Positive end-expiratory pressure setting in adults with acute lung injury and acute respiratory distress syndrome: a randomized controlled trial. [Treatment of acute respiratory distress syndrome using pressure and volume controlled ventilation with lung protective strategy]. Mechanical ventilation guided by esophageal pressure in acute lung injury. Airway pressure release ventilation during acute lung injury: A prospective multicenter trial Incidence and Outcomes of Pediatric Acute Lung Injury Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. Efficacy of positive end-expiratory pressure titration after the alveolar recruitment manoeuvre in patients with acute respiratory distress syndrome Comparison of volume controlled with pressure controlled ventilation during one-lung anaesthesia. Work of breathing during lung-protective ventilation in patients with acute lung injury and acute respiratory distress syndrome: a comparison between volume and pressure-regulated breathing modes. A randomized prospective trial of airway pressure release ventilation and low tidal volume ventilation in adult trauma patients with acute respiratory failure. 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. Lower tidal volume ventilation and plasma cytokine markers of inflammation in patients with acute lung injury* Beta-Agonist Lung injury TrIal-2 (BALTI-2): a multicentre, randomised, double-blind, placebo-controlled trial and economic evaluation of intravenous infusion of salbutamol versus placebo in patients with acute respiratory distress syndrome. Etiology and Outcomes of ARDS in a Rural-Urban Fringe Hospital of South India 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. Effects of short-term pressure-controlled ventilation on gas exchange, airway pressures, and gas distribution in patients with acute lung injury/ARDS: comparison with volume-controlled ventilation. Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. Prone position and positive end-expiratory pressure in acute respiratory distress syndrome* ARDSNet lower tidal volume ventilatory strategy may generate intrinsic positive end-expiratory pressure in patients with acute respiratory distress syndrome. Impact of Distinct Definitions of Acute Lung Injury on Its Incidence and Outcomes in Brazilian ICUs: Prospective Evaluation of 7,133 Patients* Methods for combining randomized clinical trials: strengths and limitations. High values of the pulmonary artery wedge pressure in patients with acute lung injury and acute respiratory distress syndrome Comparison of volume control and pressure control ventilation: is flow waveform the difference? Cardiorespiratory effects of pressure-controlled ventilation with and without inverse ratio in the adult respiratory distress syndrome. An attempt to validate the modification of the American-European consensus definition of acute lung injury/acute respiratory distress syndrome by the Berlin definition in a university hospital Volume-controlled ventilation and pressure-controlled inverse ratio ventilation: a comparison of their effects in ARDS patients. Effects of Pressure‐controlled with Different I: E Ratios Versus Volume‐controlled Ventilation on Respiratory Mechanics, Gas Exchange, and Hemodynamics in Patients with Adult Respiratory Distress Syndrome Efficacy of low tidal volume ventilation in patients with different clinical risk factors for acute lung injury and the acute respiratory distress syndrome. Incidence and outcomes of acute lung injury. Neuromuscular blocking agents decrease inflammatory response in patients presenting with acute respiratory distress syndrome* Higher versus lower positive end-expiratory pressures in patients with the acute respiratory distress syndrome. [A comparison of ventilation techniques in ARDS. Volume controlled vs pressure regulated volume control]. Patient comfort during pressure support and volume controlled-continuous mandatory ventilation. Patient-ventilator synchrony during pressure-targeted versus flow-targeted small tidal volume assisted ventilation. Effect of inspiratory flow pattern and inspiratory to expiratory ratio on nonlinear elastic behavior in patients with acute lung injury. Randomized, prospective trial of pressure‐limited versus volume‐controlled ventilation in severe respiratory failure Long-term effects of spontaneous breathing during ventilatory support in patients with acute lung injury. Combined effects of prone positioning and airway pressure release ventilation on gas exchange in patients with acute lung injury Decelerating flow ventilation effects in acute respiratory failure. Evaluation of a ventilation strategy to prevent barotrauma in patients at high risk for acute respiratory distress syndrome. Pressure- and Volume-Limited Ventilation Strategy Group. Comparison of breathing comfort during weaning with two ventilatory modes. Volume-controlled versus biphasic positive airway pressure ventilation in leukopenic patients with severe respiratory failure. Pressure-controlled ventilation improves oxygenation during laparoscopic obesity surgery compared with volume-controlled ventilation. Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: a randomized clinical trial. The effects of pressure control versus volume control assisted ventilation on patient work of breathing in acute lung injury and acute respiratory distress syndrome. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome* Mechanical Ventilation with Lower Tidal Volumes and Positive End-expiratory Pressure Prevents Alveolar Coagulation in Patients without Lung Injury
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 OBJECTIVE To investigate the significance and effect of pressure controlled ventilation ( PCV ) as well as volume controlled ventilation ( VCV ) by lung protective strategy on respiratory mechanics , blood gas analysis and hemodynamics in patients with acute respiratory distress syndrome ( ARDS ) . METHODS Fifty patients with ARDS were r and omly divided into PCV and VCV groups with permissive hypercapnia and open lung strategy . Changes in respiratory mechanics , blood gas analysis and hemodynamics were compared between two groups . RESULTS Peak inspiration pressure ( PIP ) in PCV group was significantly lower than that in VCV group , while mean pressure of airway ( MPaw ) was significantly higher than that in VCV after 24 hours mechanical ventilation . After 24 hours mechanical ventilation , there were higher central venous pressure ( CVP ) and slower heart rate ( HR ) in two groups , CVP was significantly higher in VCV compared with PCV , and PCV group had slower HR than VCV group , the two groups had no differences in mean blood pressure ( MBP ) at various intervals . All patients showed no ventilator-induced lung injury . Arterial blood oxygenations were obviously improved in two groups after 24 hours mechanical ventilation , PCV group had better partial pressure of oxygen in artery ( PaO2 ) than VCV group . CONCLUSION Both PCV and VCV can improve arterial blood oxygenations , prevent ventilator-induced lung injury , and have less disturbance in hemodynamic parameters .  PCV with lung protective ventilatory strategy should be early use for patients with ARDS 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 . Objective To evaluate the feasibility of airway pressure release ventilation ( APRV ) in providing ventilatory support to patients with acute lung injury of diverse etiology and mild-to-moderate severity . Design Prospect i ve , multicenter , nonr and omized crossover trial . Setting ICUs in six major referral hospitals . Patients Fifty adult patients with respiratory failure requiring mechanical ventilation and positive end-expiratory airway pressure . Interventions After optimization of continuous positive airway pressure ( CPAP ) , conventional ventilation and APRV were administered sequentially for 30 mins . During APRV , the CPAP level and airway pressure release level were adjusted to prevent hypoxemia , while the degree of ventilatory support was adjusted by altering the frequency of pressure release . Measurements and Main Results Circulatory and ventilatory pressures , arterial blood gases and pH , heart rate , and respiratory rate were measured . Alveolar ventilation was augmented adequately in 47 of 50 patients by APRV . Adjustment of APRV required an increase in mean CPAP from 13 ± 3 ( SD ) to 21 ± 9 cm H2O and a release pressure of 6 ± 5 cm H2O . This airway pressure pattern produced a mean airway pressure comparable to that pressure achieved during conventional ventilation . Failure of APRV in three patients could be attributed to an inadequate level of CPAP or an inadequate APRV rate . While maintaining oxygenation of arterial blood and circulatory function  , APRV allowed a substantial ( 55 ± 17 % ; p < .0001 ) reduction in peak airway pressure compared with conventional positive pressure ventilation adjusted to deliver a comparable or lower level of ventilatory support . Conclusions APRV is a feasible alternative to conventional mechanical ventilation for augmentation of alveolar ventilation in patients with acute lung injury of mild-to-moderate severity OBJECTIVE : This population -based , prospect i ve , cohort study was design ed to determine the population incidence and outcomes of pediatric acute lung injury . METHODS : Between 1999 and 2000 , 1 year of screening was performed at all hospitals admitting critically ill children in King County , Washington . County residents 0.5 to 15 years of age who required invasive ( through endotracheal tube or tracheostomy ) or noninvasive ( through full face mask ) mechanical ventilation , regardless of the duration of mechanical ventilation , were screened . From this population , children meeting North American-European Consensus Conference acute lung injury criteria were eligible for enrollment . Postoperative patients who received mechanical ventilation for < 24 hours were excluded . Data collected included the presence of predefined cardiac conditions , demographic and physiological data , duration of mechanical ventilation , and deaths . US Census population figures were used to estimate incidence . Associations between outcomes and subgroups identified a priori were assessed . RESULTS : Thirty-nine children met the criteria for acute lung injury , result ing in a calculated incidence of 12.8 cases per 100000 person-years . Severe sepsis ( with pneumonia as the infection focus ) was the most common risk factor . The median 24-hour Pediatric Risk of Mortality III score was 9.0 , and the mean ± SD was 11.7 ± 7.5 . The hospital mortality rate was 18 % , lower than that reported previously for pediatric acute lung injury . There were no statistically significant associations between age , gender , or risk factors and outcomes . CONCLUSIONS : We present the first population -based estimate of pediatric acute lung injury incidence in the United States . Population incidence and mortality rates are lower than those for adult acute lung injury . Low mortality rates in pediatric acute lung injury may necessitate clinical trial outcome measures other than death 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 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 Pressure controlled ventilation ( PCV ) is an alternative mode of ventilation which is used widely in severe respiratory failure . In this study , PCV was used for one-lung anaesthesia and its effects on airway pressures , arterial oxygenation and haemodynamic state were compared with volume controlled ventilation ( VCV ) . We studied 48 patients undergoing thoracotomy .  After two-lung ventilation with VCV , patients were allocated r and omly to one of two groups . In the first group ( n = 24 ) , one-lung ventilation was started by VCV and the ventilation mode was then switched to PCV . Ventilation modes were performed in the opposite order in the second group ( n = 24 ) . We observed that peak airway pressure ( P = 0.000001 ) , plateau pressure ( P = 0.01 ) and pulmonary shunt ( P = 0.03 ) were significantly higher during VCV , whereas arterial oxygen tension ( P = 0.02 ) was significantly higher during PCV .  Peak airway pressure ( Paw ) decreased consistently during PCV in every patient and the percentage reduction in Paw was 4 - 35 % ( mean 16.1 ( SD 8.4 ) % ) . Arterial oxygen tension increased in 31 patients using PCV and the improvement in arterial oxygenation during PCV correlated inversely with preoperative respiratory function tests . We conclude that PCV appeared to be an alternative to VCV in patients requiring one-lung anaesthesia and may be superior to VCV in patients with respiratory disease BACKGROUND Pressure-control ventilation ( PCV ) and pressure-regulated volume-control ( PRVC ) ventilation are used during lung-protective ventilation because the high , variable , peak inspiratory flow rate ( V ( I ) ) may reduce patient work of breathing ( WOB ) more than the fixed V ( I ) of volume-control ventilation ( VCV ) . Patient-triggered breaths during PCV and PRVC may result in excessive tidal volume ( V(T ) ) delivery unless the inspiratory pressure is reduced , which in turn may decrease the peak V ( I ) . We tested whether PCV and PRVC reduce WOB better than VCV with a high , fixed peak V ( I ) ( 75 L/min ) while also maintaining a low V(T ) target . METHODS Fourteen nonconsecutive patients with acute lung injury or acute respiratory distress syndrome were studied prospect ively , using a r and om presentation of ventilator modes in a crossover , repeated- measures design . A target V(T ) of 6.4 + 0.5 mL/kg was set during VCV and PRVC . During PCV the inspiratory pressure was set to achieve the same V(T ) . WOB and other variables were measured with a pulmonary mechanics monitor ( Bicore CP-100 ) . RESULTS There was a nonsignificant trend toward higher WOB ( in J/L ) during PCV ( 1.27 + 0.58 J/L ) and PRVC ( 1.35 + 0.60 J/L ) , compared to VCV ( 1.09 + 0.59 J/L ) . While mean V(T ) was not statistically different between modes , in 40 % of patients , V(T ) markedly exceeded the lung-protective ventilation target during PRVC and PCV . CONCLUSIONS During lung-protective ventilation , PCV and PRVC offer no advantage in reducing WOB , compared to VCV with a high flow rate , and in some patients did not allow control of V(T ) to be as precise BACKGROUND Airway pressure release ventilation ( APRV ) is a mode of mechanical ventilation , which has demonstrated potential benefits in trauma patients . We therefore sought to compare relevant pulmonary data and safety outcomes of this modality to the recommendations of the Adult Respiratory Distress Syndrome Network . METHODS Patients admitted after traumatic injury requiring mechanical ventilation were r and omized under a 72-hour waiver of consent to a respiratory protocol for APRV or low tidal volume ventilation ( LOVT ) .  Data were collected regarding demographics , Injury Severity Score , oxygenation , ventilation , airway pressure , failure of modality , tracheostomy , ventilator-associated pneumonia , ventilator days , length of stay ( LOS ) , pneumothorax , and mortality . RESULTS Sixty-three patients were enrolled during a 21-month period ending in February 2006 . Thirty-one patients were assigned to APRV and 32 to LOVT . Patients were well matched for demographic variables with no differences between groups . Mean Acute Physiology and Chronic Health Evaluation II score was higher for APRV than LOVT ( 20.5 ± 5.35 vs. 16.9 ± 7.17 ) with a p value = 0.027 . Outcome variables showed no differences between APRV and LOVT for ventilator days ( 10.49 days ± 7.23 days vs. 8.00 days ± 4.01 days ) , ICU LOS ( 16.47 days ± 12.83 days vs. 14.18 days ± 13.26 days ) , pneumothorax ( 0 % vs. 3.1 % ) , ventilator-associated pneumonia per patient ( 1.00 ± 0.86 vs. 0.56 ± 0.67 ) , percent receiving tracheostomy ( 61.3 % vs. 65.6 % ) , percent failure of modality ( 12.9 % vs. 15.6 % ) , or percent mortality ( 6.45 % vs. 6.25 % ) . CONCLUSIONS For patients sustaining significant trauma requiring mechanical ventilation for greater than 72 hours , APRV seems to have a similar safety profile as the LOVT . Trends for APRV patients to have increased ventilator days , ICU LOS , and ventilator-associated pneumonia may be explained by initial worse physiologic derangement demonstrated by higher Acute Physiology and Chronic Health Evaluation II scores 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 Objectives : To evaluate the association between interleukin-6 , interleukin-8 , and interleukin-10 and clinical outcomes including mortality in patients with acute lung injury and to determine whether lower tidal volume ventilation was associated with a decrease in plasma cytokines in patients with acute lung injury . Design : Multiple-center , r and omized trial . Setting : Intensive care units in ten university centers . Patients : The study included 861 patients enrolled in the National Heart , Lung and Blood Institute Acute Respiratory Distress Syndrome Clinical Network trial of lower tidal volumes compared with traditional tidal volumes for acute lung injury . Interventions : Patients were r and omized to a 6 mL/kg or a 12 mL/kg tidal volume strategy that has been previously described . Measurements and Main Results : Baseline plasma levels of interleukin-6 , interleukin-8 , and interleukin-10 were each associated with an increased risk of death in both logistic regression analyses controlling for ventilator group ( odds ratio 1.63 per log-10 increment , 95 % confidence interval 1.33–1.98 ; odds ratio 2.33 per log-10 increment , 95 % confidence interval 1.79–3.03 ; odds ratio 2.02 per log-10 increment , 95 % confidence interval 1.47–2.76 , respectively ) and multivariate analyses controlling for ventilation strategy , Acute Physiology and Chronic Health Evaluation III score , Pao2/Fio2 ratio , creatinine , platelet count , and vasopressor use ( odds ratio 1.63 per log-10 increment , 95 % confidence interval 0.93–1.49 ; odds ratio 1.73 per log-10 increment , 95 % confidence interval 1.29–2.34 ; odds ratio 1.23 per log-10 increment , 95 % confidence interval 0.86–1.76 , respectively ) . Interleukin-6 and interleukin-8 levels were also associated with a significant decrease in ventilator free and organ failure free days .  