PROSpect: Prone and Oscillation Pediatric Clinical Trial

Inclusion criteria: Intubated and mechanically ventilated with high moderate-severe PARDS for \<48 hours per PALICC guidelines (chest imaging consistent with acute pulmonary parenchymal disease and OI ≥12 or OSI ≥10). We require two blood gases meeting moderate-severe PARDS criteria (separated by at least 4 ± 2 hours during which time the clinical team is actively working to recruit lung volume and optimize the patient's hemodynamic status per PALICC guidelines; specifically, incremental and decremental PEEP changes to optimize lung volume). A second blood gas is not required for OI ≥16. Exclusion criteria: * Perinatal related lung disease * Unrepaired congenital diaphragmatic hernia or congenital/acquired diaphragm paralysis * Respiratory failure explained by cardiac failure or fluid overload * Cyanotic heart disease * Cardiomyopathy * Unilateral lung disease * Primary pulmonary hypertension * Intubated for status asthmaticus * Obstructive airway disease (e.g., Severe airways disease without parenchymal involvement or disease characterized by hypercapnia with FiO2 \<0.30 and/or evidence of increased resistance visible on the flow - time scalar and/or presence of intrinsic PEEP) * Active air leak * Bronchiolitis obliterans * Post hematopoietic stem cell transplant; specifically, patients receiving continuous supplemental oxygen for three or more days prior to intubation; receiving noninvasive ventilation for more than 24 hours prior to intubation; receiving more than one vasoactive medication at time of meeting inclusion criteria; spending more than four days in the PICU prior to intubation; supported on or with immediate plans for renal replacement therapies; with two or more allogeneic transplants; who relapsed after the transplant; or with diffuse alveolar hemorrhage * Post lung transplant * Home ventilator dependent with baseline Oxygen Saturation Index (OSI) \>6 * Neuromuscular respiratory failure * Critical airway (e.g., post laryngotracheal surgery or new tracheostomy) or anatomical obstruction of the lower airway (e.g., mediastinal mass) * Facial surgery or trauma in previous 2 weeks * Head trauma (managed with hyperventilation) * Intracranial bleeding * Unstable spine, femur or pelvic fractures * Open abdomen * Currently receiving more than 6 consecutive hours of either prone positioning or HFOV * Supported on ECMO during the current admission * Family/medical team not providing full support (patient treatment considered futile) * Previously enrolled in current study * Enrolled in any other interventional clinical trial not approved for co-enrollment * Known pregnancy