Acute respiratory failure in intensive care units. FINNALI: a prospective cohort study Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. Mechanical ventilation guided by esophageal pressure in acute lung injury. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. Mechanisms of physiological dead space response to PEEP after acute oleic acid lung injury. Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome Lung recruitment in patients with the acute respiratory distress syndrome. High positive end-expiratory pressure levels promote bacterial translocation in experimental pneumonia Ventilation strategy using low tidal volumes, recruitment maneuvers, and high positive end-expiratory pressure for acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial* ARDSnet ventilatory protocol and alveolar hyperinflation: role of positive end-expiratory pressure. Temporal hemodynamic effects of permissive hypercapnia associated with ideal PEEP in ARDS. Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Regional effects and mechanism of positive end-expiratory pressure in early adult respiratory distress syndrome. Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome. Reversibility of lung collapse and hypoxemia in early acute respiratory distress syndrome. Respective effects of end-expiratory and end-inspiratory pressures on alveolar recruitment in acute lung injury* Immediate effects of positive end-expiratory pressure and low and high tidal volume ventilation upon gas exchange and compliance in patients with acute lung injury. Incidence and outcomes of acute lung injury. Recruitment Maneuvers after a Positive End-expiratory Pressure Trial Do Not Induce Sustained Effects in Early Adult Respiratory Distress Syndrome Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. Statistical evaluation of ventilator-free days as an efficacy measure in clinical trials of treatments for acute respiratory distress syndrome PEEP-induced changes in lung volume in acute respiratory distress syndrome. Two methods to estimate alveolar recruitment The relation of pneumothorax and other air leaks to mortality in the acute respiratory distress syndrome.
Objective To evaluate the incidence , treatment and mortality of  acute respiratory failure ( ARF ) in Finnish intensive care units ( ICUs ) . Study design Prospect i ve multicentre cohort study . Methods All adult patients in 25 ICUs were screened for use of invasive or non-invasive ventilatory support during an 8-week period . Patients needing ventilatory support for more than 6 h were included and defined as ARF patients . Risk factors for ARF and details of prior chronic health status were assessed .  Ventilatory and concomitant treatments  were evaluated and recorded daily throughout the ICU stay . ICU and 90-day mortalities were assessed . Results A total of 958 ( 39 % ) from the 2,473 admitted patients were treated with ventilatory support for more than 6 h. Incidence of ARF , acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) was 149.5 , 10.6 and 5.0/100,000 per year , respectively . Ventilatory support was started with non-invasive interfaces in 183 of 958 ( 19 % ) patients . Ventilatory modes allowing triggering of spontaneous breaths were preferred ( 81 % ) . Median tidal volume/predicted body weight was 8.7 ( 7.6–9.9 ) ml/kg and plateau pressure 19 ( 16–23 ) cmH2O . The 90-day mortality of ARF was 31 % . Conclusions While the incidence of ARF requiring ventilatory support is higher , the incidence of ALI and ARDS seems to be lower in Finl and than previously reported in other countries . Tidal volumes are higher than recommended in the concept of lung protective strategy . However , restriction of peak airway pressure was used in the majority of ARF patients CONTEXT The need for lung protection is universally accepted , but the optimal level of positive end-expiratory pressure ( PEEP ) in patients with acute lung injury ( ALI ) or acute respiratory distress syndrome remains debated . OBJECTIVE To compare the effect on outcome of a strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation to one aim ed at minimizing alveolar distension in patients with ALI . DESIGN , SETTING , AND PATIENTS A multicenter r and omized controlled trial of 767 adults ( mean [ SD ] age , 59.9 [ 15.4 ] years ) with ALI conducted in 37 intensive care units in France from September 2002 to December 2005 . INTERVENTION Tidal volume was set at 6 mL/kg of predicted body weight in both strategies . Patients were r and omly assigned to a moderate PEEP strategy ( 5 - 9 cm H(2)O ) ( minimal distension strategy ; n = 382 ) or to a level of PEEP set to reach a plateau pressure of 28 to 30 cm H(2)O ( increased recruitment strategy ; n = 385 ) . MAIN OUTCOME MEASURES The primary end point was mortality at 28 days . Secondary end points