Patients with sepsis had the highest cytokine levels and the greatest risk of death per cytokine elevation . By day 3 , the 6 mL/kg strategy was associated with a greater decrease in interleukin-6 and interleukin-8 levels . There was a 26 % reduction in interleukin-6 ( 95 % confidence interval , 12–37 % ) and a 12 % reduction in interleukin-8 ( 95 % confidence interval , 1–23 % ) in the 6 mL/kg group compared with the 12 mL/kg group . Conclusions : In patients with acute lung injury , plasma interleukin-6 and interleukin-8 levels are associated with morbidity and mortality . The severity of inflammation varies with clinical risk factor , suggesting that clinical risk factor should be considered when both developing and testing therapeutic interventions . Low tidal volume ventilation is associated with a more rapid attenuation of the inflammatory response BACKGROUND Acute respiratory distress syndrome ( ARDS ) is a major cause of mortality in intensive care patients and lacks effective treatments . A previous r and omised controlled Phase II trial suggested that an intravenous ( i.v . ) infusion of salbutamol may be beneficial , as it reduced extravascular lung water and plateau airway pressure . The Beta-Agonist Lung injury TrIal-2 ( BALTI-2 ) was initiated to evaluate the effects of this intervention on mortality in patients with ARDS . OBJECTIVES To evaluate whether or not , in patients with ARDS , an i.v . infusion of salbutamol given at 15 μg/kg ideal body weight (IBW)/hour for up to 7 days , compared with a placebo ( 0.9 % sodium chloride ) infusion , reduces 28-day all-cause mortality and other clinical outcomes . To evaluate salbutamol 's clinical effectiveness and its cost-effectiveness in subgroups of patients . DESIGN A multicentre , r and omised , placebo-controlled trial . SETTING Forty-six intensive care units ( ICUs ) in the UK . PARTICIPANTS Patients were eligible if they ( 1 ) were intubated and mechanically ventilated patients in participating ICUs ; ( 2 ) were within 72 hours of onset of ARDS ; ( 3 ) fulfilled American-European Consensus Conference definition for ARDS { acute-onset , severe hypoxaemic respiratory failure [ partial pressure of oxygen in arterial blood/fraction of inspired oxygen ≤ 26.7 kPa ( 200 mmHg ) ] and bilateral infiltrates on the chest radiograph in the absence of clinical evidence of left atrial hypertension } ; and ( 4 ) were aged ≥ 16 years . INTERVENTIONS Intravenous infusion of salbutamol ( 15 μg/kg IBW/hour ) or placebo ( 0.9 % saline ) for up to 7 days . MAIN OUTCOME MEASURES All-cause mortality 28 days after r and omisation , mortality at ( first ) discharge from ICU , mortality at ( first ) discharge from hospital , number of ventilator-free days , number of organ failure-free days , mortality at 12 months post r and omisation , side effects ( tachycardia/new arrhythmia/lactic acidosis ) sufficient to stop treatment with trial drug , health-related quality of life ( European Quality of Life-5 Dimensions and Short Form question naire-12 items at 6 and 12 months after r and omisation ) , length of stay in critical care unit and length of stay in hospital . RESULTS Forty-six ICUs recruited patients to the trial . A total of 326 patients were r and omised ; 162 were allocated to salbutamol and 164 to placebo . One patient in each group withdrew consent . Recruitment was stopped after the second interim analysis because of safety concerns . Salbutamol  increased 28-day mortality : 55 ( 34 % ) of 161 patients died in the salbutamol group compared with 38 ( 23 % ) of 163 in the placebo group ( risk ratio 1.47 , 95 % confidence interval 1.03 to 2.08 ) . CONCLUSIONS Treatment with i.v . salbutamol early in the course of ARDS was poorly tolerated , is unlikely to be beneficial and could worsen outcomes . Further trials of β-agonists in patients with ARDS are unlikely to be conducted . Some questions remain , such as whether or not there may be benefit at a different dose or in specific population s , but any studies investigating these would require a very strong rationale . TRIAL REGISTRATION Current Controlled Trials IS RCT N38366450 . FUNDING The National Institute for Health Research Health Technology Assessment programme Objectives . Etiology and outcomes of acute lung injury in tropical countries may be different from those of western nations . We describe the etiology and outcomes of illnesses causing acute lung injury in a rural populace . Study Design . A prospect i ve observational study . Setting . Medical ICU of a teaching hospital in a rural-urban fringe location . Patients . Patients ≥13 years , admitted between December 2011 and May 2013 , satisfying AECC criteria for ALI/ARDS . Results . Study had 61 patients ; 46 had acute lung injury at admission .  Scrub typhus was the commonest cause ( 7/61 ) and tropical infections contributed to 26 % of total cases . Increasing ARDS severity was associated with older age , higher FiO2 and APACHE/SOFA scores , and longer duration of ventilation . Nonsurvivors were generally older , had shorter duration of illness , a nontropical infection , and higher total WBC counts , required longer duration of ventilation , and had other organ dysfunction and higher mean APACHE scores . The mortality rate of ARDS was 36.6 % ( 22/61 ) in our study . Conclusion . Tropical infections form a major etiological component of acute lung injury in a developing country like India . Etiology and outcomes of ARDS may vary depending upon the geographic location and seasonal illnesses 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 STUDY OBJECTIVES The potential clinical benefits of pressure-controlled ventilation ( PCV ) over volume-controlled ventilation ( VCV ) in patients with acute lung injury ( ALI ) or ARDS still remain debated . We compared PCV with VCV in patients with ALI/ARDS with respect to the following physiologic end points : ( 1 ) gas exchange and airway pressures , and ( 2 ) CT scan intrapulmonary gas distribution at end-expiration . DESIGN Prospect i ve , observational study . SETTING A multidisciplinary ICU in a nonuniversity , acute-care hospital . PATIENTS Ten patients with ALI or ARDS ( 9 men and 1 woman ; age range , 17 to 80 years ) . INTERVENTIONS Sequential ventilation in PCV and VCV with a constant inspiratory/expiratory ratio , tidal volume , respiratory rate , and total positive end-expiratory pressure ; measurement of gas exchange and airway pressures ; and achievement of CT sections at lung base , hilum , and apex for the quantitative analysis of lung densities and of aerated vs nonaerated zones . RESULTS PaO(2 ) , PaCO(2 ) , and PaO(2)/fraction of inspired oxygen ratio levels did not differ between PCV and VCV .  Peak airway pressure ( Ppeak ) was significantly lower in PCV compared with VCV ( 26 + /- 2 cm H(2)O vs 31 + /- 2 cm H(2)O ; p < 0.001 ; mean + /- SEM ) . The surface areas of the nonaerated zones as well as the total areas at each section level were unchanged in PCV compared with VCV , except at the apex level , where there was a significantly greater nonaerated area in VCV ( 11 + /- 2 cm(2 ) vs 9 + /- 2 cm(2 ) ; p < 0.05 ) . The total mean CT number of each lung ( 20 lungs from 10 patients ) was similar in the two modes , as were the density values at the basal and apical levels ; the hilum mean CT number was - 442 + /- 28 Hounsfield units ( HU ) in VCV and - 430 + /- 26 HU in PCV ( p < 0.005 ) . CONCLUSIONS These data show that PCV allows the generation of lower Ppeaks through the precise titration of the lung distending pressure , and might be applied to avoid regional overdistension by means of a more homogeneous gas distribution 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 determine whether positive end-expiratory pressure ( PEEP ) and prone position present a synergistic effect on oxygenation and if the effect of PEEP is related to computed tomography scan lung characteristic . Design Prospect i ve r and omized study . Setting French medical intensive care unit . Patients Twenty-five patients with acute respiratory distress syndrome . Interventions After a computed tomography scan was obtained , measurements were performed in all patients at four different PEEP levels ( 0 , 5 , 10 , and 15 cm H2O ) applied in r and om order in both supine and prone positions . Measurements and Main Results Analysis of variance showed that PEEP ( p < .001 ) and prone position ( p < .001 ) improved oxygenation , whereas the type of infiltrates did not influence oxygenation . PEEP and prone position presented an additive effect on oxygenation . Patients presenting diffuse infiltrates exhibited an increase of Pao2/Fio2 related to PEEP whatever the position , whereas patients presenting localized infiltrates did not have improved oxygenation status when PEEP was increased in both positions . Prone position ( p < .001 ) and PEEP ( p < .001 ) reduced the true pulmonary shunt . Analysis of variance showed that prone position ( p < .001 ) and PEEP ( p < .001 ) reduced the true pulmonary shunt . The decrease of the shunt related to PEEP was more pronounced in patients presenting diffuse infiltrates . A lower inflection point was identified in 22 patients ( 88 % ) in both supine and prone positions . There was no difference in mean lower inflection point value between the supine and the prone positions ( 8.8 ± 2.7 cm H2O vs. 8.4 ± 3.4 cm H2O , respectively ) . Conclusions PEEP and prone positioning present additive effects . The prone position , not PEEP , improves oxygenation in patients with acute respiratory distress syndrome with localized infiltrates The ARDSNet trial revealed that the use of a smaller tidal volume ( VT ) reduced mortality by 22 % . However , three earlier studies that lowered VT did not find a decrease in mortality . We tested the hypothesis that the increased respiratory rate used in the ARDSNet lower VT strategy might have led to intrinsic positive end-expiratory pressure ( PEEP(i ) ) , raising total PEEP ( PEEP(total ) ) . Ten patients with acute respiratory distress syndrome ( ARDS ) were ventilated using the ARDSNet lower VT protocol . Respiratory rate was then reduced ( 10 - 15 breaths/minute ) to obtain a VT of 12 ml/kg ( ARDSNet traditional VT ) . PEEP on the ventilator ( PEEP(nominal ) : 10.1 + /- 0.7 cm H2O ) , FIO2 ( 0.7 + /- 0.1 ) , and minute ventilation ( VE : 12.4 + /- 1.7 L/minute ) were set using the ARDSNet protocol and maintained constant during the two ventilatory strategies . Values of airway pressure at end-expiration of a regular breath ( PEEP(external ) ) and 3 - 5 seconds after the onset of an end-expiratory occlusion ( PEEP(total ) ) were measured . PEEP(i ) was calculated by subtracting PEEP(external ) from PEEP(total ) . PEEP(total ) and PEEP(i ) were , respectively , 16.3 + /- 2.9 and 5.8 + /- 3.0 cm H2O during the lower VT strategy and 11.7 + /- 0.9 and 1.4 + /- 1.0 cm H2O during the traditional VT strategy ( p < 0.01 ) . The reduced mortality observed with the ARDSNet strategy may have been due to the protective effect of a higher PEEP(total ) Objectives : Evaluation of prevalence and outcomes of acute lung injury in a large cohort of critically ill patients in Brazil and comparison of predictive receiver operating characteristic curve mortality of American European Consensus conference definition with new Berlin definition of acute respiratory distress syndrome . Design : A 15-month prospect i ve , multicenter , observational study . Setting : Fourteen medical ICUs in Espirito Santo , a state of Brazil . Patients : Mechanically ventilated patients who fulfilled American European Consensus conference criteria of acute lung injury or Berlin definition of acute respiratory distress syndrome . Interventions : Clinical and respiratory data were collected for 7 consecutive days and on the 14 and 28 days . Twenty-eight day mortality , hospital mortality , and predictive receiver operating characteristic curve mortality were calculated . Measurements and Main Results : Of 7,133 patients , 130 patients ( 1.8 % ) fulfilled criteria for acute lung injury ( American European Consensus conference ) or acute respiratory distress syndrome ( Berlin definition ) . Median time for diagnosis was 2 days ( interquartile range , 0–3 d ) . Main risk factors were pneumonia ( 35.3 % ) and nonpulmonary sepsis ( 31.5 % ) . Mean age was 44.2 ± 15.9 years , and 61.5 % were men .  Mean Acute Physiology and Chronic Health Evaluation II score was 20.7 ± 7.9 . Mean PaO2/FIO2 was 206 ± 61.5 , significantly lower in nonsurvivors on day 7 ( p = 0.003 ) . Mean mechanical ventilation time was 21 ± 15 days . Length of ICU stay was 26.4 ± 18.7 days . Twenty-eight-day mortality was 38.5 % ( 95 % CI , 30.1–46.8 ) ; hospital mortality was 49.2 % ( 95 % CI , 40.6–57.8 ) . Predictive 28-day mortality area under the receiver operating characteristic curve for American European Consensus conference definition was 0.5625 ( 95 % CI , 0.4783–0.6467 ) and for the Berlin definition 0.5664 ( 95 % CI , 0.4759–0.6568 ; p = 0.9510 ) . Conclusions : In our population , prevalence of acute lung injury was low , most cases were diagnosed 2 days after ICU admission , and Berlin definition was not different from American European Consensus conference definition in predicting mortality . There are still several problems with the global epidemiology , definition , and mortality predictive indices that should be added to the classification of this still lethal syndrome to improve its predictive mortality power in the future Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Abstract Objective . To determine the incidence and severity of pulmonary artery wedge pressure ( PAWP ) elevation in patients with ALI/ARDS . In addition , to examine the effects of clinical variables on the presence of a high PAWP ( > 18 mmHg ) and the effect of an elevated PAWP on mortality . Design and patients . Post hoc analysis of 120 patients with or at high risk of ARDS , enrolled in a r and omized controlled trial of pressure- and volume-limited ventilation . Patients with or at high risk of congestive heart failure were excluded from the original study . Setting . Eight tertiary intensive care units . Measurements and results . Pulmonary artery catheters were inserted at the discretion of the attending physician , and  PAWP  was collected every 8 h when present . Of 120 subjects 71 ( 59 % ) had a pulmonary artery catheter ( 44 at r and omization , 27 later ) . The mean maximum PAWP reading among patients was 22.5 mmHg ( 95 % CI 21.2–23.8 ) and mean median was 16.6 mmHg ( 95 % CI 15.6–17.5 ) . Patients who met st and ard criteria for ARDS were more likely to develop a high PAWP . In a multivariate stepwise logistic regression model a persistently elevated PAWP ( median > 18 mmHg ) was a strong predictor of mortality after correction for baseline differences ( OR estimate 6.82 ; 95 % CI 1.66–37.81 ) . Conclusions . We conclude that in this group of patients a PAWP higher than 18 mmHg is common . M and ating a PAWP of 18 mmHg or less may negatively impact clinical trials in which ARDS is an inclusion /exclusion criteria or an endpoint OBJECTIVE To examine the hypothesis that a decelerating inspiratory flow waveform is responsible for improvements in gas exchange during pressure control ventilation for acute lung injury . DESIGN Prospect i ve , controlled , crossover study . MEASUREMENTS AND MAIN RESULTS Twenty-five patients with acute lung injury requiring mechanical ventilation with a positive-end expiratory pressure > or = 10 cm H2O , ventilator frequency of > or = 8 bpm , inspired oxygen concentration of > or = 0.50 , peak inspiratory pressure > or = 40 cm H2O , and requiring sedation and paralysis were studied . Patients were ventilated at a tidal volume of 10 mliters/kg , respiratory frequency was set to maintain a pH > 7.30 and PaCO2 < 50 mm Hg , and positive end-expiratory pressure ( PEEP ) set to maintain Pao2 > 70 mm Hg or Sao2 > 93 % with an Fio2 < or = 0.50 . In r and om sequence , ventilator mode was changed from volume control with a square flow waveform , pressure control ventilation with a decelerating flow waveform , or volume control ventilation with a decelerating flow waveform .  Tidal volume , minute ventilation , and airway pressures were continuously measured at the proximal airway . After 2 hours of ventilation in each mode , arterial and mixed venous blood gases were drawn and cardiac output determined by thermodilution . Dead space to tidal volume ratio was determined from mixed expired gas concentrations and Paco2 . During volume control ventilation with a square flow waveform , Pao2 was decreased ( 75 + /- 11 mm Hg vs. 85 + /- 9 mm Hg and 89 + /- 12 mm Hg ) , p < 0.05 , and peak inspiratory pressure was increased ( 50 + /- 9 cm H2O vs. 42 + /- 7 cm H2O and 39 + /- 9 cm H2O ) p < 0.05 compared to volume control with a decelerating flow waveform and pressure control ventilation . Mean airway pressure was also lower with volume control with a square flow waveform ( 17 + /- 4 cm H2O vs. 20 + /- 4 cm H2O and 21 + /- 3 cm H2O ) compared to volume control with a decelerating flow waveform and pressure control ventilation . There were no differences in hemodynamic parameters . CONCLUSIONS Both pressure control ventilation and volume control ventilation with a decelerating flow waveform provided better oxygenation at a lower peak inspiratory pressure and higher mean airway pressure compared to volume control ventilation with a square flow waveform . The results of our study suggest that the reported advantages of pressure control ventilation over volume control ventilation with a square flow waveform can be accomplished with volume control ventilation with a decelerating flow waveform To assess the cardiorespiratory effects of pressure-controlled ventilation ( PCV ) and pressure-controlled inverse ratio ventilation ( PC-IRV ) , we compared pressure-controlled ventilation with an inspiratory-to-expiratory time ratio ( I/E ) of 1/2 ( PCV ) and of 2/1 ( PC-IRV ) to volume-controlled ventilation ( VCV ) with an I/E of 1/2 in 10 patients suffering from the adult respiratory distress syndrome . In all modes , the inspiratory oxygen fraction , tidal volume , respiratory rate , and total positive end-expiratory pressure ( PEEPt = applied PEEP + intrinsic PEEP ) were kept constant . Each ventilatory mode was applied for 1 h in a r and omized order . No significant differences in PaO2 were observed among the three modes . The PaCO2 was lower ( p < 0.05 ) in PC-IRV ( 39 + /- 4 mm Hg ) than in PCV ( 43 + /- 5 mm Hg ) and in VCV ( 45 + /- 5 mm Hg ) . The peak airway pressure was significantly lower in PC-IRV than in PCV ( p < 0.05 ) and in PCV than in VCV ( p < 0.05 ) , but plateau pressure was not different in the 3 modes . The mean airway pressure ( mPaw ) was significantly higher ( p < 0.05 ) in PC-IRV ( 21.4 + /- 0.7 cm H2O ) than in PCV ( 17.1 + /- 0.7 cm H2O ) and VCV ( 16.4 + /- 0.5 cm H2O ) . As a consequence of this increased mPaw , PC-IRV induced a decrease in cardiac index ( CI ) ( 3.3 + /- 0.2 vs 3.7 + /- 0.2 L/min/m2 in VCV ; p < 0.05 ) and hence in oxygen delivery ( DO2 ) ( 424 + /- 28 vs 469 + /- 38 ml/min/m2 in VCV ; p < 0.05 ) . Our results suggest that neither PCV nor PC-IRV bring any benefit over VCV in terms of arterial oxygenation . Moreover , the increase in mPaw induced by PC-IRV may be deleterious to the CI and DO2 Purpose The Berlin definition for acute respiratory distress syndrome ( ARDS ) is a new proposal for changing the American-European consensus definition but has not been assessed prospect ively as yet . In the present study , we aim ed to determine ( 1 ) the prevalence and incidence of ARDS with both definitions , and ( 2 ) the initial characteristics of patients with ARDS and 28-day mortality with the Berlin definition . Methods We performed a 6-month prospect i ve observational study in the ten adult ICUs affiliated to the Public University Hospital in Lyon , France , from March to September 2012 . Patients under invasive or noninvasive mechanical ventilation , with PaO2/FiO2 < 300 mmHg regardless of the positive end-expiratory pressure ( PEEP ) level , and acute onset of new or increased bilateral infiltrates or opacities on chest X-ray were screened