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: Objective : The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial . We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach result ing in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome . Design : A prospect i ve , multicenter , pilot , r and omized controlled trial . Setting : A network of 20 multidisciplinary ICUs . Patients : Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study . Interventions : At 12 - 36 hours after acute respiratory distress syndrome onset , patients were  assessed under st and ardized ventilator setting s ( FIO2≥0.5 , positive end-expiratory pressure ≥10 cm H2O ) . If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg , patients were r and omized to open lung approach or Acute Respiratory Distress Syndrome network protocol . All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight . Measurements and Main Results : From 1,874 screened patients with acute respiratory distress syndrome , 200 were r and omized : 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol . Main outcome measures were 60-day and ICU mortalities , and ventilator-free days . Mortality at day-60 ( 29 % open lung approach vs. 33 % Acute Respiratory Distress Syndrome Network protocol , p = 0.18 , log rank test ) , ICU mortality ( 25 % open lung approach vs. 30 % Acute Respiratory Distress Syndrome network protocol , p = 0.53 Fisher ’s exact test ) , and ventilator-free days ( 8 [ 0 - 20 ] open lung approach vs. 7 [ 0 - 20 ] d Acute Respiratory Distress Syndrome network protocol , p = 0.53 Wilcoxon rank test ) were not significantly different . Airway driving pressure ( plateau pressure - positive end-expiratory pressure ) and PaO2/FIO2 improved significantly at 24 , 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol . Barotrauma rate was similar in both groups . Conclusions : In patients with established acute respiratory distress syndrome , open lung approach improved oxygenation and driving pressure , without detrimental effects on mortality , ventilator-free days , or barotrauma . This pilot study supports the need for a large , multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome Importance The effects of recruitment maneuvers and positive end-expiratory pressure ( PEEP ) titration on clinical outcomes in patients with acute respiratory distress syndrome ( ARDS ) remain uncertain . Objective To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy . Design , Setting , and Participants Multicenter , r and omized trial conducted at 120 intensive care units ( ICUs ) from 9 countries from November 17 , 2011 , through April 25 , 2017 , enrolling adults with moderate to severe ARDS . Interventions An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory – system compliance ( n = 501 ; experimental group ) or a control strategy of low PEEP ( n = 509 ) . All patients received volume-assist control mode until weaning . Main Outcomes and Measures The primary outcome was all-cause mortality until 28 days . Secondary outcomes were length of ICU and hospital stay ; ventilator-free days through day 28 ; pneumothorax requiring drainage within 7 days ; barotrauma within 7 days ; and ICU , in-hospital , and 6-month mortality . Results A total of 1010 patients ( 37.5 % female ; mean [ SD ] age , 50.9 [ 17.4 ] years ) were enrolled and followed up . At 28 days , 277 of 501 patients ( 55.3 % ) in the experimental group and 251 of 509 patients ( 49.3 % ) in the control group had died ( hazard ratio [ HR ] , 1.20 ; 95 % CI , 1.01 to 1.42 ; P = .041 ) . Compared with the control group , the experimental group strategy increased 6-month mortality ( 65.3 % vs 59.9 % ; HR , 1.18 ; 95 % CI , 1.01 to 1.38 ; P = .04 ) , decreased the number of mean ventilator-free days ( 5.3 vs 6.4 ; difference , −1.1 ; 95 % CI , −2.1 to −0.1 ; P = .03 ) , increased the risk of pneumothorax requiring drainage ( 3.2 % vs 1.2 % ; difference , 2.0 % ; 95 % CI , 0.0 % to 4.0 % ; P = .03 ) , and the risk of barotrauma ( 5.6 % vs 1.6 % ; difference , 4.0 % ; 95 % CI , 1.5 % to 6.5 % ; P = .001 ) . There were no significant differences in the length of ICU stay , length of hospital stay , ICU mortality , and in-hospital mortality . Conclusions and Relevance In patients with moderate to severe ARDS , a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality . These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients . Trial Registration clinical trials.gov Identifier : Objective : To determine whether differences in lung morphology assessed by computed tomography ( CT ) affect the response to positive end-expiratory pressure (PEEP).¶ Design : Prospect i ve study over a 53-month period.¶ Setting : Fourteen-bed surgical intensive care unit of a university hospital.