were hospital mortality at 60 days , ventilator-free days , and organ failure-free days at 28 days . RESULTS The 28-day mortality rate in the minimal distension group was 31.2 % ( n = 119 ) vs 27.8 % ( n = 107 ) in the increased recruitment group ( relative risk , 1.12 [ 95 % confidence interval , 0.90 - 1.40 ] ; P = .31 ) . The hospital mortality rate in the minimal distension group was 39.0 % ( n = 149 ) vs 35.4 % ( n = 136 ) in the increased recruitment group ( relative risk , 1.10 [ 95 % confidence interval , 0.92 - 1.32 ] ; P = .30 ) . The increased recruitment group compared with the minimal distension group had a higher median number of ventilator-free days ( 7 [ interquartile range { IQR } , 0 - 19 ] vs 3 [ IQR , 0 - 17 ] ; P = .04 ) and organ failure-free days ( 6 [ IQR , 0 - 18 ] vs 2 [ IQR , 0 - 16 ] ; P = .04 ) . This strategy also was associated with higher compliance values , better oxygenation , less use of adjunctive therapies , and larger fluid requirements . CONCLUSIONS A strategy for setting PEEP aim ed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality . However , it did improve lung function and reduced the duration of mechanical ventilation and the duration of organ failure . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00188058 BACKGROUND Survival of patients with acute lung injury or the acute respiratory distress syndrome ( ARDS ) has been improved by ventilation with small tidal volumes and the use of positive end-expiratory pressure ( PEEP ) ; however , the optimal level of PEEP has been difficult to determine . In this pilot study , we estimated transpulmonary pressure with the use of esophageal balloon catheters . We reasoned that the use of pleural-pressure measurements , despite the technical limitations to the accuracy of such measurements , would enable us to find a PEEP value that could maintain oxygenation while preventing lung injury due to repeated alveolar collapse or overdistention . METHODS We r and omly assigned patients with acute lung injury or ARDS to undergo mechanical ventilation with PEEP adjusted according to measurements of esophageal pressure ( the esophageal-pressure-guided group ) or according to the Acute Respiratory Distress Syndrome Network st and ard-of-care recommendations ( the control group ) . The primary end point was improvement in oxygenation . The secondary end points included respiratory-system compliance and patient outcomes . RESULTS The study reached its stopping criterion and was terminated after 61 patients had been enrolled . The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen at 72 hours was 88 mm Hg higher in the esophageal-pressure-guided group than in the control group ( 95 % confidence interval , 78.1 to 98.3 ; P=0.002 ) . This effect was persistent over the entire follow-up time ( at 24 , 48 , and 72 hours ; P=0.001 by repeated- measures analysis of variance ) . Respiratory-system compliance was also significantly better at 24 , 48 , and 72 hours in the esophageal-pressure-guided group ( P=0.01 by repeated- measures analysis of variance ) . CONCLUSIONS As compared with the current st and ard of care , a ventilator strategy using esophageal pressures to estimate the transpulmonary pressure significantly improves oxygenation and compliance . Multicenter clinical trials are needed to determine whether this approach should be widely adopted . ( Clinical Trials.gov number , NCT00127491 . 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 In acute increased-permeability edema , the Bohr physiological dead space ( VD/VTCO2 ) can be influenced by changes in anatomic dead space , ventilation-perfusion ( VA/Q ) heterogeneity , shunt , and the Haldane effect . We used the multiple inert gas elimination technique to assess the effect of positive end-expiratory pressure ( PEEP ) on each of these components of VD/VTCO2 in 14 pentobarbital-anesthetized dogs with increased permeability edema induced by infused oleic acid . PEEP of 5 , 10 , 15 , and 20 cmH2O was applied in r and om sequence . Following injury VD/VTCO2 increased . It decreased with 5 or 10 cmH2O PEEP but increased progressively at higher PEEP levels . The decrease in VD/VTCO2 at 5 or 10 cmH2O PEEP was due to reductions in shunt and midrange VA/Q heterogeneity . The increase in VD/VTCO2 that occurred with higher PEEP levels was due to increased ventilation to high VA/Q regions and a larger anatomic dead space . Haldane effect magnified the shunt component of VD/VTCO2 but reduced the influence of midrange VA/Q heterogeneity 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 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 Objective A previous study in piglets with experimental pneumonia showed that reducing atelectasis by means of open lung ventilation attenuated bacterial translocation compared to conventional ventilation setting s. This study examined the effect of open lung ventilation with higher than necessary positive end-expiratory pressures ( PEEP ) on bacterial translocation . Design and setting Prospect i ve animal study in a university-affiliated research laboratory . SubjectsThirty piglets . Interventions Animals were surfactant-depleted by whole-lung lavage and infected with group B streptococci . Thereafter the animals were ventilated for 5 h according to either a conventional ventilation strategy , open lung strategy , or open lung/high-PEEP strategy .  