Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. Lung recruitment in patients with the acute respiratory distress syndrome. 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. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial* Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome. Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. An early PEEP/FIO2 trial identifies different degrees of lung injury in patients with acute respiratory distress syndrome.
CONTEXT The need for lung protection is universally accepted , but the optimal level of positive end-expiratory pressure ( PEEP ) in patients with acute lung injury ( ALI ) or acute respiratory distress syndrome remains debated . OBJECTIVE To compare the effect on outcome of a strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation to one aim ed at minimizing alveolar distension in patients with ALI . DESIGN , SETTING , AND PATIENTS A multicenter r and omized controlled trial of 767 adults ( mean [ SD ] age , 59.9 [ 15.4 ] years ) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005 . INTERVENTION Tidal volume was set at 6 mL/kg of predicted body weight in both strategies . Patients were r and omly assigned to a moderate PEEP strategy ( 5 - 9 cm H(2)O ) ( minimal distension strategy ; n = 382 ) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O ( increased recruitment strategy ; n = 385 ) . MAIN OUTCOME MEASURES The primary end point was mortality at 28 days . Secondary end points were hospital mortality at 60 days , ventilator-free days , and organ failure-free days at 28 days . RESULTS The 28-day mortality rate in the minimal distension group was 31.2 % ( n = 119 ) vs 27.8 % ( n = 107 ) in the increased recruitment group ( relative risk , 1.12 [ 95 % confidence interval , 0.90 - 1.40 ] ; P = .31 ) . The hospital mortality rate in the minimal distension group was 39.0 % ( n = 149 ) vs 35.4 % ( n = 136 ) in the increased recruitment group ( relative risk , 1.10 [ 95 % confidence interval , 0.92 - 1.32 ] ; P = .30 ) . The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days ( 7 [ interquartile range { IQR } , 0 - 19 ] vs 3 [ IQR , 0 - 17 ] ; P = .04 ) and organ failure-free days ( 6 [ IQR , 0 - 18 ] vs 2 [ IQR , 0 - 16 ] ; P = .04 ) . This strategy also was associated with higher compliance values , better oxygenation , less use of adjunctive therapies , and larger fluid requirements . CONCLUSIONS A strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality . However , it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00188058 BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use BACKGROUND In the acute respiratory distress syndrome ( ARDS ) , positive end-expiratory pressure ( PEEP ) may decrease ventilator-induced lung injury by keeping lung regions open that otherwise would be collapsed . Since the effects of PEEP probably depend on the recruitability of lung tissue , we conducted a study to examine the relationship between the percentage of potentially recruitable lung , as indicated by computed tomography ( CT ) , and the clinical and physiological effects of PEEP . METHODS Sixty-eight patients with acute lung injury or ARDS underwent whole-lung CT during breath-holding sessions at airway pressures of 5 , 15 , and 45 cm of water . The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration was restored at airway pressures between 5 and 45 cm of water . RESULTS The percentage of potentially recruitable lung varied widely in the population , accounting for a mean ( + /-SD ) of 13+/-11 percent of the lung weight , and was highly correlated with the percentage of lung tissue in which aeration was maintained after the application of PEEP ( r2=0.72 , P<0.001 ) . On average , 24 percent of the lung could not be recruited . Patients with a higher percentage of potentially recruitable lung ( greater than the median value of 9 percent ) had greater total lung weights ( P<0.001 ) , poorer oxygenation ( defined as a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ) ( P<0.001 ) and respiratory-system compliance ( P=0.002 ) , higher levels of dead space ( P=0.002 ) , and higher rates of death ( P=0.02 ) than patients with a lower percentage of potentially recruitable lung . The combined physiological variables predicted , with a sensitivity of 71 percent and a specificity of 59 percent , whether a patient 's proportion of potentially recruitable lung was higher or lower than the median . CONCLUSIONS In ARDS , the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP CONTEXT Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome . Instituting additional strategies to open collapsed lung tissue may further reduce mortality . OBJECTIVE To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original " open-lung approach , " combining low tidal volume , lung recruitment maneuvers , and high positive-end-expiratory pressure . DESIGN AND SETTING R and omized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada , Australia , and Saudi Arabia . PATIENTS Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250 . INTERVENTIONS The control strategy included target tidal volumes of 6 mL/kg of predicted body weight , plateau airway pressures not exceeding 30 cm H2O , and conventional levels of positive end-expiratory pressure ( n = 508 ) . The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight , plateau pressures not exceeding 40 cm H2O , recruitment maneuvers , and higher positive end-expiratory pressures ( n = 475 ) . MAIN OUTCOME MEASURE All-cause hospital mortality . RESULTS Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment . Tidal volumes remained similar in the 2 groups , and mean positive end-expiratory pressures were 14.6 ( SD , 3.4 ) cm H2O in the experimental group vs 9.8 ( SD , 2.7 ) cm H2O among controls during the first 72 hours ( P < .001 ) . All-cause hospital mortality rates were 36.4 % and 40.4 % , respectively ( relative risk [ RR ] , 0.90 ; 95 % confidence interval [ CI ] , 0.77 - 1.05 ; P = .19 ) . Barotrauma rates were 11.2 % and 9.1 % ( RR , 1.21 ; 95 % CI , 0.83 - 1.75 ; P = .33 ) . The experimental group had lower rates of refractory hypoxemia ( 4.6 % vs 10.2 % ; RR , 0.54 ; 95 % CI , 0.34 - 0.86 ; P = .01 ) , death with refractory hypoxemia ( 4.2 % vs 8.9 % ; RR , 0.56 ; 95 % CI , 0.34 - 0.93 ; P = .03 ) , and previously defined eligible use of rescue therapies ( 5.1 % vs 9.3 % ; RR , 0.61 ; 95 % CI , 0.38 - 0.99 ; P = .045 ) . CONCLUSIONS For patients with acute lung injury and acute respiratory distress syndrome , a multifaceted protocol ized ventilation strategy design ed to recruit and open the lung result ed in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocol ized ventilation strategy . This " open-lung " strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00182195 Objective : It has been shown in a two-center study that high positive end-expiratory pressure ( PEEP ) and low tidal volume ( LTV ) improved outcome in ARDS . However , that study involved patients with underlying diseases unique to the study area , was conducted at only two centers , and enrolled a small number of patients . We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system ( Pflex ) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome ( ARDS ) . Design : R and omized , controlled clinical trial . Setting : Network of eight Spanish multidisciplinary intensive care units ( ICUs ) under the acronym of ARIES ( Acute Respiratory Insufficiency : España Study ) . Patients : All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study . If 24 hrs after meeting ARDS criteria , the Pao2/Fio2 remained ≤200 mm Hg on st and ard ventilator setting s , patients were r and omized into two groups : control and Pflex/LTV . Interventions : In the control group , tidal volume was 9–11 mL/kg of predicted body weight ( PBW ) and PEEP ≥5 cm H2O . In the Pflex/LTV group , tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O . In both groups , Fio2 was set to maintain arterial oxygen saturation > 90 % and Pao2 70–100 mm Hg , and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg . Measurements and Main Results : The study was stopped early based on an efficacy stopping rule as described in the methods . Of 103 patients who were enrolled ( 50 control and 53 Pflex ) , eight patients ( five in control , three in Pflex ) were excluded from the final evaluation because the r and om group assignment was not performed in one center according to protocol . Main outcome measures were ICU and hospital mortality , ventilator-free days , and nonpulmonary organ dysfunction . ICU mortality ( 24 of 45 [ 53.3 % ] vs. 16 of 50 [ 32 % ] , p = .040 ) , hospital mortality ( 25 of 45 [ 55.5 % ] vs. 17 of 50 [ 34 % ] , p = .041 )  , and ventilator-free days at day 28 ( 6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV , p = .008 ) all favored Pflex/LTV . The mean difference in the number of additional organ failures postr and omization was higher in the control group ( p < .001 ) . Conclusions : A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs , limitation of airway pressure , allowing hypercapnia if necessary , is already used for ventilation of acute respiratory distress syndrome ( ARDS ) . Whether a systematic and more drastic reduction is necessary is debatable . A multicenter r and omized study was undertaken to compare a strategy aim ed at limiting the end-inspiratory plateau pressure to 25 cm H2O , using tidal volume ( VT ) below 10 ml/kg of body weight , versus a more conventional ventilatory approach ( with regard to current practice ) using VT at 10 ml/kg or above and close to normal PaCO2 . Both arms used a similar level of positive end-expiratory pressure . A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers . The two groups were similar at inclusion . Patients in the two arms were ventilated with different VT ( 7.1 + /- 1.3 versus 10.3 + /- 1.7 ml/kg at Day 1 , p < 0.001 ) and plateau pressures ( 25.7 + /- 5 . 