04047nas a2200565   4500000000100000008004100001653001100042653001100053653000900064653002400073653000900097653002200106653001600128653001100144653001500155653003000170653001800200653002700218653002800245653001800273653002900291653001500320653002700335653001300362653001900375100001700394700001700411700001800428700001300446700002000459700001700479700001400496700001800510700001900528700001800547700001700565700001500582700001900597700002200616700001700638700002500655700001600680700001900696700011000715245006900825300001200894490000800906520255300914022001403467       2018                            d10aFemale10aHumans10aAged10aDouble-Blind Method10aMale10aTreatment Outcome10aMiddle Aged10aApache10aRecurrence10aRenal Replacement Therapy10aSurvival Rate10aInfusions, Intravenous10aRespiration, Artificial10aShock, Septic10aAnti-Inflammatory Agents10aBacteremia10aChemotherapy, Adjuvant10aFungemia10aHydrocortisone1 aGlass Parisa1 aFinfer Simon1 aRhodes Andrew1 aLi Qiang1 aBellomo Rinaldo1 aVenkatesh B.1 aMyburgh J1 aPerner Anders1 aBillot Laurent1 aCorrea Maryam1 aCohen Jeremy1 aWebb Steve1 aMcArthur Colin1 aJoyce Christopher1 aArabi Yaseen1 aRajbhandari Dorrilyn1 aHarward Meg1 aThompson Kelly1 aADRENAL Trial Investigators and the Australian–New Zealand Intensive Care Society Clinical Trials Group00aAdjunctive Glucocorticoid Therapy in Patients with Septic Shock.  a797-8080 v3783 a<p><b>BACKGROUND: </b>Whether hydrocortisone reduces mortality among patients with septic shock is unclear.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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 .).</p>  a1533-4406