Open Lung Approach for the Acute Respiratory Distress Syndrome: A Pilot, Randomized Controlled Trial* Effect of Lung Recruitment and Titrated Positive End-Expiratory Pressure (PEEP) vs Low PEEP on Mortality in Patients With Acute Respiratory Distress Syndrome: A Randomized Clinical Trial Respiratory effects of different recruitment maneuvers in acute respiratory distress syndrome Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome Lung recruitment in patients with the acute respiratory distress syndrome. Driving pressure and survival in 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. Alveolar recruitment maneuver attenuates extravascular lung water in acute respiratory distress syndrome Clinical efficacy and safety of recruitment maneuver in patients with acute respiratory distress syndrome using low tidal volume ventilation: a multicenter randomized controlled clinical trial. [Comparison of the effects of BiPAP ventilation combined with lung recruitment maneuvers and low tidal volume A/C ventilation in patients with acute respiratory distress syndrome]. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. Lung morphology predicts response to recruitment maneuver in patients with acute respiratory distress syndrome Impact of the driving pressure on mortality in obese and non-obese ARDS patients: a retrospective study of 362 cases Effects of Stepwise Lung Recruitment Maneuvers in Patients with Early Acute Respiratory Distress Syndrome: A Prospective, Randomized, Controlled Trial Maximal Recruitment Open Lung Ventilation in Acute Respiratory Distress Syndrome (PHARLAP): A Phase II, Multicenter, Randomized, Controlled Trial. Personalised mechanical ventilation tailored to lung morphology versus low positive end-expiratory pressure for patients with acute respiratory distress syndrome in France (the LIVE study): a multicentre, single-blind, randomised controlled trial. Epidemiology, Patterns of Care, and Mortality for Patients With Acute Respiratory Distress Syndrome in Intensive Care Units in 50 Countries.
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 : Introduction Alveolar derecruitment may occur during low tidal volume ventilation and may be prevented by recruitment maneuvers ( RMs ) . The aim of this study was to compare two RMs in acute respiratory distress syndrome ( ARDS ) patients . Methods Nineteen patients with ARDS and protective ventilation were included in a r and omized crossover study . Both RMs were applied in each patient , beginning with either continuous positive airway pressure ( CPAP ) with 40 cm H2O for 40 seconds or extended sigh ( eSigh ) consisting of a positive end-expiratory pressure maintained at 10 cm H2O above the lower inflection point of the pressure-volume curve for 15 minutes . Recruited volume , arterial partial pressure of oxygen/fraction of inspired oxygen ( PaO2/FiO2 ) , and hemodynamic parameters were recorded before ( baseline ) and 5 and 60 minutes after RM . All patients had a lung computed tomography ( CT ) scan before study inclusion . Results Before RM , PaO2/FiO2 was 151 ± 61 mm Hg . Both RMs increased oxygenation , but the increase in PaO2/FiO2 was significantly higher with eSigh than CPAP at 5 minutes ( 73 % ± 25 % versus 44 % ± 28 % ; P < 0.001 ) and 60 minutes ( 68 % ± 23 % versus 35 % ± 22 % ; P < 0.001 ) . Only eSigh significantly increased recruited volume at 5 and 60 minutes ( 21 % ± 22 % and 21 % ± 25 % ; P = 0.0003 and P = 0.001 , respectively ) . The only difference between responders and non-responders was CT lung morphology . Eleven patients were considered as recruiters with eSigh ( 10 with diffuse loss of aeration ) and 6 with CPAP ( 5 with diffuse loss of aeration ) . During CPAP , 2 patients needed interruption of RM due to a drop in systolic arterial pressure . Conclusion Both RMs effectively increase oxygenation , but CPAP failed to increase recruited volume . When the lung is recruited with an eSigh adapted for each patient , alveolar recruitment and oxygenation are superior to those observed with CPAP Introduction In acute respiratory distress syndrome ( ARDS ) , adequate positive end-expiratory pressure ( PEEP ) may decrease ventilator-induced lung injury by minimising overinflation and cyclic recruitment-derecruitment of the lung . We evaluated whether setting the PEEP using decremental PEEP titration after an alveolar recruitment manoeuvre ( ARM ) affects the clinical outcome in patients with ARDS . Methods Fifty-seven patients with early ARDS were r and omly assigned to a group given decremental PEEP titration following ARM or a table-based PEEP ( control ) group . PEEP  and  inspired fraction of oxygen ( FiO2 )  in the control group were set according to the table-based combinations of FiO2 and PEEP of the ARDS network , by which we aim ed to achieve a PEEP level compatible with an oxygenation target . In the decremental PEEP titration group , the oxygen saturation and static compliance were monitored as the patients performed the ARM along with the extended sigh method , which is design ed to gradually apply and withdraw a high distending pressure over a prolonged period , and the decremental titration of PEEP . Results The baseline characteristics did not differ significantly between the control and decremental PEEP titration groups . Initial oxygenation improved more in the decremental PEEP titration group than in the control group . However , dynamic compliance , tidal volume and PEEP were similar in the two groups during the first week . The duration of use of paralysing or sedative agents , mechanical ventilation , stay in the intensive care unit and mortality at 28 days did not differ significantly between the decremental PEEP titration and control groups . Conclusions The daily decremental PEEP titration after ARM showed only initial oxygenation improvement compared with the table-based PEEP method . Respiratory mechanics and patient outcomes did not differ between the decremental PEEP titration and control groups . Trial registration Clinical Trials.gov identifier : IS RCT N79027921 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 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 BACKGROUND Mechanical-ventilation strategies that use lower end-inspiratory ( plateau ) airway pressures , lower tidal volumes ( VT ) , and higher positive end-expiratory pressures ( PEEPs ) can improve survival in patients with the acute respiratory distress syndrome ( ARDS ) , but the relative importance of each of these components is uncertain . Because respiratory-system compliance ( CRS ) is strongly related to the volume of aerated remaining functional lung during disease ( termed functional lung size ) , we hypothesized that driving pressure ( ΔP = VT/CRS ) , in which VT is intrinsically normalized to functional lung size ( instead of predicted lung size in healthy persons ) , would be an index more strongly associated with survival than VT or PEEP in patients who are not actively breathing . METHODS Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported r and omized trials , we examined ΔP as an independent variable associated with survival . In the mediation analysis , we estimated the isolated effects of changes in ΔP result ing from r and omized ventilator setting s while minimizing confounding due to the baseline severity of lung disease . RESULTS Among ventilation variables , ΔP was most strongly associated with survival . A 1-SD increment in ΔP ( approximately 7 cm of water ) was associated with increased mortality ( relative risk , 1.41 ; 95 % confidence interval [ CI ] , 1.31 to 1.51 ; P<0.001 ) , even in patients receiving " protective " plateau pressures and VT ( relative risk , 1.36 ; 95 % CI , 1.17 to 1.58 ; P<0.001 ) . Individual changes in VT or PEEP after r and omization were not independently associated with survival ; they were associated only if they were among the changes that led to reductions in ΔP ( mediation effects of ΔP , P=0.004 and P=0.001 , respectively ) . CONCLUSIONS We found that ΔP was the ventilation variable that best stratified risk . Decreases in ΔP owing to changes in ventilator setting s were strongly associated with increased survival . ( Funded by Fundação de Amparo e Pesquisa do Estado de São Paulo and others . ) 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 Background : The alveolar recruitment maneuver ( RM ) has been reported to improve oxygenation in acute respiratory distress syndrome ( ARDS ) and may be related to reduced extravascular lung water ( EVLW ) in animals . This study was design ed to investigate the effects of RM on EVLW in patients with ARDS . Methods : An open label , prospect i ve , r and omized controlled trial including patients with ARDS was conducted in hospitals in North Taiwan between 2010 and 2016 . The patients were divided into 2 groups ( with and without RM ) . The primary endpoint was the comparison of the EVLW index between the 2 groups . Results : Twenty-four patients with ARDS on mechanical ventilator support were r and omized to receive ventilator treatment with RM ( RM group , n = 12 ) or without RM ( non-RM group , n = 12 ) . Baseline demographic characteristics were similar between the 2 groups . After recruitment , the day 3 extravascular lung water index ( EVLWI ) ( 25.3 ± 9.3 vs 15.5 ± 7.3 mL/kg , P = .008 ) and the arterial oxygen tension/fractional inspired oxygen ratio ( PaO2/FiO2 ) ( 132.3 ± 43.5 vs 185.6 ± 38.8 mL/kg , P = .003 ) both improved over that of day 1 . However , both EVLWI and PaO2/FiO2 did not significantly change from day 1 to 3 in the non-RM group . Conclusion : RM is a feasible method for improving oxygenation and the EVLW index in patients with ARDS , as well as for decreasing ventilator days and intensive care unit stay duration BACKGROUND The recruitment maneuver ( RM ) has been shown to improve oxygenation in some patients with acute respiratory distress syndrome . But there is a lack of st and ardization and lack of clinical studies to prove the improvement on clinical outcome . We conducted this study to evaluate the clinical efficacy and safety of the RM in patients with acute respiratory distress syndrome ( ARDS ) using low tidal volume ventilation . METHODS We r and omly assigned 110 patients with ARDS from 14 Chinese intensive care units ( ICUs ) at the tertiary teaching hospitals . Patients with PaO2 ≤ 200 mmHg at FiO2 1.0 and PEEP ≥ 10 cmH2O were included in the study . Patients were r and omized into two groups : control group and RM group . The tidal volume was set to 6 - 8 ml per kilogram of predicted body weight ( PBW ) in both groups . RM was performed by continuous positive airway pressure ( CPAP ) of 40 cmH2O maintained for 40 seconds . RMs was conducted every eight hours for the first five days , or stopped within five days if the patient reached the weaning st and ard . RESULTS One hundred and ten patients had completed the requirements for the primary study goals , 55 from the RM group and 55 control patients . Baseline characteristics remained similar in the two groups . In the RM group the PaO2/FiO2 was significantly increased compared to baseline at 120 minutes after RM on day one and day two ( P = 0.007 and P = 0.001 ) . There were no significant differences between the RM and control group in hospital mortality ( 41.8 % vs. 56.4 % , P = 0.13 ) , 28-day mortality ( 29.1 % vs. 43.6 % , P = 0.11 ) and ventilator-free days at day 28 ( 10.8 ± 10.1 vs. 7.4 ± 10.0 , P = 0.08 ) . ICU mortality ( 32.7 % vs. 52.7 % , P = 0.03 ) , the rate of survival with unassisted breathing for at least 48 consecutive hours at day 28 ( 58.2 % vs. 36.2 % , P = 0.02 ) , and nonpulmonary organ failure-free days at day 28 ( 17.4 ± 11.1 vs. 13.0 ± 12.0 , P = 0.03 ) favored the RM group . There was no significant difference in mean blood pressure and heart rate before RM and at 30 , 60 , 120 minutes after RM . There was no incidence of barotraumas . CONCLUSIONS RM was safe and useful for improving oxygenation in patients with ARDS who were ventilated with a low tidal volume , with a beneficial impact on their clinical outcome OBJECTIVE To compare the effects of BiPAP ventilation combined with lung recruitment maneuvers ( LRM ) with low tidal volume A/C ventilation in patients with acute respiratory distress syndrome ( ARDS ) . METHODS A prospect i ve , r and omized comparison of BiPAP mechanical ventilation combined with lung recruitment maneuvers ( test group ) with low tidal volume A/C ventilation ( control group ) was conducted in 28 patients with ARDS .  FiO2/PaO2 ratio , respiratory system compliance ( Cs ) , central venous pressure ( CVP ) , duration of ventilation support were recorded at 0 h , 48 h and 72 h separately . The ventilation associated lung injury and mortality at 28 d were also recorded . RESULTS The FiO2/PaO2 ratio were ( 298+/-16 ) and ( 309+/-16 ) cm H2O , Cs were ( 38.4+/-2.2 ) and ( 42.0+/-1.3 ) ml/cm H2O , CVP were ( 13.8+/-0.8 ) and ( 11.6+/-0.7 ) cm H2O in the test group at 48 h and 72 h separately . In the control group , FiO2/PaO2 ratio were ( 212+/-12 ) and ( 246+/-17 ) cm H2O , Cs were ( 29.5+/-1.3 ) and ( 29.0+/-1.0 ) ml/cm H2O , CVP were 18.6+/-1.1 and ( 16.8+/-1.0 ) cm H2O . The results were better in the test group as compared with the control group ( t=10.03 - 29.68 , all P<0.01 ) . The duration of ventilation support in the test group was shorter than the control group [ ( 14+/-3 ) d vs ( 19+/-3 ) d , t=4.80 , P<0.01 ] . The mortality in 28 d and ventilation associated lung injury were similar in the two groups . CONCLUSION The results show that combination of LRM with BiPAP mode ventilation , as compared with the control group , contributes to improved FiO2/PaO2 ratio , pulmonary compliance , stable hemodynamic and shorter duration of ventilation support in patients with ARDS 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 Objectives : The impact of recruitment maneuvers on gas exchange , hemodynamics , alveolar recruitment , and hyperinflation is highly variable among patients with acute respiratory distress syndrome . The objective was to determine whether differences in lung morphology , defined as differences in the pulmonary distribution of aeration loss , predict the response to recruitment maneuvers . Design : Prospect i ve study . Setting : A 16-bed medical – surgical intensive care unit in a university hospital . Measurements and Main Results : Nineteen consecutive patients with early acute lung injury/acute respiratory distress syndrome were studied .  Computed tomography scans , respiratory mechanics , hemodynamics , and gas exchange were obtained at zero end-expiratory pressure during an open-lung ventilation ( controlled mode , tidal volume 6 mL/kg of ideal body weight , positive end-expiratory pressure set 2 cm H2O above the lower inflection point of the inspiratory pressure volume curve at zero end-expiratory pressure ) during a recruitment maneuver ( continuous positive airway pressure of 40 cm H2O for 40 secs ) , and , finally , 5 mins after the recruitment maneuver during open-lung ventilation . Nine patients presented focal and 10 presented nonfocal lung morphology at zero end-expiratory pressure . Recruitment maneuver-induced recruited volume after 5 mins of open-lung ventilation was 48 ± 66 mL and 417 ± 293 mL in patients with focal and nonfocal lung morphology , respectively ( p = .0009 ) . Recruitment maneuver-induced alveolar hyperinflation represented 23 % ± 14 % and 8 % ± 9 % of total lung volume in patients with focal and nonfocal morphology , respectively ( p = .007 ) . In patients with focal lung morphology , hyperinflated lung volume was significantly greater during and 5 mins after ( 316 ± 155 mL ) than immediately before recruitment maneuvers ( 150 ± 175 mL ; p = .0407 . Conclusion : Lung morphology at zero end-expiratory pressure predicts the response to recruitment maneuvers . Patients with focal lung morphology are at risk for significant hyperinflation during the recruitment maneuvers , and lung recruitment is rather limited Purpose The relation between driving pressure ( plateau pressure-positive end-expiratory pressure ) and mortality has never been studied in obese ARDS patients . The main objective of this study was to evaluate the relationship between 90-day mortality and driving pressure in an ARDS population ventilated in the intensive care unit ( ICU ) according to obesity status . Methods We conducted a retrospective single-center study of prospect ively collected data of all ARDS patients admitted consecutively to a mixed medical-surgical adult ICU from January 2009 to May 2017 .  Plateau pressure , compliance of the respiratory system ( Crs ) and driving pressure of the respiratory system within 24 h of ARDS diagnosis were compared between survivors and non-survivors at day 90 and between obese ( body mass index ≥ 30 kg/m2 ) and non-obese patients . Cox proportional hazard modeling was used for mortality at day 90 . Results Three hundred sixty-two ARDS patients were included , 262 ( 72 % ) non-obese and 100 ( 28 % ) obese patients . Mortality rate at day 90 was respectively 47 % ( 95 % CI , 40–53 ) in the non-obese and 46 % ( 95 % CI , 36–56 ) in the obese patients . Driving pressure at day 1 in the non-obese patients was significantly lower in survivors at day 90 ( 11.9 ± 4.2 cmH2O ) than in non-survivors ( 15.2 ± 5.2 cmH2O , p < 0.001 ) . Contrarily , in obese patients , driving pressure at day 1 was not significantly different between survivors ( 13.7 ± 4.5 cmH2O ) and non-survivors ( 13.2 ± 5.1 cmH2O , p = 0.41 ) at day 90 . After three multivariate Cox analyses , plateau pressure [ HR = 1.04 ( 95 % CI 1.01–1.07 ) for each point of increase ] , Crs [ HR = 0.97 ( 95 % CI 0.96–0.99 ) for each point of increase ] and driving pressure [ HR = 1.07 ( 95 % CI 1.04–1.10 ) for each point of increase ] , respectively , were independently associated with 90-day mortality in non-obese patients , but not in obese patients . Conclusions Contrary to non-obese ARDS patients , driving pressure was not associated with mortality in obese ARDS patients Since the clinical benefit of lung recruitment maneuvers ( LRMs ) is still conflicting , we performed this prospect i ve , r and omized , controlled study to investigate whether LRMs should be used in the routine management of acute respiratory distress syndrome ( ARDS ) . This trial was conducted in four intensive care units ( ICUs ) to compare application of a modified stepwise LRMs with solely lung-protective ventilation in patients with moderate to severe ARDS within 72 h from the onset . The primary outcome was 28-day mortality , and the secondary outcomes were ventilator-free days and ICU-free days . We collected data on 120 ARDS patients from 2009 to 2012 , and there was no difference in  28-day mortality between the two groups ( 28.3 % vs. 30.0 % , p = 0.84 ) . However , among survivors , patients in the LRM group had a significant longer median duration of ventilator-free days ( 18 vs. 13 days ; p = 0.04 ) and ICU-free days ( 16 vs. 11 days ; p = 0.03 ) at 28 days than in the control group . The respiratory system compliance was significantly higher in the LRM group from day 1 to day 7 . The occurrence rate of barotrauma was similar in both groups . We concluded that LRMs combined with lung-protective ventilation in early ARDS may improve patient outcomes RATIONALE Open lung ventilation strategies have been recommended in patients with acute respiratory distress syndrome ( ARDS ) . OBJECTIVE To determine whether a maximal lung recruitment strategy reduces ventilator-free days in patients with ARDS . METHODS A phase II multicenter , r and omized , controlled trial in adults with moderate to severe ARDS . Patients received either maximal lung recruitment , titrated positive end expiratory pressure and further tidal volume limitation or control ' protective ' ventilation . MEASUREMENTS The primary outcome was ventilator-free days at day 28 . Secondary outcomes included mortality , barotrauma , new use of hypoxemic adjuvant therapies , ICU and hospital stay . MAIN RESULTS Enrolment halted on 2nd October 2017 following publication of the Alveolar Recruitment Trial , when 115 of a planned 340 patients had been r and omized ( 57 % male , mean age 53.6 years ) . At 28-days after r and omization , there was no difference in ventilator-free days between the maximal lung recruitment and the control ventilation strategies , median [ IQR ] 16[0 - 21 ] , n=57 versus 14.5[0 - 21.5 ] , n=56 , P=0.95 , mortality 24.6 % ( n=14/56 ) versus 26.8 % ( n=15/56 ) , P=0.79 , or the rate of barotrauma 5.2 % ( n=3/57 ) versus 10.7 % ( n=6/56 ) , P=0.32 . However , in the intervention group there was reduced use of new hypoxemic adjuvant therapies ( i.e. inhaled nitric oxide , extracorporeal membrane oxygenation , prone ) ( median [ IQR ] change from baseline 0 ( 0 - 1 ) vs 1 ( 0 - 1 ) ; P=0.004 ) and increased rates of new cardiac arrhythmia ( n=17 , 29 % versus n=7 , 13 % , P=0.03 ) . CONCLUSIONS Compared to control ventilation , maximal lung recruitment did not reduce the duration of ventilation free days or mortality and was associated with increased cardiovascular adverse events but lower use of hypoxemic adjuvant therapies . Clinical trial registration available at www . clinical trials.gov , ID : NCT01667146 BACKGROUND The effect of personalised mechanical ventilation on clinical outcomes in patients with acute respiratory distress syndrome ( ARDS ) remains uncertain and needs to be evaluated . We aim ed to test whether a mechanical ventilation strategy that was personalised to individual patients ' lung morphology would improve the survival of patients with ARDS when compared with st and ard of care . METHODS We design ed a multicentre , single-blind , stratified , parallel-group , r and omised controlled trial enrolling patients with moderate-to-severe ARDS in 20 university or non-university intensive care units in France . Patients older than 18 years with early ARDS for less than 12 h were r and omly assigned ( 1:1 ) to either the control group or the personalised group using a minimisation algorithm and stratified according to the study site , lung morphology , and duration of mechanical ventilation . Only the patients were masked to allocation . In the control group , patients received a tidal volume of 6 mL/kg per predicted bodyweight and positive end-expiratory pressure ( PEEP ) was selected according to a low PEEP and fraction of inspired oxygen table , and early prone position was encouraged . In the personalised group , the treatment approach was based on lung morphology ;  patients with focal ARDS received a tidal volume of 8 mL/kg , low PEEP , and prone position . Patients with non-focal ARDS received a tidal volume of 6 mL/kg , along with recruitment manoeuvres and high PEEP . The primary outcome was 90-day mortality as established by intention-to-treat analysis . This study is registered online with Clinical Trials.gov , NCT02149589 . FINDINGS From June 12 , 2014 , to Feb 2 , 2017 , 420 patients were r and omly assigned to treatment . 11 patients were excluded in the personalised group and nine patients were excluded in the control group ; 196 patients in the personalised group and 204 in the control group were included in the analysis . In a multivariate analysis , there was no difference in 90-day mortality between the group treated with personalised ventilation and the control group in the intention-to-treat analysis ( hazard ratio [ HR ] 1·01 ; 95 % CI 0·61 - 1·66 ; p=0·98 ) . However , misclassification of patients as having focal or non-focal ARDS by the investigators was observed in 85 ( 21 % ) of 400 patients . We found a significant interaction between misclassification and r and omised group allocation with respect to the primary outcome ( p<0·001 ) . In the subgroup analysis , the 90-day mortality of the misclassified patients was higher in the personalised group ( 26 [ 65 % ] of 40 patients ) than in the control group ( 18 [ 32 % ] of 57 patients ; HR 2·8 ; 95 % CI 1·5 - 5·1 ; p=0·012 . INTERPRETATION Personalisation of mechanical ventilation did not decrease mortality in patients with ARDS , possibly because of the misclassification of 21 % of patients . A ventilator strategy misaligned with lung morphology substantially increases mortality . Whether improvement in ARDS phenotyping can decrease mortality should be assessed in a future clinical trial . FUNDING French Ministry of Health ( Programme Hospitalier de Recherche Clinique InterRégional 2013 ) IMPORTANCE Limited information exists about the epidemiology , recognition , management , and outcomes of patients with the acute respiratory distress syndrome ( ARDS ) . OBJECTIVES To evaluate intensive care unit ( ICU ) incidence and outcome of ARDS and to assess clinician recognition , ventilation management , and use of adjuncts-for example prone positioning-in routine clinical practice for patients fulfilling the ARDS Berlin Definition . DESIGN , SETTING , AND PARTICIPANTS The Large Observational Study to Underst and the Global Impact of Severe Acute Respiratory Failure ( LUNG SAFE ) was an international , multicenter , prospect i ve cohort study of patients undergoing invasive or noninvasive ventilation  , conducted during 4 consecutive weeks in the winter of 2014 in a convenience sample of 459 ICUs from 50 countries across 5 continents . EXPOSURES Acute respiratory distress syndrome . MAIN OUTCOMES AND MEASURES The primary outcome was ICU incidence of ARDS . Secondary outcomes included assessment of clinician recognition of ARDS , the application of ventilatory management , the use of adjunctive interventions in routine clinical practice , and clinical outcomes from ARDS . RESULTS Of 29,144 patients admitted to participating ICUs , 3022 ( 10.4 % ) fulfilled ARDS criteria . Of these , 2377 patients developed ARDS in the first 48 hours and whose respiratory failure was managed with  invasive mechanical ventilation . The period prevalence of mild ARDS was 30.0 % ( 95 % CI , 28.2%-31.9 % ) ; of moderate ARDS , 46.6 % ( 95 % CI , 44.5%-48.6 % ) ; and of severe ARDS , 23.4 % ( 95 % CI , 21.7%-25.2 % ) . ARDS represented 0.42 cases per ICU bed over 4 weeks and represented 10.4 % ( 95 % CI , 10.0%-10.7 % ) of ICU admissions and 23.4 % of patients requiring mechanical ventilation . Clinical recognition of ARDS ranged from 51.3 % ( 95 % CI , 47.5%-55.0 % ) in mild to 78.5 % ( 95 % CI , 74.8%-81.8 % ) in severe ARDS . Less than two-thirds of patients with ARDS received a tidal volume 8 of mL/kg or less of predicted body weight . Plateau pressure was measured in 40.1 % ( 95 % CI , 38.2 - 42.1 ) , whereas 82.6 % ( 95 % CI , 81.0%-84.1 % ) received a positive end-expository pressure ( PEEP ) of less than 12 cm H2O . Prone positioning was used in 16.3 % ( 95 % CI , 13.7%-19.2 % ) of patients with severe ARDS . Clinician recognition of ARDS was associated with higher PEEP , greater use of neuromuscular blockade , and prone positioning . Hospital mortality was 34.9 % ( 95 % CI , 31.4%-38.5 % ) for those with mild , 40.3 % ( 95 % CI , 37.4%-43.3 % ) for those with moderate , and 46.1 % ( 95 % CI , 41.9%-50.4 % ) for those with severe ARDS . CONCLUSIONS AND RELEVANCE Among ICUs in 50 countries , the period prevalence of ARDS was 10.4 % of ICU admissions . This syndrome appeared to be underrecognized and undertreated and associated with a high mortality rate . These findings indicate the potential for improvement in the management of patients with ARDS . TRIAL REGISTRATION clinical trials.gov Identifier : NCT02010073
Among acute respiratory distress syndrome ( ARDS ) patients in intensive care units , the efficacy of lung recruitment maneuver ( LRM ) use is uncertain taking into account the most recent r and omized controlled trials ( RCTs ) .
We aim ed to estimate the effect of LRMs on mortality from ARDS .