Timing, method and discontinuation of hydrocortisone administration for septic shock patients

Table 1 Univariate analysis of demographic, clinical characteristics and outcomes of the study population according to method of administration of hydrocortisone

Characteristics	Continuous infusion (n = 32)	IV bolus (n = 32)	P value
Age, median (IQR)	50 (37-64)	61 (39-70)	0.19
Male gender, n (%)	12 (37.5)	14 (51.9)	0.27
Oncologic disease, n (%)	15 (46.9)	10 (37)	0.45
Surgical patients, n (%)	25 (78.1)	17 (63)	0.2
Infection source, n (%)
Pneumonia	13 (40.6)	13 (48.1)	0.56
Ventilator associated	7 (21.8)	6 (22.2)	0.87
Health care associated	3 (9.3)	4 (12.5)	0.66
Community acquired	3 (9.3)	3 (11.1)	0.52
Abdomen	14 (43.7)	10 (37)	0.6
Soft tissue	4 (12.5)	1 (3.7)	0.23
Urinary tract	1 (3.1)	2 (7.4)	0.45
Other	0 (0)	1 (3.7)	0.27
Diabetes, n (%)	8 (25)	4 (14.8)	0.33
Acute kidney injury, n (%)	14 (43.7)	17 (63)	0.14
Baseline creatinine, mg/dL, median (IQR)	0.8 (0.7-1.4)	1.1 (0.7-1.5)	0.32
ARDS, n (%)	10 (31.2)	11 (40.7)	0.45
APACHE II score (SD)	21 ± 6	21.7 ± 5.6	0.76
SOFA score (SD)	10 ± 2.9	11 ± 2.7	0.16
Vasopressin use, n (%)	12 (37.5)	4 (14.8)	0.5
Maximum NE dose (mcg/kg per minute), median (IQR)	0.25 (0.17-0.36)	0.33 (0.20-0.39)	0.55
Hydrocortisone dose (mg/kg per day), median (IQR)	2.63 ± 0.27	2.75 ± 0.31	0.13
NE to hydrocortisone (h), median (IQR)	8 (4-19.5)	14 (8-31.5)	0.01
Time to shock reversal (h), median (IQR)	59 (47.5-90.5)	108 (63.2-189)	0.001
Shock relapse, n (%)	4 (18.2)	7 (38.9)	0.14
Hydrocortisone tapered, n (%)	10 (41.7)	13 (68.4)	0.08
Diuretic use, n (%)	19 (59.4)	11 (40.7)	0.15
New onset hypernatremia, n (%)	17 (53.1)	18 (66.7)	0.29
New onset hypokalemia, n (%)	12 (37.5)	18 (66.7)	0.02
New onset hyperglycemia, n (%)	19 (59.4)	23 (85.2)	0.03
Superinfection, n (%)	3 (9.4)	5 (18.5)	0.31
Wound dehiscence, n (%)	3 (9.4)	2 (7.4)	0.78
UGIB, n (%)	1 (3.1)	0 (0)	0.35
ICU-AW, n (%)	8 (25)	9 (33.3)	0.48
Vasopressor-free days, median (IQR)	3 (2-5)	2 (0-3.7)	0.12
ICU LOS, median (IQR)	8.5 (6-13)	9 (5-13)	0.81
30-d mortality, n (%)	10 (31.2)	15 (55.6)	0.06

APACHE II: Acute physiology and chronic health evaluation; ARDS: Acute respiratory distress syndrome; ICU-AW: Intensive care unit acquired weakness; ICU LOS: Intensive care unit length of stay; IQR: Interquartile range; NE: Norepinephrine; SOFA: Sequential Organ Failure Assessment; UGIB: Upper gastrointestinal bleeding.

Table 2 Univariate and multivariate logistic regression analysis for relevant factors associated with new-onset hyperglycemia

Variable	Univariate		P value	Multivariate	P value
	NO-H (n = 42)	No NO-H (n = 17)		Adjusted OR (95%CI)
Bolus hydrocortisone, n (%)	19 (45.2)	13 (76.5)	0.04	3.2 (0.5-26.5)	0.99
Hydrocortisone taper, n (%)	20 (64.5)	3 (27.3)	0.03	5.3 (1.8-34.5)	0.04
Diabetes, n (%)	11 (26.2)	1 (5.9)	0.08	6.2 (0.4-79.0)	0.95

Goodness-of-fit (Hosmer-Lemeshow).χ² = 0.019, P = 1.00; AUC, 0.88 (0.75-0.96), P = 0.0001. NO-H: New-onset hyperglycemia; OR: Odds ratio.

Table 3 Univariate and multivariate logistic regression analysis for relevant factors associated with new-onset hypokalemia

Variable	Univariate		P value	Multivariate	P value
	NO-HK (n = 30)	No NO-HK (n = 29)		Adjusted OR (95%CI)
Bolus hydrocortisone, n (%)	12 (40)	20 (69)	0.02	8.5 (1.2-59.9)	0.03
Hydrocortisone taper, n (%)	17 (77.3)	6 (30)	0.002	10.6 (1.5-73.3)	0.01
AKI, n (%)	13 (43.3)	18 (62.1)	0.08	0.1 (0.01-0.8)	0.03
Diuretic use, n (%)	20 (66.7)	10 (34.5)	0.01	6.3 (0.95-42.0)	0.05

Goodness-of-fit (Hosmer-Lemeshow). χ² = 5.52, P = 0.59; AUC, 0.88 (0.74-0.95), P = 0.0001. AKI: Acute kidney injury; HK: Hypokalemia; OR: Odds ratio.

Table 4 Univariate and multivariate logistic regression analysis for relevant factors associated with shock reversal

Variable	Univariate		P value	Multivariate	P value
	Shock reversal (n = 30)	No-reversal (n = 29)		Adjusted OR (95%CI)
Age (yr), SD	53 ± 16.3	50 ± 16.3	0.46
Male gender, n (%)	15 (36.6)	11 (61.1)	0.08	1.4 (0.21-10.1)	0.68
Medical disease, n (%)	11 (26.8)	6 (33.3)	0.61
Oncologic disease, n (%)	20 (48.8)	5 (27.8)	0.13	1.0 (0.18-6.3)	0.92
AKI, n (%)	17 (41.5)	14 (77.8)	0.01	0.3 (0.05-2.0)	0.23
ARDS, n (%)	12 (29.3)	9 (50)	0.12	2.7 (0.4-16.9)	0.27
Superinfection, n (%)	5 (12.2)	3 (16.7)	0.68
APACHE II score (SD)	20 ± 5.4	23 ± 6.4	0.16	1.1 (0.9-1.3)	0.18
SOFA score (SD)	10 ± 3.0	10 ± 2.4	0.69
Vasopressin use, n (%)	10 (24.4)	6 (33.3)	0.48	2.5 (0.4-15.4)	0.31
Early hydrocortisone ( ≤ 13 h from NE), n (%)	28 (68.3)	2 (11.1)	0.0001	13.8 (1.4-129)	0.02
NE dose at hydrocortisone initiation ≤ 0.28 μg/kg per minute, n (%)	28 (68.3)	2 (11.1)	0.0001	32.4 (2.7-382)	0.005

Goodness-of-fit (Hosmer-Lemeshow). χ² = 7.01, P = 0.53; AUC, 0.91 (0.80-0.96), P≤ 0.0001. AKI: Acute kidney injury: APACHE II: Acute physiology and chronic health evaluation; ARDS: Acute respiratory distress syndrome; NE: Norepinephrine; SOFA: Sequential organ failure assessment.