0 versus 31.7 + /- 6.6 cm H2O at Day 1 , p < 0.001 ) , result ing in different PaCO2 ( 59.5 + /- 15.0 versus 41.3 + /- 7.6 mm Hg , p < 0.001 ) and pH ( 7.28 + /- 0.09 versus 7.4 + /- 0.09 , p < 0.001 ) , but a similar level of oxygenation . The new approach did not reduce mortality at Day 60 ( 46.6 % versus 37.9 % in control subjects , p = 0.38 ) , the duration of mechanical ventilation ( 23.1 + /- 20.2 versus 21.4 + /- 16 . 3 d , p = 0.85 ) , the incidence of pneumothorax ( 14 % versus 12 % , p = 0 . 78 ) , or the secondary occurrence of multiple organ failure ( 41 % versus 41 % , p = 1 ) . We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O RATIONALE Tidal volume and plateau pressure limitation decreases mortality in acute respiratory distress syndrome .  Computed tomography demonstrated a small , normally aerated compartment on the top of poorly aerated and nonaerated compartments that may be hyperinflated by tidal inflation . OBJECTIVES We hypothesized that despite tidal volume and plateau pressure limitation , patients with a larger nonaerated compartment are exposed to tidal hyperinflation of the normally aerated compartment . MEASUREMENTS AND MAIN RESULTS Pulmonary computed tomography  at end-expiration and end-inspiration was obtained in 30 patients ventilated with a low tidal volume ( 6 ml/kg predicted body weight ) . Cluster analysis identified 20 patients in whom tidal inflation occurred largely in the normally aerated compartment ( 69.9 + /- 6.9 % ; " more protected " ) , and 10 patients in whom tidal inflation occurred largely within the hyperinflated compartments ( 63.0 + /- 12.7 % ; " less protected " ) . The nonaerated compartment was smaller and the normally aerated compartment was larger in the more protected patients than in the less protected patients ( p = 0.01 ) . Pulmonary cytokines were lower in the more protected patients than in the less protected patients ( p < 0.05 ) . Ventilator-free days were 7 + /- 8 and 1 + /- 2 d in the more protected and less protected patients , respectively ( p = 0.01 ) . Plateau pressure ranged between 25 and 26 cm H(2)O in the more protected patients and between 28 and 30 cm H(2)O in the less protected patients ( p = 0.006 ) . CONCLUSIONS Limiting tidal volume to 6 ml/kg predicted body weight and plateau pressure to 30 cm H(2)O may not be sufficient in patients characterized by a larger nonaerated compartment BACKGROUND Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome ( ARDS ) receive positive end-expiratory pressure ( PEEP ) of 5 to 12 cm of water . Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention . We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients . METHODS We r and omly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels , which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen . RESULTS Mean ( + /-SD ) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group ( P<0.001 ) . The rates of death before hospital discharge were 24.9 percent and 27.5 percent , respectively ( P=0.48 ; 95 percent confidence interval for the difference between groups , -10.0 to 4.7 percent ) . From day 1 to day 28 , breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group ( P=0.50 ) . CONCLUSIONS These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water , clinical outcomes are similar whether lower or higher PEEP levels are used OBJECTIVE To assess the safety and potential efficacy of a mechanical ventilation strategy design ed to reduce stretch-induced lung injury in acute respiratory distress syndrome . DESIGN Prospect i ve , r and omized , controlled clinical trial . SETTING Eight intensive care units in four teaching hospitals . PATIENTS Fifty-two patients with acute respiratory distress syndrome . INTERVENTIONS Traditional tidal volume patients : tidal volume 10 - 12 mL/kg ideal body weight , reduced if inspiratory plateau pressure was > 55 cm H2O ( 7.3 kPa ) . Small tidal volume patients : tidal volume 5 - 8 mL/kg ideal body weight , to keep plateau pressure < 30 cm H2O ( 4.0 kPa ) . MEASUREMENTS AND MAIN RESULTS Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg , respectively ( p < .001 ) , with mean plateau pressure = 30.6 and 24.9 cm H2O ( 3.3 kPa ) , respectively ( p < .001 ) . There were no significant differences in requirements for positive end-expiratory pressure or FIO2 , fluid intakes/outputs , requirements for vasopressors , sedatives , or neuromuscular blocking agents , percentage of patients that achieved unassisted breathing , ventilator days , or mortality . CONCLUSIONS The reduced tidal volume strategy used in this study was safe . Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a ) the sample size was too small to discern small treatment effects ; b ) the differences in tidal volumes and plateau pressures were modest ; or c ) reduced tidal volume ventilation is not beneficial BACKGROUND In patients with the acute respiratory distress syndrome , massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury . We determined whether a ventilatory strategy design ed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome . METHODS We r and omly assigned 53 patients with early acute respiratory distress syndrome ( including 28 described previously ) , all of whom were receiving identical hemodynamic and general support , to conventional or protective mechanical ventilation . Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure ( PEEP ) for acceptable oxygenation , with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels ( 35 to 38 mm Hg ) . Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve , a tidal volume of less than 6 ml per kilogram , driving pressures of less than 20 cm of water above the PEEP value , permissive hypercapnia , and preferential use of pressure-limited ventilatory modes . RESULTS After 28 days , 11 of 29 patients ( 38 percent ) in the protective-ventilation group had died , as compared with 17 of 24 ( 71 percent ) in the conventional-ventilation group ( P<0.001 ) . The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group ( P=0.005 ) : the rates of clinical barotrauma were 7 percent and 42 percent , respectively ( P=0.02 ) , despite the use of higher PEEP and mean airway pressures in the protective-ventilation group . The difference in survival to hospital discharge was not significant ; 13 of 29 patients ( 45 percent ) in the protective-ventilation group died in the hospital , as compared with 17 of 24 in the conventional-ventilation group ( 71 percent , P=0.37 ) . CONCLUSIONS As compared with conventional ventilation , the protective strategy was associated with improved survival at 28 days , a higher rate of weaning from mechanical ventilation , and a lower rate of barotrauma in patients with the acute respiratory distress syndrome .  Protective ventilation was not associated with a higher rate of survival to hospital discharge BACKGROUND A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome . The goal is to reduce lung injury due to overdistention . However , the efficacy of this approach has not been established . METHODS Within 24 hours of intubation , patients at high risk for the acute respiratory distress syndrome were r and omly assigned to either pressure- and volume-limited ventilation ( limited-ventilation group ) , with the peak inspiratory pressure maintained at 30 cm of water or less and the tidal volume at 8 ml per kilogram of body weight or less , or to conventional ventilation ( control group ) , with the peak inspiratory pressure allowed to rise as high as 50 cm of water and the tidal volume at 10 to 15 ml per kilogram . All other ventilatory variables were similar in the two groups . RESULTS A total of 120 patients with similar clinical features underwent r and omization ( 60 in each group ) . The patients in the limited-ventilation and control groups were exposed to different mean ( + /-SD ) tidal volumes ( 7.2+/-0.8 vs. 10.8+/-1.0 ml per kilogram , respectively ; P<0.001 ) and peak inspiratory pressures ( 23.6+/-5.8 vs. 34.0+/-11.0 cm of water , P<0.001 ) . Mortality was 50 percent in the limited-ventilation group and 47 percent in the control group ( relative risk , 1.07 ; 95 percent confidence interval , 0.72 to 1.57 ; P=0.72 ) . In the limited-ventilation group , permissive hypercapnia ( arterial carbon dioxide tension , > 50 mm Hg ) was more common ( 52 percent vs. 28 percent , P=0.009 ) , more marked ( 54.4+/-18.8 vs. 45.7+/-9.8 mm Hg , P=0.002 ) , and more prolonged ( 146+/-265 vs. 25+/-22 hours , P=0.017 ) than in the control group . The incidence of barotrauma , the highest multiple-organ-dysfunction score , and the number of episodes of organ failure were similar in the two groups ; however , the numbers of patients who required paralytic agents ( 23 vs. 13 , P=0.05 ) and dialysis for renal failure ( 13 vs. 5 , P= 0.04 ) were greater in the limited-ventilation group than in the control group . CONCLUSIONS In patients at high risk for the acute respiratory distress syndrome , a strategy of mechanical ventilation that limits peak inspiratory pressure and tidal volume does not appear