Introduction
Patients and methods
Study population
Data collection
Medication
Microbiology and diagnosis of infections
Statistical analysis
Results
Cohort description
Control group (n = 7,626) | Corticosteroid exposure group (n = 2,632) |
P
| |
---|---|---|---|
Age (years) | 72 (48–84) | 67 (43–82) | 0.0001 |
Female | 2,860 (38) | 1,147 (44) | 0.0001 |
Body mass index (kg/m2) | 26 (20–35) | 26 (20–35) | 0.8 |
Peripheral arterial disease | 777 (10) | 221 (8) | 0.008 |
Cerebral vascular disease | 159 (2) | 23 (1) | 0.0001 |
Neurological disease (degenerative brain disease) | 1,048 (14) | 396 (15) | 0.1 |
Congestive heart failure | 974 (13) | 361 (14) | 0.2 |
Hypertension | 3,687 (48) | 995 (38) | 0.0001 |
Diabetes mellitus | 1,359 (18) | 436 (17) | 0.1 |
Liver disease | 636 (8) | 351 (13) | 0.0001 |
Malignancy | 1,179 (15) | 685 (26) | 0.0001 |
Chronic obstructive pulmonary disease | 870 (11) | 565 (21) | 0.0001 |
Pulmonary disease (restrictive and obstructive) | 1,025 (13) | 663 (25) | 0.0001 |
Renal disease | 577 (8) | 223 (8) | 0.9 |
Connective tissue disease | 88 (1) | 197 (7) | 0.0001 |
Cachexia | 157 (2) | 126 (5) | 0.0001 |
Charlson comorbidity score | 1 (0–4) | 2 (0–5) | 0.0001 |
Indications for corticosteroids | |||
Relative adrenal insufficiency | - | 1,022 (39) | - |
Anti-inflammatory action | - | 1,270 (48) | - |
Immunosuppression | - | 340 (13) | - |
Types of admission | |||
Coronary care unit | 1,561 (20) | 211 (8) | 0.0001 |
Medical | 2,623 (34) | 1,168 (44) | 0.0001 |
Surgical | 3,442 (46) | 1,253 (48) | 0.1 |
Corticosteroid exposure and hospital care and intensive care
Control group (n = 7,626) | Corticosteroid exposure group (n = 2,632) |
P
| |
---|---|---|---|
Hospital and intensive care | |||
Maximal daily Sequential Organ Failure Assessment | 3 (0–9) | 4 (1–11) | 0.0001 |
Mechanical ventilation | 1,889 (25) | 765 (29) | 0.0001 |
Mechanical ventilation ≥ 96 hours | 297 (4) | 372 (14) | 0.0001 |
Tracheostomy | 124 (2) | 204 (8) | 0.0001 |
Intensive care stay (days) | 1.2 (0.2–4.6) | 1.9 (0.3–9.6) | 0.0001 |
Hospital stay (days) | 5.1 (1.3–12.4) | 6.8 (2.0–19.0) | 0.0001 |
Corticosteroid exposure | |||
Hydrocortisone | 0 | 293 (11) | |
Dexamethasone | 0 | 783 (30) | |
Methyl prednisone or prednisone | 0 | 1,556 (59) | |
Start day of corticosteroids | 0 | 0 (0–4) | |
Corticosteroid exposure time (days) | 0 | 3 (1–13) | |
Total hydrocortisone equivalent (mg) | 0 | 900 (100–6,600) | |
Concurrent medication | |||
Catecholamine infusions | 2,973 (39) | 1,291 (49) | 0.0001 |
Antibacterial antibiotics | 5,217 (68) | 2,318 (88) | 0.0001 |
Antifungal antibiotics | 419 (5) | 557 (21) | 0.0001 |
Diuretics | 4,360 (57) | 1,702 (65) | 0.0001 |
Insulin | 2,424 (32) | 1,266 (48) | 0.0001 |
Proton pump inhibitors or Histamin-2 blockade | 5,142 (67) | 2,205 (84) | 0.0001 |
Hospital diagnosis category | |||
Cardiovascular | 2,348 (31) | 790 (30) | 0.5 |
Respiratory | 1,346 (18) | 774 (29) | 0.0001 |
Neurological | 876 (11) | 440 (17) | 0.0001 |
Fluid and electrolytes abnormalities | 1,504 (20) | 694 (26) | 0.0001 |
Postoperative complications | 856 (11) | 406 (15) | 0.0001 |
Gastrointestinal | 1,023 (13) | 381 (14) | 0.2 |
Acute renal failure | 375 (5) | 265 (10) | 0.0001 |
Hospital outcome | |||
Hospital death | 327 (4) | 261 (10) | 0.0001 |
Discharge to a care facility | 1,562 (20) | 762 (29) | 0.0001 |
Corticosteroids and infectious complications and clinical outcome
Control group (n = 7,626) | Corticosteroid exposure group (n = 2,632) |
P
| |
---|---|---|---|
Microbiology | |||
Number of patients with cultures | 3,185 (42) | 1,764 (67) | 0.0001 |
Infection confirmed | 1,785 (23) | 1,215 (46) | 0.0001 |
Location of infection | n = 1,785 | n = 1,215 | |
Pulmonary | 578 (32) | 489 (40) | 0.0001 |
Abdomen | 197 (11) | 147 (12) | 0.4 |
Genital–urinary tract | 703 (39) | 425 (35) | 0.02 |