Blood sample s for blood gas analysis and blood bacterial counts were taken every hour . After 5 h of ventilation surviving animals were killed , and lung colony forming units and lung mechanics parameters were determined . Results All animals in both open lung groups survived but only 30 % of those in the conventional ventilation group . Open lung ventilation result ed in significantly less bacterial translocation than either conventional or high-PEEP ventilation . Lung function in the conventional ventilated group was significantly less than in the two open lung groups . Conclusions The lowest level of bacterial translocation was observed during optimal ventilation ( open lung ) which was achieved by using individually tailored setting s. Deviation to either side can be harmful , as shown by the increased bacterial translocation during conventional and high-PEEP ventilation 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 RATIONALE In patients with acute respiratory distress syndrome ( ARDS ) , a focal distribution of loss of aeration in lung computed tomography predicts low potential for alveolar recruitment and susceptibility to alveolar hyperinflation with high levels of positive end-expiratory pressure ( PEEP ) . OBJECTIVES We tested the hypothesis that , in this cohort of patients , the table-based PEEP setting criteria of the National Heart , Lung , and Blood Institute 's ARDS Network ( ARDSnet ) low tidal volume ventilatory protocol could induce tidal alveolar hyperinflation . METHODS In 15 patients , physiologic parameters and plasma inflammatory mediators were measured during two ventilatory strategies , applied r and omly : the ARDSnet and the stress index strategy . The latter used the same ARDSnet ventilatory pattern except for the PEEP level , which was adjusted based on the stress index , a monitoring tool intended to quantify tidal alveolar hyperinflation and /or recruiting/derecruiting that occurs during constant-flow ventilation , on a breath-by-breath basis . MEASUREMENTS AND MAIN RESULTS In all patients , the stress index revealed alveolar hyperinflation during application of the ARDSnet strategy , and consequently , PEEP was significantly decreased ( P < 0.01 ) to normalize the stress index value . Static lung elastance ( P = 0.01 ) , plasma concentrations of interleukin-6 ( P < 0.01 ) , interleukin-8 ( P = 0.031 ) , and soluble tumor necrosis factor receptor I ( P = 0.013 ) were significantly lower during the stress index as compared with the ARDSnet strategy -guided ventilation . CONCLUSIONS Alveolar hyperinflation in patients with focal ARDS ventilated with the ARDSnet protocol is attenuated by a physiologic approach to PEEP setting based on the stress index measurement 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 OBJECTIVE To test the hypothesis that positive end-expiratory pressure ( PEEP ) prevents the collapse of a given lung region when it is equal to or greater than the hydrostatic pressure superimposed ( SPL ) to that region . DESIGN Intervention study with sequential levels of PEEP applied in r and om order to a cohort of patients with adult respiratory distress syndrome ( ARDS ) . SETTING Referral center for ARDS in a university hospital . PATIENTS Ten ARDS patients ( with Murray scores > 2.5 ) . INTERVENTION Basal computed tomographic ( CT ) section taken at 0 , 2 , 4 , 5 , 6 , 8 , 10 , 12 , 14 , 15 , and 20 cm H2O PEEP . MAIN OUTCOME MEASURES Basal lung CT sections were divided into 10 equal levels from the ventral to dorsal surfaces . In each level SPL was measured from density and height . The inflation of the level was measured as the gas/tissue ratio ( g/t ) ; g/t changes with PEEP were defined as the g/t-P curve . The slope of the g/t-P curve was defined as level compliance ( ie , the ratio of change in the g/t of the level to the change in pressure ) . A linear g/t-P curve was the criterion to detect inflation without recruitment ( ie , new pulmonary units opening at a given pressure ) . A biphasic g/t-P curve ( change of compliance after an inflection point ) was the criterion to detect recruitment . Pflex was defined as the pressure at which the inflection point occurred . RESULTS The SPL increased from level 1 ( ventral ) to level 10 ( dorsal ) ( r = .91 ; P < .01 ) . The number of linear g/t-P curves decreased from level 1 to level 10 ( r = .98 ; P < .01 ) , while the number of biphasic g/t-P curves increased ( r = .95 ; P < .01 ) . The Pflex increased from level 1 to 10 ( r = .97 ; P < .01 ) and Pflex was similar to SPL ( Pflex = 1.05 + 0.9 SPL ; r = .75 ; P < .01 ) . CONCLUSIONS The increased SPL causes compression atelectasis ; this is prevented when PEEP to a given lung region is equal to or greater than the SPL 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 day preceding the barotrauma event ( one-day lag ) , and concurrent with the barotrauma event . During the first four study days , the cumulative incidence of barotrauma was 13 % ( 95 % confidence interval [ CI ] 10.6 to 15.6 % ) . In a forward stepwise Cox proportional hazards analysis using time-dependent variables , higher concurrent positive end-expiratory pressure ( PEEP ) was associated with an increased risk of early barotrauma ( relative hazard [ RH ] 1.67 per 5-cm H2O increment ; 95 % CI 1.35 - 2.07 ) . Once concurrent PEEP was selected into the model , no other airway pressure was related to barotrauma , including plateau pressure . In the multivariate analysis , higher concurrent PEEP was also related to a greater risk of barotrauma ( RH 1.93 ; 95 % CI 1.44 - 2.60 ) , controlling for age , ventilator group ( 6 versus 12 ml/kg ) , baseline PEEP , baseline plateau pressure , baseline tidal volume , Acute Physiology and Chronic Health Evaluation score , vasopressor use , serum albumin , hepatic failure , and coagulopathy . When one-day lagged values of PEEP were analyzed , higher PEEP was associated with a greater risk of barotrauma ( RH 1.38 per 5-cm H2O increment ; 95 % CI 1.09 - 1.76 ) . Controlling for the covariates , higher PEEP was related to an increased risk of barotrauma ( RH 1.50 ; 95 % CI 0.98- 2.30 ) . In conclusion , higher PEEP may increase the likelihood of early barotrauma in ALI/ARDS RATIONALE The hypothesis that lung collapse is detrimental during the acute respiratory distress syndrome is still debatable . One of the difficulties is the lack of an efficient maneuver to minimize it . OBJECTIVES To test if a bedside recruitment strategy , capable of reversing hypoxemia and collapse in > 95 % of lung units , is clinical ly applicable in early acute respiratory distress syndrome . METHODS Prospect i ve assessment of a stepwise maximum-recruitment strategy using multislice computed tomography and continuous blood-gas hemodynamic monitoring . MEASUREMENTS AND MAIN RESULTS Twenty-six patients received sequential increments in inspiratory airway pressures , in 5 cm H(2)O steps , until the detection of Pa(O(2 ) ) + Pa(CO(2 ) ) > or= 400 mm Hg . Whenever this primary target was not met , despite inspiratory pressures reaching 60 cm H(2)O , the maneuver was considered incomplete . If there was hemodynamic deterioration or barotrauma , the maneuver was to be interrupted . Late assessment of recruitment efficacy was performed by computed tomography ( 9 patients ) or by online continuous monitoring in the intensive care unit ( 15 patients ) up to 6 h. It was possible to open the lung and to keep the lung open in the majority ( 24/26 ) of patients , at the expense of transient hemodynamic effects and hypercapnia but without major clinical consequences . No barotrauma directly associated with the maneuver was detected . There was a strong and inverse relationship between arterial oxygenation and percentage of collapsed lung mass ( R = - 0.91 ; p < 0.0001 ) . CONCLUSIONS It is often possible to reverse hypoxemia and fully recruit the lung in early acute respiratory distress syndrome . Due to transient side effects , the required maneuver still awaits further evaluation before routine clinical application Objective A low tidal volume can induce alveolar derecruitment in patients with acute lung injury . This study was undertaken to evaluate whether this result ed mainly from the decrease in tidal volume per se or from the reduction in end-inspiratory plateau pressure and whether there is any benefit in raising the level of positive end-expiratory pressure ( PEEP ) while plateau pressure is kept constant . Design Prospect i ve crossover study . Setting Medical intensive care unit of a university teaching hospital . Patients Fifteen adult patients ventilated for acute lung injury ( Pao2/Fio2 , 158 ± 34 mm Hg ; lung injury score , 2.7 ± 0.6 ) . Interventions Three combinations were tested : PEEP at the lower inflection point with 6 mL/kg tidal volume , PEEP at the lower inflection point with 10 mL/kg tidal volume , and high PEEP with tidal volume at 6 mL/kg , keeping the plateau pressure similar to the preceding condition . Measurements and Main Results Pressure-volume curves at zero PEEP