INTRODUCTION
Acute respiratory distress syndrome (ARDS) is the most challenging problem in critically ill patients, resulting in poor prognosis (1). Mechanical ventilation is one of the most significant treatment methods for patients with ARDS. The goals of mechanical ventilation are to maintain adequate gas exchange and minimize ventilator-induced lung injury (2). Reduction of mortality benefit from using small tidal volume in patients with ARDS has been established (3). However, controversy over application of open lung strategy (OLS) still exists to date. OLS that includes high positive end expiratory pressure (PEEP) and lung recruitment maneuvers (RMs) during mechanical ventilation in patients with ARDS was first depicted by Lachmann (4) in 1992. Xi et al. (5) found that the RMs were safe and useful for improving oxygenation and survival with unassisted breathing at day 28 in patients with ARDS. Briel et al. (6) investigated the association between higher versus lower PEEP levels among adult patients with acute lung injury (ALI) or ARDS and found that higher level of PEEP was associated with improved survival among patients with ARDS. However, a series of multiple-center randomized controlled trials demonstrated that OLS in patients with ALI and ARDS did not reduce mortality rate (7–9). The latest research also revealed that the OLS improved oxygenation without detrimental effects on mortality in patients with established ARDS (3). We thus systematically reviewed the current literature and performed a systematic review and meta-analysis to assess whether the OLS is associated with reducing mortality in patients with ARDS.
PATIENTS AND METHODS
The systematic review and meta-analysis was performed using the guidelines proposed by the Cochrane Collaboration in the Cochrane Handbook (10).
Study selection criteria
Patients
Patients with ARDS who received OLS during mechanical ventilation were focused in this review.
Outcomes
The primary outcome was mortality among patients with ARDS. Meanwhile, ventilator-free days, intensive care unit (ICU) length of stay (LOS), ventilator parameters and blood gas analysis after OLS, were also analyzed.
Study designs
Randomized controlled trials that compared mechanical ventilation using OLS with conventional ventilation or ventilation using other strategies for patients with ARDS were identified.
Search methods and quality assessment
Study selection
Systematic methods were used to identify relevant randomized controlled trials on OLS and compared them with conventional or other strategic ventilation methods in patients with ARDS. We identified studies by electronically searching Medline, Embase, Web of Science, and the Cochrane Central Register for Controlled Trials (CENTRAL), using search terms as: “acute lung injury,” “ALI,” “acute respiratory distress syndrome,” “ARDS,” “open lung,” “lung recruitment,” “recruitment maneuvers,” “RMs,” “positive end-expiratory pressure,” and “PEEP” updated to June 22, 2016. Reference lists from included studies were screened manually to identify potentially eligible trials. Studies were considered without date restriction. Studies with both English and Chinese languages were also identified.
Data extraction
The study data were extracted by using a standardized data collection form. Two authors independently screened the titles and abstracts of enrolled studies. Full texts were then assessed for eligibility by the two authors, to confirm disagreement in existence according to the exclusion criteria. Any disagreement was resolved by the third author through consensus.
The inclusion criteria of this meta-analysis included: patients who were definitely diagnosed with ALI or ARDS; studies that compared OLS with other strategies during mechanical ventilation; studies that provided data available to calculate relative risk (RR) or mean difference (MD) with 95% confidence interval (CI); randomized controlled trial studies.
The exclusion criteria were as follows: OLS was used in all patients to confirm its effect on ALI or ARDS, without control group; OLS was not mentioned in original papers; studies that failed to acquire final outcomes; non-adult studies; non-RCT such as reviews, letters, before and after study, case control study, and case report.
Assessment of risk for bias
We used Cochrane Collaboration Tool to assess the risk of bias for identified studies (11). The tool consisted of seven sections as follows: random sequence generation; allocation concealment; blinding of participants and personnel; blinding of outcome assessment; incomplete outcome data; selective reporting; other bias. Judgment as “low,” “unclear,” or “high” risk of bias was provided in each of the sections for each study. Studies with low risk of bias for all the sections were considered to be at low risk of bias. Studies with high risk of bias for one or more sections were considered to be at high risk of bias. Two authors independently completed the assessment.