from ICU admission up to discharge . Patients with cardiogenic pulmonary edema were excluded . Patients were further classified into specific categories by using the American-European Consensus Conference and the Berlin definition criteria . The complete data set was measured at the time of inclusion . Patient outcome was measured at day 28 after inclusion . Results During the study period 3,504 patients were admitted and 278 fulfilled the American-European Consensus Conference criteria . Among them , 18 ( 6.5 % ) did not comply with the Berlin criterion PEEP ≥ 5 cmH2O and 20 ( 7.2 % ) had PaO2/FiO2 ratio ≤200 while on noninvasive ventilation . By using the Berlin definition in the remaining 240 patients ( n = 42 mild , n = 123 moderate , n = 75 severe ) , the overall prevalence was 6.85 % and it was 1.20 , 3.51 , and 2.14 % for mild , moderate , and severe ARDS , respectively ( P > 0.05 between the three groups ) . The incidence of ARDS amounted to 32 per 100,000 population per year , with values for mild , moderate , and severe ARDS of 5.6 , 16.3 , and 10 per 100,000 population per year , respectively ( P < 0.05 between the three groups ) . The 28-day mortality was 35.0 % . It amounted to 30.9 % in mild , 27.9 % in moderate , and 49.3 % in severe categories ( P < 0.01 between mild or moderate and severe , P = 0.70 between mild and moderate ) . In the Cox proportional hazard regression analysis ARDS stage was not significantly associated with patient death at day 28 . Conclusions The present study did not vali date the Berlin definition of ARDS . Neither the stratification by severity nor the PaO2/FiO2 at study entry was independently associated with mortality Volume-controlled ventilation with positive end-expiratory pressure ( PEEP ) ( CPPV ) is the conventional ventilatory approach in adult respiratory distress syndrome ( ARDS ) patients , but some reports suggest that pressure-controlled ventilation with an inverse inspiratory to expiratory ratio ( PCIRV ) may improve gas exchange in these patients . We analysed the acute effects on gas exchange , lung mechanics and haemodynamics induced by CPPV and PCIRV in ARDS patients .  CPPV and PCIRV were applied r and omly in ARDS patients . During CPPV , external PEEP was titrated according to the initial inflection point in the static pressure-volume ( P-V ) curve of the respiratory system , or it was 10 cmH2O when there was no inflection . During PCIRV , external PEEP was not applied , and inspiratory to expiratory ( I/E ) ratio was inversed until total PEEP was equal to the inflection point in the P-V curve , or it was 10 cmH2O . Respiratory rate , fractional inspiratory oxygen ( FIO2 ) , and tidal volume ( VT ) were kept constant in both modes . Eight ARDS patients were studied prospect ively and admitted to a general Intensive Care Unit ( ICU ) of a University Hospital .  Haemodynamic measurements , airflow ( V ) , airway pressure ( Paw ) and VT were obtained using st and ard methods . We did not observe any significant change between CPPV and PCIRV with respect to : arterial oxygen tension ( PaO2 ) 117 + /- 12 vs 107 + /- 15 mmHg ( 16 + /- 2 vs 14 + /- 2 kPa ) , arterial carbon dioxide tension ( PaCO2 ) 40 + /- 2 vs 39 + /- 2 mmHg ( 6 + /- 0.3 vs 5 + /- 0.3 kPa ) , intrapulmonary shunt function ( QS/QT ) 36 + /- 3 vs 38 + /- 4 % , cardiac output ( CO ) 7.1 + /- 0.7 vs 7 + /- 0.8 l.min-1 , and total PEEP 9.7 + /- 0.6 vs 9 + /- 0.3 cmH2O . Oxygen transport and total respiratory system compliance remained unchanged in both modes . Mean Paw was slightly lower during CPPV ( 17 + /- 1 cmH2O ) than during PCIRV ( 19 + /- 1 cmH2O ) . PCIRV does not appear to have clinical advantages over CPPV in terms of gas exchange , haemodynamics , or static lung mechanics when using the same total PEEP and minute ventilation Background : Pressure-controlled ( PCV ) and pressure-controlled inverse ratio ventilation ( PCIRV ) have been proposed instead of volume-controlled conventional ratio ventilation ( VC ) with positive end-expiratory pressure ( PEEP ) for patients with adult respiratory distress syndrome ( ARDS ) . The advantages advocated with the use of PCIRV are to decrease airway pressures and to improve gas exchange . However , most studies did not compare PCIRV and VC while keeping both the level of ventilation and end-expiratory alveolar pressure ( total-PEEP ) constant . Methods : Nine patients with moderate to severe ARDS ( lung injury score 2.83 ± 0.18 ) had their lungs ventilated with VC , PCV with a conventional ratio ( I : E 1:2 ; PC 1/2 ) , and PCIRV ( I : E 2:1 and 3:1 ; PC 2/1 and PC 3/1 , respectively ) . Ventilator setting s were adjusted to keep tidal volume , respiratory rate , Fio2 , and total-PEEP constant in every mode . With each mode , a complete set of ventilatory , hemodynamic , and gas exchange parameters was obtained after 30 min . Results : In PC 3/1 , the data obtained could not be strictly compared to the other modes because total-PEEP was higher despite external-PEEP being set at zero . For the other modes ( VC , PC 1/2 , and PC 2/1 ) , despite differences in peak airway pressures , no difference was noted for end-inspiratory and end-expiratory static airway pressures ( which better reflect alveolar pressures ) nor for lung and respiratory system compliance . Arterial oxygenation deteriorated slightly with PC 2/1 despite a higher mean airway pressure , whereas alveolar ventilation tended to be slightly , but not significantly , improved ( lower Paco2 ) . A decrease in systolic and mean arterial pressure also was observed with PC 2/1 without other significant hemodynamic change . Conclusions : In this prospect i ve controlled study , no short-term beneficial effect of PCV or PCIRV could be demonstrated over conventional VC with PEEP in patients with ARDS In patients with acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) , a recent ARDS Network r and omized controlled trial demonstrated that a low tidal volume ( VT ) mechanical ventilation strategy ( 6 ml/kg ) reduced mortality by 22 % compared with traditional mechanical ventilation ( 12 ml/kg ) . In this study , we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network r and omized controlled trials . The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality . The risk of death ( before discharge home with unassisted breathing ) was highest in patients with sepsis ( 43 % ) ; intermediate in subjects with pneumonia ( 36 % ) , aspiration ( 37 % ) , and other risk factors ( 35 % ) ; and lowest in those with trauma ( 11 % ) ( p < 0.0001 ) . Despite these differences in mortality , there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor ( p = 0.76 , for interaction between ventilator group and risk factor ) . There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes : proportion of patients achieving unassisted breathing ( p = 0.59 ) , ventilator-free days ( p = 0.58 ) , or development of nonpulmonary organ failure ( p = 0.44 ) . Controlling for demographic and clinical covariates did not appreciably affect these results . After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions , there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups . In conclusion , we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS 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 Objective : To evaluate the effects of neuromuscular blocking agents ( NMBAs ) on pulmonary and systemic inflammation in patients with acute respiratory distress syndrome ventilated with a lung-protective strategy . Design : Multiple-center , prospect i ve , controlled , and r and omized trial . Setting : One medical and two medical – surgical intensive care units . Patients : A total of 36 patients with acute respiratory distress syndrome ( Pao2/Fio2 ratio of ≤200 at a positive end-expiratory pressure of ≥5 cm H2O ) were included within 48 hrs of acute respiratory distress syndrome onset . Interventions : Patients were r and omized to receive conventional therapy plus placebo ( n = 18 ) or conventional therapy plus NMBAs ( n = 18 ) for 48 hrs . Both groups were ventilated with a lung-protective strategy ( tidal volume between 4 and 8 mL/kg ideal body weight , plateau pressure of ≤30 cm H2O ) . Measurements and Main Results : Bronchoalveolar lavages and blood sample s were performed , before r and omization and at 48 hrs , to determine the concentrations of tumor necrosis factor-α , interleukin (IL)-1β , IL-6 , and IL-8 . Pao2/Fio2 ratio was evaluated before r and omization and at 24 , 48 , 72 , 96 , and 120 hrs . A decrease over time in IL-8 concentrations ( p = .034 ) was observed in the pulmonary compartment of the NMBA group . At 48 hrs after r and omization , pulmonary concentrations of IL-1β ( p = .005 ) , IL-6 ( p = .038 ) , and IL-8 ( p = .017 ) were lower in the NMBA group as compared with the control group . A decrease over time in IL-6 ( p = .05 ) and IL-8 ( p = .003 ) serum concentrations was observed in the NMBA group . At 48 hrs after r and omization , serum concentrations of IL-1β ( p = .037 ) and IL-6 ( p = .041 ) were lower in the NMBA group as compared with the control group . A sustained improvement in Pao2/Fio2 ratio was observed and was reinforced in the NMBA group ( p < .001 ) . Conclusion : Early use of NMBAs decrease the proinflammatory response associated with acute respiratory distress syndrome and mechanical ventilation 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 OBJECTIVE Comparison between effects of a new method of mechanical ventilation ( PRVC ) and Volume Controlled ventilation in the ARDS treatment . DESIGN Prospect i ve study from March 1995 to March 