Methylprednisolone infusion in early severe ARDS: results of a randomized controlled trial.

OBJECTIVE: To determine the effects of low-dose prolonged methylprednisolone infusion on lung function in patients with early severe ARDS.

DESIGN: Randomized, double-blind, placebo-controlled trial.

SETTING: ICUs of five hospitals in Memphis.

PARTICIPANTS: Ninety-one patients with severe early ARDS (</= 72 h), 66% with sepsis.

INTERVENTIONS: Patients were randomized (2:1 fashion) to methylprednisolone infusion (1 mg/kg/d) vs placebo. The duration of treatment was up to 28 days. Infection surveillance and avoidance of paralysis were integral components of the protocol.

MAIN OUTCOME MEASURE: The predefined primary end point was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7.

RESULTS: In intention-to-treat analysis, the response of the two groups (63 treated and 28 control) clearly diverged by day 7, with twice the proportion of treated patients achieving a 1-point reduction in LIS (69.8% vs 35.7%; p = 0.002) and breathing without assistance (53.9% vs 25.0%; p = 0.01). Treated patients had significant reduction in C-reactive protein levels, and by day 7 had lower LIS and multiple organ dysfunction syndrome scores. Treatment was associated with a reduction in the duration of mechanical ventilation (p = 0.002), ICU stay (p = 0.007), and ICU mortality (20.6% vs 42.9%; p = 0.03). Treated patients had a lower rate of infections (p = 0.0002), and infection surveillance identified 56% of nosocomial infections in patients without fever.

CONCLUSIONS: Methylprednisolone-induced down-regulation of systemic inflammation was associated with significant improvement in pulmonary and extrapulmonary organ dysfunction and reduction in duration of mechanical ventilation and ICU length of stay.