In adult patients with acute respiratory distress syndrome (ARDS), the beneficial effects of prone position (PP) have been well investigated and explored; it reduces intrapulmonary shunt (Qs/Qt) and enhances lung recruitment, modifying both lung ventilation (VA) and lung perfusion (Q) distribution, finally generating an improvement in VA/Q matching and reversing oxygenation impairment;it reduces right ventricular afterload, increase cardiac index in subjects with preload reserve and reverse acute cor pulmonale in severe ARDS patients, but in infants and children there is still a lack of clear evidence. Taken together, these effects explain why PP improves oxygenation, limits the occurrence of ventilator-induced lung injury and improves survival.

Prone position is simple to perform in infants and in some neonatal and pediatric intensive care units is already commonly accomplished. However, a detailed analysis of the respective effects of high PEEP and prone position is lacking in infants/children with ARDS, while these two tools may interfere and/or act coherently. A recent multicenter, retrospective analysis of patients with pediatric acute respiratory distress syndrome (PARDS) describes how patients managed with lower PEEP relative to FIO2 than recommended by the ARDSNet model had higher mortality, suggesting that future clinical trials targeting PEEP management in PARDS are needed. We designed a physiological study to investigate the physiological effects of prone positioning on lung recruitability in infants/children with acute respiratory distress syndrome.

Each patient meeting inclusion criteria will be evaluated for the presence of the oxygenation criterion. After neuromuscular paralysis (or apnoeic ventilation as per PICU protocol), and endotracheal suctioning, eligible patients will be ventilated for 30 min with PEEP = 5 cmH2O in the semi-recumbent position, with a tidal volume limited to 6 mL/kg and a Plateau Pressure less than 30 cmH2O. FiO2 will be titrated to obtain and SpO2 >92 % and <98 %. Afterward, arterial blood gas analysis (ABG) will be performed to compute PaO2/FiO2 ratio to confirm the presence of the inclusion and the absence of exclusion criteria.Patients showing PaO2/FiO2 ≤ 200 mmHg will be enrolled. Eligible patients will undergo the following protocol:

• Verify the presence of airway closure with airway opening pressure (AOP) > PEEP5cmH2O;
• PEEP will be initially set at 12 cmH2O (providing that plateau and driving pressures do not exceed 30 cmH2O and 15 cmH2O, respectively) for 40 minutes to stabilize lung volumes; afterwards, respiratory mechanics will be assessed through standard occlusions and arterial blood gases will be analyzed. Subsequently, a 4-steps decremental PEEP trial (PEEP 12 to 10 to 8 to 5 cmH2O) will be conducted. Each PEEP step will last 8 minutes, and all other ventilator settings will remain unchanged throughout the procedure. At the end of each PEEP step respiratory mechanics will be assessed by the ventilator through 1-second end-inspiratory and end-expiratory holds: plateau pressure [Pplat] and total PEEP [PEEPtot] will be measured, and driving pressure [ΔP=Pplat-PEEPtot] and respiratory system compliance [Crs = VT/ΔP] will be assessed;
• End-expiratory lung impedance (EELI) will be measured by electrical impedance tomography (EIT)

Inclusion Criteria:

• PaO2/FiO2 < 200 in the supine position, with a standard PEEP of 5 cmH2O;
• PaCO2 <45mmHg;
• Absence of history of chronic respiratory disease or heart failure or congenital heart disease (Modified Ross heart failure classification for children < II);
• Not underweight infants/children defined as a low body mass index (BMI) for age;
• Absence of any contraindication to PP (Appendix 1);
• Written informed consent of both parents and the legal guardian.

Exclusion Criteria:

• Barotrauma;
• Less than 4 weeks of age (new-born physiology);
• Exacerbation of asthma;
• Chest trauma;
• Pulmonary oedema/haemorrhage;
• Severe Neutropenia (<500 WBC/mm3);
• Haemodynamic instability (Systolic blood pressure < 5th percentile or mean arterial pressure < 5th percentile adjusted by age);
• Lactic acidosis (lactate >5 mmol/L) and/or clinically diagnosed shock;
• Metabolic Acidosis (pH <7.30 with normal- or hypo-carbia);
• Chronic kidney failure requiring dialysis before PICU admission;
• Upper gastrointestinal bleeding.
• Refusal to sign written informed consent of both parents and the legal guardian.