Statistical analysis
We estimated the RR with 95% CI for dichotomous outcomes. Mean and standard deviation were used to calculate difference for continuous variables. If the included studies only reported the median, range, and size of the trials, we estimated their mean and variance by using two simple formulae (12). We conducted predefined subgroup analysis of mortality according to the population (European-American population versus Asian population) and the intervention (high positive end-expiratory pressure only vs. high positive end-expiratory pressure combined with RMs). Statistical heterogeneity across studies were tested by using I2 statistics, which is a quantitative measure for inconsistency, with suggested thresholds of 0% to 25% for zero, 25% to 50% for low, 50% to 75% for moderate, and >75% for high heterogeneity, respectively (13). Heterogeneity was assessed by using random-effects model (14). Sensitivity analysis was conducted by sequentially omitting one study each time to identify the potential influence. The potential publication bias was evaluated by using funnel plots and Egger test (15). The results were considered statistically significant at a two-sided P value less than 0.05. We performed all statistical analyses by using Review Manger 5.2 software (RevMan, The Cochrane Collaboration, Oxford, UK) and Stata 13.0 software (StataCorp, College Station, Tex).
RESULTS
A total of 458 studies from electronic bibliographic databases were identified and we removed 62 duplicate studies. After the initial evaluation of the titles and abstracts, 330 studies were excluded because they did not meet the predefined inclusion criteria. The remaining 66 studies were identified for full review and 51 studies were excluded due to inappropriate study design (n = 18), lack of relevant intervention (n = 12), inappropriate study patients (n = 11), no outcomes of interest to review (n = 9), and overlapping data (n = 1). Eventually, 15 randomized controlled trials (RCTs) (3, 5, 7–9, 16–25) that compared OLS with other strategies during mechanical ventilation among patients with ALI and ARDS were included in our meta-analysis. The flowchart for identification of relevant studies is presented in Figure 1.
;)
Fig. 1: Flow chart depicting the process of identification of the studies.
Study characteristics
Table 1 shows the design of all included studies. There were 1,563 patients in the OLS group and 1,571 patients in the control group. Nine trials (3, 7–9, 16–19, 21) were performed in European-American countries and six trials (5, 20, 22–25) were performed in Asian countries. There were nine multiple-center RCTs (3, 5, 7–9, 16, 18, 19, 21) and six single-center RCTs (17, 20, 22–25). Twelve studies enrolled patients with ARDS (3, 5, 16–25) and three studies enrolled patients with ALI or ARDS (7–9). Of all the 15 included trials, there were five performing OLS with high PEEP (8, 9, 16, 19, 22), four with RMs (5, 17, 24, 25), five with high PEEP and RMs (3, 7, 18, 20, 23), and one without elaboration (21). Mortality was the primary outcome in our meta-analysis. There were nine trials with a total of 2,834 patients reporting hospital mortality (3, 5, 7–9, 16–18, 20), while nine trials with 2,384 patients reporting 28-day mortality (3, 5, 7, 9, 18–22), six trials with 1,498 patients reporting ICU mortality (3, 5, 7, 16, 18, 20).
Table 1: Study design
The included 15 studies were published from 1998 to 2016. Acute Physiology and Chronic Health Evaluation II (APACHE II) before randomization was conducted in 13 studies (3, 5, 7, 16–25), while APACHE III were conducted in two studies (8, 17). Lung injury indices were calculated in four studies (16, 18–20), and lung compliance was tested in five studies (17, 18, 20, 22, 25). Ventilator parameters and blood gas analysis before randomization were also reported: PaO2/FiO2 in all 15 studies (3, 5, 7–9, 16–25), PaCO2 in eight studies (3, 16–18, 21–24), tidal volume in 12 studies (3, 5, 7–9, 16–18, 20–22, 24), PEEP in 12 studies (3, 5, 7, 9, 16–18, 20–24), and plateau pressure in nine studies (3, 5, 7, 9, 16–18, 22, 24). The baseline characteristics for the included studies are shown in Table 2.
