| 1 28‐Day all‐cause mortality |
50 |
11233 |
Risk Ratio (M‐H, Random, 95% CI) |
0.91 [0.84, 0.99] |
| 1.1 Studies reporting actual 28‐day mortality |
32 |
9387 |
Risk Ratio (M‐H, Random, 95% CI) |
0.94 [0.87, 1.00] |
| 1.2 Studies reporting short‐term mortality at other timing |
18 |
1846 |
Risk Ratio (M‐H, Random, 95% CI) |
0.71 [0.52, 0.95] |
| 2 28‐Day all‐cause mortality ‐ sensitivity analysis based on methodological quality |
38 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 2.1 Adequate generation of allocation sequence |
35 |
10076 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.93 [0.87, 0.99] |
| 2.2 Adequate allocation concealment |
34 |
9972 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.93 [0.87, 0.99] |
| 2.3 Blinded trials |
34 |
9894 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.93 [0.87, 0.99] |
| 2.4 Studies judged at low risk of bias |
17 |
7896 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.91 [0.84, 0.98] |
| 3 28‐Day all‐cause mortality by subgroups based on study drug |
47 |
11017 |
Risk Ratio (M‐H, Random, 95% CI) |
0.92 [0.84, 1.00] |
| 3.1 Hydrocortisone |
25 |
6518 |
Risk Ratio (M‐H, Random, 95% CI) |
0.94 [0.83, 1.05] |
| 3.2 Hydrocortisone plus fludrocortisone |
3 |
1564 |
Risk Ratio (M‐H, Random, 95% CI) |
0.87 [0.77, 0.98] |
| 3.3 Prednisone/Prednisolone |
5 |
1236 |
Risk Ratio (M‐H, Random, 95% CI) |
0.97 [0.71, 1.33] |
| 3.4 Methylprednisolone/Dexamethasone |
14 |
1699 |
Risk Ratio (M‐H, Random, 95% CI) |
0.81 [0.61, 1.09] |
| 4 28‐Day all‐cause mortality by subgroups based on treatment dose/duration |
44 |
10812 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.92 [0.86, 0.97] |
| 4.1 Long course of low‐dose corticosteroids |
39 |
9902 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.91 [0.86, 0.97] |
| 4.2 Short course of high‐dose corticosteroids |
5 |
910 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.96 [0.80, 1.16] |
| 5 28‐Day all‐cause mortality based on mode of drug administration |
45 |
9978 |
Risk Ratio (M‐H, Random, 95% CI) |
0.90 [0.82, 0.99] |
| 5.1 Intravenous bolus |
27 |
4749 |
Risk Ratio (M‐H, Random, 95% CI) |
0.92 [0.83, 1.02] |
| 5.2 Continuous infusion |
18 |
5229 |
Risk Ratio (M‐H, Random, 95% CI) |
0.84 [0.66, 1.07] |
| 6 28‐Day all‐cause mortality based on mode of drug termination |
47 |
10906 |
Risk Ratio (M‐H, Random, 95% CI) |
0.91 [0.83, 1.00] |
| 6.1 Without taper off |
30 |
8770 |
Risk Ratio (M‐H, Random, 95% CI) |
0.87 [0.78, 0.98] |
| 6.2 With taper off |
17 |
2136 |
Risk Ratio (M‐H, Random, 95% CI) |
1.04 [0.92, 1.18] |
| 7 28‐Day all‐cause mortality by subgroups based on age |
45 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
| 7.1 Adults |
40 |
10169 |
Risk Ratio (M‐H, Random, 95% CI) |
0.91 [0.83, 1.00] |
| 7.2 Children |
5 |
278 |
Risk Ratio (M‐H, Random, 95% CI) |
1.08 [0.56, 2.09] |
| 8 28‐Day all‐cause mortality by subgroups based on targeted population |
50 |
|
Risk Ratio (M‐H, Random, 95% CI) |
Subtotals only |
| 8.1 Sepsis |
10 |
1358 |
Risk Ratio (M‐H, Random, 95% CI) |
1.10 [0.89, 1.37] |
| 8.2 Septic shock only |
23 |
7428 |
Risk Ratio (M‐H, Random, 95% CI) |
0.91 [0.83, 1.00] |
| 8.3 Sepsis and ARDS |
4 |
311 |
Risk Ratio (M‐H, Random, 95% CI) |
0.66 [0.45, 0.98] |
| 8.4 Sepsis and community‐acquired pneumonia |
13 |
2038 |
Risk Ratio (M‐H, Random, 95% CI) |
0.71 [0.50, 1.00] |
| 9 28‐Day mortality in participants with critical illness‐related corticosteroid insufficiency |
12 |
1079 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.92 [0.82, 1.03] |
| 10 90‐Day all‐cause mortality |
7 |
5934 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.93 [0.87, 1.00] |
| 11 Long‐term mortality |
7 |
6236 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.97 [0.91, 1.03] |
| 12 Intensive care unit mortality |
18 |
7267 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.89 [0.83, 0.96] |
| 13 Hospital mortality |
26 |
8183 |
Risk Ratio (M‐H, Random, 95% CI) |
0.90 [0.82, 0.99] |
| 14 Number of participants with shock reversal at day 7 |
16 |
6711 |
Risk Ratio (M‐H, Random, 95% CI) |
1.23 [1.13, 1.34] |
| 15 Number of participants with shock reversal at 28 days |
13 |
6779 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.06 [1.03, 1.08] |
| 16 SOFA score at day 7 |
10 |
2157 |
Mean Difference (IV, Random, 95% CI) |
‐1.37 [‐1.84, ‐0.90] |
| 17 Length of intensive care unit stay for all participants |
21 |
7612 |
Mean Difference (IV, Random, 95% CI) |
‐1.07 [‐1.95, ‐0.19] |
| 18 Length of intensive care unit stay for survivors |
10 |
778 |
Mean Difference (IV, Fixed, 95% CI) |
‐2.19 [‐3.93, ‐0.46] |
| 19 Length of hospital stay for all participants |
22 |
8795 |
Mean Difference (IV, Random, 95% CI) |
‐1.63 [‐2.93, ‐0.33] |
| 20 Length of hospital stay for survivors |
9 |
710 |
Mean Difference (IV, Random, 95% CI) |
‐4.11 [‐8.50, 0.28] |
| 21 Number of participants with adverse events |
31 |
|
Risk Ratio (M‐H, Fixed, 95% CI) |
Subtotals only |
| 21.1 Gastroduodenal bleeding |
26 |
5231 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.07 [0.85, 1.35] |
| 21.2 Superinfection |
25 |
5356 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.06 [0.95, 1.19] |
| 21.3 Hyperglycaemia |
20 |
8594 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.17 [1.13, 1.22] |
| 21.4 Hypernatraemia |
6 |
5069 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.66 [1.34, 2.06] |
| 21.5 Muscle weakness |
6 |
6145 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.21 [1.01, 1.44] |
| 21.6 Neuropsychiatric event |
8 |
6941 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.86 [0.53, 1.39] |
| 21.7 Stroke |
4 |
2842 |
Risk Ratio (M‐H, Fixed, 95% CI) |
0.83 [0.41, 1.68] |
| 21.8 Cardiac event |
6 |
3567 |
Risk Ratio (M‐H, Fixed, 95% CI) |
1.12 [0.66, 1.88] |