¶ Patients and participants : Seventy-one consecutive patients with early adult respiratory distress syndrome (ARDS).¶ Measurements and results : Fast spiral thoracic CT was performed at zero end-expiratory pressure ( ZEEP ) and after implementation of PEEP 10 cmH2O . Hemodynamic and respiratory parameters were measured in both conditions . PEEP-induced overdistension and alveolar recruitment were quantified by specifically design ed software ( Lungview ) . Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung , characterized by a CT attenuation ranging between –900 and –800 HU in ZEEP conditions . Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS . PEEP-induced alveolar recruitment of the lower lobes was significantly correlated with their lung volume ( gas + tissue ) at functional residual capacity . PEEP-induced alveolar recruitment was greater in the lower lobes with “ inflammatory atelectasis ” than in the lower lobes with “ mechanical atelectasis . ” Lung morphology as assessed by CT markedly influenced the effects of PEEP : in patients with diffuse CT attenuations PEEP induced a marked alveolar recruitment without overdistension , whereas in patients with lobar CT attenuations PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas . These results can be explained by the uneven distribution of regional compliance characterizing patients with lobar CT attenuations ( compliant upper lobes and stiff lower lobes ) contrasting with a more even distribution of regional compliances observed in patients with diffuse CT attenuations.¶ Conclusions : In patients with ARDS , the cardiorespiratory effects of PEEP are affected by lung morphology rather than by the cause of the lung injury ( primary versus secondary ARDS ) . The regional distribution of the loss of aeration and the type of atelectasis –“mechanical ” with a massive loss of lung volume , or “ inflammatory ” with a preservation of lung volume – characterizing the lower lobes are the main determinants of the cardiorespiratory effects of PEEP Acute Respiratory Distress Syndrome ( ARDS ) is a common entity in critical care . ARDS is associated with many diagnoses , including trauma and sepsis , can lead to multiple organ failure and has high mortality . The present article is a narrative review of the literature on ARDS , including ARDS pathophysiology and therapeutic options currently being evaluated or in use in clinical practice . The literature review covers relevant publications until January 2011 . Recent developments in the therapeutic approach to ARDS include refinements of mechanical ventilatory support with emphasis on protective lung ventilation using low tidal volumes , increased PEEP with use of recruitment maneuvers to promote reopening of collapsed lung alveoli , prone position as rescue therapy for severe hypoxemia , and high frequency ventilation . Supportive measures in the management of ARDS include attention to fluid balance , restrictive transfusion strategies , and minimization of sedatives and neuromuscular blocking agents . Inhaled bronchodilators such as inhaled nitric oxide and prostagl and ins confer short term improvement without proven effect on survival , but are currently used in many centers . Use of corticosteroids is also important , and appropriate timely use may reduce mortality . Finally , extra corporeal oxygenation methods are very useful as rescue therapy in patients with intractable hypoxemia , even though a survival benefit has not , to this date been demonstrated . Despite intense ongoing research on the pathophysiology and treatment of ARDS , mortality remains high . Many pharmacologic and supportive strategies have shown promising results , but data from large r and omized clinical trials are needed to fully evaluate the true effectiveness of these therapies . Keywords ARDS ; Pathophysiology ; Introduction Tidal volume and plateau pressure minimisation are the st and ard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome ( ARDS ) . Open lung strategies , including higher positive end-expiratory pressure ( PEEP ) and recruitment manoeuvres to date have not proven efficacious . This study examines the effectiveness and safety of a novel open lung strategy , which includes permissive hypercapnia , staircase recruitment manoeuvres ( SRM ) and low airway pressure with PEEP titration . Method Twenty ARDS patients were r and omised to treatment or ARDSnet control ventilation strategies . The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O . Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1 , 3 , 5 and 7 ( mean ± SE ) . Duration of ventilation , ICU stay and hospital stay ( median and interquartile range ) and hospital survival were determined . Results There were significant overall differences between groups when considering plasma IL-8 and TNF-α . For plasma IL-8 , the control group was 41 % higher than the treatment group over the seven-day period ( ratio 1.41 ( 1.11 to 1.79 ) , P = 0.01 ) , while for TNF-α the control group was 20 % higher over the seven-day period ( ratio 1.20 ( 1.01 to 1.42 ) P = 0.05 ) . PaO2/FIO2 ( 204 ± 9 versus 165 ± 9 mmHg , P = 0.005 ) and static lung compliance ( 49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O , P < 0.001 ) were higher in the treatment group than the control group over seven days . There was no difference in duration of ventilation ( 180 ( 87 to 298 ) versus 341 ( 131 to 351 ) hrs , P = 0.13 ) , duration of ICU stay ( 9.9 ( 5.6 to 14.8 ) versus 16.0 ( 8.1 to 19.3 ) days , P = 0.19 ) and duration of hospital stay ( 17.9 ( 13.7 to 34.5 ) versus 24.7 ( 20.5 to 39.8 ) days , P = 0.16 ) between the treatment and control groups . Conclusions This open lung strategy was associated with greater amelioration in some systemic cytokines , improved oxygenation and lung compliance over seven days . A larger trial powered to examine clinical ly-meaningful outcomes is warranted . Trial registration Introduction To investigate haemodynamic and respiratory changes during lung recruitment and decremental positive end-expiratory pressure ( PEEP ) titration for open lung ventilation in patients with acute respiratory distress syndrome ( ARDS ) a prospect i ve , clinical trial was performed involving 12 adult patients with ARDS treated in the surgical intensive care unit in a university hospital . Methods A software programme ( Open Lung Tool ™ ) incorporated into a st and ard ventilator controlled the recruitment ( pressure-controlled ventilation with fixed PEEP at 20 cmH2O and increased driving pressures at 20 , 25 and 30 cmH2O for two minutes each ) and PEEP titration ( PEEP lowered by 2 cmH2O every two minutes , with tidal volume set at 6 ml/kg ) . The open lung PEEP ( OL-PE 
    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: Objective : The open lung approach is a mechanical ventilation strategy involving lung recruitment and a decremental positive end-expiratory pressure trial . We compared the Acute Respiratory Distress Syndrome network protocol using low levels of positive end-expiratory pressure with open lung approach result ing in moderate to high levels of positive end-expiratory pressure for the management of established moderate/severe acute respiratory distress syndrome . Design : A prospect i ve , multicenter , pilot , r and omized controlled trial . Setting : A network of 20 multidisciplinary ICUs . Patients : Patients meeting the American-European Consensus Conference definition for acute respiratory distress syndrome were considered for the study . Interventions : At 12 - 36 hours after acute respiratory distress syndrome onset , patients were  assessed under st and ardized ventilator setting s ( FIO2≥0.5 , positive end-expiratory pressure ≥10 cm H2O ) . If Pao2/FIO2 ratio remained less than or equal to 200 mm Hg , patients were r and omized to open lung approach or Acute Respiratory Distress Syndrome network protocol . All patients were ventilated with a tidal volume of 4 to 8 ml/kg predicted body weight . Measurements and Main Results : From 1,874 screened patients with acute respiratory distress syndrome , 200 were r and omized : 99 to open lung approach and 101 to Acute Respiratory Distress Syndrome network protocol . Main outcome measures were 60-day and ICU mortalities , and ventilator-free days . Mortality at day-60 ( 29 % open lung approach vs. 33 % Acute Respiratory Distress Syndrome Network protocol , p = 0.18 , log rank test ) , ICU mortality ( 25 % open lung approach vs. 30 % Acute Respiratory Distress Syndrome network protocol , p = 0.53 Fisher ’s exact test ) , and ventilator-free days ( 8 [ 0 - 20 ] open lung approach vs. 7 [ 0 - 20 ] d Acute Respiratory Distress Syndrome network protocol , p = 0.53 Wilcoxon rank test ) were not significantly different . Airway driving pressure ( plateau pressure - positive end-expiratory pressure ) and PaO2/FIO2 improved significantly at 24 , 48 and 72 hours in patients in open lung approach compared with patients in Acute Respiratory Distress Syndrome network protocol . Barotrauma rate was similar in both groups . Conclusions : In patients with established acute respiratory distress syndrome , open lung approach improved oxygenation and driving pressure , without detrimental effects on mortality , ventilator-free days , or barotrauma . This pilot study supports the need for a large , multicenter trial using recruitment maneuvers and a decremental positive end-expiratory pressure trial in persistent acute respiratory distress syndrome Importance The effects of recruitment maneuvers and positive end-expiratory pressure ( PEEP ) titration on clinical outcomes in patients with acute respiratory