Adjunctive glucocorticoid therapy in patients with septic shock

B. Venkatesh, S. Finfer, J. Cohen, D. Rajbhandari, Y. Arabi, R. Bellomo, L. Billot, M. Correa, P. Glass, M. Harward, C. Joyce, Q. Li, C. McArthur, A. Perner, A. Rhodes, K. Thompson, S. Webb, J. Myburgh

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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 languageEnglish
Pages (from-to)797-808
Number of pages12
JournalNew England Journal of Medicine
Volume378
Issue number9
DOIs
Publication statusPublished - 1 Mar 2018

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Septic Shock
Glucocorticoids
Hydrocortisone
Placebos
Artificial Respiration
Confidence Intervals
Therapeutics
Recurrence
Intensive Care Units
Mortality
Shock
Odds Ratio
Fungemia
Renal Replacement Therapy
Random Allocation
Bacteremia
Blood Transfusion
Ventilation
Biomedical Research
Cause of Death

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Venkatesh, B., Finfer, S., Cohen, J., Rajbhandari, D., Arabi, Y., Bellomo, R., ... Myburgh, J. (2018). Adjunctive glucocorticoid therapy in patients with septic shock. 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. / Adjunctive glucocorticoid therapy in patients with septic shock. In: New England Journal of Medicine. 2018 ; Vol. 378, No. 9. pp. 797-808.
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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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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 2018, 'Adjunctive glucocorticoid therapy in patients with septic shock' New England Journal of Medicine, vol. 378, no. 9, pp. 797-808. https://doi.org/10.1056/NEJMoa1705835

Adjunctive glucocorticoid therapy in patients with septic shock. / 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.

In: New England Journal of Medicine, Vol. 378, No. 9, 01.03.2018, p. 797-808.

Research output: Contribution to journalArticle

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T1 - Adjunctive glucocorticoid therapy in patients with septic shock

AU - Venkatesh, B.

AU - Finfer, S.

AU - Cohen, J.

AU - Rajbhandari, D.

AU - Arabi, Y.

AU - Bellomo, R.

AU - Billot, L.

AU - Correa, M.

AU - Glass, P.

AU - Harward, M.

AU - Joyce, C.

AU - Li, Q.

AU - McArthur, C.

AU - Perner, A.

AU - Rhodes, A.

AU - Thompson, K.

AU - Webb, S.

AU - Myburgh, J.

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.)

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Venkatesh B, Finfer S, Cohen J, Rajbhandari D, Arabi Y, Bellomo R et al. Adjunctive glucocorticoid therapy in patients with septic shock. New England Journal of Medicine. 2018 Mar 1;378(9):797-808. https://doi.org/10.1056/NEJMoa1705835