Table 1.

Study description

				Treatments
				Intervention group			Control group
Study	PaO2/FIO2 (mmHg)	Patients (centres)	Mortality time points	Aim	Ventilation strategy	Recruitment manoeuvres	Aim	Ventilation strategy
Studies investigating higher PEEP with TV reduction
Amato 1998*	< 200	53 (2)	28 days In hospital In ICU	Maintaining lung recruitment with higher PEEP, lower TV plus RMs	TV < 6 mL/kg PEEP = PFLEX + 2 cmH2O PDRIV < 20 cmH2O PPEAK < 40 cmH2O	CPAP of 35–40 cmH2O for 40s	Maintaining oxygenation, using low PEEP and high TV	TV = 12 mL/kg PEEP ≥ 5 cmH2O Stepwise PEEP titration table targeting PaO2 ≥ 80 mmHg
Villar 2006*	< 200	95 (8)	In-hospital In ICU	Maintaining oxygenation while increasing lung recruitment, with higher PEEP and lower TV	TV 5–8 mL/kg PEEP = PFLEX + 2 cmH2O	No	Maintaining oxygenation using low PEEP and high TV	TV 9–11 mL/kg PEEP ≥ 5 cmH2O
Studies investigating higher PEEP without recruitment manoeuvres
Brower 2004	< 300	549 (23)	In-hospital	Maintaining oxygenation prioritizing PEEP over FIO2 (higher PEEP levels)	TV 6 mL/kg Higher PEEP/FIO2 table	Only in first 80 patients	Maintaining oxygenation prioritizing FIO2 over PEEP (lower PEEP levels)	TV 6 mL/kg Lower PEEP/FIO2 table PPLAT < 30 cmH2O
Mercat 2008	< 300	767 (37)	28 days in-hospital	Increasing alveolar recruitment while limiting hyperinflation with higher PEEP	TV 6 mL/kg Highest PEEP resulting in PPLAT < 28––30 cmH2O	Not recommended	Minimizing alveolar distension with a moderate-low PEEP strategy	TV 6 mL/kg PEEP 5–9 cmH2O
Talmor 2008	< 300	61 (1)	28 days	Maintaining oxygenation setting PEEP based on transpulmonary pressure	TV 6 mL/kg PEEP set to achieve: End-expiratory transpulmonary pressure 0–10 cmH2O End-inspiratory transpulmonary pressure < 25 cmH2O	No	Maintaining oxygenation	TV 6 mL/kg Lower PEEP/FIO2 table PPLAT < 30 cmH2O
Studies investigating higher PEEP with recruitment manoeuvres
Meade 2008	< 250	983 (30)	28 days In-hospital In ICU	Maintaining an ‘open-lung approach’ based on oxygenation goals	TV 6 mL/kg Higher PEEP/FIO2 table PPLAT < 40 cmH2O	CPAP 40 cmH2O for 40 s	Maintaining oxygenation	TV 6 mL/kg Lower PEEP/FIO2 table PPLAT < 30 cmH2O
Huh 2009	< 200	57 (1)	28 days 60 days In ICU	Individualisation of PEEP according to compliance and oxygenation	TV 6 mL/kg PEEP set with a decremental trial at the lowest value without decrease in saturation or compliance	PEEP increased from baseline to 25 cmH2O	Maintaining oxygenation	TV 6 mL/kg Lower PEEP/FIO2 table
Hodgson 2011	< 200	20 (1)	In-hospital	Lung recruitment and individualisation of PEEP according to oxygenation	TV < 6 mL/kg Decremental PEEP until desaturation ≥1%	PEEP increased to 40 cmH2O and reduced to 15 cmH2O	Maintaining oxygenation	TV 6 mL/kg Lower PEEP/FIO2 table
Kacmarek 2016	< 200	200 (20)	28 days 60 days In-hospital In ICU	Maintaining an ‘open-lung approach’	TV 6 mL/kg Decremental PEEP to the best dynamic compliance	PPEAK 50-60 cmH2O PEEP 35–45 cmH2O	Maintaining oxygenation	TV 6 mL/kg Lower PEEP/FIO2 table
Cavalcanti 2017	< 200	1004 (120)	28 days In-hospital In ICU	Maintaining an ‘open-lung approach’	TV 6 mL/kg PEEP ≥ 11 cmH2O, set to the lowest PDRIV in a decremental titration	PPLAT ≤ 50 cmH2O PEEP increased to 35 cmH2O	Maintaining oxygenation	TV 6 mL/kg Lower PEEP/FIO2 table
Hodgson 2019	< 200		28 days 60 days In-hospital In ICU 6 months	Lung recruitment and individualisation of PEEP according to oxygenation	TV < 6 mL/kg Decremental PEEP until desaturation ≥ 2%	PEEP increased to 40 cmH2O and reduced to 15 cmH2O	Maintaining oxygenation	TV 6 mL/kg Lower PEEP/FIO2 table
Studies investigating recruitment manoeuvres alone
Xi 2010	200	110 (14)	28 days In-hospital In ICU	Maintaining lung recruitment with RMs only	TV 6–8 mL/kg Lower PEEP/FIO2 table RM performed by CPAP	CPAP of 40 cmH2O for 40s	Maintaining oxygenation	TV 6-8 mL/kg Lower PEEP/FIO2 table PPLAT < 30 cmH2O

*Excluded from the meta-analysis as the intervention group received a lower tidal volume compared to the control group

PEEP positive end-expiratory pressure, TV tidal volume, CPAP continuous positive airway pressure, P_FLEX lower inflection point, P_DRIV driving pressure, P_PEAK:peak pressure, RM, recruitment manoeuvre.