and at set PEEP were recorded , and recruitment was calculated as the volume difference between both curves for pressures ranging from 15 to 30 cm H2O . Arterial blood gases were measured for all patients . For a similar PEEP at the lower inflection point ( 10 ± 3 cm H2O ) , tidal volume reduction ( 10 to 6 mL/kg ) led to a significant derecruitment . A low tidal volume ( 6 mL/kg ) with high PEEP ( 14 ± 3 cm H2O ) , however , induced a significantly greater recruitment and a higher Pao2 than the two other strategies . Conclusion At a given plateau pressure ( i.e. , similar end-inspiratory distension ) , lowering tidal volume and increasing PEEP increase recruitment and Pao2 BACKGROUND Protective ventilation , in general , includes low tidal volume ventilation and maintaining end-inspiratory plateau pressures less than 35 cmH2O . Recent clinical studies have determined that such an approach results in improved survival in patients with moderate to severe acute lung injury and acute respiratory distress syndrome . However , experimental evidence suggests that repeated end-expiratory collapse and reexpansion contributes to ventilator-induced lung injury . We sought to determine the immediate effects of specific tidal volume-PEEP combinations upon oxygenation and static compliance in patients with moderate to severe acute lung injury . METHODS Fourteen patients were prospect ively studied and were treated with each of 10 tidal volume-PEEP combinations , applied in r and om order . After 5 minutes at each tidal volume-PEEP combination , PaO2/FIO2 and static compliance were recorded . Comparisons were made between low and high tidal volume ventilation as well as across five PEEP levels . RESULTS At both low ( 6 mL/kg ) and high ( 10 mL/kg ) tidal volume ventilation , PaO2/FIO2 increased with increasing PEEP , up to 20 cmH2O . Similar changes in static compliance were not evident . Static compliance was highest at PEEP of 10 and 15 cmH2O , regardless of tidal volume . With PEEP set at 5 cmH2O , static compliance was significantly lower with 6 mL/kg than with 10 mL/kg tidal volumes . Overall , static compliance was lowest for both tidal volume conditions with PEEP set at 25 cmH2O . CONCLUSION Low tidal volume ventilation with PEEP set at 5 cmH2O results in poor oxygenation and compliance in patients with moderate to severe acute lung injury . Similarly , PEEP set at 25 cmH2O did not improve oxygenation or compliance BACKGROUND Acute lung injury is a critical illness syndrome consisting of acute hypoxemic respiratory failure with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension . Despite recent advances in our underst and ing of the mechanism and treatment of acute lung injury , its incidence and outcomes in the United States have been unclear . METHODS We conducted a prospect i ve , population -based , cohort study in 21 hospitals in and around King County , Washington , from April 1999 through July 2000 , using a vali date d screening protocol to identify patients who met the consensus criteria for acute lung injury . RESULTS A total of 1113 King County residents undergoing mechanical ventilation met the criteria for acute lung injury and were 15 years of age or older . On the basis of this figure , the crude incidence of acute lung injury was 78.9 per 100,000 person-years and the age-adjusted incidence was 86.2 per 100,000 person-years . The in-hospital mortality rate was 38.5 percent . The incidence of acute lung injury increased with age from 16 per 100,000 person-years for those 15 through 19 years of age to 306 per 100,000 person-years for those 75 through 84 years of age . Mortality increased with age from 24 percent for patients 15 through 19 years of age to 60 percent for patients 85 years of age or older ( P<0.001 ) . We estimate that each year in the United States there are 190,600 cases of acute lung injury , which are associated with 74,500 deaths and 3.6 million hospital days . CONCLUSIONS Acute lung injury has a substantial impact on public health , with an incidence in the United States that is considerably higher than previous reports have suggested Background : Recruitment maneuvers performed in early adult respiratory distress syndrome remain a matter of dispute in patients ventilated with low tidal volumes and high levels of positive end-expiratory pressure ( PEEP ) . In this prospect i ve , r and omized controlled study the authors evaluated the impact of recruitment maneuvers after a PEEP trial on oxygenation and venous admixture ( Qs/Qt ) in patients with early extrapulmonary adult respiratory distress syndrome . Methods : After a PEEP trial 30 consecutive patients ventilated with low tidal volumes and high levels of PEEP were r and omly assigned to either undergo a recruitment maneuver or not . Data were recorded at baseline , 3 min after the recruitment maneuver , and 30 min after baseline . Recruitment maneuvers were performed with a sustained inflation of 50 cm H2O maintained for 30 s. Results : Compared with baseline the ratio of the arterial oxygen partial pressure to the fraction of inspired oxygen ( Pao2/Fio2 ) and Qs/Qt improved significantly at 3 min after the recruitment maneuver ( Pao2/Fio2 , 139 ± 46 mm Hg versus 246 ± 111 mm Hg , P < 0.001 ; Qs/Qt , 30.8 ± 5.8 % versus 21.5 ± 9.7 % , P < 0.005 ) , but baseline values were reached again within 30 min . No significant differences in Pao2/Fio2 and Qs/Qt were detected between the recruitment maneuver group and the control group at baseline and after 30 min ( recruitment maneuver group [ n = 15 ] : Pao2/Fio2 , 139 ± 46 mm Hg versus 138 ± 39 mm Hg ; Qs/Qt , 30.8 ± 5.8 % versus 29.2 ± 7.4 % ; control group : [ n = 15 ] : Pao2/Fio2 , 145 ± 33 mm Hg versus 155 ± 52 mm Hg ; Qs/Qt , 30.2 ± 8.5 % versus 28.1 ± 5.4 % ) . Conclusion : In patients with early extrapulmonary adult respiratory distress syndrome who underwent a PEEP trial , recruitment maneuvers failed to induce a sustained improvement of oxygenation and venous admixture BACKGROUND Most patients requiring mechanical ventilation for acute lung injury and the acute respiratory distress syndrome ( ARDS ) receive positive end-expiratory pressure ( PEEP ) of 5 to 12 cm of water . Higher PEEP levels may improve oxygenation and reduce ventilator-induced lung injury but may also cause circulatory depression and lung injury from overdistention . We conducted this trial to compare the effects of higher and lower PEEP levels on clinical outcomes in these patients . METHODS We r and omly assigned 549 patients with acute lung injury and ARDS to receive mechanical ventilation with either lower or higher PEEP levels , which were set according to different tables of predetermined combinations of PEEP and fraction of inspired oxygen . RESULTS Mean ( + /-SD ) PEEP values on days 1 through 4 were 8.3+/-3.2 cm of water in the lower-PEEP group and 13.2+/-3.5 cm of water in the higher-PEEP group ( P<0.001 ) . The rates of death before hospital discharge were 24.9 percent and 27.5 percent , respectively ( P=0.48 ; 95 percent confidence interval for the difference between groups , -10.0 to 4.7 percent ) . From day 1 to day 28 , breathing was unassisted for a mean of 14.5+/-10.4 days in the lower-PEEP group and 13.8+/-10.6 days in the higher-PEEP group ( P=0.50 ) . CONCLUSIONS These results suggest that in patients with acute lung injury and ARDS who receive mechanical ventilation with a tidal-volume goal of 6 ml per kilogram of predicted body weight and an end-inspiratory plateau-pressure limit of 30 cm of water , clinical outcomes are similar whether lower or higher PEEP levels are used 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 Objective Trials of potential new therapies in acute lung injury are difficult and expensive to conduct . This article is design ed to determine the utility , behavior , and statistical properties of a new primary end point for such trials , ventilator-free days , defined as days alive and free from mechanical ventilation . Describing the nuances of this outcome measure is particularly important because using it , while ignoring mortality , could result in misleading conclusions . Design To develop a model for the duration of ventilation and mortality and fit the model by using data from a recently completed clinical trial . To determine the appropriate test statistic for the new measure and derive a formula for power . To determine a formula for the probability that the test statistic will reject the null hypothesis and mortality will simultaneously show improvement . To plot power curves for the test statistic and determine sample sizes for reasonable alternative hypotheses . Setting Intensive care units . Patients Patients with acute respiratory distress syndrome or acute lung injury as defined by the American-European Consensus Conference . Main Results The proposed model fit the clinical data . Ventilator-free days were improved by lower tidal volume ventilation , but the improvement was mostly caused by the improved mortality rate , so trials that expected similar effects would only have modest increase in power if they used ventilator-free days as their primary end point rather than 28-day mortality . Similar results were obtained using the model in two groups segregated by low or high Acute Physiology and Chronic Health Evaluation score . On the other h and , if patients are divided into two groups on the basis of the lung injury score , both the duration of ventilation and mortality are lower in the low lung injury score group . A trial of a treatment that had a similar clinical effect would have a large increase in power , allowing for a reduction in the required sample size . Conclusions Use of ventilator-free days as a trial end point allows smaller sample sizes if it is assumed that the treatment being tested simultaneously reduces the duration of ventilation and improves mortality . It is unlikely that a treatment that led to higher mortality could lead to a statistically significant improvement in ventilator-free days . This would be especially true if the treatment were also required to produce a nominal improvement in mortality Purpose Lung volumes , especially functional residual capacity ( FRC ) , are decreased in acute respiratory distress syndrome ( ARDS ) .  