Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

Balasubramanian Venkatesh; Simon Finfer; Jeremy Cohen; Dorrilyn Rajbhandari; Yaseen Arabi; Rinaldo Bellomo; Laurent Billot; Maryam Correa; Parisa Glass; Meg Harward; Christopher Joyce; Qiang Li; Colin McArthur; Anders Perner; Andrew Rhodes; Kelly Thompson; Steve Webb; John Myburgh; ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group

doi:10.1056/nejmoa1705835

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

Balasubramanian Venkatesh, Simon Finfer, Jeremy Cohen, Dorrilyn Rajbhandari, Yaseen Arabi, Rinaldo Bellomo, Laurent Billot, Maryam Correa, Parisa Glass, Meg Harward, Christopher Joyce, Qiang Li, Colin McArthur, Anders Perner, Andrew Rhodes, Kelly Thompson, Steve Webb, John Myburgh, ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group

Department of Clinical Medicine

329 Citations (Scopus)

Abstract

BACKGROUND: Whether hydrocortisone reduces mortality among patients with septic shock is unclear. METHODS: We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. RESULTS: From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P = 0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P = 0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia. CONCLUSIONS: Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109.)

Original language	English
Journal	The New England Journal of Medicine
Volume	378
Issue number	9
Pages (from-to)	797-808
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1705835
Publication status	Published - 1 Mar 2018

Keywords

APACHE
Aged
Anti-Inflammatory Agents/adverse effects
Bacteremia/etiology
Chemotherapy, Adjuvant
Double-Blind Method
Female
Fungemia/etiology
Humans
Hydrocortisone/adverse effects
Infusions, Intravenous
Male
Middle Aged
Recurrence
Renal Replacement Therapy
Respiration, Artificial
Shock, Septic/complications
Survival Rate
Treatment Outcome

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Venkatesh, B., Finfer, S., Cohen, J., Rajbhandari, D., Arabi, Y., Bellomo, R., Billot, L., Correa, M., Glass, P., Harward, M., Joyce, C., Li, Q., McArthur, C., Perner, A., Rhodes, A., Thompson, K., Webb, S., Myburgh, J., & ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group (2018). Adjunctive Glucocorticoid Therapy in Patients with Septic Shock. The New England Journal of Medicine, 378(9), 797-808. https://doi.org/10.1056/nejmoa1705835

Venkatesh, B, Finfer, S, Cohen, J, Rajbhandari, D, Arabi, Y, Bellomo, R, Billot, L, Correa, M, Glass, P, Harward, M, Joyce, C, Li, Q, McArthur, C, Perner, A, Rhodes, A, Thompson, K, Webb, S, Myburgh, J & ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group 2018, 'Adjunctive Glucocorticoid Therapy in Patients with Septic Shock', The New England Journal of Medicine, vol. 378, no. 9, pp. 797-808. https://doi.org/10.1056/nejmoa1705835

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title = "Adjunctive Glucocorticoid Therapy in Patients with Septic Shock",

abstract = "BACKGROUND: Whether hydrocortisone reduces mortality among patients with septic shock is unclear. METHODS: We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. RESULTS: From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P = 0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P = 0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia. CONCLUSIONS: Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109.)",

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author = "Balasubramanian Venkatesh and Simon Finfer and Jeremy Cohen and Dorrilyn Rajbhandari and Yaseen Arabi and Rinaldo Bellomo and Laurent Billot and Maryam Correa and Parisa Glass and Meg Harward and Christopher Joyce and Qiang Li and Colin McArthur and Anders Perner and Andrew Rhodes and Kelly Thompson and Steve Webb and John Myburgh and {ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group}",

