DESIGN: This pilot study over April 2016 to September 2019 adopts a before-and-after comparison design of a lung-protective mechanical ventilation protocol. All admissions to the PICU were screened daily for fulfillment of the Pediatric Acute Lung Injury Consensus Conference criteria and included.

SETTING: Multidisciplinary PICU.

PATIENTS: Patients with pediatric acute respiratory distress syndrome.

INTERVENTIONS: Lung-protective mechanical ventilation protocol with elements on peak pressures, tidal volumes, end-expiratory pressure to FIO2 combinations, permissive hypercapnia, and permissive hypoxemia.

MEASUREMENTS AND MAIN RESULTS: Ventilator and blood gas data were collected for the first 7 days of pediatric acute respiratory distress syndrome and compared between the protocol (n = 63) and nonprotocol groups (n = 69). After implementation of the protocol, median tidal volume (6.4 mL/kg [5.4-7.8 mL/kg] vs 6.0 mL/kg [4.8-7.3 mL/kg]; p = 0.005), PaO2 (78.1 mm Hg [67.0-94.6 mm Hg] vs 74.5 mm Hg [59.2-91.1 mm Hg]; p = 0.001), and oxygen saturation (97% [95-99%] vs 96% [94-98%]; p = 0.007) were lower, and end-expiratory pressure (8 cm H2O [7-9 cm H2O] vs 8 cm H2O [8-10 cm H2O]; p = 0.002] and PaCO2 (44.9 mm Hg [38.8-53.1 mm Hg] vs 46.4 mm Hg [39.4-56.7 mm Hg]; p = 0.033) were higher, in keeping with lung protective measures. There was no difference in mortality (10/63 [15.9%] vs 18/69 [26.1%]; p = 0.152), ventilator-free days (16.0 [2.0-23.0] vs 19.0 [0.0-23.0]; p = 0.697), and PICU-free days (13.0 [0.0-21.0] vs 16.0 [0.0-22.0]; p = 0.233) between the protocol and nonprotocol groups. After adjusting for severity of illness, organ dysfunction and oxygenation index, the lung-protective mechanical ventilation protocol was associated with decreased mortality (adjusted hazard ratio, 0.37; 95% CI, 0.16-0.88).