distress syndrome ( ARDS ) remain uncertain . Objective To determine if lung recruitment associated with PEEP titration according to the best respiratory-system compliance decreases 28-day mortality of patients with moderate to severe ARDS compared with a conventional low-PEEP strategy . Design , Setting , and Participants Multicenter , r and omized trial conducted at 120 intensive care units ( ICUs ) from 9 countries from November 17 , 2011 , through April 25 , 2017 , enrolling adults with moderate to severe ARDS . Interventions An experimental strategy with a lung recruitment maneuver and PEEP titration according to the best respiratory – system compliance ( n = 501 ; experimental group ) or a control strategy of low PEEP ( n = 509 ) . All patients received volume-assist control mode until weaning . Main Outcomes and Measures The primary outcome was all-cause mortality until 28 days . Secondary outcomes were length of ICU and hospital stay ; ventilator-free days through day 28 ; pneumothorax requiring drainage within 7 days ; barotrauma within 7 days ; and ICU , in-hospital , and 6-month mortality . Results A total of 1010 patients ( 37.5 % female ; mean [ SD ] age , 50.9 [ 17.4 ] years ) were enrolled and followed up . At 28 days , 277 of 501 patients ( 55.3 % ) in the experimental group and 251 of 509 patients ( 49.3 % ) in the control group had died ( hazard ratio [ HR ] , 1.20 ; 95 % CI , 1.01 to 1.42 ; P = .041 ) . Compared with the control group , the experimental group strategy increased 6-month mortality ( 65.3 % vs 59.9 % ; HR , 1.18 ; 95 % CI , 1.01 to 1.38 ; P = .04 ) , decreased the number of mean ventilator-free days ( 5.3 vs 6.4 ; difference , −1.1 ; 95 % CI , −2.1 to −0.1 ; P = .03 ) , increased the risk of pneumothorax requiring drainage ( 3.2 % vs 1.2 % ; difference , 2.0 % ; 95 % CI , 0.0 % to 4.0 % ; P = .03 ) , and the risk of barotrauma ( 5.6 % vs 1.6 % ; difference , 4.0 % ; 95 % CI , 1.5 % to 6.5 % ; P = .001 ) . There were no significant differences in the length of ICU stay , length of hospital stay , ICU mortality , and in-hospital mortality . Conclusions and Relevance In patients with moderate to severe ARDS , a strategy with lung recruitment and titrated PEEP compared with low PEEP increased 28-day all-cause mortality . These findings do not support the routine use of lung recruitment maneuver and PEEP titration in these patients . Trial Registration clinical trials.gov Identifier : Objective : To determine whether differences in lung morphology assessed by computed tomography ( CT ) affect the response to positive end-expiratory pressure (PEEP).¶ Design : Prospect i ve study over a 53-month period.¶ Setting : Fourteen-bed surgical intensive care unit of a university hospital.¶ Patients and participants : Seventy-one consecutive patients with early adult respiratory distress syndrome (ARDS).¶ Measurements and results : Fast spiral thoracic CT was performed at zero end-expiratory pressure ( ZEEP ) and after implementation of PEEP 10 cmH2O . Hemodynamic and respiratory parameters were measured in both conditions . PEEP-induced overdistension and alveolar recruitment were quantified by specifically design ed software ( Lungview ) . Overdistension occurred only in the upper lobes and was significantly correlated with the volume of lung , characterized by a CT attenuation ranging between –900 and –800 HU in ZEEP conditions . Cardiorespiratory effects of PEEP were similar in patients with primary and secondary ARDS . PEEP-induced alveolar recruitment of the lower lobes was significantly correlated with their lung volume ( gas + tissue ) at functional residual capacity . PEEP-induced alveolar recruitment was greater in the lower lobes with “ inflammatory atelectasis ” than in the lower lobes with “ mechanical atelectasis . ” Lung morphology as assessed by CT markedly influenced the effects of PEEP : in patients with diffuse CT attenuations PEEP induced a marked alveolar recruitment without overdistension , whereas in patients with lobar CT attenuations PEEP induced a mild alveolar recruitment associated with overdistension of previously aerated lung areas . These results can be explained by the uneven distribution of regional compliance characterizing patients with lobar CT attenuations ( compliant upper lobes and stiff lower lobes ) contrasting with a more even distribution of regional compliances observed in patients with diffuse CT attenuations.