1997 . PLACE Intensive Care Unit of Sanremo Hospital . PATIENTS Nine patients , six males and three females , average age 49.2 years , average SAPS 35.5 , with moderate to severe ARDS related to various etiologies . INTERVENTIONS Patient were first ventilated with Siemens Servo Ventilators 300 in Volume controlled . They were then ventilated with Pressure-regulated Volume Control maintaining the same ventilation parameters ( TV , RR , FiO2 , PEEP and I : E ratio ) . MEASUREMENTS After a 60 minute stabilisation period in each method , Peak inspiratory pressure , Static Compliance , PaO2 , PaCO2 , AaDO2 and cardiovascular parameters were measured . RESULTS With the PRVC ventilation an important decrease of PIP and an improvement of PaO2 and SaO2 were observed . CONCLUSIONS Although it is not possible to draw any conclusion on morbidity and mortality in patients treated with PRVC versus VC , for gas exchange and compliance improvement and for inspiratory pressure decrease with consequent reduction of barotrauma , it may be affirm that PCRV seems to be the best ventilation methods in the ARDS treatment BACKGROUND Pressure-support ventilation ( PSV ) is more comfortable than volume controlled-continuous m and atory ventilation ( VC-CMV ) in acute hypercapnic respiratory failure , in patients undergoing noninvasive ventilation . Physiologic measurements of patient status have been compared in PSV and VC-CMV in endotracheally intubated patients , but patient perception of comfort has not been measured in this population . OBJECTIVE To determine if PSV is more comfortable than VC-CMV ( volume-cycled , flow-limited ) in intubated mechanically ventilated patients . METHODS In a r and omized prospect i ve trial , patients underwent PSV and VC-CMV for 30 min each , separated by a 30 min washout with the baseline ventilation mode ( pressure-regulated volume-control ventilation [ PRVC ] ) . The level of pressure support was set as the plateau pressure on VC-CMV with a tidal volume of 8 mL/kg minus the end-expiratory pressure . After each mode the patient was asked to mark his or her comfort level on a visual analog scale . RESULTS Eleven of the 14 patients were more comfortable during PSV . The baseline mean comfort score ( during PRVC ) was 62 + /- 18 ( 95 % confidence interval 51.7 - 72.5 ) . The mean comfort score for PSV was 83 + /- 11 ( 95 % confidence interval 76.9 - 89.6 ) . The mean comfort score for VC-CMV was 70 + /- 18 ( 95 % confidence interval 59.4 - 79.9 ) . PSV was significantly more comfortable than VC-CMV ( p = 0.02 ) or PRVC ( p = 0.009 ) , whereas the comfort scores for VC-CMV and PRVC were not significantly different ( p = 0.278 ) . Respiratory rate , blood pressure , heart rate , minute ventilation , and blood oxygen saturation showed no difference between PRVC , VC-CMV , and PSV . CONCLUSIONS On average the patients felt more comfortable during PSV than during VC-CMV or PRVC , so PSV may be the preferred mode for awake intubated patients PURPOSE Low tidal volume ( V(T ) ) delivered by flow-targeted breaths reduces ventilator-induced lung injury but may increase patient breathing effort because of limited flow . We hypothesized that a variable-flow , pressure-targeted breath would improve breathing effort versus a fixed flow-targeted breath . MATERIAL S AND METHODS We compared pressure assist-control ventilation and volume assist-control ventilation ( VACV ) in 12 patients with acute respiratory failure receiving 6 to 8 mL/kg V(T ) . Backup frequency , V(T ) , inspiratory time , applied positive end-expiratory pressure and fraction of inspired oxygen were held constant . Patient breathing effort was assessed by airway pressure ( Paw ) drop below baseline 0.1 second after the breath initiation ( P(0.1 ) ) , the maximal Paw drop during the triggering phase ( Ptr ) , the magnitude of ventilator work during flow delivery , and the presence of an active expiratory effort during cycling and air trapping judged by the magnitude of residual flow at end-expiration . RESULTS Compared with VACV , pressure assist-control ventilation decreased P(0.1 ) , Ptr ( by 25 % and 16 % , respectively ) , and evidence for trapped gas but not ventilator work during flow delivery or cycle dys-synchrony . Peak inspiratory flow was comparable between the 2 modes . CONCLUSIONS In patients receiving small V(T ) VACV with increased breathing effort , variable-flow , pressure-targeted ventilation may provide more comfort by decreasing respiratory drive during the triggering phase Ventilatory modes employing different inspiratory flow patterns and inspiratory to expiratory ratios may alter lung strain in acute lung injury patients . To determine whether variations in lung strain existed between pressure-controlled , volume-controlled , and pressure-controlled inverse ratio modes of ventilation , we r and omly applied each for 30 minutes in 18 acute lung injury patients , keeping tidal volume , respiratory rate , fractional inspired oxygen , and total positive end-expiratory pressure constant . After each mode , a multiple linear regression analysis of dynamic airway pressure and airflow was performed with a volume-dependent single compartment model of the equation of motion , and an index of nonlinear elastic behavior was calculated . In five additional patients , concurrent dynamic computerized axial tomography scanning at juxtadiaphragmatic and subcarinal levels was added . Although static mechanics , oxygenation , and hemodynamics were no different between pressure-controlled , volume-controlled , and pressure-controlled inverse ratio ventilation , we found significant differences in nonlinear behavior . This was least with pressure-controlled followed by volume-controlled ventilation , and pressure-controlled inverse ratio ventilation had the greatest nonlinear elastic behavior . Dynamic computerized axial tomography analysis revealed more overinflated units in the left subcarinal slice with pressure-controlled inverse ratio ventilation .  Ventilator flow pattern and inspiratory to expiratory ratio independently influence lung strain in acute lung injury ; however , further studies are needed to determine the biologic significance Objective : Volume‐controlled ventilation is frequently chosen as the initial mode of ventilatory support in patients with hypoxic respiratory failure . Recent data , however , suggest that pressure‐limited ventilation , using a rapidly decelerating flow delivery pattern , may produce a more desirable clinical effect through reduced peak airway pressures and increased static compliance , tissue oxygen delivery , and consumption . This study was performed to assess the feasibility and utility of early and sustained use of pressure‐limited ventilation in patients with this clinical syndrome . Design : R and omized , prospect i ve trial . Setting : Medical intensive care unit ( ICU ) of a university hospital . Patients : The study encompassed all patients ( n = 27 ) receiving care in a medical ICU for acute , severe hypoxic respiratory failure ( Pao2/ Fio2 ratio of < 150 ) during a 6‐month period . Interventions : Ventilatory support via either pressure‐limited or volume‐controlled ventilation , initiated within 24 hrs of endotracheal intubation . Measurements : On‐line monitoring of the following ten ventilatory variables at 1‐min intervals for 72 hrs or until extubation or death ( maximum of 43,200 data points per patient ) : peak airway pressure , mean airway pressure , end‐tidal CO2 concentration , CO2 minute excretion , inspiratory tidal volume , expiratory tidal volume , pause pressure , end‐expiratory pressure , static thoracic compliance , and inspiratory resistance . Additionally , Pao2/FIO2 values and Acute Physiology and Chronic Health Evaluation ( APACHE ) II scores were recorded on a daily basis , as were significant clinical events and changes in ventilator setting s. Results : Although the severity of illness at study entry as determined by APACHE II score and Pao2/Fio2 was similar in patients treated with pressure‐limited or volume‐controlled ventilation , peak airway pressure was consistently lower in patients r and omized to pressure‐limited ventilation ( p = .05 at 12 hrs postintubation ) . The use of pressure‐limited ventilation also was associated with a more rapid increase in static compliance ( p = .05 ) than that found with volume‐controlled ventilation . There was a trend toward more rapid normalization of CO2 minute excretion in patients treated with pressure‐limited ventilation . Pressure‐limited treated patients who survived their illness and were extubated , required fewer days of mechanical ventilation than did patients r and omized to volume‐controlled treated ventilation ( p = .05 ) . No pneumothoraces occurred in any study patients . One volume‐controlled patient developed subcutaneous emphysema . Pressure‐limited ventilation was well tolerated , and sedation requirements were equivalent in the two groups . Conclusions : Pressure‐limited ventilation can be used safely and is well tolerated as an initial mode of ventilatory support in patients with acute hypoxic respiratory failure . Because the early initiation of pressure‐limited ventilation is associated with lower peak airway pressure and more rapid improvement in static thoracic compliance than volume‐controlled ventilation , pressure‐limited ventilation may have a beneficial role when used as the primary ventilatory modality in patients with this clinical condition . ( Crit Care Med 1994 ; 22:22‐32 Improved gas exchange has been observed during spontaneous breathing with airway pressure release ventilation ( APRV ) as compared with controlled mechanical ventilation . This study was design ed to determine whether use of APRV with spontaneous breathing as a primary ventilatory support modality better prevents deterioration of cardiopulmonary function than does initial controlled mechanical ventilation in patients at risk for acute respiratory distress syndrome ( ARDS ) . Thirty patients with multiple trauma were r and omly assigned to either breathe spontaneously with APRV ( APRV Group ) ( n = 15 ) or to receive pressure-controlled , time-cycled mechanical ventilation ( PCV ) for 72 h followed by weaning with APRV ( PCV Group ) ( n = 15 ) . Patients maintained spontaneous breathing during APRV with continuous infusion of sufentanil and midazolam ( Ramsay sedation score [ RSS ] of 3 ) . Absence of spontaneous breathing ( PCV Group ) was induced with sufentanil and midazolam ( RSS of 5 ) and neuromuscular blockade . Primary use of APRV was associated with increases ( p < 0.05 ) in respiratory system compliance ( CRS ) , arterial oxygen tension ( PaO2 ) , cardiac index ( CI ) , and oxygen delivery ( DO2 ) , and with reductions ( p < 0.05 ) in venous admixture ( QVA/QT ) , and oxygen extraction . In contrast , patients who received 72 h of PCV had lower CRS , PaO2 , CI , DO2 , and Q VA/Q T values ( p < 0.05 ) and required higher doses of sufentanil ( p < 0.05 ) , midazolam ( p < 0.05 ) , noradrenalin ( p < 0.05 ) , and dobutamine ( p < 0.05 ) . CRS , PaO2 ) , CI and DO2 were lowest ( p < 0.05 ) and Q VA/Q T was highest ( p < 0.05 ) during PCV . Primary use of APRV was consistently associated with a shorter duration of ventilatory support  ( APRV Group : 15 + /- 2 d [ mean + /- SEM ] ; PCV Group : 21 + /- 2 d ) ( p < 0.05 ) and length of intensive care unit ( ICU ) stay  ( APRV Group : 23 + /- 2 d ; PCV Group : 30 + /- 2 d ) ( p < 0.05 ) . These findings indicate that maintaining spontaneous breathing during APRV requires less sedation and improves cardiopulmonary function , presumably by recruiting nonventilated lung units , requiring a shorter duration of ventilatory support and ICU stay Background : Prone positioning has been shown to improve oxygenation in 60–70 % of patients with acute lung injury ( ALI ) or acute respiratory distress syndrome ( ARDS ) . Another way to improve matching of ventilation to perfusion is the use of partial ventilatory support . Preserving spontaneous breathing during mechanical ventilation has been shown to improve oxygenation in comparison with controlled mechanical ventilation . However , no r and omized studies are available exploring the effects of preserved spontaneous breathing on gas exchange in combination with prone positioning . Our aim was to determine whether the response of oxygenation to the prone position differs between pressure‐controlled synchronized intermittent m and atory ventilation with pressure support ( SIMV‐PC/PS ) and airway pressure release ventilation with unsupported spontaneous breathing ( APRV ) PURPOSE The purpose of this article is to analyze the effect of a pressure-regulated volume-controlled ventilation mode on lung mechanics and gas exchange in patients with acute respiratory failure . MATERIAL S AND METHODS We ventilated 10 patients with two pressure-limited modes : pressure-controlled ventilation ( PC ) and pressure-regulated volume-controlled ventilation ( PRVC ) in r and om order , for 1 hour each . Patients were stabilized on volume-controlled ventilation ( VC ) for 30 minutes before , between , and at the end of PC and PRVC to reach baseline conditions . At the end of every VC period and at 30 and 60 minutes of PC and PRVC , respiratory mechanics , gasometrics , and hemodynamic parameters were collected . RESULTS We found no significant differences between the three VC periods . Comparing VC with the two pressure-limited ventilation modes , peak pressure decreased from 29.4+/-9.1 cm H2O ( VC ) to 25.9+/-8.4 ( PC 60 minutes ) and 26.1+/-8.2 ( PRVC 60 minutes ) , and PaCO2 decreased significantly from 38.6+/-3.1 mm Hg ( VC ) to 36.7+/-2.8 ( PC 60 minutes ) and 36.8+/-2.9 ( PRVC 60 minutes ) . CONCLUSIONS Pressure-limited ventilation allows mechanical ventilation for the same tidal volume as VC but results in a lower peak inspiratory pressure and a slightly lower PaCO2 . The mechanism responsible for this gas exchange effect is unknown but is probably related to a better air distribution of the decelerated flow . The clinical relevance of this phenomenon remains to be established BACKGROUND A strategy of mechanical ventilation that limits airway pressure and tidal volume while permitting hypercapnia has been recommended for patients with the acute respiratory distress syndrome . The goal is to reduce lung injury due to overdistention . However , the efficacy of this approach has not been established . METHODS Within 24 hours of intubation , patients at high risk for the acute respiratory distress syndrome were r and omly assigned to either pressure- and volume-limited ventilation ( limited-ventilation group ) , with the peak inspiratory pressure maintained at 30 cm of water or less and the tidal volume at 8 ml per kilogram of body weight or less , or to conventional ventilation ( control group ) , with the peak inspiratory pressure allowed to rise as high as 50 cm of water and the tidal volume at 10 to 15 ml per kilogram . All other ventilatory variables were similar in the two groups . RESULTS A total of 120 patients with similar clinical features underwent r and omization ( 60 in each group ) . The patients in the limited-ventilation and control groups were exposed to different mean ( + /-SD ) tidal volumes ( 7.2+/-0.8 vs. 10.8+/-1.0 ml per kilogram , respectively ; P<0.001 ) and peak inspiratory pressures ( 23.6+/-5.8 vs. 34.0+/-11.0 cm of water , P<0.001 ) . Mortality was 50 percent in the limited-ventilation group and 47 percent in the control group ( relative risk , 1.07 ; 95 percent confidence interval , 0.72 to 1.57 ; P=0.72 ) . In the limited-ventilation group , permissive hypercapnia ( arterial carbon dioxide tension , > 50 mm Hg ) was more common ( 52 percent vs. 28 percent , P=0.009 ) , more marked ( 54.4+/-18.8 vs. 45.7+/-9.8 mm Hg , P=0.002 ) , and more prolonged ( 146+/-265 vs. 25+/-22 hours , P=0.017 ) than in the control group . The incidence of barotrauma , the highest multiple-organ-dysfunction score , and the number of episodes of organ failure were similar in the two groups ; however , the numbers of patients who required paralytic agents ( 23 vs. 13 , P=0.05 ) and dialysis for renal failure ( 13 vs. 5 , P= 0.04 ) were greater in the limited-ventilation group than in the control group . CONCLUSIONS In patients at high risk for the acute respiratory distress syndrome , a strategy of mechanical ventilation that limits peak inspiratory pressure and tidal volume does not appear to reduce mortality and may increase morbidity In twenty-one patients ventilated for > or = 3 days , we compared similar levels of partial support provided by synchronized intermittent m and atory ventilation ( SIMV ) and pressure support ventilation ( PSV ) in terms of breathing comfort . On a single day , eligible subjects experienced , in r and om order , both SIMV and PSV weaning protocol s ( sequential 20 % reductions in support at timed intervals ) separated by a 1 to 3 h rest . Breathing comfort was defined by subjective ratings of dyspnea and anxiety . Subjects reported significant levels of preweaning dyspnea and anxiety despite resting for at least 6 h. Dyspnea and anxiety were not significantly different between the two methods at any level of support . Our findings suggest that dyspnea and anxiety are higher than expected on " full " ventilator support , and that comfort may not differ between PSV and SIMV during active withdrawal of machine support OBJECTIVE To study comparatively the effects of volume-controlled vs. biphasic positive airway pressure mechanical ventilation on respiratory mechanics and oxygenation in leukopenic patients with severe respiratory failure . DESIGN Prospect i ve , comparative study . SETTING Medical intensive care unit of a university hospital . PATIENTS Leukopenic ( < 1000 leukocytes/microliter ) patients ( n=20 ) after cytoreductive chemotherapy requiring mechanical ventilation for severe respiratory failure ( Murray score of > 2.5 ) . INTERVENTION Patients were assigned in a consecutive , alternating manner to receive either volume-controlled or biphasic positive airway pressure mechanical ventilation , starting within 12 to 24 hrs after endotracheal intubation . MEASUREMENTS AND MAIN RESULTS Tidal volume , inspiratory flow , peak inspiratory and positive end-expiratory pressures , FIO2 , and arterial blood gas analyses were recorded hourly for a study period of 48 hrs . Biphasic positive airway pressure ventilation was associated with a significant reduction in peak inspiratory pressure ( mean differences at 24 , 36 , and 48 hrs : 4.4 , 3.4 , and 4.2 cm H2O ; p = .024 , .019 , and .013 , respectively ) and positive end-expiratory pressures ( mean differences at 24 , 36 , and 48 hrs : 1.6 , 1.4 , and 1.5 cm H20 ; p = .023 , .024 , and .023 , respectively ) at significantly lower FIO2 ( mean differences at 12 , 24 , 36 , and 48 hrs ; p = .007 , .015 , .016 , and .011 , respectively ) . PaO2/FIO2 ratios and CO2 removal were similar under ventilatory conditions . CONCLUSIONS Biphasic positive airway pressure ventilation offers the advantage of significantly reduced peak inspiratory and positive end-expiratory pressures at a lower FIO2 and with at least similar oxygenation and CO2 removal as achieved by volume-controlled