J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://www.jocmr.org

Original Article

Volume 13, Number 1, January 2021, pages 48-63

Optimal Upper Limits of Plateau Pressure for Patients With Acute Respiratory Distress Syndrome During the First Seven Days: A Meta-Regression Analysis

Figure 2. Univariable meta-regression analysis of the effect of plateau pressure on short-term mortality on days 1, 3 and 7. The position of each circle represents the mortality rate (y-axis) and plateau pressure (x-axis) of each study arm, and circle size is proportional to sample size. (a) Meta-regression analysis of the effect of plateau pressure on day 1 on short-term mortality, including 14 studies and 28 study arms. Mean (SD) plateau pressure was 28.1 (3.7) cm H₂O. (b) Meta-regression analysis of the effect of plateau pressure on day 3 on short-term mortality, including 11 studies and 22 study arms. Mean (SD) plateau pressure was 25.5 (3.4) cm H₂O. (c) Meta-regression analysis of the effect of plateau pressure on day 7 on short-term mortality, including 12 studies and 24 study arms. Mean (SD) plateau pressure was 25.8 (4.7) cm H₂O. SD: standard deviation.

Figure 3. Univariable meta-regression analysis of the effect of plateau pressure at selected cutoff values on day 1. The position of each circle represents the mortality rate (y-axis) and plateau pressure (x-axis) of each study arm, and circle size is proportional to sample size. (a) Meta-regression analysis of the effect of plateau pressure less than 27 cm H₂O on short-term mortality on day 1, including 10 studies and 12 study arms. Mean (SD) plateau pressure was 24.9 (1.7) cm H₂O. (b) Meta-regression of plateau pressure above 27 cm H₂O on day 1 on short-term mortality, including 12 studies and 16 arms. Mean (SD) plateau pressure was 30.6 (2.7) cm H₂O. (c) Meta-regression of plateau pressure less than 30 cm H₂O on day 1 on short-term mortality, including 11 studies and 18 arms. Mean (SD) plateau pressure was 25.8 (2.0) cm H₂O. (d) Meta-regression of plateau pressure above 30 cm H₂O on day 1 on short-term mortality, including seven studies and 10 arms. Mean (SD) plateau pressure was 32.2 (1.9) cm H₂O. (e) Meta-regression of plateau pressure less than 32 cm H₂O on day 1 on short-term mortality, including 13 studies and 22 arms. Mean (SD) plateau pressure was 26.7 (2.6) cm H₂O. (f) Meta-regression of plateau pressure above 32 cm H₂O on day 1 on short-term mortality, including five studies and six arms. Mean (SD) plateau pressure was 33.3 (1.8) cm H₂O. SD: standard deviation.

Figure 4. Univariable meta-regression of age and APACHE 2 scores at the time of admission to the ICU on short-term mortality. The position of each circle represents the mortality rate (y-axis) and plateau pressure (x-axis) of each study arm, and circle size is proportional to sample size. (a) Meta-regression of age on short-term mortality, including 14 studies and 28 arms. Mean (SD) age was 50.7 (8.5) years. (b) Meta-regression of APACHE 2 scores on short-term mortality, including eight studies and 16 arms. Mean (SD) APACHE 2 score was 20.5 (3.9). SD: standard deviation; APACHE: acute physiology and chronic health evaluation.

Table 1. Previous Study Populations and Protocols [1-4, 8, 21-29]

Author, year

Sample size (n)