Positive end-expiratory pressure ( PEEP ) contributes to increased end-expiratory lung volume ( EELV ) and to improved oxygenation , but differentiating recruitment of previously nonaerated lung units from distension of previously open lung units remains difficult . This study evaluated simple methods derived from bedside EELV measurements to assess PEEP-induced lung recruitment while monitoring strain . Methods Prospect i ve multicenter study in 30 mechanically ventilated patients with ARDS in five university hospital ICUs . Two PEEP levels were studied , each for 45 min , and  EELV ( nitrogen washout/washin technique )  was measured at both levels , with the difference ( Δ ) reflecting PEEP-induced lung volume changes . Alveolar recruitment was measured using pressure-volume ( PV ) curves . High and low recruiters were separated based on median recruitment at high PEEP . Minimum predicted increase in lung volume computed as the product of ΔPEEP by static compliance was subtracted from ΔEELV as an independent estimate of recruitment . Estimated and measured recruitments were compared . Strain induced by PEEP was also calculated from the same measurements . Results FRC was 31 ± 11 % of predicted . Median [ 25th–75th percentiles ] PEEP-induced recruitment was 272 [ 187–355 ] mL. Estimated recruitment correlated with recruited volume measured on PV curves ( ρ = 0.68 ) , with a slope close to identity . The ΔEELV/FRC ratio differentiated high from low recruiters ( 110 [ 76–135 ] vs. 55 [23–70]% , p = 0.001 ) . Strain increase due to PEEP was larger in high recruiters ( p = 0.002 ) . Conclusion PEEP-induced recruitment and strain can be assessed at the bedside using EELV measurement . We describe two bedside methods for predicting low or high alveolar recruitment during ARDS BACKGROUND In patients with the acute respiratory distress syndrome , pneumothorax and other air leaks - any extrusion of air outside the tracheobronchial tree - have been attributed to high ventilatory pressures or volumes and linked to increased mortality . METHODS We analyzed data from a prospect i ve trial of aerosolized synthetic surfactant in 725 patients with the acute respiratory distress syndrome induced by sepsis . We compared the ventilatory pressures and volumes in the patients without any air leaks ( the highest values during the five-day study ) with the pressures and volumes in those with pneumothorax or with any air leaks ( the highest values during the 16- and 24-hour periods before the complication developed ) . RESULTS Fifty patients ( 6.9 percent ) had pneumothorax and 77 ( 10.6 percent ) had pneumothorax or other air leaks .  There were no significant differences between patients with air leaks and those without air leaks in any pressure or volume examined . Overall mortality at 30 days was 40.0 percent ( 95 percent confidence interval , 36.4 to 43.6 ) ; among the patients with pneumothorax , it was 46.0 percent ( 95 percent confidence interval , 32.2 to 59.8 ) , and among those without pneumothorax , it was 39.3 percent ( 95 percent confidence interval , 35.6 to 43.0 ; P=0.35 ) . The mortality rate was 45.5 percent ( 95 percent confidence interval , 34.4 to 56.6 ) in the group with any air leaks and 39.0 percent ( 95 percent confidence interval , 35.3 to 42.8 ) in the group without air leaks ( P=0.28 ) . CONCLUSIONS In patients with sepsis-induced acute respiratory distress syndrome who were receiving mechanical ventilation with conventional pressures and volumes , there were no significant correlations between high ventilatory pressures or volumes and the development of pneumothorax or other air leaks . Pneumothorax or other air leaks were not associated with a significantly increased mortality rate
BACKGROUND Mortality in patients with acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) remains high .
These patients require mechanical ventilation , but this modality has been associated with ventilator-induced lung injury .
High levels of positive end-expiratory pressure ( PEEP ) could reduce this condition and improve patient survival .
OBJECTIVES To assess the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS .