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Effects of methylprednisolone infusion on markers of inflammation, coagulation, and angiogenesis in early acute respiratory distress syndrome*

Seam, Nitin MD; Meduri, G. Umberto MD; Wang, Honghui; Nylen, Eric S. MD; Sun, Junfeng; Schultz, Marcus J. MD, PhD; Tropea, Margaret; Suffredini, Anthony F. MD, FCCM

doi: 10.1097/CCM.0b013e318232da5e
Clinical Investigations

Objective: Evaluate the effects of methylprednisolone on markers of inflammation, coagulation, and angiogenesis during early acute respiratory distress syndrome.

Design: Retrospective analysis.

Setting: Four intensive care units.

Subjects: Seventy-nine of 91 patients with available samples enrolled in a randomized, blinded controlled trial.

Interventions: Early methylprednisolone infusion (n = 55) compared with placebo (n = 24).

Measurements and Main Results: Interleukin-6, tumor necrosis factor α, vascular endothelial growth factor, protein C, procalcitonin, and proadrenomedullin were measured in archived plasma. Changes from baseline to day 3 and day 7 were compared between groups and in subgroups based on the precipitating cause of acute respiratory distress syndrome. Methylprednisolone therapy was associated with greater improvement in Lung Injury Score (p = .003), shorter duration of mechanical ventilation (p = .005), and lower intensive care unit mortality (p = .05) than control subjects. On days 3 and 7, methylprednisolone decreased interleukin-6 and increased protein C levels (all p < .0001) compared with control subjects. Proadrenomedullin levels were lower by day 3 with methylprednisolone treatment (p = .004). Methylprednisolone decreased interleukin-6 by days 3 and 7 in patients with pulmonary causes of acute respiratory distress syndrome but only at day 3 in those with extrapulmonary causes of acute respiratory distress syndrome. Protein C levels were increased with methylprednisolone on days 3 and 7 in patients with infectious and/or pulmonary causes of acute respiratory distress syndrome (all p < .0001) but not in patients with noninfectious or extrapulmonary causes of acute respiratory distress syndrome. Proadrenomedullin levels were decreased with methylprednisolone on day 3 in patients with infectious or extrapulmonary causes of acute respiratory distress syndrome (both p ≤ .008) but not in noninfectious or pulmonary acute respiratory distress syndrome. Tumor necrosis factor, vascular endothelial growth factor, and procalcitonin were elevated but not differentially affected by methylprednisolone therapy.

Conclusions: In early acute respiratory distress syndrome, administration of methylprednisolone was associated with improvement in important biomarkers of inflammation and coagulation and clinical outcomes. Biomarker changes varied with the precipitating cause of acute respiratory distress syndrome, suggesting that the underlying mechanisms and response to anti-inflammatory therapy may vary with the cause of acute respiratory distress syndrome.

From the Pulmonary Section (NS), Veterans Affairs Medical Center, Washington, DC; the Division of Pulmonary/Critical Care Medicine (GUM), University of Tennessee Health Sciences Center and Memphis Veterans Affairs Medical Center, Memphis, TN; the Critical Care Medicine Department (NS, HW, JS, MT, AFS), Clinical Center, National Institutes of Health, Bethesda, MD; the Endocrinology Section (ESN), Veterans Affairs Medical Center, Washington, DC; and the Department of Intensive Care Medicine (MJS), Academic Medical Center–University of Amsterdam, Amsterdam, The Netherlands.

* See also p. 679.

This research was supported by the Intramural Research Program of the Critical Care Medicine Department of the National Institutes of Health.

Dr. Seam, Mr. Wang, Mr. Sun, and Dr. Suffredini received funding from the National Institutes of Health. The remaining authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: nitin.seam@va.gov

© 2012 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins