title: Hydrocortisone treatment in early sepsis-associated acute respiratory distress syndrome: results of a randomized controlled trial.
abstract: Authors of recent meta-analyses have reported that prolonged glucocorticoid treatment is associated with significant improvements in patients with severe pneumonia or acute respiratory distress syndrome (ARDS) of multifactorial etiology. A prospective randomized trial limited to patients with sepsis-associated ARDS is lacking. The objective of our study was to evaluate the efficacy of hydrocortisone treatment in sepsis-associated ARDS.
  
  
  
  In this double-blind, single-center (Siriraj Hospital, Bangkok), randomized, placebo-controlled trial, we recruited adult patients with severe sepsis within 12 h of their meeting ARDS criteria. Patients were randomly assigned (1:1 ratio) to receive either hydrocortisone 50 mg every 6 h or placebo. The primary endpoint was 28-day all-cause mortality; secondary endpoints included survival without organ support on day 28.
  
  
  
  Over the course of 4 years, 197 patients were randomized to either hydrocortisone (n = 98) or placebo (n = 99) and were included in this intention-to-treat analysis. The treatment group had significant improvement in the ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen and lung injury score (p = 0.01), and similar timing to removal of vital organ support (HR 0.74, 95 % CI 0.51-1.07; p = 0.107). After adjustment for significant covariates, day 28 survival was similar for the whole group (HR 0.80, 95 % CI 0.46-1.41; p = 0.44) and for the larger subgroup (n = 126) with Acute Physiology and Chronic Health Evaluation II score <25 (HR 0.57, 95 % CI 0.24-1.36; p = 0.20). With the exception of hyperglycemia (80.6 % vs. 67.7 %; p = 0.04), the rate of adverse events was similar. Hyperglycemia had no impact on outcome.
  
  
  
  In sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit.
  
  
  
  ClinicalTrials.gov identifier NCT01284452 . Registered on 18 January 2011.
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, No. 2, Prannok Road, Bangkoknoi, Bangkok, 10700, Thailand. surat_ty@yahoo.co.uk.
authors.forename: Surat
authors.identifier: 0000-0003-3772-2990
authors.initials: S
authors.lastname: Tongyoo
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, No. 2, Prannok Road, Bangkoknoi, Bangkok, 10700, Thailand.
authors.forename: Chairat
authors.initials: C
authors.lastname: Permpikul
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, No. 2, Prannok Road, Bangkoknoi, Bangkok, 10700, Thailand.
authors.forename: Wasineenart
authors.initials: W
authors.lastname: Mongkolpun
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, No. 2, Prannok Road, Bangkoknoi, Bangkok, 10700, Thailand.|Faculty of Medicine, Prince of Songkla University, Songkla, Thailand.
authors.forename: Veerapong
authors.initials: V
authors.lastname: Vattanavanit
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, No. 2, Prannok Road, Bangkoknoi, Bangkok, 10700, Thailand.
authors.forename: Suthipol
authors.initials: S
authors.lastname: Udompanturak
authors.affiliation: Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Kocak
authors.affiliation: Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Memphis Veterans Affairs Medical Center, Memphis, TN, USA.
authors.forename: G Umberto
authors.initials: GU
authors.lastname: Meduri
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001784:Blood Gas Analysis / Q000706:statistics & numerical data; D004311:Double-Blind Method; D005260:Female; D017052:Hospital Mortality; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous / Q000379:methods / Q000706:statistics & numerical data; D007362:Intensive Care Units / Q000458:organization & administration / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000209:etiology* / Q000401:mortality; D018805:Sepsis / Q000150:complications* / Q000188:drug therapy; D013785:Thailand
chemical_list: D006854:Hydrocortisone
keywords: ARDS; Glucocorticoid treatment; Hydrocortisone; Randomized trial; Septic shock; Severe sepsis