mechanical ventilation . Our results are in line with previous reports on nonleukopenic patients and suggest that the positive effects of pressure-limited mechanical ventilation are independent of circulating white blood cells . Further studies are m and atory to demonstrate clinical benefit in this critically ill patient population BACKGROUND We compared pressure and volume-controlled ventilation ( PCV and VCV ) in morbidly obese patients undergoing laparoscopic gastric b and ing surgery . METHODS Thirty-six patients , BMI > 35 kg m(-2 ) , no major obstructive or restrictive respiratory disorder , and Pa(CO(2))<6.0 kPa , were r and omized to receive either VCV or PCV during the surgery . Ventilation setting s followed two distinct algorithms aim ing to maintain end-tidal CO(2 ) ( E'(CO(2 ) ) ) between 4.40 and 4.66 kPa and plateau pressure ( P(plateau ) ) as low as possible . Primary outcome variable was peroperative P(plateau ) . Secondary outcomes were Pa(O(2 ) ) ( Fi(O(2 ) ) at 0.6 in each group ) and Pa(CO(2 ) ) during surgery and 2 h after extubation . Pressure , flow , and volume time curves were recorded . RESULTS There were no significant differences in patient characteristics and co-morbidity in the two groups . Mean pH , Pa(O(2 ) ) , Sa(O(2 ) ) , and the Pa(O(2))/Fi(O(2 ) ) ratio were higher in the PCV group , whereas Pa(CO(2 ) ) and the E'(CO(2))-Pa(CO(2 ) ) gradient were lower ( all P<0.05 ) . Ventilation variables , including plateau and mean airway pressures , anaesthesia-related variables , and postoperative cardiovascular variables , blood gases , and morphine requirements after the operation were similar . CONCLUSIONS The changes in oxygenation can only be explained by an improvement in the lungs ventilation/perfusion ratio . The decelerating inspiratory flow used in PCV generates higher instantaneous flow peaks and may allow a better alveolar recruitment . PCV improves oxygenation without any side-effects OBJECTIVES Respiratory support for patients recovering from cardiopulmonary bypass and cardiac surgery uses large tidal volumes and a minimal level of positive end-expiratory pressure . Recent data indicate that these ventilator setting s might cause pulmonary and systemic inflammation in patients with acute lung injury . We examined the hypothesis that high tidal volumes and low levels of positive end-expiratory pressure might worsen the inflammatory response associated to cardiopulmonary bypass . METHODS Forty patients undergoing elective coronary artery bypass were r and omized to be ventilated after cardiopulmonary bypass disconnection  with high tidal volume/low positive end-expiratory pressure ( 10 - 12 mL/kg and 2 - 3 cm H2O , respectively ) or low tidal volume/high positive end-expiratory pressure ( 8 mL/kg and 10 cm H2O , respectively ) . Interleukin 6 and interleukin 8 levels were measured in the bronchoalveolar lavage fluid and plasma . Sample s were taken before sternotomy ( time 0 ) , immediately after cardiopulmonary bypass separation ( time 1 ) , and after 6 hours of mechanical ventilation ( time 2 ) . RESULTS Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and plasma significantly increased at time 1 in both groups but further increased at time 2 only in patients ventilated with high tidal volume/low positive end-expiratory pressure . Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and in the plasma at time 2 were higher with high tidal volume/low positive end-expiratory pressure than with low tidal volume/high positive end-expiratory pressure . CONCLUSION Mechanical ventilation might be a cofactor able to influence the inflammatory response after cardiac surgery BACKGROUND Patient work of breathing ( WOB ) during assisted ventilation is reduced when inspiratory flow ( V(I ) ) from the ventilator exceeds patient flow dem and . Patients in acute respiratory failure often have unstable breathing patterns and their requirements for V(I ) may change from breath to breath . Volume control ventilation ( VCV ) traditionally incorporates a pre-set ventilator V(I ) that remains constant even under conditions of changing patient flow dem and . In contrast , pressure control ventilation ( PCV ) incorporates a variable decelerating flow wave form with a high ventilator V(I ) as inspiration commences . We compared the effects of flow patterns on assisted WOB during VCV and PCV . METHODS WOB was measured with a BICORE CP-100 monitor ( incorporating a Campbell Diagram ) in a prospect i ve , r and omized cross-over study of 18 mechanically ventilated adult patients with acute lung injury ( ALI ) or acute respiratory distress syndrome ( ARDS ) .  Tidal volume , inspiratory time , and mean ventilator V(I ) were constant in each mode . RESULTS At comparable levels of respiratory drive and minute ventilation , patient WOB was significantly lower with PCV than with VCV ( 0.59 + /- 0.42 J/L vs 0.70 + /- 0.58 J/L , respectively , p < 0.05 ) . Ventilator peak V(I ) was significantly higher with PCV than with VCV ( 103.2 + /- 22.8 L/min vs 43.8 L/min , respectively , p < 0.01 ) . CONCLUSIONS In the setting of ALI and ARDS , PCV significantly reduced patient WOB relative to VCV . The decrease in patient WOB was attributed to the higher ventilator peak V(I ) of PCV Objective To evaluate the effects of a 48-hr neuromuscular blocking agents ( NMBA ) infusion on gas exchange over a 120-hr time period in patients with acute respiratory distress syndrome . Design Multiple center , prospect i ve , controlled , and r and omized trial . Setting Four adult medical or mixed medical-surgical intensive care units . Patients A total of 56 patients with acute respiratory distress syndrome with a Pao2/Fio2 ratio of < 150 at a positive end-expiratory pressure of ≥5 cm H2O . Interventions After r and omization , patients received either conventional therapy without NMBA ( control group ) or conventional therapy plus NMBA for the next 48 hrs . The initial ventilator mode was volume-assist/control . The ventilator remained on assist-control mode throughout the initial 48-hr period in both groups . Tidal volume was 6–8 mL/kg ideal body weight . Measurements and Main Results When analyzed for the entire 120 hrs , there was a significant effect of  the  NMBA on the course of Pao2/Fio2 ratio ( p = .021 ) . Separate comparisons at each time point indicated that patients r and omized to the NMBA group had a higher Pao2/Fio2 at 48 , 96 , and 120 hrs after r and omization . Moreover , a decrease of positive end-expiratory pressure ( p = .036 ) was only found in the NMBA group . Two-way repeated- measures analysis of variance exhibited a decrease in positive end-expiratory pressure over time ( p = .036 ) . Concerning short-term effects , there was no modification of Pao2/Fio2 ratio 1 hr after r and omization in either group . Only one patient ( from the control group ) developed pneumothorax . Conclusions Use of NMBA during a 48-hr period in patients with acute respiratory distress syndrome is associated with a sustained improvement in oxygenation Background : Alveolar fibrin deposition is a hallmark of acute lung injury , result ing from activation of coagulation and inhibition of fibrinolysis . Previous studies have shown that mechanical ventilation with high tidal volumes may aggravate lung injury in patients with sepsis and acute lung injury . The authors sought to determine the effects of mechanical ventilation on the alveolar hemostatic balance in patients without preexistent lung injury . Methods : Patients scheduled for an elective surgical procedure ( lasting ≥ 5 h ) were r and omly assigned to mechanical ventilation with either higher tidal volumes of 12 ml/kg ideal body weight and no positive end-expiratory pressure ( PEEP ) or lower tidal volumes of 6 ml/kg and 10 cm H2O PEEP . After induction of anesthesia and 5 h later bronchoalveolar lavage fluid and blood sample s were obtained , and markers of coagulation and fibrinolysis were measured . Results : In contrast to mechanical ventilation with lower tidal volumes and PEEP ( n = 21 ) , the use of higher tidal volumes without PEEP ( n = 19 ) caused activation of bronchoalveolar coagulation , as reflected by a marked increase in thrombin – antithrombin complexes , soluble tissue factor , and factor VIIa after 5 h of mechanical ventilation . Mechanical ventilation with higher tidal volumes without PEEP caused an increase in soluble thrombomodulin in lavage fluids and lower levels of bronchoalveolar activated protein C in comparison with lower tidal volumes and PEEP . Bronchoalveolar fibrinolytic activity did not change by either ventilation strategy . Conclusions : Mechanical ventilation with higher tidal volumes and no PEEP promotes procoagulant changes , which are largely prevented by the use of lower tidal volumes and PEEP
BACKGROUND Acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) account for one-quarter of cases of acute respiratory failure in intensive care units ( ICUs ) .
A third to half of patients will die in the ICU , in hospital or during follow-up .
Mechanical ventilation of people with ALI/ARDS allows time for the lungs to heal , but ventilation is invasive and can result in lung injury .
It is uncertain whether ventilator-related injury would be reduced if pressure delivered by the ventilator with each breath is controlled , or whether the volume of air delivered by each breath is limited .
OBJECTIVES To compare pressure-controlled ventilation ( PCV ) versus volume-controlled ventilation ( VCV ) in adults with ALI/ARDS to determine whether PCV reduces in-hospital mortality and morbidity in intubated and ventilated adults .