Meduri

Methylprednisolone Infusion in Early Severe ARDS

Meduri G et al. Chest 2007; 131:954–63.

Clinical Question

  • In patients with early ARDS, does continuous methylprednisolone compared to placebo reduce lung injury scores within 7 days?

Design

  • Randomised, controlled trial
  • 2:1 block computer-generated randomisation
  • Double blinded until analysis

Setting

  • Multi-centre study in Memphis, USA
  • April 1997 to April 2002

Population

  • 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

Intervention

  • 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.

Control

  • 0.9% saline or oral placebo

Outcome

  • 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)

Authors’ Conclusions

  • 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.

Strengths

  • Double blinded
  • Intention-to-treat analysis with only 13% drop-out (which is less than between group difference in outcome)

Weaknesses

  • 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.

Links

Full text pdf / abstract / doi: 10.1378/chest.06-2100

Editorial, Commentaries or Blogs

Metadata

Summary author: @DuncanChambler
Summary date: May 2014
Peer-review editor: @stevemathieu75

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