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There is a high incidence of developing acute respiratory distress syndrome (ARDS) in pediatric patients with major burns, and this development leads to higher mortality. High-frequency oscillatory ventilation (HFOV) has been used to treat pediatric patients with severe ARDS. The decision of when to start HFOV in the pediatric burn victim with ARDS is debatable. We hypothesize that earlier institution of HFOV in these patients may lead to better outcomes. A single center, retrospective chart review of pediatric burn patients with ARDS from 1996 to 2007 was completed. Daily partial pressure of oxygen in arterial blood (PaO2):fraction of inspired oxygen (FiO2) and oxygenation index was calculated for each patient. Means and SDs were compared for those treated with early (0–48 hours) institution of HFOV with those who received it late (48–72 hours). We found a trend toward improved PaO2:FiO2 and oxygenation index (OI) in the early treated group; however, this trend was not statistically significant. There was no statistically significant difference in length of stay, length of time on HFOV, or adverse events. There was, however, a trend toward more barotraumas in the late treated group. Early (within 24–36 hours of burn injury) HFOV may improve PaO2:FiO2 and OI in patients with major burns. A multicenter prospective trial is needed to have enough statistical power to answer questions of PaO2:FiO2 and OI improvement at statistically significant level, as well as to determine whether there is any overall survival benefit.