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Adjunctive glucocorticoid therapy in patients with septic shock

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dc.contributor.authorVenkatesh, B.
dc.contributor.authorFinfer, S.
dc.contributor.authorCohen, J.
dc.contributor.authorRajbhandari, D.
dc.contributor.authorArabi, Y.
dc.contributor.authorBellomo, R.
dc.contributor.authorBillot, L.
dc.contributor.authorCorrea, M.
dc.contributor.authorGlass, P.
dc.contributor.authorHarward, M.
dc.contributor.authorJoyce, C.
dc.contributor.authorLi, Q.
dc.contributor.authorMcArthur, C.
dc.contributor.authorPerner, A.
dc.contributor.authorRhodes, A.
dc.contributor.authorThompson, K.
dc.contributor.authorWebb, S.
dc.contributor.authorMyburgh, J.
dc.date.issued2018
dc.description.abstractBACKGROUND 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.
dc.description.statementofresponsibilityB. 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, and J. Myburgh, for the ADRENAL Trial Investigators and the Australian, New Zealand Intensive Care Society Clinical Trials Group
dc.identifier.citationNew England Journal of Medicine, 2018; 378(9):797-808
dc.identifier.doi10.1056/NEJMoa1705835
dc.identifier.issn0028-4793
dc.identifier.issn1533-4406
dc.identifier.urihttps://hdl.handle.net/2440/135382
dc.language.isoen
dc.publisherMassachusetts Medical Society
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1004108
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1124926
dc.rightsCopyright © 2018 Massachusetts Medical Society. All rights reserved.
dc.source.urihttps://doi.org/10.1056/nejmoa1705835
dc.subjectADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group
dc.subjectHumans
dc.subjectBacteremia
dc.subjectFungemia
dc.subjectShock, Septic
dc.subjectRecurrence
dc.subjectHydrocortisone
dc.subjectAnti-Inflammatory Agents
dc.subjectTreatment Outcome
dc.subjectChemotherapy, Adjuvant
dc.subjectRespiration, Artificial
dc.subjectRenal Replacement Therapy
dc.subjectInfusions, Intravenous
dc.subjectAPACHE
dc.subjectSurvival Rate
dc.subjectDouble-Blind Method
dc.subjectAged
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectMale
dc.subject.meshHumans
dc.subject.meshBacteremia
dc.subject.meshFungemia
dc.subject.meshShock, Septic
dc.subject.meshRecurrence
dc.subject.meshHydrocortisone
dc.subject.meshAnti-Inflammatory Agents
dc.subject.meshTreatment Outcome
dc.subject.meshChemotherapy, Adjuvant
dc.subject.meshRespiration, Artificial
dc.subject.meshRenal Replacement Therapy
dc.subject.meshInfusions, Intravenous
dc.subject.meshAPACHE
dc.subject.meshSurvival Rate
dc.subject.meshDouble-Blind Method
dc.subject.meshAged
dc.subject.meshMiddle Aged
dc.subject.meshFemale
dc.subject.meshMale
dc.titleAdjunctive glucocorticoid therapy in patients with septic shock
dc.typeJournal article
pubs.publication-statusPublished

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