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Methylprednisolone Infusion in Early Severe ARDS^*Results of a Randomized Controlled Trial

^* From the Memphis Lung Research Program (Dr. Meduri, Ms. Carson, Ms. Gibson, and Ms. Umberger), Baptist Memorial Hospital (Dr. Golden), Regional Medical Center (Dr. Freire), the Veterans Affairs Medical Center Memphis (Dr. Zaman), and St. Francis Hospital (Dr. Taylor), Memphis, TN.

Correspondence to: G. Umberto Meduri, MD, FCCP, Division of Pulmonary Division of Pulmonary, Critical Care, and Sleep Medicine, University of Tennessee Health Science Center, 956 Court Ave, Room H316, Memphis, TN 38163; e-mail: umeduri{at}utmem.edu

Abstract

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.

Key Words: ARDS • duration of mechanical ventilation • glucocorticoid treatment • infections • systemic inflammation

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