Comparison 1.

Steroids versus control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 28‐Day all‐cause mortality	27	3176	Risk Ratio (M‐H, Random, 95% CI)	0.87 [0.76, 1.00]
2 All‐cause mortality by subgroup based on mortality rate	20	2570	Risk Ratio (M‐H, Fixed, 95% CI)	0.95 [0.86, 1.06]
2.1 Studies reporting 28‐day mortality	18	1966	Risk Ratio (M‐H, Fixed, 95% CI)	0.90 [0.80, 1.00]
2.2 Studies reporting only 14‐day mortality	2	604	Risk Ratio (M‐H, Fixed, 95% CI)	1.21 [0.93, 1.59]
3 28‐Day all‐cause mortality by subgroups based on methodological quality	20		Risk Ratio (M‐H, Random, 95% CI)	Subtotals only
3.1 Adequate generation of allocation sequence	19	2342	Risk Ratio (M‐H, Random, 95% CI)	0.97 [0.86, 1.10]
3.2 Adequate allocation concealment	18	2283	Risk Ratio (M‐H, Random, 95% CI)	0.96 [0.84, 1.09]
3.3 Blinded trials	18	2259	Risk Ratio (M‐H, Random, 95% CI)	0.95 [0.84, 1.08]
4 28‐Day all‐cause mortality by subgroups based on treatment dose/duration	27		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
4.1 Long course of low‐dose corticosteroids	22	2266	Risk Ratio (M‐H, Fixed, 95% CI)	0.87 [0.78, 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 by subgroups based on targeted population	26		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
5.1 Sepsis	6	826	Risk Ratio (M‐H, Fixed, 95% CI)	1.11 [0.91, 1.34]
5.2 Septic shock only	12	1444	Risk Ratio (M‐H, Fixed, 95% CI)	0.88 [0.78, 0.99]
5.3 Sepsis and ARDS	3	114	Risk Ratio (M‐H, Fixed, 95% CI)	0.46 [0.25, 0.85]
5.4 Sepsis and community‐acquired pneumonia	5	763	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.38, 1.02]
6 28‐Day mortality in participants with critical illness‐related corticosteroid insufficiency	8	583	Risk Ratio (M‐H, Random, 95% CI)	0.88 [0.76, 1.02]
7 Intensive care unit mortality	13	1463	Risk Ratio (M‐H, Random, 95% CI)	0.82 [0.68, 1.00]
8 Hospital mortality	17	2014	Risk Ratio (M‐H, Random, 95% CI)	0.85 [0.73, 0.98]
8.1 Long course of low‐dose corticosteroids	14	1708	Risk Ratio (M‐H, Random, 95% CI)	0.91 [0.82, 1.01]
8.2 Short course of high‐dose corticosteroids	3	306	Risk Ratio (M‐H, Random, 95% CI)	0.72 [0.33, 1.60]
9 Number of participants with shock reversal at day 7	12	1561	Risk Ratio (M‐H, Random, 95% CI)	1.31 [1.14, 1.51]
9.1 Shock reversal at day 7 in trials on long course of low‐dose corticosteroids	10	1258	Risk Ratio (M‐H, Random, 95% CI)	1.34 [1.22, 1.46]
9.2 Shock reversal at day 7 in trials on short course of high‐dose corticosteroids	2	303	Risk Ratio (M‐H, Random, 95% CI)	1.07 [0.64, 1.79]
10 Number of participants with shock reversal at 28 days	7	1013	Risk Ratio (M‐H, Random, 95% CI)	1.11 [1.02, 1.21]
11 SOFA score at day 7	8	1132	Mean Difference (IV, Random, 95% CI)	‐1.53 [‐2.04, ‐1.03]
12 Length of ICU stay for all participants	12	1384	Mean Difference (IV, Random, 95% CI)	‐1.68 [‐3.27, ‐0.09]
13 Length of ICU stay for survivors	10	778	Mean Difference (IV, Fixed, 95% CI)	‐2.19 [‐3.93, ‐0.46]
14 Length of hospital stay for all participants	12	1802	Mean Difference (IV, Random, 95% CI)	‐0.97 [‐2.55, 0.61]
15 Length of hospital stay for survivors	9	710	Mean Difference (IV, Random, 95% CI)	‐4.11 [‐8.50, 0.28]
16 Number of participants with adverse events	21		Risk Ratio (M‐H, Fixed, 95% CI)	Subtotals only
16.1 Gastroduodenal bleeding	19	2382	Risk Ratio (M‐H, Fixed, 95% CI)	1.24 [0.92, 1.67]
16.2 Superinfections	19	2567	Risk Ratio (M‐H, Fixed, 95% CI)	1.02 [0.87, 1.20]
16.3 Hyperglycaemia	13	2081	Risk Ratio (M‐H, Fixed, 95% CI)	1.26 [1.16, 1.37]
16.4 Hypernatraemia	3	805	Risk Ratio (M‐H, Fixed, 95% CI)	1.64 [1.28, 2.09]
16.5 Neuromuscular weakness	3	811	Risk Ratio (M‐H, Fixed, 95% CI)	0.62 [0.21, 1.88]