Table 3.

Baseline characteristics of study population for steroid timing and dose according to 28-day survival.

	Survived at day 28 (N = 935)	Died (N = 594)	p-value
Age	69 [61–76]	70 [62–79]	0.023
Sex			0.802
Men	572 (61.2%)	368 (62.0%)
Women	363 (38.8%)	226 (38.0%)
SOFA score (max)	11 [8–13]	14 [11–16]	< 0.001
APACHE II score	26 [19–32]	33 [25–39]	< 0.001
Infection focus*
Respiratory*	262 (28.0%)	256 (43.1%)	< 0.001
GI*	243 (26.0%)	149 (25.1%)	0.738
Hepatobiliary*	220 (23.5%)	94 (15.8%)	< 0.001
GU*	200 (21.4%)	97 (16.3%)	0.018
Others*	103 (11.0%)	95 (16.0%)	0.006
Comorbidities
Hypertension	384 (41.1%)	243 (40.9%)	0.993
Diabetes	332 (35.5%)	195 (32.8%)	0.308
Cardiac disease	125 (13.4%)	98 (16.5%)	0.106
Stroke	102 (10.9%)	70 (11.8%)	0.656
Chronic lung disease	49 (5.2%)	44 (7.4%)	0.106
Chronic renal disease	78 (8.3%)	54 (9.1%)	0.678
Chronic liver disease	124 (13.3%)	70 (11.8%)	0.443
Hematologic malignancy	106 (11.3%)	87 (14.6%)	0.069
Metastatic cancer	330 (35.3%)	238 (40.1%)	0.067
Clinical data
Lactate (nearest to initial steroid administration) (mmol/L)	4.4 [3.0–6.5]	6.5 [4.2–10.1]	< 0.001
Use of ≥ 2 types of vasopressors	683 (73.0%)	500 (84.2%)	< 0.001
Epinephrine use	47 (5.0%)	48 (8.1%)	0.021
Dopamine use	6 (0.6%)	13 (2.2%)	0.015
Vasopressin use	663 (70.9%)	463 (77.9%)	0.003
Vasopressor dose at first hydrocortisone administration
Norepinephrine-equivalent dose (µg/kg/min)**	0.300 [0.225–0.475]	0.400 [0.275–0.550]	< 0.001
Norepinephrine dose (µg/kg/min)	0.274 [0.200–0.400]	0.320 [0.200–0.439]	< 0.001
Vasopressin dose (U/min)	0.020 [0.000–0.030]	0.030 [0.000–0.040]	< 0.001
Norepinephrine-equivalent dose (µg/kg/min) as categorical variable (< 0.250 µg/kg/min, ≥ 0.250 µg/kg/min)**			< 0.001
Norepinephrine-equivalent dose < 0.250 µg/kg/min	267 (28.6%)	101 (17.0%)
Norepinephrine-equivalent dose ≥ 0.250 µg/kg/min	668 (71.4%)	493 (83.0%)
Norepinephrine-equivalent dose (µg/kg/min) as categorical variable (< 0.250 µg/kg/min, 0.250–0.500 µg/kg/min, > 0.500 µg/kg/min)**			< 0.001
Norepinephrine-equivalent dose < 0.25 µg/kg/min	267 (28.6%)	101 (17.0%)
Norepinephrine-equivalent dose 0.250–0.500 µg/kg/min	506 (54.1%)	325 (54.7%)
Norepinephrine-equivalent dose > 0.500 µg/kg/min	162 (17.3%)	168 (28.3%)
Time from first vasopressor to first hydrocortisone administration
Vasopressor to hydrocortisone time (h)	2.7 [1.2–6.0]	2.8 [1.2–6.4]	0.613
Vasopressor to hydrocortisone time as categorical variable (< 6 h, 6–12 h, > 12 h)			0.719
Vasopressor to hydrocortisone time < 6 h	698 (74.7%)	433 (72.9%)
Vasopressor to hydrocortisone time 6–12 h	149 (15.9%)	99 (16.7%)
Vasopressor to hydrocortisone time > 12 h	88 (9.4%)	62 (10.4%)
Time from ED visit to first hydrocortisone administration
ED visit to hydrocortisone time (h)	5.6 [2.9–9.4]	5.5 [2.6–9.7]	0.797
Hydrocortisone dose
Hydrocortisone dose (mg/day)	250 [200–300.0]	250 [200–300]	0.539
Hydrocortisone dose as categorical variable (< 200 mg/day, 200–300 mg/day, > 300 mg/day)			0.658
Hydrocortisone dose  < 200 mg/day	80 (8.6%)	56 (9.4%)
Hydrocortisone dose 200–300 mg/day	650 (69.5%)	400 (67.3%)
Hydrocortisone dose  > 300 mg/day	205 (21.9%)	138 (23.2%)

*Mixed infections are possible.

** Norepinephrine-equivalent dose (µg/kg/min) = Norepinephrine dose (µg/kg/min) + epinephrine dose (µg/kg/min) + 1/100 × dopamine dose (µg/kg/min) + 0.06 × phenylephrine dose (µg/kg/min) + 2.5 × vasopressin dose (U/min) + 0.0025 × angiotensin II dose (ng/kg/min) + 10 × terlipressin dose (µg/kg/min) + 0.2 × methylene blue dose (mg/kg/h) + 1/8 × metaraminol dose (µg/kg/min) + 0.02 × hydroxocobalamin dose (g) + 0.4 × midodrine dose (µg/kg/min).