Abstract
BackgroundAuthors 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.MethodsIn 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.ResultsOver 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.ConclusionsIn sepsis-associated ARDS, hydrocortisone treatment was associated with a significant improvement in pulmonary physiology, but without a significant survival benefit.Trial registrationClinicalTrials.gov identifier NCT01284452. Registered on 18 January 2011.
Highlights
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
In sepsis and ARDS, systemic inflammation is activated by the nuclear factor-κB (NF-κB) signaling system and downregulated by activated glucocorticoid receptor α (GRα) [7]
Experimental [9] and clinical research [7] shows that corticosteroid insufficiency (CIRCI) can be improved with quantitatively and temporally adequate glucocorticoid administration, and a new meta-analysis provides support for its use in ARDS of multifactorial etiology [10]
Summary
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. Acute respiratory distress syndrome (ARDS) is a secondary disease that follows—usually within 6–48 h—a primary disease of multifactorial etiology (most frequently pneumonia and extrapulmonary sepsis [1]) associated with severe systemic inflammation. In sepsis and ARDS, systemic inflammation is activated by the nuclear factor-κB (NF-κB) signaling system and downregulated by activated glucocorticoid receptor α (GRα) [7] In these patients, inadequate (endogenous glucocorticoid-activated) GRα-mediated downregulation of proinflammatory transcription factor NF-κB in circulating and tissue cells leads to higher initial levels and persistent elevation over time of plasma and bronchoalveolar lavage markers of inflammation, hemostasis, and tissue repair [7]. Experimental [9] and clinical research [7] shows that CIRCI can be improved with quantitatively and temporally adequate glucocorticoid administration, and a new meta-analysis provides support for its use in ARDS of multifactorial etiology [10]
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