Methylprednisolone Infusion in Early Severe ARDS
Meduri G et al. Chest 2007; 131:954–63.
- In patients with early ARDS, does continuous methylprednisolone compared to placebo reduce lung injury scores within 7 days?
- Randomised, controlled trial
- 2:1 block computer-generated randomisation
- Double blinded until analysis
- Multi-centre study in Memphis, USA
- April 1997 to April 2002
- Inclusion: Adults that met ARDS diagnostic criteria (American-European Consensus definition)
- Exclusion: Already on steroid therapy, or steroids contra-indicated, morbid obesity, burns, severe liver disease.
- 500 assessed of which 91 randomised
- 28 days of methylprednisolone in tapering dosage
- 1mg/kg loading dose, followed by 1 mg/kg/day for 14 days, then 0.5 mg/kg/day for 7 days, 0.25 mg/kg/day for 4 days and finally 0.123 mg/kf/day for 3 days.
- Given as continuous intravenous infusion until able to take a single oral dose daily.
- 0.9% saline or oral placebo
- Primary outcome: 1-point improvement in Lung Injury Score (LIS) was seen in 69% of those treated with methylprednisolone versus 35.7% of those who received placebo (p=0.002)
- Secondary outcomes: Mean LIS scores 2.14+/-0.12 vs 2.68+/-0.14 (p=0.004) favouring methylprednisolone. Number of patients breathing without assistance 54% vs 25% (p=0.01)
- Glucocorticoid treatment-induced down-regulation of systemic inflammation in ARDS is associated with a significant improvement in pulmonary and extrapulmonary organ dysfunction and a reduction in duration of mechanical ventilation and ICU length of stay.
- Double blinded
- Intention-to-treat analysis with only 13% drop-out (which is less than between group difference in outcome)
- Group sequential clinical trial will bias toward positive outcome
- A baseline difference between groups existed regarding “catecholamine-dependent shock”, which was twice as high in the placebo group (p=0.03). This would favour a positive outcome with the intervention, due to poorer outcomes in the placebo group.
- Open-label treatment with methylprednisolone for all non-responders at days 7–9 confuses the findings.
- Underpowered to detect statistically significant difference in mortality, which may be more clinically relevant than lung injury scores.
The Bottom Line
- Patients with ARDS should not be given early methylprednisolone based on this study alone, due to methodological concerns.