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Double-Blind, Placebo-Controlled Pilot Randomized Trial of Methylprednisolone Infusion in Pediatric Acute Respiratory Distress Syndrome

Drago, Bonny B. MD1; Kimura, Dai MD2; Rovnaghi, Cynthia R. MS3; Schwingshackl, Andreas MD, PhD2; Rayburn, Mark PharmD4; Meduri, G. Umberto MD5; Anand, Kanwaljeet J. S. MBBS, DPhil, FAAP, FCCM, FRCPCH2

Pediatric Critical Care Medicine: March 2015 - Volume 16 - Issue 3 - p e74–e81
doi: 10.1097/PCC.0000000000000349
Online Clinical Investigations
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Objective: Low-dose methylprednisolone therapy in adults with early acute respiratory distress syndrome reduces systemic inflammation, duration of mechanical ventilation, and ICU length of stay. We report a pilot randomized trial of glucocorticoid treatment in early pediatric acute respiratory distress syndrome.

Design: Double-blind, placebo-controlled randomized clinical trial.

Setting: Le Bonheur Children’s Hospital, Memphis, TN.

Patients: Children (0–18 yr) with acute respiratory distress syndrome undergoing mechanical ventilation.

Interventions: Patients were randomly assigned to steroid or placebo groups within 72 hours of intubation. IV methylprednisolone administered as loading dose (2 mg/kg) and continuous infusions (1 mg/kg/d) on days 1–7 and then tapered over days 8–14. Both groups were ventilated according to the Acute Respiratory Distress Syndrome Network protocol modified for children. Daily surveillance was performed for adverse effects.

Measurements and Main Results: Thirty-five patients were randomized to the steroid (n = 17, no death) and placebo groups (n = 18, two deaths). No differences occurred in length of mechanical ventilation, ICU stay, hospital stay, or mortality between the two groups. At baseline, higher plateau pressures (p = 0.006) and lower Pediatric Logistic Organ Dysfunction scores (p = 0.04) occurred in the steroid group; other characteristics were similar. Despite higher plateau pressures on days 1 (p = 0.006) and 2 (p = 0.025) due to poorer lung compliance in the steroid group, they had lower PaCO2 values on days 2 (p = 0.009) and 3 (p = 0.014), higher pH values on day 2 (p = 0.018), and higher PaO2/FIO2 ratios on days 8 (p = 0.047) and 9 (p = 0.002) compared with the placebo group. Fewer patients in the steroid group required treatment for postextubation stridor (p = 0.04) or supplemental oxygen at ICU transfer (p = 0.012). Steroid therapy was not associated with detectable adverse effects.

Conclusion: This study demonstrates the feasibility of administering low-dose glucocorticoid therapy and measuring clinically relevant outcomes in pediatric acute respiratory distress syndrome. Changes in oxygenation and/or ventilation are consistent with early acute respiratory distress syndrome pathophysiology and results of similar clinical trials in adults. We propose and design a larger randomized trial to define the role of glucocorticoid therapy in pediatric acute respiratory distress syndrome.

1Prohealth Pediatrics, New York, NY.

2Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN.

3Pain Neurobiology Laboratory, University of Tennessee Health Science Center, Memphis, TN.

4Department of Clinical Pharmacy, Le Bonheur Children’s Hospital & College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN.

5Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Memphis Veterans Affairs Medical Center, Memphis, TN.

ClinicalTrials.gov number: NCT01274260.

Supported, in part, by the American Medical Association Foundation (Seed Grant Program, 2011) and Le Bonheur Children’s Foundation. The sponsors had no role in the 1) study design; 2) data collection, data analysis, or interpretation of data; 3) the writing of this article; or 4) the decision to submit the article for publication.

Dr. Anand consulted for AstraZeneca, Inc.; received support for article research from AMA Foundation and the Le Bonheur Foundation; and received royalty payments from UpToDate, Inc. and Elsevier Science Publishers. His institution received grant support from the NIH/NICHD. Dr. Drago received support for article research from the American Medical Association (AMA). Her institution received grant support from AMA seed research grant. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: kanand@uthsc.edu

©2015The Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies