1. Study characteristics.

Study with publication year	Definition of ARDS	Inclusion criteria (PaO₂/ FIO₂)	PEEP value (high group)	PEEP value (low group)	Primary outcome	Secondary outcomes
Amato 1998	Clinical diagnosis of ARDS with LIS ≥ 2.5		Mean PEEP 16.4 ± 0.4 during first 36 hours	Mean PEEP 8.7 ± 0.4 during first 36 hours	Mortality at Day 28	Mortality before hospital discharge Barotrauma Weaning rate adjusted for APACHE II score Mortality in intensive care unit (ICU) Death after weaning of MV Nosocomial pneumonia Use of paralysing agents > 24 hours Neuropathy after extubation Dialysis required Packed red cells infused
Brower 2004	AECC	≤ 300	Mean PEEP values on Days 1 through 4 were 13.2 ± 3.5 cmH₂O	Mean PEEP values on Days 1 through 4 were 8.3 ± 3.2 cmH₂O	Mortality before hospital discharge	VFDs Days not spent in ICU Days free without organ failure Barotrauma Breathing without assistance by Day 28
Cavalcanti 2017	AECC	≤ 200	Mean PEEP 15.2 cmH₂O during first 72 hours	Mean PEEP 11.2 cmH₂O during first 72 hours	Mortality at Day 28	LOS in ICU LOS in hospital VFDs Pneumothorax requiring drainage within 7 days Barotrauma within 7 days Mortality in ICU Mortality before hospital discharge Mortality at 6 months
Hodgson 2011	AECC	≤ 200	Mean PEEP 13.5 cmH₂O during first 72 hours	Mean PEEP: 9.6 cmH₂O during first 72 hours	Measurement of plasma cytokines during first 7 days	PaO₂/FIO₂ ratio Static lung compliance LOS in ICU LOS in hospital Days of MV Mortality before hospital discharge Rescue therapies (numbers of patients) SOFA score (Day 7)
Hodgson 2019	Berlin	≤ 200	Mean PEEP 14.7 cmH₂O during first 72 hours	Mean PEEP 11 cmH₂O during first 72 hours	VFDs	Physiological outcomes: PaCO₂, PaO₂/FIO₂, PEEP, driving pressure, plateau pressure to Day 7 Clinical outcomes: mortality in the ICU, mortality before hospital discharge, mortality at Day 28, mortality at Day 90, mortality at Day 180, use of new hypoxaemic adjuvant therapies, days of MV, days of ICU, days of hospitalisation Safety outcomes: rate of barotrauma, rate of severe hypotension, new cardiac arrhythmias, desaturation, any related serious adverse events Measurement of serum biomarkers (IL‐6 and IL‐8)
Kacmarek 2016	Established ARDS	≤ 200	Mean PEEP 15 cmH₂O during first 72 hours	Mean PEEP 11.1 cmH₂O during first 72 hours	Mortality at Day 60	VFDs Barotrauma Development of extrapulmonary organ failure LOS in ICU LOS in hospital Mortality in ICU Mortality before hospital discharge
Meade 2008	AECC	≤ 250	Mean PEEP 13.7 cmH₂O during first 72 hours	Mean PEEP 9.4 cmH₂O during first 72 hours	Mortality before hospital discharge	Mortality during MV Mortality in ICU Mortality at Day 28 Barotrauma Refractory hypoxaemia Refractory acidosis Refractory barotrauma Use of rescue therapies in response to refractory hypoxaemia, refractory acidosis, or refractory barotrauma Days of MV LOS in ICU LOS in hospital
Mercat 2008	AECC	≤ 300	Mean PEEP values on Days 1 through 3 were 14 cmH₂O	Mean PEEP values on Days 1 through 3 were 6.9 cmH₂O	Mortality at Day 28	Mortality at Day 60 Mortality before hospital discharge censored on Day 60 VFDs Days free without organ failure Barotrauma between Day 1 and Day 28
Talmor 2008	AECC	≤ 300	Mean PEEP 17 ± 6 cmH₂O during first 72 hours	Mean PEEP 10 ± 4 cmH₂O during first 72 hours	Improvement in oxygenation	Indexes of lung mechanics and gas exchange (respiratory system compliance and ratio of physiological dead space to tidal volume) VFDs LOS in ICU Days not spent in ICU Mortality at Day 28 Mortality at Day 180 Days of ventilation among survivors
Villar 2006	Established ARDS	≤ 200	Mean PEEP 12.6 cmH₂O during first 72 hours	Mean PEEP 8.8 cmH₂O during first 72 hours	Mortality in ICU	Mortality before hospital discharge VFDs Extrapulmonary organ failure Barotrauma

Lung Injury Severity (LIS) score (Murray 1988): range 0 (normal) to 4 (most severe). LIS > 2.5 = ARDS.

American‐European Consensus Conference (AECC) definitions: ALI criteria: acute onset, PaO₂/FIO₂≤ 300 (regardless of PEEP level), bilateral pulmonary infiltrates and lack of evidence of left heart failure. ARDS has the same clinical characteristics as ALI, except that PaO₂/FIO₂ in ARDS is ≤ 200 (Bernard 1994).

Berlin definition: mild ARDS: 200 mmHg < PaO₂/FIO₂ ≤ 300 mmHg with PEEP or CPAP ≥ 5 cmH₂O; moderate ARDS: 100 mmHg < PaO₂/FIO₂ ≤ 200 mmHg with PEEP ≥ 5 cmH₂O; severe ARDS: PaO₂/FIO₂ ≤ 100 mmHg with PEEP ≥ 5 cmH₂O (Ranieri 2012).

Established ARDS: patients who meet ARDS criteria after 24 hours of standard ventilatory setting.