¶ Conclusions : In patients with ARDS , the cardiorespiratory effects of PEEP are affected by lung morphology rather than by the cause of the lung injury ( primary versus secondary ARDS ) . The regional distribution of the loss of aeration and the type of atelectasis –“mechanical ” with a massive loss of lung volume , or “ inflammatory ” with a preservation of lung volume – characterizing the lower lobes are the main determinants of the cardiorespiratory effects of PEEP Acute Respiratory Distress Syndrome ( ARDS ) is a common entity in critical care . ARDS is associated with many diagnoses , including trauma and sepsis , can lead to multiple organ failure and has high mortality . The present article is a narrative review of the literature on ARDS , including ARDS pathophysiology and therapeutic options currently being evaluated or in use in clinical practice . The literature review covers relevant publications until January 2011 . Recent developments in the therapeutic approach to ARDS include refinements of mechanical ventilatory support with emphasis on protective lung ventilation using low tidal volumes , increased PEEP with use of recruitment maneuvers to promote reopening of collapsed lung alveoli , prone position as rescue therapy for severe hypoxemia , and high frequency ventilation . Supportive measures in the management of ARDS include attention to fluid balance , restrictive transfusion strategies , and minimization of sedatives and neuromuscular blocking agents . Inhaled bronchodilators such as inhaled nitric oxide and prostagl and ins confer short term improvement without proven effect on survival , but are currently used in many centers . Use of corticosteroids is also important , and appropriate timely use may reduce mortality . Finally , extra corporeal oxygenation methods are very useful as rescue therapy in patients with intractable hypoxemia , even though a survival benefit has not , to this date been demonstrated . Despite intense ongoing research on the pathophysiology and treatment of ARDS , mortality remains high . Many pharmacologic and supportive strategies have shown promising results , but data from large r and omized clinical trials are needed to fully evaluate the true effectiveness of these therapies . Keywords ARDS ; Pathophysiology ; Introduction Tidal volume and plateau pressure minimisation are the st and ard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome ( ARDS ) . Open lung strategies , including higher positive end-expiratory pressure ( PEEP ) and recruitment manoeuvres to date have not proven efficacious . This study examines the effectiveness and safety of a novel open lung strategy , which includes permissive hypercapnia , staircase recruitment manoeuvres ( SRM ) and low airway pressure with PEEP titration . Method Twenty ARDS patients were r and omised to treatment or ARDSnet control ventilation strategies . The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O . Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1 , 3 , 5 and 7 ( mean ± SE ) . Duration of ventilation , ICU stay and hospital stay ( median and interquartile range ) and hospital survival were determined . Results There were significant overall differences between groups when considering plasma IL-8 and TNF-α . For plasma IL-8 , the control group was 41 % higher than the treatment group over the seven-day period ( ratio 1.41 ( 1.11 to 1.79 ) , P = 0.01 ) , while for TNF-α the control group was 20 % higher over the seven-day period ( ratio 1.20 ( 1.01 to 1.42 ) P = 0.05 ) . PaO2/FIO2 ( 204 ± 9 versus 165 ± 9 mmHg , P = 0.005 ) and static lung compliance ( 49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O , P < 0.001 ) were higher in the treatment group than the control group over seven days . There was no difference in duration of ventilation ( 180 ( 87 to 298 ) versus 341 ( 131 to 351 ) hrs , P = 0.13 ) , duration of ICU stay ( 9.9 ( 5.6 to 14.8 ) versus 16.0 ( 8.1 to 19.3 ) days , P = 0.19 ) and duration of hospital stay ( 17.9 ( 13.7 to 34.5 ) versus 24.7 ( 20.5 to 39.8 ) days , P = 0.16 ) between the treatment and control groups . Conclusions This open lung strategy was associated with greater amelioration in some systemic cytokines , improved oxygenation and lung compliance over seven days . A larger trial powered to examine clinical ly-meaningful outcomes is warranted . Trial registration Introduction To investigate haemodynamic and respiratory changes during lung recruitment and decremental positive end-expiratory pressure ( PEEP ) titration for open lung ventilation in patients with acute respiratory distress syndrome ( ARDS ) a prospect i ve , clinical trial was performed involving 12 adult patients with ARDS treated in the surgical intensive care unit in a university hospital . Methods A software programme ( Open Lung Tool ™ ) incorporated into a st and ard ventilator controlled the recruitment ( pressure-controlled ventilation with fixed PEEP at 20 cmH2O and increased driving pressures at 20 , 25 and 30 cmH2O for two minutes each ) and PEEP titration ( PEEP lowered by 2 cmH2O every two minutes , with tidal volume set at 6 ml/kg ) . The open lung PEEP ( OL-PE 
    Output:
    