human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 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 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 
    Output:
    
agent
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 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 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 
    Output:
    