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Acute hypoxemic respiratory failure (AHRF) is one of the hallmarks of acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which are caused by an inflammatory process initiated by any of a number of potential systemic and/or pulmonary insults that result in heterogeneous disruption of the capillary-pithelial interface. In these critically sick patients, optimizing the management of oxygenation is crucial. Physicians managing pediatric patients with ALI or ARDS are faced with a complex array of options influencing oxygenation. Certain treatment strategies can influence clinical outcomes, such as a lung protective ventilation strategy that specifies a low tidal volume (6 mL/kg) and a plateau pressure limit (30 cm H2O). Other strategies such as different levels of positive end expiratory pressure, altered inspiration to expiration time ratios, recruitment maneuvers, prone positioning, and extraneous gases or drugs may also affect clinical outcomes. This article reviews state-of-the-art strategies on the management of oxygenation in acute hypoxemic respiratory failure in children.