Chest

Chest

Volume 131, Issue 4, April 2007, Pages 954-963
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Original Research
Critical Care Medicine
Methylprednisolone Infusion in Early Severe ARDS: Results of a Randomized Controlled Trial

https://doi.org/10.1378/chest.06-2100Get rights and content

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.

Section snippets

Patients

This investigation was conducted between April 1997 and April 2002 in the medical and surgical ICUs of Baptist Memorial Medical Center and East Hospitals, the Regional Medical Center, St. Francis Hospital, University of Tennessee Bowld Medical Center, and the Veterans Affairs Medical Center, all in Memphis, TN. Each institutional review board approved the study protocol, and informed consent was obtained from patients or their legally authorized representative prior to enrollment. Adult

Results

Figure 1 shows progress through the phases of the trial. Data are reported as intention to treat for methylprednisolone vs placebo groups. Over the study period, the number of patients recruited each year was as follows: 10, 23, 25, 18, 11, and 4 patients. The baseline characteristics of each group at study entry were similar (Table 1),2526 with the exception of a higher proportion of patients with catecholamine-dependent shock in the control group. In per-protocol analysis (Web repository) the

Discussion

This is the first randomized controlled trial investigating the efficacy and safety of low-dose prolonged methylprednisolone administration in early ARDS. This study tested a pathophysiologic model that placed dysregulated systemic inflammation at the pathogenetic core of ARDS,1 and evaluated the effect of prolonged low-dose glucocorticoid treatment on biological and physiologic responses related to inflammation. The surrogate marker for pulmonary inflammation was LIS; the markers for systemic

ACKNOWLEDGMENT

This work is dedicated to the memory of our patient Sharon Johnson, a tireless source of inspiration and love. We are grateful to Drs. Scott Sinclair, Harold Dickson, and David Armbruster for critical review of the manuscript. We wish to recognize the support of our critical care colleagues and nurses at the participating hospitals who assisted with the recruitment of patients. Members of the Data Safety Monitoring Committee included Drs. Harold Dickson (Chair), Husni Dweik, Melissa Appleton,

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    • Cited by (0)

    This study was supported by the Baptist Memorial Health Care Foundation and the Assisi Foundation of Memphis.

    The authors have no conflicts of interest to disclose.

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    Copyright © 2007 The American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.