Country

Inclusion criteria

Intervention

Control

Ventilator modes

Tidal volume

Airway pressure

PEEP

Ventilator modes

Tidal volume

Airway pressure

PEEP

^aPEEP > 20 cm H₂O permitted if profoundly hypoxemic. ^bP_flex: PEEP set on day 1 at the lower inflection point on the pressure-volume curve of the respiratory system. ^cARDSnet protocol. ^dRM: PCV driving pressure of 15 cm H₂O with a PEEP of 25 cm H₂O for 1 min, 35 cm H₂O for 1 min and 45 cm H₂O for 2 min. ^eRM: PCV, peak pressure between 50 and 60 cm H₂O, and PEEP 35 - 45 cm H₂O. ^fP_flux = the maximum compliance PEEP. ^gRM 40s breath-hold at 40 cm H₂O. AC: assist control; ASV: adaptive support ventilation; ARDS: acute respiratory distress syndrome; HFO: high frequency oscillation; HFOV: high frequency oscillation ventilation; IBW: ideal body weight; LIS: lung injury score; MV: minute volume; PEEP: positive end-expiratory pressure; PBW: predicted body weight; PCV: pressure control ventilation; P_peak: peak airway pressure; Pplat: plateau pressure; Pflex: pressure at the lower inflection point; PSV: pressure support ventilation; PRVC: pressure-regulated volume control; RM: recruitment management; SIMV: synchronized intermittent-mandatory ventilation; SRM: staircase recruitment management ; VCV: volume-control ventilation.

Brower et al, 1999 [21]

USA

1. PaO₂/FiO₂ ≤ 200 mm Hg

AC or SIMV/VCV

5 - 8 mL/kg IBW

P_plat ≤ 30 cm H₂O

Predetermined protocol

AC or SIMV/VCV

10 - 12 mL/kg IBW

P_plat: ≤ 45 - 55 cm H₂O

Predetermined protocol

2. Bilateral infiltrates

Titrated to FiO₂ - PEEP table

Range: 5 - 20 cm H₂O

Range: 5 - 20 cm H₂O^a

Villar et al, 2006 [22]

103

International

1. PaO₂/FiO₂ ≤ 200 mm Hg

AC/VCV

5 - 8 mL/kg PBW

P_peak ≤ 35 - 40 cm H₂O

P_flex^b + 2 cm H₂O (day1) or 13 cm H₂O

AC/VCV

9 - 11 mL/kg PBW

P_peak: ≤ 35 - 40 cm H₂O

PEEP ≥ 5 cm H₂O

2. Bilateral infiltrates

3. Meet above criteria during 24 h on standard ventilator settings

Hodgson et al, 2011 [23]

Australia

1. PaO₂/FiO₂ ≤ 200 mm Hg

PCV with SRM

< 6 mL/kg IBW

P_plat ≤ 30 cm H₂O

2.5 cm H₂O above the derecruitment point

VCV

< 6 mL/kg IBW

P_plat ≤ 30 cm H₂O

Predetermined protocol^c

2. Bilateral infiltrates

Titrated to FiO₂ - PEEP table

3. Age > 15 years old

Range: 5 - 24 cm H₂O

Agarwal et al, 2013 [24]

India

1. PaO₂/FiO₂ ≤ 200 mm Hg

ASV

%MV was set according to the initial minute ventilation attained with VCV

P_plat ≤ 35 cm H₂O

Predetermined protocol^c

VCV

< 6 mL/kg IBW

P_plat ≤ 30 - 35 cm H₂O

Predetermined protocol^c

2. Bilateral infiltrates

Titrated to FiO₂ - PEEP table

3. Acute onset dyspnea (< 7 days)

Range: 5 - 24 cm H₂O

Amato et al, 1998 [25]

Brazil

1. PaO₂/FiO₂ ≤ 200 mm Hg

Pressure-limited modes (PSV, PCV, PRVC)

< 6 mL/kg IBW

Driving pressure ≤ 20 cm H₂O

2 cm H₂O above P_flex

AC/VCV

12 mL/kg IBW

Predetermined protocol

2. Bilateral infiltrates

P_peak ≤ 40 cm H₂O

Titrated to FiO₂ - PEEP table

3. LIS ≥ 2.5

Range: 5 - 24 cm H₂O

4. One or more underlying disease processes known to be associated with ARDS

Cavalcanti et al, 2017 [1]

1,023

International

1. PaO₂/FiO₂ ≤ 200 mm Hg with PEEP of ≥ 10 cm H₂O

VCV + RM^d

4 - 6 mL/kg IBW

P_plat ≤ 30 cm H₂O

PEEP associated set with best compliance + 2 cm H₂O

VCV

4 - 6 mL/kg IBW

P_plat ≤ 30 cm H₂O

Predetermined protocol^c

2. Bilateral infiltrates

Titrated to FiO₂ - PEEP table

3. Mechanical ventilation for < 72 h prior to inclusion

Brower et al, 2004 [26]