Table 2: Baseline characteristics of patients in included studies
Assessment of risk for bias in included studies
The details on risk for bias are shown in Figure 2. Ten studies (3, 5, 7–9, 16–19, 21) were judged to be at low risk for bias in the random sequence generation, allocation concealment, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. One study (20) was judged to have unclear risk of bias in the random sequence generation, while three studies (20, 22, 25) were at unclear risk for bias in allocation concealment. Five studies (20, 22–25) had unclear risk of bias in blinding of participants and personnel.
Fig. 2: Risk of bias summary of all included trials.
Primary outcomes
Hospital mortality
Nine studies that included 1,409 patients from the OLS group and 1,425 patients from control group reported hospital mortality. The hospital mortality for all the included patients was 36.5%. As shown in Figure 3A, 34.4% patients from the OLS group died compared with 38.5% patients from the control group. Pooled analysis of these nine studies showed that there was significant difference in the hospital mortality among the OLS and control groups in the random-effects model (RR, 0.88; 95% CI, 0.80–0.97; P = 0.009). There was no substantial heterogeneity among the studies (chi-square = 7.62, P = 0.470, I2 = 0%).
Fig. 3: Forest plot for mortality associated with open lung strategy in acute respiratory distress syndrome.A, Hospital mortality. B, Twenty-eight-day mortality. C, ICU mortality. ICU indicates intensive care unit.
28-Day mortality
A total of nine studies that included 1,184 patients from the OLS group and 1,200 patients from the control group reported 28-day mortality. The overall 28-day mortality was 30.8%. About 28.3% patients from the OLS group died compared with 33.3% patients from the control group. Pooled analysis showed that there was significant difference in the 28-day mortality among the OLS and control groups in the random-effects model (RR, 0.83; 95% CI, 0.71–0.96; P = 0.010), with no substantial heterogeneity (chi-square = 9.52, P = 0.300, I2 = 16%) (Fig. 3B).
ICU mortality
Six studies that included 738 patients from the OLS group and 760 patients from the control group reported ICU mortality. The overall ICU mortality was 34.7%. About 31.0% patients from the OLS group died compared with 38.3% patients from the control group. Pooled analysis showed that there was significant difference in the ICU mortality between OLS and control groups in the random-effects model (RR, 0.77; 95% CI, 0.65–0.92; P = 0.003). There was no evidence for heterogeneity among the studies (chi-square = 6.14, P = 0.290, I2 = 19%). The details are shown in Figure 3C.
Subgroup analysis of mortality
As shown in Figure 4, nine studies (3, 7–9, 16–19, 21), including OLS group with 1,379 patients and control group with 1,386 patients, were enrolled to analyze mortality among the European-American population subgroup. About 34.1% patients in the OLS group died compared with 37.7% patients from the control group. There was significant difference in mortality between OLS group and control group (RR, 0.89; 95% CI, 0.80–0.99; P = 0.04), with no substantial heterogeneity (chi-square = 8.60, P = 0.38, I2 = 7%) among the European-American population. Similarly, there were three studies (5, 20, 22), including OLS group with 141 patients and control group with 142 patients, in the Asian population subgroup. Pool analysis showed that the OLS was associated with lower mortality in comparison to control group (RR 0.72, 95% CI: 0.54–0.95; P = 0.02). There was no substantial heterogeneity among the studies (chi-square = 1.72, P = 0.42, I2 = 0%) (Fig. 4).
Fig. 4: Forest plot for subgroup analysis of mortality according to populations.
As shown in Figure 5, six studies performed OLS during mechanical ventilation with high PEEP only (8, 9, 16, 17, 19, 22). About 31.2% patients from the OLS group died compared with 35.1% patients from the control group. There was no significant difference in mortality among OLS group and control group (RR, 0.83; 95% CI, 0.66–1.04; P = 0.11), with low heterogeneity (chi-square = 8.28, P = 0.14, I2 = 40%). Four studies performed OLS during mechanical ventilation with high PEEP and RMs and reported mortality (3, 7, 18, 20). About 36.2% patients from the OLS group died compared with 41.2% patients from the control group. There was significant difference in mortality between OLS group and control group (RR, 0.87; 95% CI, 0.76–0.99; P = 0.04), with no substantial heterogeneity (chi-square = 1.95, P = 0.58, I2 = 0%).
Fig. 5: Forest plot for subgroup analysis of mortality according to interventions.PEEP indicates positive end expiratory pressure; RMs, recruitment maneuvers.
Secondary outcomes
Ventilator-free days at 28-day
Four studies that included 399 patients from the OLS group and 392 patients from the control group reported ventilator-free days at 28-day, with continuous variables (5, 8, 16, 19). As shown in Figure 6, there was no significant difference among the two groups (MD; 3.32 d; 95% CI, −0.49 to 7.12; P = 0.09), with high heterogeneity (chi-square = 14.64, P = 0.002, I2 = 80%).
Fig. 6: Forest plot for ventilator-free days at 28-day and ICU length of stay associated with open lung strategy in acute respiratory distress syndrome.ICU indicates intensive care unit.
ICU length of stay
Three studies, including 141 patients from the OLS group and 142 patients from the control group, reported ICU LOS with continuous variables (5, 20, 22). There was no significant difference in ICU length of stay among the groups (MD; 1.60 d; 95% CI, −2.99 to 6.20; P = 0.49), with low heterogeneity (chi-square = 3.57, P = 0.17, I2 = 44%) (Fig. 6).
Parameters for mechanical ventilation and blood gas analysis
The results from parameters of mechanical ventilation and blood gas analysis on Day 1, Day 3, and Day 7 after randomization are presented in Table 3. There was no substantial evidence for heterogeneity among the studies as regards to PaO2/FiO2 on Day 7 (chi-square = 2.90, P = 0.57, I2 = 0%), PaCO2 on Day 3 (chi-square = 6.82, P = 0.34, I2 = 12%) and Day 7 (chi-square = 1.20, P = 0.75, I2 = 0%), compliance on Day 1 (chi-square = 0.62, P = 0.73, I2 = 0%) and Day 3 (chi-square = 0.39, P = 0.82, I2 = 0%). There was also moderate to high evidence for heterogeneity among the studies in the remaining parameters. Sensitivity analysis was performed for each outcome by omitting one study from the sequence and results were still similar, indicating a low degree of stability in these outcomes.
Table 3: Pooled analysis of ventilator parameters and blood gas analysis
Publication bias
As shown in Figure 7, we did not detect the evidence of publication bias for RR of mortality by funnel plots and Egger test (P = 0.929).
Fig. 7: Assessment of publication bias by using funnel plot and Egger test. A, Funnel plot. B, Egger test.
DISCUSSION
Key findings
An overall literature search was performed in our systematic review, without restriction for language or publication date, to lower the risk of missing important studies as much as possible. We included studies designed with randomized controlled trials to compare the effect of OLS with other strategies during mechanical ventilation among patients with ALI or ARDS. The meta-analysis showed significant effect of OLS during mechanical ventilation in hospital, 28-day, and ICU mortality. Subgroup analysis revealed that the OLS in European-American population and Asian population patients with ARDS were both associated with reduction of mortality. Moreover, the subgroup analysis also revealed that the OLS was associated with reduction of mortality when using high PEEP combined with RMs. However, the meta-analysis failed to demonstrate that the OLS was associated with reduction on ventilator-free days at 28-day and ICU length of stay.
Comparison with previous studies
There were a few systematical review and meta-analysis studies that evaluated the effect of high PEEP during mechanical ventilation in patients with ALI and ARDS (26–33). We compared findings from our study with these studies in Table 4. Five meta-analysis studies (26–28, 31, 33) demonstrated that high PEEP was associated with reduction of mortality, while three meta-analysis studies (29, 30, 32) showed that high PEEP was not associated with a survival benefit. There were, however, some problems in these studies. First, of all the eight studies, seven of them compared high PEEP rather than OLS with conventional strategy on mortality among patients with ALI or ARDS (26–32). The latest meta-analysis (33) evaluated the effects of 26 mechanical ventilation strategy on mortality, not referring to OLS. Second, all the studies did not include the latest RCT (3) and seven studies included less than 10 RCTs. Meanwhile, two studies (26, 27) included the same RCTs as the other two studies (29–31).
