Table 1.
Participant characteristics
| Healthy subjects (n = 20) |
P value* | Acute phase of cie (n = 40) |
Subacute phase of cie (n = 40) |
Prolonged phase of cie (n = 40) |
P value** | |
|---|---|---|---|---|---|---|
| Demography and anthropometry | ||||||
| Male gender—no. (%) | 13 (65) | 0.94 | 28 (70) | 24 (60) | 25 (63) | 0.62 |
| Age—year (mean ± SEM) | 63 ± 3 | 0.58 | 67 ± 2 | 65 ± 2 | 62 ± 2 | 0.30 |
| BMIa—kg/m2 (mean ± SEM) | 26.2 ± 0.7 | 0.94 | 25.2 ± 0.8 | 25.6 ± 0.8 | 27.6 ± 1.3 | 0.20 |
| Admission characteristics | ||||||
| Diabetes mellitus—no. (%) | 6 (15) | 6 (15) | 8 (20) | 0.79 | ||
| Malignancy—no. (%) | 6 (15) | 12 (30) | 13 (33) | 0.14 | ||
| APACHE II scoreb—(mean ± SEM) | 30 ± 1 | 31 ± 1 | 31 ± 1 | 0.78 | ||
| Emergency admission—no. (%) | 8 (20) | 8 (20) | 9 (23) | 0.95 | ||
| Diagnostic admission categories | 1.00 | |||||
| Cardiac surgery—no. (%) | 9 (23) | 9 (23) | 9 (23) | |||
| Complicated other surgery—no. (%) | 10 (25) | 10 (25) | 10 (25) | |||
| Multiple trauma and burns—no. (%) | 16 (40) | 16 (40) | 16 (40) | |||
| Medical—no. (%) | 5 (12) | 5 (12) | 5 (12) | |||
| ICUc day on testday 1—median and IQR | 4 (3–5) | 9 (7–12) | 19 (17–22) | < 0.0001 | ||
| Patient characteristics on testday 1 | ||||||
| On mechanical ventilatory support—no. (%) | 35 (88) | 30 (75) | 25 (63) | 0.03 | ||
| On renal replacement therapy—no. (%) | 6 (15) | 5 (13) | 6 (15) | 0.93 | ||
| Infection—no. (%) | 30 (75) | 32 (80) | 33 (83) | 0.70 | ||
| Sepsisd—no. (%) | 27 (68) | 30 (75) | 30 (75) | 0.69 | ||
| Septic shockd—no. (%) | 21 (53) | 15 (38) | 19 (48) | 0.38 | ||
| Plasma ACTH—pg/mL [median (IQR)] | 21 (15–33) | 0.54 | 14 (11–32) | 19 (14–27) | 27 (17–41) | 0.009 |
| Plasma total cortisol—µg/dL [median (IQR)] | 13 (11–16) | < 0.0001 | 24 (16–33) | 24 (20–31) | 23 (17–29) | 0.47 |
| Plasma free cortisol—µg/dL [median (IQR)] | 0.5 (0.4–0.7) | < 0.0001 | 2.6 (1.2–4.6) | 2.1 (1.4–4.5) | 2.0 (1.1–3.0) | 0.26 |
| Plasma CBG—µg/mL (mean ± SEM) | 52 ± 2 | < 0.0001 | 37 ± 1 | 41 ± 1 | 43 ± 1 | 0.002 |
| Plasma albumin—g/dL (mean ± SEM) | 6.4 ± 0.1 | < 0.0001 | 3.9 ± 0.2 | 3.9 ± 0.1 | 3.8 ± 0.1 | 0.86 |
| Clinical outcomes | ||||||
| Days in ICU—median (IQR) | 11 (8–18) | 18 (13–26) | 30 (28–44) | < 0.0001 | ||
| ICU non-survivor—no. (%) | 8 (20) | 9 (23) | 9 (23) | 0.95 | ||
*The comparison between healthy subjects and all patients
**The comparison between patient cohorts. For all patients combined, total median (IQR) plasma ACTH was 20 (13–35) pg/ml, plasma cortisol 24 (18–30) µg/dL and free cortisol 2.3 (1.3–3.4) µg/dL
aThe body-mass index (BMI) is the weight in kilograms divided by the square of the height in meters
bThe Acute Physiology and Chronic Health Evaluation II (APACHE II) score reflects severity of illness, with higher values indicating more severe illness, and can range from 0 to 71 [50]
cICU denotes intensive care unit
dIncidence of sepsis and septic shock was defined according to [51, 52]
eci denotes critical illness