549

USA

1. PaO₂/FiO₂ ≤ 300 mm Hg

AC/VCV

6 mL/kg IBW

P_plat ≤ 30 cm H₂O

Higher PEEP at least 12 cm H₂O

AC/VCV

6 mL/kg IBW

P_plat ≤ 30 cm H₂O

Lower PEEP at least 5 cm H₂O

2. Bilateral infiltrates

Kacmarek et al, 2016 [4]

200

USA

1. PaO₂/FiO₂ ≤ 300 mm Hg

PCV with RM^e

4 - 8 mL/kg IBW

P_plat ≤ 30 cm H₂O

3 cm H₂O above P_flex^f

VCV

4 - 8 mL/kg IBW

P_plat ≤ 30 cm H₂O

Predetermined protocol^c

2. Bilateral infiltrates

Titrated to FiO₂ - PEEP table

3. Age > 18 years old

Range: 5 - 24 cm H₂O

4. Within 48 h of meeting above criteria

Mercat et al, 2008 [27]

767

France

1. PaO₂/FiO₂ ≤ 150 mm Hg for > 12 h with PEEP of ≥ 8 cm H₂O

AC/VCV

6 mL/kg IBW

P_plat ≤ 30 cm H₂O

PEEP was kept as high as possible without increasing the maximal inspiratory P_plat above 28 to 30 cm H₂O

AC/VCV

6 mL/kg IBW

P_plat ≤ 30 cm H₂O

Between 5 and 9 cm H₂O

2. Bilateral infiltrates

3. Acute onset dyspnea (<48 h)

Esteban et al, 2000 [28]

Spain

1. PaO₂/FiO₂ ≤ 200 mm Hg

PCV

P_plat ≤ 35 cm H₂O

PEEP ≥ 5 cm H₂O

VCV

P_plat ≤ 35 cm H₂O

PEEP ≥ 5 cm H₂O

2. Bilateral infiltrates

3. One or more underlying disease processes known to be associated with ARDS

Brochard et al, 1998 [29]

106

France

1. LIS ≥ 2.5 for less than 72 h

AC/PCV

6-10 mL/kg IBW

P_peak ≤ 25 cm H₂O

The lowest PEEP which can be above 200 mm Hg of PaO₂/FiO₂ during pure oxygen before randomization

AC/VCV

10 - 15 mL/kg IBW

P_plat ≤ 60 cm H₂O

The lowest PEEP which can be above 200 mm Hg of PaO₂/FiO₂ during pure oxygen before randomization

2. Bilateral infiltrates

3. Age above 17 and below 76 years old

Meade et al, 2008 [3]

985

Canada, Australia

1. PaO₂/FiO₂ ≤ 250 mm Hg

AC/PCV with RM^g

4-8 mL/kg IBW

P_plat ≤ 40 cm H₂O

Determined by a single pressure-volume curve analysis at enrollment (Range: 5 - 24 cm H₂O)

AC/VCV

4 - 8 mL/kg IBW

P_plat ≤ 30 cm H₂O

Predetermined protocol^c

Saudi Arabia

2. Bilateral infiltrates

Titrated to FiO₂ - PEEP table

3. New respiratory symptom (< 28 days)

Range: 5 - 24 cm H₂O

ARDSnet, 2000 [8]

861

USA

1. PaO₂/FiO₂ ≤ 300 mm Hg

AC/VCV

6 mL/kg IBW (4 - 8 mL/kg IBW)

P_plat ≤ 30 cm H₂O

Predetermined protocol^c

AC/VCV

12 mL/kg IBW

P_plat ≤ 50 cm H₂O

Predetermined protocol^c

2. Bilateral infiltrates

Titrated to FiO₂ - PEEP table

3. Within 36 h of meeting above criteria

Range: 5 - 24 cm H₂O

Zhou et al, 2017 [2]