Table 4: Comparison of our study with relevant studies
For comparison, our systematic review and meta-analysis included 15 RCTs with more than 3,000 patients with ALI or ARDS. We included all the RCT studies that implemented OLS during mechanical ventilation and accurately represented the efficacy of OLS among the patients with ALI or ARDS.
Clinical implications
The American-European Consensus Conference (AECC) published ARDS definition in 1994 (34). The AECC defined ARDS as acute onset of hypoxemia with bilateral infiltrates on frontal chest radiograph and without evidence of left atrial hypertension. They also defined acute lung injury using almost the same criteria but less severe hypoxemia. However, a series of issues about AECC definition have emerged. Berlin definition published in 2012 contained four aspects: timing: within 1 week of a known clinical insult or new or worsening respiratory symptoms; chest imaging: bilateral opacities, not fully explained by effusions, lobar/lung collapse, or nodules; origin of edema: respiratory failure not fully explained by cardiac failure or fluid overload, and need objective assessment to exclude hydrostatic edema if no risk factor present; oxygenation: mild: 200 mm Hg<PaO2/FiO2≤300 mm Hg with PEEP or continuous positive airway pressure ≥5 cm H2O; moderate: 100 mm Hg<PaO2/FiO2≤200 mm Hg with PEEP ≥5 cm H2O; severe: PaO2/FiO2≤100 mm Hg with PEEP≥5 cm H2O (35). According to the Berlin definition, the ALI terminology is not used anymore, while mild, moderate, and severe ARDS terminology are used. ALI is classified as mild ARDS in the Berlin definition. We therefore still included studies that enrolled patients with acute lung injury in our study, to clearly know the responsiveness of patients with different degrees of ARDS to OLS treatment. When the ARDS occurs, lungs with extensive collapse need higher pressures to ventilate them (36). We in our study also found that the high PEEP combined with RMs can reduce mortality, while application of high PEEP alone cannot reduce mortality, suggesting that a certain positive end-expiratory pressure and sufficient pressure are both of importance in opening the collapsing alveoli. One possible scenario, however, is that the OLS may overstretch already open lung units, amplifying tensions at the borders of closed and open lung units (36). One of the outcomes of excessive expansion of the alveoli is barotrauma, which includes pneumothorax, pneumomediastinum, or subcutaneous emphysema. Of 15 included studies in this analysis, there were five described barotrauma, all with less than 10% incidences. It is therefore essential to perform multicenter trials by using more proper RMs and PEEP to evaluate the effect of OLS in patients with ARDS.
Our systematical review and meta-analysis included only RCTs. This is the first one to evaluate the effect of OLS during mechanical ventilation in patients with ALI or ARDS. We conducted an exhaustive literature search and included studies in both English and Chinese languages. A total of 15 RCTs with more than 3,000 patients were performed across Asia, America, and Oceania. We performed predefined subgroup analysis according to the population and also performed predefined subgroup analysis according to the intervention. The subgroup analysis may help clinicians make decision when they encounter patients with ALI or ARDS. Two authors independently assessed the risk for bias and performed statistical analysis.
Limitations
There were, however, some limitations in the present study. First, although the 15 studies were included in the present systematic review and meta-analysis, three of the included studies failed to provide data on mortality, which was the main outcome in this study. Second, of all the included studies, there were seven studies enrolling patient cases fewer than 60, hence there was potential evidence for heterogeneity in the outcomes. Third, we performed meta-analysis to assess the effect of overall OLS rather than specific methods on mortality, which may lead to a potential bias; hence we performed the subgroup analysis to avoid this bias. Fourth, because of different definitions of barotrauma in the included studies, we did not analyze the effect of OLS on barotrauma, which is one of the most common complications of OLS. The results from the analysis of barotrauma may yield a higher risk of bias. Last, we identified only published studies to assess the effect of OLS among the patients with ALI or ARDS; hence, potential evidence for publication bias possibly existed in this study.
CONCLUSIONS
The present systematic review and meta-analysis showed the benefit of OLS on mortality during mechanical ventilation among patients with ARDS.