Bloodstream | 500 (28) | 376 (31) | 0.09 |
Soft tissue | 165 (9) | 90 (7) | 0.08 |
Vascular catheters | 156 (9) | 158 (13) | 0.0002 |
Skeletal | 54 (3) | 24 (2) | 0.08 |
Central nervous system | 46 (3) | 47 (4) | 0.05 |
Head and neck | 17 (1) | 21 (2) | 0.07 |
Other | 16 (1) | 9 (1) | 0.7 |
Temporal characteristics | n = 1,785 | n = 1,215 | |
Infection episode ≤ 2 days after admission | 1,228 (69) | 820 (67) | 0.5 |
Infection episode >2 days after admission | 883 (49) | 669 (55) | 0.003 |
Recurrent infectiona | 633 (35) | 521 (43) | 0.0001 |
Day of last infection episode during a hospital stay | 2 (0–13) | 3 (0–19) | 0.003 |
Interval between first and last infection episodes (days) | 0 (0–10) | 0 (0–15) | 0.0001 |
Interval between first and last infection episodes >2 days | 434 (24) | 402 (33) | 0.0001 |
Types of microorganisms (culture or microscopy) | n = 1,785 | n = 1,215 | |
Bacterial | |||
Gram-positive cocci | 1,255 (70) | 903 (74) | 0.02 |
Gram-negative bacilli | 744 (42) | 487 (40) | 0.4 |
Other types of bacillib | 299 (17) | 221 (18) | 0.3 |
Anaerobesc | 182 (10) | 112 (9) | 0.4 |
Gram-negative cocci | 66 (4) | 38 (3) | 0.4 |
Fungal | 404(23) | 508 (42) | 0.0001 |
Number of types of microorganisms per location | 1 (1–4) | 2 (1–6) | 0.0001 |
Polymicrobial infectiond | 838 (47) | 683 (56) | 0.0001 |
Wald chi-square | Odds ratio (95% confidence interval) |
P
| |
---|---|---|---|
Hospital death
a
| |||
Preadmission comorbidities | |||
Age per decade | 22 | 3.2 (1.9–5.6) | <0.0001 |
Female | 6 | 1.3 (1.0–1.5) | 0.0176 |
Malignancy | 18 | 1.7 (1.3–2.2) | <0.0001 |
Hospital and intensive care | |||
Medical admission | 112 | 3.2 (2.6–3.9) | <0.0001 |
Mechanical ventilation | 74 | 2.6 (2.1–3.2) | <0.0001 |
Maximal daily Sequential Organ Failure Assessment score >8 | 136 | 3.8 (3.0–4.8) | <0.0001 |
Corticosteroid exposure (hydrocortisone, dexamethasone, methyl prednisone or prednisone) | 11 | 1.4 (1.1–1.7) | 0.001 |
Hospital diagnosis category | |||
Acute renal failure | 81 | 3.0 (2.4–3.9) | <0.0001 |
Cardiovascular | 62 | 2.2 (1.8–2.7) | <0.0001 |
Neurological | 69 | 2.6 (2.1–3.3) | <0.0001 |
Respiratory | 16 | 1.5 (1.2–1.8) | <0.0001 |
Discharge to care facility
b
| |||
Preadmission comorbidities | |||
Age per decade | 137 | 7.9 (5.6–11.1) | <0.0001 |
Female | 19 | 1.3 (1.1–1.4) | <0.0001 |
Cerebral vascular disease | 24 | 1.6 (1.3–2.0) | <0.0001 |
Degenerative brain disease | 212 | 2.7 (2.3–3.0) | <0.0001 |
Congestive heart failure | 13 | 1.3 (1.1–1.5) | 0.00040 |
Chronic obstructive pulmonary disease | 4 | 1.1 (0.9–1.3) | 0.05880 |
Cachexia | 11 | 1.6 (1.2–2.1) | 0.00040 |
Diabetes mellitus | 6 | 1.2 (1.0–1.4) | 0.01 |
Hospital and intensive care | |||
Medical admission | 118 | 1.9 (1.7–2.1) | <0.0001 |
Corticosteroid exposure | |||
Total hydrocortisone equivalent >900 mg | 6 | 1.2 (1.0–1.4) | 0.01 |
Maximal daily Sequential Organ Failure Assessment score ≥ 4 | 21 | 1.3 (1.2–1.5) | <0.0001 |
Hospital-acquired infection | 124 | 2.2 (1.9–2.6) | <0.0001 |
Antifungal antibiotics | 10 | 1.3 (1.1–1.6) | 0.00160 |
Tracheostomy | 63 | 2.9 (2.3–3.8) | <0.0001 |
Hospital diagnosis category | |||
Neurological | 57 | 1.7 (1.5–2.0) | <0.0001 |
Respiratory | 10 | 1.2 (1.1–1.4) | 0.00200 |
Postoperative complications | 28 | 1.5 (1.3–1.7) | <0.0001 |
Fluid and electrolyte abnormalities | 13 | 1.2 (1.1–1.4) | 0.00030 |
Discussion
Infectious complications and mortality after corticosteroids
Metabolic and neuromuscular sequels of corticosteroids
Study limitations
Conclusion
Key messages
-
Corticosteroids increased the risk for death or disability in critical illness.
-
Corticosteroids exacerbated hospital-acquired infections, and metabolic and neuromuscular sequels of critical illness.
-
Careful appraisal of the indications for corticosteroids use in critical illness is necessary to balance the benefits and risks from exposure.