138

China

1. PaO₂/FiO₂ ≤ 250 mm Hg

APRV

Not restricted

P_high ≤ 30 cm H₂O

Minimum PEEP level to atelectasis

VCV

6 mL/kg IBW

P_plat ≤ 30 cm H₂O

Adjusted by the PEEP - FiO2 table

2. Bilateral infiltrates

3. Mechanical ventilation for < 48 h prior to inclusion

**Table 2.** Study Implementation
Author, year	Intervention comparison	Population	Tidal volume, mL/kg/PBW	Plateau pressure, cm H₂O	PEEP, cm H₂O
Data are presented as mean (SD) if there is no asterisk. ^aData are presented as median (IQR). ^bData are presented as mean (SE). ^cData are measured at 36 h after study enrollment. APACHE: acute physiology and chronic health evaluation; IQR: interquartile range; LIS: lung injury score; PBW: predicted body weight; PEEP: positive end-expiratory pressure; SAPS: simplified acute physiology score; SD: standard deviation; SE: standard error; SOFA: sequential organ failure assessment.
Brower et al, 1999 [21]	Intervention	46.9 (17.1)	LIS: 2.8 (0.5)	129 (51)	7.8 (0.4)	7.3 (0.9)	7.5 (1)	28.4 (7.7)	23.9 (5.3)	22.2 (6.1)	9.7 (3)	7.9 (4.5)	5.6 (4.2)
			APACHE 3: 90.6 (26.4)
	Control	49.8 (14.4)	LIS: 2.7 (0.5)	150 (69)	10.2 (0.7)	10 (1)	10 (0.7)	32.3 (7.3)	29 (8.2)	31.9 (10.8)	8.7 (3.5)	7.8 (4.2)	6 (4.2)
			APACHE 3: 84.6 (27.1)
Villar et al, 2006 [22]	Intervention	45.3 (26 - 62)^a	LIS: 2.9 (0.4)	-	7.3 (0.9)	7.1 (0.9)	-	30.6 (6)	28.4 (5.4)	-	14.1 (2.8)	11.2 (3.1)	-
			APACHE 2: 18 (7)
	Control	53.7 (40 - 69)^a	LIS: 2.8 (0.5)	-	10.2 (1.2)	10 (1)	-	32.6 (6.2)	32.5 (7.5)	-	9 (2.7)	8.7 (2.8)	-
			APACHE 2: 18 (6)
Hodgson et al, 2011 [23]	Intervention	60 (15.8)	APACHE 2: 20.1 (3)^b	-	-	-	-	27.6 (1.5)^b	24.2 (2.4)^b	21 (2.1)^b	15 (1)^b	12.1 (1.5)^b	8.5 (1.8)^b
			SOFA: 8.6 (0.9)^b
	Control	58 (12.6)	APACHE 2: 20.1 (3)^b	-	-	-	-	26.9 (1.4)^b	24 (2.1)^b	20 (3.4)^b	10 (0.5)^b	9.3 (1.4)^b	7.8 (2)^b
			SOFA: 8.4 (0.5)^b
Agarwal et al, 2013 [24]	Intervention	31.4 (14.9)	APACHE 2: 17 (8.9)	107.3 (41.9)	-	-	-	26.6 (8.7)	22.4 (13.2)	25.9 (11.9)	12.6 (4.9)	9.3 (4.9)	10.1 (5.5)
			SOFA: 7.4 (4)
	Control	29.7 (11.6)	APACHE 2: 17 (9.7)	96.6 (34.5)	-	-	-	26.5 (4.1)	23.3 (11.1)	24.0 (8.6)	12.1 (3.8)	9.3 (4.4)	8.1 (3.9)
			SOFA: 8.2 (4.4)
Amato et al, 1998 [25]	Intervention	33 (13)	LIS: 3.4 (0.4)	112 (10)	348 (6)^c	-	-	30.1 (0.7)^c	-	-	16.4 (0.4)^c	-	-
			APACHE 2: 28 (7)
	Control	36 (14)	LIS: 3.2 (0.4)	134 (14)	768 (13)^c	-	-	36.8 (0.9)^c	-	-	8.7 (0.4)^c	-	-
			APACHE 2: 27 (6)
Cavalcanti et al, 2017 [1]	Intervention	51.3 (17.4)	SAPS 3: 63.5 (18.1)	119 (43.5)	5.6 (1.1)	5.8 (1.6)	6.1 (1.3)	27.9 (4.5)	26.3 (5.7)	24.1 (6.1)	16.2 (3.9)	14.2 (4.2)	11.6 (4.0)
	Control	50.6 (17.4)	SAPS 3: 62.7 (18.1)	117.2 (41.9)	5.7 (0.6)	5.8 (0.5)	6.2 (1.4)	25.4 (4.5)	24.0 (5.8)	23.2 (6.0)	12.0 (3.4)	10.5 (3.7)	9.6 (3.2)
Brower et al, 2004 [26]	Intervention	54 (17)	APACHE 3: 96 33)	151 (67)	6 (0.9)	5.8 (1)	5.8 (1.2)	27 (6)	26 (7)	26 (6)	14.7 (3.5)	12.9 (4.5)	12.9 (4)
	Control	49 (17)	APACHE 3: 91 (30)	165 (77)	6.1 (0.8)	6.1 (1.1)	6.2 (1.3)	24 (7)	24 (6)	26 (8)	8.9 (3.5)	8.5 (3.7)	8.4 (4.3)
Kacmarek et al, 2016 [4]	Intervention	52.2 (15.1)	APACHE 2: 18 (10)	133.4 (43.5)	5.6 (1.1)	5.8 (1.2)	6.8 (1.5)	27.9 (3.8)	26.2 (3.9)	23.7 (6)	15.8 (3.8)	14.3 (3.9)	11.2 (4.4)
	Control	53.4 (14.5)	APACHE 2: 17 (6)	128.3 (30.5)	6.2 (0.7)	6.4 (1.1)	6.7 (1.6)	25.2 (4.6)	24.5 (5.1)	24.8 (5.9)	11.6 (2.5)	10.7 (3.3)	10.5 (3.9)
Mercat et al, 2008 [27]	Intervention	60 (16)	SAPS2: 50 (16)	144 (58)	6.1 (0.3)	6.2 (0.5)	6.8 (1.3)	27.5 (2.4)	26.5 (4.2)	24.3 (5.8)	14.6 (3.2)	13.4 (4.7)	8.9 (5.1)
	Control	60 (15)	SAPS2: 49 (16)	143 (57)	6.1 (0.4)	6.2 (0.6)	6.4 (0.9)	21.1 (4.7)	20.7 (5)	21.1 (5.6)	7.1 (1.8)	6.7 (1.8)	6.2 (2.1)
Esteban et al, 2000 [28]	Intervention	56 (17)	LIS: 2.8 (0.6)	126 (47)	8 (1.9)		8.1 (2.4)	33 (6)		34 (8)	11 (4)		10 (4)
			SAPS2: 39 (14)
	Control	54 (16)	LIS: 2.9 (0.5)	131 (48)	8 (2.5)		8.3 (2.6)	32 (5)		34 (7)	12 (4)		12 (5)
			SAPS2: 42 (17)
Brochard et al, 1998 [29]	Intervention	57 (15.3)	LIS: 3 (0.3)	144 (61)	7.1 (1.3)		7.4 (1.3)	25.7 (5)		24.5 (5.7)	10.7 (2.9)		9.6 (3)
			APACHE 2: 18 (7)
			SAPS2: 35 (12)
	Control	56.5 (15.3)	LIS: 3 (0.3)	155 (68)	10.3 (1.7)		10.7 (1.8)	31.7 (6.6)		30.5 (9.4)	10.7 (2.3)		8.5 (2.8)
			APACHE 2: 17 (8)
			SAPS2: 36 (13)
Meade et al, 2008 [3]	Intervention	54.5 (16.5)	APACHE 2: 24.8 (7.8)	144.8 (47.9)	6.8 (1.4)	6.9 (1.5)	6.9 (1.3)	30.2 (6.3)	28.6 (6)	28.8 (6.3)	15.6 (3.9)	11.8 (4.1)	10.3 (4.3)
	Control	56.9 (16.5)	APACHE 2: 25.9 (7.7)	144.6 (49.2)	6.8 (1.3)	6.7 (1.5)	7 (1.6)	24.9 (5.1)	24.7 (5.7)	25.1 (6.8)	10.1 (3)	8.8 (3)	8 (3.1)
ARDSnet, 2000 [8]	Intervention	51 (17)	APACHE 3: 81 (28)	138 (64)	6.2 (0.9)	6.2 (1.1)	6.5 (1.4)	25 (7)	26 (7)	26 (7)	9.4 (3.6)	9.2 (3.6)	8.1 (3.4)
	Control	52 (18)	APACHE 3: 84 (28)	134 (58)	11.8 (0.8)	11.8 (0.8)	11.4 (1.4)	33 (9)	34 (9)	37 (9)	8.6 (3.6)	8.6 (4.2)	9.1 (4.2)
Zhou et al, 2017 [2]	Intervention	51.5 (15)	APACHE 2: 22.0 (7.9)	121.7 (46.8)	7.3 (1.2)	7.8 (1.9)	7.4 (1.2)	22.7 (4.3)	19.3 (3.9)	18.6 (4.5)	7.0 (1.6)	6.9 (1.8)	6.5 (1.3)
	Control	52.0 (15.1)	APACHE 2: 20.2 (7.6)	138.3 (56.1)	7.2 (1.1)	7.7 (1.1)	7.5 (1.0)	24.3 (4.3)	23.3 (4.6)	23.0 (4.6)	12.0 (2.1)	10.4 (2.8)	10.3 (2.1)

