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: 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 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 The associated use of permissive hypercapnia ( PHY ) and high PEEP levels ( PEEP(IDEAL ) ) has been recently indicated as part of a lung-protective-approach ( LPA ) in acute respiratory distress syndrome ( ARDS ) . However , the net hemodynamic effect produced by this association is not known . We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients ( mean age 34 + /- 13 yr ) with ARDS , focusing on its immediate ( after 1 h ) , early ( first 36 h ) , and late ( 2nd-7th d ) consequences . Twenty-five patients were su bmi tted to LPA -- with the combined use of permissive hypercapnia ( PHY ) , VT < 6 ml/kg , distending pressures above PEEP < 20 cm H2O , and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve ( P(FLEX))- and 23 control patients were su bmi tted to conventional mechanical ventilation .  LPA was initiated at once , result ing in an immediate increase in heart rate ( p = 0.0002 ) , cardiac output ( p = 0.0002 ) , oxygen delivery ( DO2l , p = 0.0003 ) , and mixed venous Po2 ( p = 0.0006 ) , with a maintained systemic oxygen consumption ( p = 0.52 ) . The mean pulmonary arterial pressure markedly increased ( mean increment 8.8 mm Hg ; p < 0.0001 ) , but the pulmonary vascular resistance did not change ( p = 0.32 ) . Cardiac filling pressures increased ( p < 0.001 ) and the systemic vascular resistance fell ( p = 0.003 ) . All these alterations were progressively attenuated in the course of the first 36 h , despite persisting hypercapnia . Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients ( p < 0.0001 ) . No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved . A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis , with no depressant effects ascribed to high PEEP levels . In contrast , high plateau pressures were associated with cardiovascular depression . Thus , as long as sufficiently low distending pressures are concomitantly applied , the sudden installation of PHY plus PEEP(IDEAL ) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals su bmi tted to  artificial ventilation  . To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome ( ARDS ) su bmi tted to conventional mechanical ventilation ( MV ) , we evaluated the impact of a new ventilatory strategy directed at minimizing " cyclic parenchymal stretch . " After receiving pre-established levels of hemodynamic , infectious , and general care , 28 patients with early ARDS were r and omly assigned to receive either MV based on a new approach ( NA , consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve , VT < 6 ml/kg , peak pressures < 40 cm H2O , permissive hypercapnia , and stepwise utilization of pressure-limited modes ) or a conventional approach ( C = conventional volume-cycled ventilation , VT = 12 ml/kg , minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels ) . Fifteen patients were selected to receive NA , exhibiting a better evolution of the PaO2/FIO2 ratio ( p < 0.0001 ) and of compliance ( p = 0.0018 ) , requiring shorter periods under FIO2 > 50 % ( p = 0.001 ) and a lower FIO2 at the day of death ( p = 0.0002 ) . After correcting for baseline imbalances in APACHE II , we observed a higher weaning rate in NA ( p = 0.014 ) but not a significantly improved survival ( overall mortality : 5/15 in NA versus 7/13 in C , p = 0.45 ) . We concluded that the NA ventilatory strategy can markedly improve the lung function  in patients with ARDS , increasing the chances of early weaning and lung recovery during mechanical ventilation The determinants of barotrauma in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome ( ALI/ARDS ) have not been clearly established . Using data from ARDS Network r and omized controlled trials , we retrospectively examined the association between airway pressures and the risk of early barotrauma in a cohort of 718 patients with ALI/ARDS and no baseline barotrauma . We studied airway pressures at three exposure intervals : baseline , one 
    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: 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 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 The associated use of permissive hypercapnia ( PHY ) and high PEEP levels ( PEEP(IDEAL ) ) has been recently indicated as part of a lung-protective-approach ( LPA ) in acute respiratory distress syndrome ( ARDS ) . However , the net hemodynamic effect produced by this association is not known . We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients ( mean age 34 + /- 13 yr ) with ARDS , focusing on its immediate ( after 1 h ) , early ( first 36 h ) , and late ( 2nd-7th d ) consequences . Twenty-five patients were su bmi tted to LPA -- with the combined use of permissive hypercapnia ( PHY ) , VT < 6 ml/kg , distending pressures above PEEP < 20 cm H2O , and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve ( P(FLEX))- and 23 control patients were su bmi tted to conventional mechanical ventilation .  LPA was initiated at once , result ing in an immediate increase in heart rate ( p = 0.0002 ) , cardiac output ( p = 0.0002 ) , oxygen delivery ( DO2l , p = 0.0003 ) , and mixed venous Po2 ( p = 0.0006 ) , with a maintained systemic oxygen consumption ( p = 0.52 ) . The mean pulmonary arterial pressure markedly increased ( mean increment 8.8 mm Hg ; p < 0.0001 ) , but the pulmonary vascular resistance did not change ( p = 0.32 ) . Cardiac filling pressures increased ( p < 0.001 ) and the systemic vascular resistance fell ( p = 0.003 ) . All these alterations were progressively attenuated in the course of the first 36 h , despite persisting hypercapnia . Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients ( p < 0.0001 ) . No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved . A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis , with no depressant effects ascribed to high PEEP levels . In contrast , high plateau pressures were associated with cardiovascular depression . Thus , as long as sufficiently low distending pressures are concomitantly applied , the sudden installation of PHY plus PEEP(IDEAL ) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals su bmi tted to  artificial ventilation  . To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome ( ARDS ) su bmi tted to conventional mechanical ventilation ( MV ) , we evaluated the impact of a new ventilatory strategy directed at minimizing " cyclic parenchymal stretch . " After receiving pre-established levels of hemodynamic , infectious , and general care , 28 patients with early ARDS were r and omly assigned to receive either MV based on a new approach ( NA , consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve , VT < 6 ml/kg , peak pressures < 40 cm H2O , permissive hypercapnia , and stepwise utilization of pressure-limited modes ) or a conventional approach ( C = conventional volume-cycled ventilation , VT = 12 ml/kg , minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels ) . Fifteen patients were selected to receive NA , exhibiting a better evolution of the PaO2/FIO2 ratio ( p < 0.0001 ) and of compliance ( p = 0.0018 ) , requiring shorter periods under FIO2 > 50 % ( p = 0.001 ) and a lower FIO2 at the day of death ( p = 0.0002 ) . After correcting for baseline imbalances in APACHE II , we observed a higher weaning rate in NA ( p = 0.014 ) but not a significantly improved survival ( overall mortality : 5/15 in NA versus 7/13 in C , p = 0.45 ) . We concluded that the NA ventilatory strategy can markedly improve the lung function  in patients with ARDS , increasing the chances of early weaning and lung recovery during mechanical ventilation The determinants of barotrauma in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome ( ALI/ARDS ) have not been clearly established . Using data from ARDS Network r and omized controlled trials , we retrospectively examined the association between airway pressures and the risk of early barotrauma in a cohort of 718 patients with ALI/ARDS and no baseline barotrauma . We studied airway pressures at three exposure intervals : baseline , one 
    Output:
    