The relationship between high-dose corticosteroid treatment and mortality in acute respiratory distress syndrome: a retrospective and observational study using a nationwide administrative database in Japan

Abstract

BackgroundIn the 1980s, randomized-controlled trials showed that high-dose corticosteroid treatment did not improve the mortality of acute respiratory distress syndrome (ARDS). However, while the diagnostic criteria for ARDS have since changed, and supportive therapies have been improved, no randomized-controlled trials have revisited this issue since 1987; thus, the effect of high-dose corticosteroid treatment may be different in this era. We evaluated the effect of high-dose corticosteroid treatment in patients with ARDS using a nationwide administrative database in Japan in a retrospective and observational study.MethodsThis study was performed with a large population using the 2012 Japanese nationwide administrative database (diagnostic procedure combination). We evaluated the mortality of ARDS patients receiving or not receiving high-dose corticosteroid treatment within 7 days of hospital admission. We employed propensity score weighting with a Cox proportional hazards model in order to minimize the bias associated with the retrospective collection of data on baseline characteristics and compared the mortality between the high-dose and non-high-dose corticosteroid groups.ResultsData from 2707 patients were used; 927 patients were treated with high-dose corticosteroid and 1780 patients were treated without high-dose corticosteroid, within 7 days of admission. After adjusting for confounds, mortality rates within 3 months were significantly higher in the high-dose corticosteroid group compared to the non-high-dose corticosteroid group (weighted hazard ratio: 1.59; 95% CI: 1.37-1.84; P < 0.001).ConclusionsOur results suggest that high-dose corticosteroid treatment does not improve the prognosis of patients with ARDS, even in this era. However, this study has limitations owing to its retrospective and observational design.

Prolonged low-dose methylprednisolone treatment is highly effective in reducing duration of mechanical ventilation and mortality in patients with ARDS

“…Recent experimental [ 6 ] and clinical research [ 7 , 8 ] suggest that pulse dose methylprednisolone may not be beneficial in ARDS. In an experimental study, rats with lipopolysaccharide-induced acute lung injury were exposed to graded concentrations of methylprednisolone (3 mg, 30 mg, 180 mg) for up to 14 days [ 6 ].…”

“…However, by day 7, the high-dose group had partial loss of early laboratory improvements and significantly worsen pathological scores, while the lower dose group achieved continued improvement in both pathological and laboratory variables [ 6 ]. Similarly, data from two recent retrospective studies suggests that pulse dose steroids may be harmful [ 7 , 8 ]. For example, in a retrospective comparison with low-dose methylprednisolone (0.5–1 mg/kg/day; n = 165), high-dose methylprednisolone (1000 mg/day for 3 days followed by 2 mg/kg/day) was associated with higher 60-day mortality and a 10-day reduction in ventilator-free days by day 28 [ 7 ].…”

Effect of corticosteroid therapy in the early phase of acute respiratory distress syndrome: a propensity-matched cohort study

“…A nationwide Japanese study showed that the mortality rate was higher with methylprednisolone at doses greater than 500 mg/day compared to the low-dose corticosteroid therapy [12]. It remains unclear whether the administration of low to moderate doses of corticosteroids in patients with ARDS is associated with improved outcomes.…”

Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial

“…[46] A higher mortality rate has been observed in patients with ARDS who took high-dose glucocorticoids within 7 days after hospital admission, compared with those who were treated without high-dose glucocorticoid. [47] Existing studies on ARDS have not assessed the effects of glucocorticoids in identical types of patients, or identical processes of the disease. [48] Therefore, the results for these studies cannot be considered to be congruent.…”