Table 2. Study Implementation

Author, year

Intervention comparison

Population

Tidal volume, mL/kg/PBW

Plateau pressure, cm H₂O

PEEP, cm H₂O

Age

Severity score

PaO₂/FiO₂

Day1

Day3

Day7

Day1

Day3

Day7

Day1

Day3

Day7

Data are presented as mean (SD) if there is no asterisk. ^aData are presented as median (IQR). ^bData are presented as mean (SE). ^cData are measured at 36 h after study enrollment. APACHE: acute physiology and chronic health evaluation; IQR: interquartile range; LIS: lung injury score; PBW: predicted body weight; PEEP: positive end-expiratory pressure; SAPS: simplified acute physiology score; SD: standard deviation; SE: standard error; SOFA: sequential organ failure assessment.

Brower et al, 1999 [21]

Intervention

46.9 (17.1)

LIS: 2.8 (0.5)

129 (51)

7.8 (0.4)

7.3 (0.9)

7.5 (1)

28.4 (7.7)

23.9 (5.3)

22.2 (6.1)

9.7 (3)

7.9 (4.5)

5.6 (4.2)

APACHE 3: 90.6 (26.4)

Control

49.8 (14.4)

LIS: 2.7 (0.5)

150 (69)

10.2 (0.7)

10 (1)

10 (0.7)

32.3 (7.3)

29 (8.2)

31.9 (10.8)

8.7 (3.5)

7.8 (4.2)

6 (4.2)

APACHE 3: 84.6 (27.1)

Villar et al, 2006 [22]

Intervention

45.3 (26 - 62)^a

LIS: 2.9 (0.4)

7.3 (0.9)

7.1 (0.9)

30.6 (6)

28.4 (5.4)

14.1 (2.8)

11.2 (3.1)

APACHE 2: 18 (7)

Control

53.7 (40 - 69)^a

LIS: 2.8 (0.5)

10.2 (1.2)

10 (1)

32.6 (6.2)

32.5 (7.5)

9 (2.7)

8.7 (2.8)

APACHE 2: 18 (6)

Hodgson et al, 2011 [23]

Intervention

60 (15.8)

APACHE 2: 20.1 (3)^b

27.6 (1.5)^b

24.2 (2.4)^b

21 (2.1)^b

15 (1)^b

12.1 (1.5)^b

8.5 (1.8)^b

SOFA: 8.6 (0.9)^b

Control

58 (12.6)

APACHE 2: 20.1 (3)^b

26.9 (1.4)^b

24 (2.1)^b

20 (3.4)^b

10 (0.5)^b

9.3 (1.4)^b

7.8 (2)^b

SOFA: 8.4 (0.5)^b

Agarwal et al, 2013 [24]

Intervention

31.4 (14.9)

APACHE 2: 17 (8.9)

107.3 (41.9)

26.6 (8.7)

22.4 (13.2)

25.9 (11.9)

12.6 (4.9)

9.3 (4.9)

10.1 (5.5)

SOFA: 7.4 (4)

Control

29.7 (11.6)

APACHE 2: 17 (9.7)

96.6 (34.5)

26.5 (4.1)

23.3 (11.1)

24.0 (8.6)

12.1 (3.8)

9.3 (4.4)

8.1 (3.9)

SOFA: 8.2 (4.4)

Amato et al, 1998 [25]

