Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and 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. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial* 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. Airway pressures and early barotrauma in patients with acute lung injury and acute respiratory distress syndrome. Hemodynamic impact of a positive end-expiratory pressure setting in acute respiratory distress syndrome: Importance of the volume status* Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. Adjusting positive end‐expiratory pressure and tidal volume in acute respiratory distress syndrome according to the pressure–volume curve Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome.
BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use CONTEXT Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome . Instituting additional strategies to open collapsed lung tissue may further reduce mortality . OBJECTIVE To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original " open-lung approach , " combining low tidal volume , lung recruitment maneuvers , and high positive-end-expiratory pressure . DESIGN AND SETTING R and omized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada , Australia , and Saudi Arabia . PATIENTS Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250 . INTERVENTIONS The control strategy included target tidal volumes of 6 mL/kg of predicted body weight , plateau airway pressures not exceeding 30 cm H2O , and conventional levels of positive end-expiratory pressure ( n = 508 ) . The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight , plateau pressures not exceeding 40 cm H2O , recruitment maneuvers , and higher positive end-expiratory pressures ( n = 475 ) . MAIN OUTCOME MEASURE All-cause hospital mortality . RESULTS Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment . Tidal volumes remained similar in the 2 groups , and mean positive end-expiratory pressures were 14.6 ( SD , 3.4 ) cm H2O in the experimental group vs 9.8 ( SD , 2.7 ) cm H2O among controls during the first 72 hours ( P < .001 ) . All-cause hospital mortality rates were 36.4 % and 40.4 % , respectively ( relative risk [ RR ] , 0.90 ; 95 % confidence interval [ CI ] , 0.77 - 1.05 ; P = .19 ) . Barotrauma rates were 11.2 % and 9.1 % ( RR , 1.21 ; 95 % CI , 0.83 - 1.75 ; P = .33 ) . The experimental group had lower rates of refractory hypoxemia ( 4.6 % vs 10.2 % ; RR , 0.54 ; 95 % CI , 0.34 - 0.86 ; P = .01 ) , death with refractory hypoxemia ( 4.2 % vs 8.9 % ; RR , 0.56 ; 95 % CI , 0.34 - 0.93 ; P = .03 ) , and previously defined eligible use of rescue therapies ( 5.1 % vs 9.3 % ; RR , 0.61 ; 95 % CI , 0.38 - 0.99 ; P = .045 ) . CONCLUSIONS For patients with acute lung injury and acute respiratory distress syndrome , a multifaceted protocol ized ventilation strategy design ed to recruit and open the lung result ed in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocol ized ventilation strategy . This " open-lung " strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00182195 Objective : It has been shown in a two-center study that high positive end-expiratory pressure ( PEEP ) and low tidal volume ( LTV ) improved outcome in ARDS . However , that study involved patients with underlying diseases unique to the study area , was conducted at only two centers , and enrolled a small number of patients . We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system ( Pflex ) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome ( ARDS ) . Design : R and omized , controlled clinical trial . Setting : Network of eight Spanish multidisciplinary intensive care units ( ICUs ) under the acronym of ARIES ( Acute Respiratory Insufficiency : España Study ) . Patients : All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study . If 24 hrs after meeting ARDS criteria , the Pao2/Fio2 remained ≤200 mm Hg on st and ard ventilator setting s , patients were r and omized into two groups : control and Pflex/LTV . Interventions : In the control group , tidal volume was 9–11 mL/kg of predicted body weight ( PBW ) and PEEP ≥5 cm H2O . In the Pflex/LTV group , tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O . In both groups , Fio2 was set to maintain arterial oxygen saturation > 90 % and Pao2 70–100 mm Hg , and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg . Measurements and Main Results : The study was stopped early based on an efficacy stopping rule as described in the methods . Of 103 patients who were enrolled ( 50 control and 53 Pflex ) , eight patients ( five in control , three in Pflex ) were excluded from the final evaluation because the r and om group assignment was not performed in one center according to protocol . Main outcome measures were ICU and hospital mortality , ventilator-free days , and nonpulmonary organ dysfunction . ICU mortality ( 24 of 45 [ 53.3 % ] vs. 16 of 50 [ 32 % ] , p = .040 ) , hospital mortality ( 25 of 45 [ 55.5 % ] vs. 17 of 50 [ 34 % ] , p = .041 )  , and ventilator-free days at day 28 ( 6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV , p = .008 ) all favored Pflex/LTV . The mean difference in the number of additional organ failures postr and omization was higher in the control group ( p < .001 ) . Conclusions : A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS The associated use of permissive hypercapnia ( PHY ) and high PEEP levels ( PEEP(IDEAL ) ) has been recently indicated as part of a lung-protective-approach ( LPA ) in acute respiratory distress syndrome ( ARDS ) . However , the net hemodynamic effect produced by this association is not known . We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients ( mean age 34 + /- 13 yr ) with ARDS , focusing on its immediate ( after 1 h ) , early ( first 36 h ) , and late ( 2nd-7th d ) consequences . Twenty-five patients were su bmi tted to LPA -- with the combined use of permissive hypercapnia ( PHY ) , VT < 6 ml/kg , distending pressures above PEEP < 20 cm H2O , and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve ( P(FLEX))- and 23 control patients were su bmi tted to conventional mechanical ventilation .  LPA was initiated at once , result ing in an immediate increase in heart rate ( p = 0.0002 ) , cardiac output ( p = 0.0002 ) , oxygen delivery ( DO2l , p = 0.0003 ) , and mixed venous Po2 ( p = 0.0006 ) , with a maintained systemic oxygen consumption ( p = 0.52 ) . The mean pulmonary arterial pressure markedly increased ( mean increment 8.8 mm Hg ; p < 0.0001 ) , but the pulmonary vascular resistance did not change ( p = 0.32 ) . Cardiac filling pressures increased ( p < 0.001 ) and the systemic vascular resistance fell ( p = 0.003 ) . All these alterations were progressively attenuated in the course of the first 36 h , despite persisting hypercapnia . Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients ( p < 0.0001 ) . No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved . A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis , with no depressant effects ascribed to high PEEP levels . In contrast , high plateau pressures were associated with cardiovascular depression . Thus , as long as sufficiently low distending pressures are concomitantly applied , the sudden installation of PHY plus PEEP(IDEAL ) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals su bmi tted to  artificial ventilation  . To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome ( ARDS ) su bmi tted to conventional mechanical ventilation ( MV ) , we evaluated the impact of a new ventilatory strategy directed at minimizing " cyclic parenchymal stretch . " After receiving pre-established levels of hemodynamic , infectious , and general care , 28 patients with early ARDS were r and omly assigned to receive either MV based on a new approach ( NA , consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve , VT < 6 ml/kg , peak pressures < 40 cm H2O , permissive hypercapnia , and stepwise utilization of pressure-limited modes ) or a conventional approach ( C = conventional volume-cycled ventilation , VT = 12 ml/kg , minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels ) . Fifteen patients were selected to receive NA , exhibiting a better evolution of the PaO2/FIO2 ratio ( p < 0.0001 ) and of compliance ( p = 0.0018 ) , requiring shorter periods under FIO2 > 50 % ( p = 0.001 ) and a lower FIO2 at the day of death ( p = 0.0002 ) . After correcting for baseline imbalances in APACHE II , we observed a higher weaning rate in NA ( p = 0.014 ) but not a significantly improved survival ( overall mortality : 5/15 in NA versus 7/13 in C , p = 0.45 ) . We concluded that the NA ventilatory strategy can markedly improve the lung function  in patients with ARDS , increasing the chances of early weaning and lung recovery during mechanical ventilation The determinants of barotrauma in mechanically ventilated patients with acute lung injury or acute respiratory distress syndrome ( ALI/ARDS ) have not been clearly established . Using data from ARDS Network r and omized controlled trials , we retrospectively examined the association between airway pressures and the risk of early barotrauma in a cohort of 718 patients with ALI/ARDS and no baseline barotrauma . We studied airway pressures at three exposure intervals : baseline , one 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 Objective : The hemodynamic impact of positive end-expiratory pressure in acute respiratory distress syndrome and the underlying mechanisms have not been extensively investigated during low stretch ventilation . Our aim was to evaluate the hemodynamic effect of increasing positive end-expiratory pressure when tidal volume and the plateau pressure are limited and to explore the underlying mechanisms . Design : Prospect i ve study . Setting : Medical intensive care unit . Patients : Twenty-one acute respiratory distress syndrome patients ventilated with a tidal volume of 6.0 ± 0.5 mL/kg of predicted body weight . Intervention :  Positive end-expiratory pressure  was significantly increased from 5 ± 1 cm H2O to 13 ± 4 cm H2O for reaching a plateau pressure of 30 ± 1 cm H2O . At high positive end-expiratory pressure , passive leg raising was performed for increasing the central blood volume . Measurements : We performed echocardiography and pulmonary artery catheterization during positive end-expiratory pressure increase and during passive leg raising at high positive end-expiratory pressure . Main Results : With positive end-expiratory pressure elevation , the cardiac index decreased by 13 % ± 9 % . The right ventricular end-diastolic area , right atrial pressure , and pulmonary vascular resistance increased by 13 % ± 20 % , 34 % ± 24 % and 32 % ± 31 % , respectively ( p < .01 ; p = .04 ; and p < .01 vs. baseline , respectively ) . The transpulmonary pressure difference ( mean pulmonary artery pressure – pulmonary artery occlusion pressure ) increased ( p < .05 ) . Both at low and high positive end-expiratory pressure , an acute cor pulmonale was observed in the same three ( 14 % ) patients . At high positive end-expiratory pressure , the passive leg raising significantly increased the right and left ventricular end-diastolic areas and right atrial pressure  . Passive leg raising also decreased the transpulmonary pressure difference ( p < .05 ) , increased the cardiac index by 14 % ± 10 % , and decreased the pulmonary vascular resistance by 21 % ± 20 % ( both p < .01 vs. baseline ) . Conclusions : In acute respiratory distress syndrome patients , a positive end-expiratory pressure increase with limited tidal volume and plateau pressure reduced cardiac output by increasing the right ventricular afterload . Passive leg raising restored cardiac output by reducing the transpulmonary pressure difference and the pulmonary vascular resistance . This suggests that some pulmonary microvessels were collapsed by positive end-expiratory pressure elevation and were recruited by increasing the central blood volume 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 : Management of acute respiratory distress syndrome ( ARDS ) patients implies the selection of the adequate ventilatory parameters , essentially PEEP and tidal volume ( Vt ) , to prevent ventilator‐induced lung injury . These parameters should be reset as the lung injury evolves . Among the different methods proposed for the adjustment of the ventilator , the measurement of the P – V curve has emerged as a useful , although debated , tool . Our aim has been to study the relationship between the different inflection points of the P – V curve in ARDS patients , and to assess the changes in the empiric PEEP and Vt ( PEEPemp , Vtemp ) following its use 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 Mechanical ventilation may promote overdistension-induced pulmonary lesions in patients with acute respiratory distress syndrome ( ARDS ) . The static pressure-volume ( P-V ) curve of the respiratory system can be used to determine the lung volume and corresponding static airway pressure at which lung compliance begins to diminish ( the upper inflection point , or UIP ) . This fall in compliance may indicate overdistension of lung units . We prospect ively studied 42 patients receiving mechanical ventilation with an FIO2 of 0.5 or more for at least 24 h. According to the Lung Injury Score ( LIS ) , 25 patients were classified as having ARDS ( LIS > 2.5 ) , while 17 patients constituted a non-ARDS control group . The P-V curve was obtained every 2 d. Mechanical ventilation initially used st and ard setting s ( volume-control mode , a positive end-expiratory pressure [ PEEP ] adjusted to the lower inflection point on the P-V curve , and a tidal volume [ VT ] of 10 ml/kg ) . The end-inspiratory plateau pressure ( Pplat ) was compared to the UIP , and VT was lowered when the Pplat was above the UIP . In the range of lung volume studied on the P-V curves ( up to 1600 ml ) , a UIP could be shown in only one control patient ( at 23 cm H2O ) . By contrast , a UIP was present on the P-V curve obtained from all patients with ARDS , corresponding to a mean airway pressure of 26 + /- 6 cm H2O , a lung volume of 850 + /- 200 ml above functional residual capacity and 610 + /- 235 ml above PEEP . ( ABSTRACT TRUNCATED AT 250 WORDS
Purpose Methods to optimize positive end-expiratory pressure ( PEEP ) in acute respiratory distress syndrome ( ARDS ) remain controversial despite decades of research .
The pressure – volume curve ( PVC ) , a graphical ventilator relationship , has been proposed for prescription of PEEP in ARDS .
Whether the use of PVC ’s improves survival remains unclear .