Introduction
Materials and methods
Study design and process
Inclusion and exclusion criteria
Study logistics
Definitions and data collection methods
Statistical analysis
Sample size
Statistical analysis
Results
Patients’ demographics and baseline characteristics
Patients’ characteristics | Primary cohort (n = 259) | Divided by sedation level at 48 h in patients with ICU stay >48 h | ||
---|---|---|---|---|
Lightly sedated (n = 45) | Deeply sedated (n = 209) |
P value | ||
Age, mean (SD), years | 53.1 ± 15.9 | 53.6 ± 13.9 | 53.2 ± 16.3 | 0.87 |
Male (n) % | (162) 62.5 % | (25) 55.5 % | (134) 64.1 % | 0.28 |
Weight, mean (SD), kg | 68.2 ± 19.8 | 72.7 ± 22.2 | 67.4 ± 19.4 | 0.10 |
APACHE II score, mean (SD) | 21.3 ± 8.2 | 20.1 ± 7.8 | 21.6 ± 8.3 | 0.24 |
Operative admission diagnosis (n) % | (83) 32.0 % | (18) 40.7 % | (65) 31.1 % | 0.25 |
Respiratory failure admission diagnosisa (n) % | (66) 25.5 % | (13) 28.9 % | (51) 24.4 % | 0.53 |
Cardiovascular admission diagnosisa (n) % | (39) 15.4 % | (11) 24.4 % | (29) 13.9 % | 0.08 |
Vasopressors infusions (n) % | (209) 80.7 % | (28) 62.2 % | (164) 78.4 % | 0.021 |
Renal replacement therapy (n) % | (73) 28.2 % | (7) 15.6 % | (43) 20.6 % | 0.44 |
Tracheostomy after ICU admission (n) % | (36) 14 % | (7) 15.6 % | (28) 13.4 % | 0.71 |
Time to tracheostomy, median (IQR) days | 9.35 (5.63–15.34) | 11 (5.67–16) | 9.35 (5.63–13.7) | 0.86 |
Ventilation days, median (IQR) | 4.96 (2.99–8.8) | 3.95 (2.7–6.9) | 6.69 (4–11.7) | 0.008 |
28-Day coma and delirum-free days | 24 (0–26) | 28 (26–28) | 23 (0–26) | <0.0001 |
ICU length of stay, median (IQR) days | 7.19 (4.8–11) | 6.52 (4.83–6.69) | 7.7 (4.95–11.57) | 0.35 |
Hospital length of stay, median (IQR) days | 16.4 (10.0–30.7) | 17.6 (12.7–32.2) | 16.5 (9.5–28.9) | 0.08 |
ICU mortality (n) % | (66) 25.5 % | (3) 6.7 % | (63) 30.1 % | 0.001 |
Hospital mortality (n) % | (82) 31.7 % | (6) 13.4 % | (76) 36.4 % | 0.003 |
180-day mortality (n) % | (110/237) 46.4 % | (10/41) 24.4 % | (100/192) 52.1 % | 0.001 |
Sedative and analgesic prescription
Overall therapy
Prescription over first 48 h
Drugs given | During the first 48 h | During entire study | |||
---|---|---|---|---|---|
ICU days 518 n (%) | Dosea (patient−1 day−1) | ICU days 2,439 n (%) | Dosea (patient−1 day−1) | Duration treatment daysb
| |
Midazolam (mg) | 389 (75.1 %) | 28 (12–58) | 966 (39.6 %) | 31 (12–66) | 3.37 (3.4) |
Propofol (mg) | 36 (6.9 %) | 240 (100–680) | 183 (7.5 %) | 350 (100–800) | 0.71 (1.4) |
Morphine (mg) | 327 (63.1 %) | 24.5 (12.54) | 773 (31.7 %) | 25 (10–51) | 2.99 (3.23) |
Fentanyl | 168 (32.4 %) | 290 (95–620) | 771 (31.6 %) | 450 (200–780) | 2.97 (4.19) |
Dexmedetomidine | 65 (12.5 %) | 1.93 (0.9–4.3) | 334 (13.7 %) | 3.96 (1.98–7.2) | 1.29 (2.67) |
Ketamine (mg) | 16 (3.1 %) | 390 (157–750) | 46 (1.9 %) | 1,374 (315–3,840)c
| 0.18 (0.84) |
Haloperidol (mg) | 6 (1.2 %) | 7.5 (2.2–13.5) | 51 (2.1 %) | 15 (5–46)c
| 0.19 (0.79) |
Diazepam (mg) | 2 (0.4 %) | 4.2 (2.2–6) | 20 (0.8 %) | 21 (10–15)c
| 0.08 (0.69) |
Early and subsequent sedation level
Occurrence of delirium
Early sedation depth and clinical outcomes
Time to extubation | Delirium after 48 h | 180-Day mortality | |||||||
---|---|---|---|---|---|---|---|---|---|
HR | 95 % CI |
P
| HR | 95 % CI |
P
| HR | 95 % CI |
P
| |
RASS −3 to −5a
| 0.93 | 0.89–0.96 | 0.0001 | 0.98 | 0.94–1.03 | 0.46 | 1.10 | 1.04–1.15 | 0.0002 |
APACHE IIb
| 0.96 | 0.94–0.98 | 0.001 | 0.98 | 0.96–1.01 | 0.22 | 1.02 | 0.10–1.05 | 0.08 |
Age | 1.00 | 0.99–1.01 | 0.77 | 1.01 | 1.00–1.03 | 0.04 | 1.02 | 1.00–1.03 | 0.01 |
Male | 0.84 | 0.61–1.16 | 0.29 | 1.37 | 0.92–2.04 | 0.12 | 0.75 | 0.50–1.14 | 0.17 |
Operative | 1.22 | 0.74–2.04 | 0.43 | 1.10 | 0.60–1.03 | 0.75 | 0.56 | 0.26–1.21 | 0.14 |
Elective | 0.99 | 0.54–1.79 | 0.96 | 1.31 | 0.65–2.64 | 0.44 | 0.83 | 0.32–2.13 | 0.70 |
Cardiacc
| 0.84 | 0.47–1.50 | 0.56 | 1.17 | 0.59–2.32 | 0.66 | 2.22 | 0.92–5.36 | 0.07 |
Respiratoryc
| 0.82 | 0.51–1.31 | 0.41 | 0.94 | 0.51–1.73 | 0.84 | 1.14 | 0.57–2.29 | 0.71 |
Sepsisc
| 0.97 | 0.59–1.60 | 0.91 | 1.22 | 0.65–2.31 | 0.54 | 1.22 | 0.59–2.50 | 0.60 |
Gastrointesc
| 0.61 | 0.33–1.12 | 0.11 | 0.94 | 0.46–1.90 | 0.86 | 2.42 | 1.02–5.75 | 0.04 |
Vasopressors | 1.09 | 0.73–1.64 | 0.67 | 1.15 | 0.70–1.94 | 0.54 | 1.42 | 0.81–2.47 | 0.22 |
Dialysisd
| 0.53 | 0.32–0.86 | 0.01 | 1.03 | 0.60–1.76 | 0.92 | 0.94 | 0.94–2.45 | 0.09 |