Intervention

33 (13)

LIS: 3.4 (0.4)

112 (10)

348 (6)^c

30.1 (0.7)^c

16.4 (0.4)^c

APACHE 2: 28 (7)

Control

36 (14)

LIS: 3.2 (0.4)

134 (14)

768 (13)^c

36.8 (0.9)^c

8.7 (0.4)^c

APACHE 2: 27 (6)

Cavalcanti et al, 2017 [1]

Intervention

51.3 (17.4)

SAPS 3: 63.5 (18.1)

119 (43.5)

5.6 (1.1)

5.8 (1.6)

6.1 (1.3)

27.9 (4.5)

26.3 (5.7)

24.1 (6.1)

16.2 (3.9)

14.2 (4.2)

11.6 (4.0)

Control

50.6 (17.4)

SAPS 3: 62.7 (18.1)

117.2 (41.9)

5.7 (0.6)

5.8 (0.5)

6.2 (1.4)

25.4 (4.5)

24.0 (5.8)

23.2 (6.0)

12.0 (3.4)

10.5 (3.7)

9.6 (3.2)

Brower et al, 2004 [26]

Intervention

54 (17)

APACHE 3: 96 33)

151 (67)

6 (0.9)

5.8 (1)

5.8 (1.2)

27 (6)

26 (7)

26 (6)

14.7 (3.5)

12.9 (4.5)

12.9 (4)

Control

49 (17)

APACHE 3: 91 (30)

165 (77)

6.1 (0.8)

6.1 (1.1)

6.2 (1.3)

24 (7)

24 (6)

26 (8)

8.9 (3.5)

8.5 (3.7)

8.4 (4.3)

Kacmarek et al, 2016 [4]

Intervention

52.2 (15.1)

APACHE 2: 18 (10)

133.4 (43.5)

5.6 (1.1)

5.8 (1.2)

6.8 (1.5)

27.9 (3.8)

26.2 (3.9)

23.7 (6)

15.8 (3.8)

14.3 (3.9)

11.2 (4.4)

Control

53.4 (14.5)

APACHE 2: 17 (6)

128.3 (30.5)

6.2 (0.7)

6.4 (1.1)

6.7 (1.6)

25.2 (4.6)

24.5 (5.1)

24.8 (5.9)

11.6 (2.5)

10.7 (3.3)

10.5 (3.9)

Mercat et al, 2008 [27]

Intervention

60 (16)

SAPS2: 50 (16)

144 (58)

6.1 (0.3)

6.2 (0.5)

6.8 (1.3)

27.5 (2.4)

26.5 (4.2)

24.3 (5.8)

14.6 (3.2)

13.4 (4.7)

8.9 (5.1)

Control

60 (15)

SAPS2: 49 (16)

143 (57)

6.1 (0.4)

6.2 (0.6)

6.4 (0.9)

21.1 (4.7)

20.7 (5)

21.1 (5.6)

7.1 (1.8)

6.7 (1.8)

6.2 (2.1)

Esteban et al, 2000 [28]

Intervention

56 (17)

LIS: 2.8 (0.6)

126 (47)

8 (1.9)

8.1 (2.4)

33 (6)

34 (8)

11 (4)

10 (4)

SAPS2: 39 (14)

Control

54 (16)

LIS: 2.9 (0.5)

131 (48)

8 (2.5)

8.3 (2.6)

32 (5)

34 (7)

12 (4)

12 (5)

SAPS2: 42 (17)

Brochard et al, 1998 [29]

Intervention

57 (15.3)

LIS: 3 (0.3)

144 (61)

7.1 (1.3)

7.4 (1.3)

25.7 (5)

24.5 (5.7)

10.7 (2.9)

9.6 (3)

APACHE 2: 18 (7)

SAPS2: 35 (12)

Control

56.5 (15.3)

LIS: 3 (0.3)

155 (68)

10.3 (1.7)

10.7 (1.8)

31.7 (6.6)

30.5 (9.4)

10.7 (2.3)

8.5 (2.8)

APACHE 2: 17 (8)

SAPS2: 36 (13)

Meade et al, 2008 [3]

Intervention

54.5 (16.5)

APACHE 2: 24.8 (7.8)

144.8 (47.9)

6.8 (1.4)

