Key Point

Several weeks of methylprednisolone treatment started early in ARDS leads to faster recovery of lung function, fewer days of mechanical ventilation, and improved ICU survival.

SAN FRANCISCO—Two clinical trials have shown that extended methylprednisolone treatment benefits patients with unresolving ARDS by reducing inflammation and fibroproliferation, lung injury score, and duration of mechanical ventilation. What is less certain is whether a long course of methylprednisolone early in ARDS would provide a similar advantage.

Thus, such therapy was recently studied in a randomized controlled trial involving 91 mechanically ventilated patients with severe ARDS. "The findings of this study support our original hypothesis that down-regulation of systemic inflammation with methylprednisolone infusion hastens ARDS resolution and decreases the duration of ventilatory dependence," lead investigator G. Umberto Meduri, MD, Professor of Medicine at the University of Tennessee in Memphis, said at the latest meeting of the Society of Critical Care Medicine.¹

The patients in the study were treated intravenously for three weeks, starting within three days of ARDS onset. They initially received a methylprednisolone loading dose of 1 mg/kg followed by infusions of 1 mg/kg daily for 14 days; the dosage was then tapered to 0.5 mg/kg daily over seven days. If no significant improvement in lung injury score occurred after seven to nine days of study drug, the patient received open-label methylprednisolone at 2 mg/kg daily as described by Dr. Meduri and colleagues in 1998.²

By day 7, a 1-point reduction in lung injury score was observed in nearly 70% of methylprednisolone-treated patients but in only 37.5% of the controls.

"For almost all of the secondary outcome measures, methylprednisolone infusion effected a doubling of the incidence of desirable outcomes and a halving of undesirable ones," Dr. Meduri told Pulmonary Reviews. For example, the day 7 rates of extubation in the methylprednisolone and control groups were 53.9% and 25%, respectively.

The median time spent on the ventilator was five days in the methylprednisolone group versus 9.5 days in the control group. Respectively, the two groups had median ICU stays of seven and 14 days and median ICU survival rates of 79.4% and 57.4%.

Compared to controls, the methylprednisolone-treated patients also had a significantly reduced C-reactive protein level and lower day 7 lung injury and multiple-organ dysfunction syndrome scores. "Improvement by day 7 correlated with hospital survival," Dr. Meduri said. "[Patients] with relative adrenal insufficiency had less improvement with methylprednisolone (61% vs 82%)." With sepsis surveillance, 56% of nosocomial infections in treated patients were identified and treated in the absence of fever, a factor that likely affected the positive results of the study.

—Timothy Begany

References
1. Meduri GU, Golden E, Freire AX, et al. Methylprednisolone infusion in patients with early acute respiratory distress syndrome (ARDS) significantly improves lung function: results of a randomized controlled trial (RCT). Presented at: annual meeting of the Society of Critical Care Medicine, January 10, 2006; San Francisco, Calif.
2. Meduri GU, Headley AS, Golden E, et al. Effect of prolonged methylprednisolone therapy in unresolving acute respiratory distress syndrome: a randomized controlled trial. JAMA. 1998;280:159-165.

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