year = "2018",

month = mar,

day = "1",

doi = "10.1056/nejmoa1705835",

language = "English",

volume = "378",

pages = "797--808",

journal = "The New England Journal of Medicine",

issn = "0028-4793",

publisher = "Massachusetts Medical Society",

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TY - JOUR

T1 - Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

AU - Venkatesh, Balasubramanian

AU - Finfer, Simon

AU - Cohen, Jeremy

AU - Rajbhandari, Dorrilyn

AU - Arabi, Yaseen

AU - Bellomo, Rinaldo

AU - Billot, Laurent

AU - Correa, Maryam

AU - Glass, Parisa

AU - Harward, Meg

AU - Joyce, Christopher

AU - Li, Qiang

AU - McArthur, Colin

AU - Perner, Anders

AU - Rhodes, Andrew

AU - Thompson, Kelly

AU - Webb, Steve

AU - Myburgh, John

AU - ADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group

PY - 2018/3/1

Y1 - 2018/3/1

N2 - BACKGROUND: Whether hydrocortisone reduces mortality among patients with septic shock is unclear. METHODS: We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. RESULTS: From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P = 0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P = 0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia. CONCLUSIONS: Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109.)

AB - BACKGROUND: Whether hydrocortisone reduces mortality among patients with septic shock is unclear. METHODS: We randomly assigned patients with septic shock who were undergoing mechanical ventilation to receive hydrocortisone (at a dose of 200 mg per day) or placebo for 7 days or until death or discharge from the intensive care unit (ICU), whichever came first. The primary outcome was death from any cause at 90 days. RESULTS: From March 2013 through April 2017, a total of 3800 patients underwent randomization. Status with respect to the primary outcome was ascertained in 3658 patients (1832 of whom had been assigned to the hydrocortisone group and 1826 to the placebo group). At 90 days, 511 patients (27.9%) in the hydrocortisone group and 526 (28.8%) in the placebo group had died (odds ratio, 0.95; 95% confidence interval [CI], 0.82 to 1.10; P = 0.50). The effect of the trial regimen was similar in six prespecified subgroups. Patients who had been assigned to receive hydrocortisone had faster resolution of shock than those assigned to the placebo group (median duration, 3 days [interquartile range, 2 to 5] vs. 4 days [interquartile range, 2 to 9]; hazard ratio, 1.32; 95% CI, 1.23 to 1.41; P<0.001). Patients in the hydrocortisone group had a shorter duration of the initial episode of mechanical ventilation than those in the placebo group (median, 6 days [interquartile range, 3 to 18] vs. 7 days [interquartile range, 3 to 24]; hazard ratio, 1.13; 95% CI, 1.05 to 1.22; P<0.001), but taking into account episodes of recurrence of ventilation, there were no significant differences in the number of days alive and free from mechanical ventilation. Fewer patients in the hydrocortisone group than in the placebo group received a blood transfusion (37.0% vs. 41.7%; odds ratio, 0.82; 95% CI, 0.72 to 0.94; P = 0.004). There were no significant between-group differences with respect to mortality at 28 days, the rate of recurrence of shock, the number of days alive and out of the ICU, the number of days alive and out of the hospital, the recurrence of mechanical ventilation, the rate of renal-replacement therapy, and the incidence of new-onset bacteremia or fungemia. CONCLUSIONS: Among patients with septic shock undergoing mechanical ventilation, a continuous infusion of hydrocortisone did not result in lower 90-day mortality than placebo. (Funded by the National Health and Medical Research Council of Australia and others; ADRENAL ClinicalTrials.gov number, NCT01448109.)

KW - APACHE

KW - Aged

KW - Anti-Inflammatory Agents/adverse effects

KW - Bacteremia/etiology

KW - Chemotherapy, Adjuvant

KW - Double-Blind Method

KW - Female

KW - Fungemia/etiology

KW - Humans

KW - Hydrocortisone/adverse effects

KW - Infusions, Intravenous

KW - Male

KW - Middle Aged

KW - Recurrence

KW - Renal Replacement Therapy

KW - Respiration, Artificial

KW - Shock, Septic/complications

KW - Survival Rate

KW - Treatment Outcome

U2 - 10.1056/nejmoa1705835

DO - 10.1056/nejmoa1705835

M3 - Journal article

C2 - 29347874

SN - 0028-4793

VL - 378

SP - 797

EP - 808

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

IS - 9

ER -

Adjunctive Glucocorticoid Therapy in Patients with Septic Shock

Abstract

Keywords

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