6.9 (1.5)

6.9 (1.3)

30.2 (6.3)

28.6 (6)

28.8 (6.3)

15.6 (3.9)

11.8 (4.1)

10.3 (4.3)

Control

56.9 (16.5)

APACHE 2: 25.9 (7.7)

144.6 (49.2)

6.8 (1.3)

6.7 (1.5)

7 (1.6)

24.9 (5.1)

24.7 (5.7)

25.1 (6.8)

10.1 (3)

8.8 (3)

8 (3.1)

ARDSnet, 2000 [8]

Intervention

51 (17)

APACHE 3: 81 (28)

138 (64)

6.2 (0.9)

6.2 (1.1)

6.5 (1.4)

25 (7)

26 (7)

9.4 (3.6)

9.2 (3.6)

8.1 (3.4)

Control

52 (18)

APACHE 3: 84 (28)

134 (58)

11.8 (0.8)

11.4 (1.4)

33 (9)

34 (9)

37 (9)

8.6 (3.6)

8.6 (4.2)

9.1 (4.2)

Zhou et al, 2017 [2]

Intervention

51.5 (15)

APACHE 2: 22.0 (7.9)

121.7 (46.8)

7.3 (1.2)

7.8 (1.9)

7.4 (1.2)

22.7 (4.3)

19.3 (3.9)

18.6 (4.5)

7.0 (1.6)

6.9 (1.8)

6.5 (1.3)

Control

52.0 (15.1)

APACHE 2: 20.2 (7.6)

138.3 (56.1)

7.2 (1.1)

7.7 (1.1)

7.5 (1.0)

24.3 (4.3)

23.3 (4.6)

23.0 (4.6)

12.0 (2.1)

10.4 (2.8)

10.3 (2.1)

**Table 3.** Effect Size of Short-Term Mortality According to Plateau Pressure on Day 1, 3, and Day7 at Selected Cut-Off Values
	Total events (below cutoff)	Total (below cutoff)	Total events (over cutoff)	Total (over cutoff)	RR	95% CI	P value	I²
CI: confidential interval; RR: risk ratio.
Day 1
27 cm H₂O	805	2,003	813	1,957	0.99	0.86 to 1.13	0.88	59%
30 cm H₂O	379	1,024	378	988	1.00	0.78 to 1.28	0.99	69%
32 cm H₂O	177	540	225	529	0.77	0.66 to 0.89	0.0007	0%
Day 3
27 cm H₂O	352	966	356	930	0.96	0.72 to 1.27	0.75	76%
30 cm H₂O	151	485	196	479	0.76	0.64 to 0.90	0.002	0%
32 cm H₂O	151	485	196	479	0.76	0.64 to 0.90	0.002	0%
Day 7
27 cm H₂O	379	1,024	378	988	1.00	0.78 to 1.28	0.99	69%
30 cm H₂O	174	516	205	513	0.95	0.69 to 1.31	0.76	55%
32 cm H₂O	147	458	183	455	0.82	0.65 to 1.04	0.10	16%

Table 3. Effect Size of Short-Term Mortality According to Plateau Pressure on Day 1, 3, and Day7 at Selected Cut-Off Values

Total events (below cutoff)

Total (below cutoff)

Total events (over cutoff)

Total (over cutoff)

95% CI

P value

I²

CI: confidential interval; RR: risk ratio.

Day 1

27 cm H₂O

805

2,003

813

1,957

0.99

0.86 to 1.13

0.88

59%

30 cm H₂O

379

1,024

378

988

1.00

0.78 to 1.28

0.99

69%

32 cm H₂O

177

540

225

529

0.77

0.66 to 0.89

0.0007

Day 3

27 cm H₂O

352

966

356

930

0.96

0.72 to 1.27

0.75

76%

30 cm H₂O

151

485

196

479

0.76

0.64 to 0.90

0.002

32 cm H₂O

151

485

196

479

0.76

0.64 to 0.90

0.002

Day 7

27 cm H₂O

379

1,024

378

988

1.00

0.78 to 1.28

0.99

69%

30 cm H₂O

174

516

205

513

0.95

0.69 to 1.31

0.76

55%

32 cm H₂O

147

458

183

455

0.82

0.65 to 1.04

0.10

16%