 349 (59.9) | 109 (42.4) | 240 (73.6) | < 0.0001 | |
Organ dysfunction scores | |||||
SOFA (points) | 7 [5–10] | 5 [3–8] | 8 [6–11] | < 0.0001 | n = 509 |
APACHE II (points) | 15 [11–20] | 14 [9–17] | 18 [13–22] | < 0.0001 | |
Length of stay (days) | |||||
ICU | 5 [2–10] | 4 [2–8] | 5 [2–10] | 0.0554 | |
Mortality | |||||
28-day, deaths (%) | 127 (21.8) | 30 (11.7) | 97 (29.8) | < 0.0001 | |
90-day, deaths (%) | 166 (28.5) | 41 (16) | 125 (38.3) | < 0.0001 |
Bio-ADM levels and mortality
Variables | Chi-square | added chi-square | p Value (added value) | Std. HR bio-ADM | p Value |
---|---|---|---|---|---|
bio-ADM (univariate) | 54.8 | 2.3 [1.9–2.9] | < 0.0001 | ||
Adjusted for SOFA at admission | 85.1 | 10.2 | 0.0014 | 1.6 [1.2–2.1] | 0.0014 |
Adjusted for APACHE II at admission | 88.9 | 24.4 | < 0.0001 | 1.9 [1.5–2.4] | < 0.0001 |
Adjusted for covariates | 132.1 | 12.2 | 0.0005 | 1.6 [1.1–2.5] | 0.0004 |
bio-ADM (time-dependent Cox) | 80.6 | 25.8 | < 0.0001 | 2.5 [2.1–3.1] | < 0.0001 |
Adjusted for SOFA at admission | 89.3 | 11.5 | 0.0007 | 1.8 [1.4–2.2] | < 0.0001 |
Adjusted for APACHE II at admission | 108.4 | 19.5 | < 0.0001 | 2.1 [1.7–2.6] | < 0.0001 |
Adjusted for SOFA (t-d*) | 101.0 | 7.9 | 0.0049 | 1.5 [1.1–2.0] | 0.0048 |
Adjusted for lactate (t-d*) | 138.0 | 35.7 | < 0.0001 | 1.9 [1.5–2.3] | < 0.0001 |
Bio-ADM levels and organ dysfunction
Discussion
Conclusions
Acknowledgements
Centers | Name |
Cliniques Universitaires Saint-Luc, Brussels, Belgium | Laterre |
Clinique St Pierre, Ottignies, Belgium | Dugernier |
Hôpital Jolimont, Haine-St-Paul, Belgium | Huberlant |
Klinik für Operative Intensivmedizin und Intermediate Care, Universitätsklinikum der RWTH, Aachen, Germany | Marx |
Klinik für Anästhesiologie und Operative Intensivmedizin, Universitätsklinikum Köln, Köln, Germany | Hohn |
HELIOS-Klinikum Erfurt, Erfurt, Germany | Meier-Hellmann |
Klinikum Augsburg, Augsburg, Germany | Jaschinski |
Klinik für Anästhesiologie und Intensivmedizin, Jena, Germany | Kortgen |
CHU Dupuytren, Limoges, France | Francois |
CHD les Oudairies, La Roche sur Yon, France | Lascarrou |
CHU de Tours, Tours, France | Mercier |
Centre hospitalier d’Angoulême, Angoulême, France | Desachy |
CHU Angers, Angers, France | Lasocki |
Hôpital Lariboisière, Paris, France (two centers) | Mebazaa |
Hôpital Saint-Louis 1, Paris, France | Jacob |
Hôpital Louis Mourier, Colombes, France | Gaudry |
Hôpital Hautepierre, Strasbourg, France | Pottecher |
CHU Estaing, Clermont Ferrand, France | Constantin |
Hôpital Bichat Claude-Bernard, Paris, France | Sonneville |
Sant’Andrea Hospital, Rome, Italy | Disomma |
Policlinico Universitario A. Gemelli, Rome, Italy | Antonelli |
Medisch Spectrum Twente, Enschede, The Netherlands | Beishuizen |
UMC Radboudziekenhuis, Nijmegen, The Netherlands | Pickkers |