According to the results of a randomised controlled trial (RCT) reported in the journal ‘Chest’, the use of early, moderate-dose, prolonged methylprednisolone therapy successfully down-regulates systemic inflammation, reduces organ dysfunction and improves outcome of patients with severe adult respiratory distress syndrome (ARDS).
The trial involved 91 patients in the ICUs of five hospitals in the US, who had severe early ARDS (within the first 72 hours); 66% had sepsis. Participants were randomised to receive methylprednisolone infusion (n=63) or placebo (n=28) for up to 28 days. Methylprednisolone was administered as a loading dose of 1 mg/kg followed by an infusion of 1 mg/kg/d from day 1 to day 14, 0.5 mg/kg/d from day 15 to day 21, 0.25 mg/kg/d from day 22 to day 25, and 0.125 mg/kg/d from day 26 to day 28. If the patient was extubated between days 1 and 14, the patient was advanced to day 15 of drug therapy and tapered according to schedule. Once enteral intake was resumed, the methylprednisolone was converted to a single oral dose. The study’s primary endpoint was a 1-point reduction in lung injury score (LIS) or successful extubation by day 7, and the results were analysed according to the intention-to-treat principle.
The main results were as follows:
- At Day 7, 69.8% of those receiving active treatment achieved a 1-point reduction in LIS compared to 35.7% in the placebo group (p = 0.002)
- At Day 7, 53.9% of those receiving active treatment were breathing without assistance versus 25.0% of the placebo group (p = 0.01).
- Active treatment was also associated with improvements in various secondary endpoints including a reduction in the duration of mechanical ventilation (5 days versus 9.5 days; p = 0.002), ICU stay (7 days versus 14.5 days; p = 0.007), ICU mortality (20.6% versus 42.9%; p = 0.03) and a reduced rate of infections (p = 0.0002).
Chest 2007;131:954-963 (link to abstract)