to reduce mortality and may increase morbidity RATIONALE Current American-European Consensus Conference definitions for acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) are inadequate for inclusion into clinical trials due to the lack of st and ardization for measuring the oxygenation defect . OBJECTIVES We question ed whether an early assessment of oxygenation on specific ventilator setting s would identify patients with established ARDS ( persisting over 24 h ) . METHODS At the time of meeting ARDS criteria ( Day 0 ) and 24 hours later ( Day 1 ) ,  arterial blood gases  were obtained on st and ard ventilator setting s , Vt 7 ml/kg predicted body weight plus the following positive end-expiratory pressure ( PEEP ) and Fi(O(2 ) ) setting s in sequence : ( 1 ) PEEP > or= 5 cm H(2)O and Fi(O(2 ) ) > or= 0.5 , ( 2 ) PEEP > or= 5 cm H(2)O and Fi(O(2 ) ) 1.0 , ( 3 ) PEEP > or= 10 cm H(2)O and Fi(O(2))>or=0.5 , and ( 4 ) PEEP > or= 10 cm H(2)O and Fi(O(2 ) ) 1.0 . MEASUREMENTS AND MAIN RESULTS One hundred seventy patients meeting ARDS criteria ( Pa(O(2))/Fi(O(2 ) ) 128 + /- 33 mm Hg ) were enrolled .  Overall hospital mortality was 34.1 % . The st and ard ventilator setting s that best identified patients with established ARDS and predicted differences in intensive care unit ( ICU ) mortality were PEEP > or= 10 cm H(2)O and Fi(O(2 ) ) > or= 0.5 at Day 1 ( P = 0.0001 ) . Only 99 ( 58.2 % ) patients continued to meet ARDS criteria ( Pa(O(2))/Fi(O(2 ) ) , 155.8 + /- 29.8 mm Hg ; ICU mortality , 45.5 % ) , whereas 55 patients were reclassified as having ALI ( Pa(O(2))/Fi(O(2 ) ) , 246.5 + /- 25.6 mm Hg ; ICU mortality , 20 % ) and 16 patients as having acute respiratory failure ( Pa(O(2))/Fi(O(2 ) ) , 370 + /- 54 mm Hg ; ICU mortality , 6.3 % ) ( P = 0.0001 ) on these setting s. CONCLUSIONS Patients meeting current American-European Consensus Conference ARDS criteria may have highly variable levels of lung injury and outcomes . A systematic method of assessing severity of lung injury is required for enrollment of patients with ARDS into r and omized controlled trials . Clinical trial registered with www . clinical trials.gov ( NCT 00435110 )
Context Ventilation strategies to protect the lungs of patients with the acute respiratory distress syndrome ( ARDS ) include low tidal volume , limited airway pressures , and medium to high positive end-expiratory pressure ( PEEP ) , but the adoption of these strategies has been slow in some clinical setting s. Contribution This review of r and omized trial evidence for low tidal volume and high PEEP ventilation on mortality of patients with ARDS or acute lung injury found that trials were limited in number but showed mortality benefits with lower versus higher tidal volume .
The Editors The acute respiratory distress syndrome ( ARDS ) is clinical ly characterized by sudden onset , severe hypoxemia , radiographic evidence of bilateral pulmonary infiltration , and absence of left heart failure ( 13 ) .
Acute lung injury is a subset of ARDS with less severe impairment in oxygenation .
Despite apparent improvement in management and outcome of ARDS , the mortality rate in persons with the disease remains high , ranging from 35 % to 65 % ( 4 ) .
Although mechanical ventilation provides essential life support , it can worsen lung injury ( 5 ) .
Ventilator-induced lung injury is caused by excessive stress or strain to lung tissues that occurs during mechanical ventilation and aggravates inflammation and diffuse alveolar damage ( 5 , 13 ) .
Lung-protective ventilation strategies include ventilation with low Vt and limited airway pressure to reduce ventilator-induced lung injury from overdistention while allowing hypercapnia and medium to high positive end-expiratory pressure ( PEEP ) to keep alveoli open throughout the ventilator cycle ( 14 ) .
Hypercapnia and acidosis may increase intracranial pressure , induce pulmonary hypertension , depress myocardial contractility , decrease renal blood flow , and release endogenous catecholamines ( 15 ) .
In addition , prevention of cyclic derecruitment with higher PEEP may contribute to overdistention of normally aerated alveoli , counterbalancing the benefits from low Vt and limited airway pressure ventilation cycles ( 14 ) .
This may explain why most critically ill patients are still ventilated with high Vt at lower or even no PEEP ( 4 , 25 ) .
Our objective was to determine whether the different lung-protective ventilatory strategies improve outcome in critically ill adults with acute lung injury or ARDS .
Methods Data Sources and Search es We aim ed to identify all RCTs assessing the efficacy and outcomes of lower Vt ventilation , higher PEEP application , or a combination of both in adults with acute lung injury or ARDS .