APPENDIX: SEARCH STRATEGIES ON MEDLINE
- acute lung injury; ti, ab, kw.
- ALI; ti, ab, kw.
- acute respiratory distress syndrome; ti, ab, kw.
- ARDS; ti, ab, kw.
- 1 or 2 or 3 or 4
- open lung; ti, ab, kw.
- lung recruitment; ti, ab, kw.
- recruitment maneuvers; ti, ab, kw.
- alveolar recruitment; ti, ab, kw.
- positive end-expiratory pressure; ti, ab, kw.
- PEEP; ti, ab, kw.
- 6 or 7 or 8 or 9 or 10 or 11
- randomized controlled trial; pt.
- controlled clinical trial; pt.
- randomized; ti, ab.
- placebo; ti, ab.
- randomly; ti, ab.
- trial; ti.
- 13 or 14 or 15 or 16 or 17 or 18
- 5 and 12 and 19
REFERENCES
1. Leaver SK, Evans TW. Acute respiratory distress syndrome.
BMJ 2007; 335 7616:389–394.
2. Ware LB, Matthay MA. The acute respiratory distress syndrome.
N Engl J Med 2000; 342:1334–1349.
3. Kacmarek RM, Villar J, Sulemanji D, Montiel R, Ferrando C, Blanco J, Koh Y, Soler JA, Martínez D, Hernández M, et al. Open lung approach for the acute respiratory distress syndrome: a pilot, randomized controlled trial.
Crit Care Med 2016; 44 1:32–42.
4. Lachmann B. Open up the lung and keep the lung open (editorial).
Intensive Care Med 1992; 18 6:319–321.
5. Xi XM, Jiang L, Zhu B. RM group. Clinical efficacy and safety of recruitment maneuver in patients with acute respiratory distress syndrome using low tidal volume ventilation: a multicenter randomized controlled clinical trial.
Chin Med J (Engl) 2010; 123 21:3100–3105.
6. Briel M, Meade M, Mercat A, Brower RG, Talmor D, Walter SD, Slutsky AS, Pullenayegum E, Zhou Q, Cook D, et al. Higher vs lower positive end-expiratory pressure in patients with acute lung injury and acute respiratory distress syndrome: systematic review and meta-analysis.
JAMA 2010; 303 9:865–873.
7. Meade MO, Cook DJ, Guyatt GH, Slutsky AS, Arabi YM, Cooper DJ, Davies AR, Hand LE, Zhou Q, Thabane L, et al. Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.
JAMA 2008; 299 6:637–645.
8. Brower RG, Lanken PN, MacIntyre N, Matthay MA, Morris A, Ancukiewicz M, Schoenfeld D, Thompson BT. National Heart, Lung, and Blood Institute ARDS Clinical Trials Network: higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome.
N Engl J Med 2004; 351 4:327–336.
9. Mercat A, Richard JC, Vielle B, Jaber S, Osman D, Diehl JL, Lefrant JY, Prat G, Richecoeur J, Nieszkowska A, et al. Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial.
JAMA 2008; 299 6:646–655.
10. Higgins J, Green S. Cochrane handbook for systematic reviews of interventions. Version 5.1.0. The Cochrane Collaboration 2011.
11. Higgins JP, Altman DG, Gotzsche PC, Jüni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.
BMJ 2011; 343:d5928.
12. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample.
BMC Med Res Methodol 2005; 5:13.
13. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses.
BMJ 2003; 327:557–560.
14. DerSimonian R, Laird N. Meta-analysis in clinical trials.
Control Clin Trials 1986; 7:177–188.
15. Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test.
BMJ 1997; 315:629–634.
16. Villar J, Kacmarek RM, Pérez-Méndez L, Aguirre-Jaime A. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: a randomized, controlled trial.
Crit Care Med 2006; 34 5:1311–1318.
17. Hodgson CL, Tuxen DV, Davies AR, Bailey MJ, Higgins AM, Holland AE, Keating JL, Pilcher DV, Westbrook AJ, Cooper DJ, et al. A randomized controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome.
Crit Care 2011; 15 3:R133.
18. Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, et al. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome.
N Engl J Med 1998; 338 6:347–354.
19. Ranieri VM, Suter PM, Tortorella C, De Tullio R, Dayer JM, Brienza A, Bruno F, Slutsky AS. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.
JAMA 1999; 282 1:54–61.
20. Huh JW, Jung H, Choi HS, Hong SB, Lim CM, Koh Y. Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome.
Crit Care 2009; 13 1:R22.
21. Bollen CW, van Well GT, Sherry T, Beale RJ, Shah S, Findlay G, Monchi M, Chiche JD, Weiler N, Uiterwaal CS, et al. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669].
Crit Care 2005; 9 4:R430–439.
22. Zhou X, Liu D, Long Y, Zhang Q, Cui N, He H, Zhao H, Liu Y, Ding X, Du Q, et al. The effects of prone position ventilation combined with recruitment maneuvers on outcomes in patients with severe acute respiratory distress syndrome.
Zhonghua Nei Ke Za Zhi 2014; 53 6:437–441.
23. Yang GH, Wang CY, Ning R. Effects of high positive end-expiratory pressure combined with recruitment maneuvers in patients with acute respiratory distress syndrome.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2011; 23 1:28–31.
24. Yi L, Xi XM. Effects of recruitment maneuvers with low tidal volume ventilation in patients with acute respiratory distress syndrome.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2005; 17 8:472–476.
25. Wang ZY, Zhu X, Li HL, Wang TH, Yao GQ. A study on the effect of recruitment maneuver imposed on extravascular lung water in patients with acute respiratory distress syndrome.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2009; 21 10:604–608.
26. Phoenix SI, Paravastu S, Columb M, Vincent JL, Nirmalan M. Does a higher positive end expiratory pressure decrease mortality in acute respiratory distress syndrome? A systematic review and meta-analysis.
Anesthesiology 2009; 110 5:1098–1105.
27. Oba Y, Thameem DM, Zaza T. High levels of PEEP may improve survival in acute respiratory distress syndrome: a meta-analysis.
Respir Med 2009; 103 8:1174–1181.
28. Putensen C, Theuerkauf N, Zinserling J, Wrigge H, Pelosi P. Meta-analysis: ventilation strategies and outcomes of the acute respiratory distress syndrome and acute lung injury.
Ann Intern Med 2009; 151 8:566–576.
29. Li M, Zhang Q, Chen XD. A meta-analysis of effects of high PEEP versus low PEEP upon mortality in patients with acute respiratory distress syndrome.
Zhonghua Yi Xue Za Zhi 2009; 89 40:2831–2834.
30. Dasenbrook EC, Needham DM, Brower RG, Fan E. Higher PEEP in patients with acute lung injury: a systematic review and meta-analysis.
Respir Care 2011; 56 5:568–575.
31. Yang J, Liu F, Zhu X. The influence of high positive end-expiratory pressure ventilation combined with low tidal volume on prognosis of patients with acute lung injury/acute respiratory distress syndrome: a meta-analysis.
Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 2011; 23 1:5–9.
32. Santa Cruz R, Rojas JI, Nervi R, Heredia R, Ciapponi A. High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome.
Cochrane Database Syst Rev 2013; CD009098.
33. Wang C, Wang X, Chi C, Guo L, Guo L, Zhao N, Wang W, Pi X, Sun B, Lian A, et al. Lung ventilation strategies for acute respiratory distress syndrome: a systematic review and network meta-analysis.
Sci Rep 2016; 6:22855.
34. Bernard GR, Artigas A, Brigham KL, Carlet J, Falke K, Hudson L, Lamy M, Legall JR, Morris A, Spragg R. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination.
AmJ Respir Crit Care Med 1994; 149 (3 pt 1):818–824.
35. Ranieri VM, Rubenfeld GD, Thompson BT, Ferguson ND, Caldwell E, Fan E, Camporota L, Slutsky AS. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition.
JAMA 2012; 307 23:2526–2533.
36. Marini JJ. Should We Embrace the “Open Lung” Approach?
Crit Care Med 2016; 44 1:237–238.
