Prospective trial of high-frequency oscillation in adults with acute respiratory distress syndrome Prone positioning in patients with moderate and severe acute respiratory distress syndrome: a randomized controlled trial. HIGH FREQUENCY OSCILLATORY VENTILATION FOR ADULT RESPIRATORY DISTRESS SYNDROME‐A PILOT STUDY Comparison of prone positioning and high-frequency oscillatory ventilation in patients with acute respiratory distress syndrome* Selecting and Appraising Studies for a Systematic Review Lung recruitment in patients with the acute respiratory distress syndrome. High frequency oscillatory ventilation compared with conventional mechanical ventilation in adult respiratory distress syndrome: a randomized controlled trial [ISRCTN24242669] A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial* Plasma soluble intercellular adhesion molecule-1 (sICAM-1) in pediatric ARDS during high frequency oscillatory ventilation: a predictor of mortality. Tidal volume reduction for prevention of ventilator-induced lung injury in acute respiratory distress syndrome. The Multicenter Trail Group on Tidal Volume reduction in ARDS. Point: High-frequency ventilation is the optimal physiological approach to ventilate ARDS patients. Quality-adjusted survival in the first year after the acute respiratory distress syndrome. Incidence and outcomes of acute lung injury. Two-year outcomes, health care use, and costs of survivors of acute respiratory distress syndrome. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. 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. Prospective, randomized comparison of high‐frequency oscillatory ventilation and conventional mechanical ventilation in pediatric respiratory failure Open-lung Protective Ventilation with Pressure Control Ventilation, High-frequency Oscillation, and Intratracheal Pulmonary Ventilation Results in Similar Gas Exchange, Hemodynamics, and Lung Mechanics Language bias in randomised controlled trials published in English and German High-frequency oscillatory ventilation for acute respiratory distress syndrome in adults: a randomized, controlled trial. Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.
Objective To evaluate the safety and efficacy of high-frequency oscillatory ventilation ( HFOV ) in adult patients with the acute respiratory distress syndrome ( ARDS ) and oxygenation failure . Design Prospect i ve , clinical study . Setting Intensive care and burn units of two university teaching hospitals . Patients Twenty-four adults ( 10 females , 14 males , aged 48.5 ± 15.2 yrs , Acute Physiology and Chronic Health Evaluation II score 21.5 ± 6.9 ) with ARDS ( lung injury score 3.4 ± 0.6 , Pao2/Fio2 98.8 ± 39.0 mm Hg , and oxygenation index 32.5 ± 19.6 ) who met one of the following criteria : Pao2 ≤65 mm Hg with Fio2 ≥0.6 , or plateau pressure ≥35 cm H2O . Interventions HFOV was initiated in patients with ARDS after varying periods of conventional ventilation ( CV ) . Mean airway pressure ( Paw ) was initially set 5 cm H2O greater than Paw during CV , and was subsequently titrated to maintain oxygen saturation between 88 % and 93 % and Fio2 ≤0.60 . Measurements and Main Results Fio2 , Paw , pressure amplitude of oscillation , frequency , blood pressure , heart rate , and arterial blood gases were monitored during the transition from CV to HFOV , and every 8 hrs thereafter for 72 hrs . In 16 patients who had pulmonary artery catheters in place  , cardiac hemodynamics were recorded at the same time intervals . Throughout the HFOV trial , Paw was significantly higher than that applied during CV . Within 8 hrs of HFOV application , and for the duration of the trial , Fio2 and Paco2 were lower , and Pao2/Fio2 was higher than baseline values during CV . Significant changes in hemodynamic variables following HFOV initiation included an increase in pulmonary artery occlusion pressure ( at 8 and 40 hrs ) and central venous pressure ( at 16 and 40 hrs ) , and a reduction in cardiac output throughout the course of the study . There were no significant changes in systemic or pulmonary pressure associated with initiation and maintenance of HFOV . Complications occurring during HFOV  included pneumothorax in two patients and desiccation of secretions in one patient . Survival at 30 days was 33 % , with survivors having been mechanically ventilated for fewer days before institution of HFOV compared with nonsurvivors ( 1.6 ± 1.2 vs. 7.8 ± 5.8 days;p = .001 ) . Conclusions These findings suggest that HFOV has beneficial effects on oxygenation and ventilation , and may be a safe and effective rescue therapy for patients with severe oxygenation failure . In addition , early institution of HFOV may be advantageous CONTEXT Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome ( ARDS ) . OBJECTIVE To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS . DESIGN , SETTING , AND PATIENTS The Prone-Supine II Study , a multicenter , unblinded , r and omized controlled trial conducted in 23 centers in Italy and 2 in Spain . Patients were 342 adults with ARDS receiving mechanical ventilation , enrolled from February 2004 through June 2008 and prospect ively stratified into subgroups with moderate ( n = 192 ) and severe ( n = 150 ) hypoxemia . INTERVENTIONS Patients were r and omized to undergo supine ( n = 174 ) or prone ( 20 hours per day ; n = 168 ) positioning during ventilation . MAIN OUTCOME MEASURES The primary outcome was 28-day all-cause mortality . Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge , organ dysfunctions , and the complication rate related to prone positioning . RESULTS Prone and supine patients from the entire study population had similar 28-day ( 31.0 % vs 32.8 % ; relative risk [ RR ] , 0.97 ; 95 % confidence interval [ CI ] , 0.84 - 1.13 ; P = .72 ) and 6-month ( 47.0 % vs 52.3 % ; RR , 0.90 ; 95 % CI , 0.73 - 1.11 ; P = .33 ) mortality rates , despite significantly higher complication rates in the prone group . Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days ( 25.5 % vs 22.5 % ; RR , 1.04 ; 95 % CI , 0.89 - 1.22 ; P = .62 ) and at 6 months ( 42.6 % vs 43.9 % ; RR , 0.98 ; 95 % CI , 0.76 - 1.25 ; P = .85 ) . The 28-day mortality of patients with severe hypoxemia was 37.8 % in the prone and 46.1 % in the supine group ( RR , 0.87 ; 95 % CI , 0.66 - 1.14 ; P = .31 ) , while their 6-month mortality was 52.7 % and 63.2 % , respectively ( RR , 0.78 ; 95 % CI , 0.53 - 1.14 ; P = .19 ) . CONCLUSION Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00159939 OBJECTIVE To evaluate the safety and effectiveness of high-frequency oscillatory ventilation using a protocol design ed to recruit and maintain optimal lung volume in patients with severe adult respiratory distress syndrome ( ARDS ) . SETTING Surgical and medical intensive care units in a tertiary care , military teaching hospital . DESIGN A prospect i ve , clinical study . PATIENTS Seventeen patients , 17 yrs to 83 yrs of age , with severe ARDS ( Lung Injury Score of 3.81 + /- 0.23 ) failing inverse ratio mechanical conventional ventilation  ( PaO2/FiO2 ratio of 68.6 + /- 21.6 , peak inspiratory pressure of 54.3 + /- 12.7 cm H2O , positive end-expiratory pressure of 18.2 + /- 6.9 cm H2O ) . INTERVENTIONS High-frequency oscillatory ventilation was instituted after varying periods of conventional ventilation ( 5.12 + /- 4.3 days ) . We employed lung volume recruitment strategy that consisted of incremental increases in mean airway pressure to achieve a PaO2 of > or = 60 torr ( > or = 8.0 kPa ) , with an FiO2 of < or = 0.6 . MEASUREMENTS AND MAIN RESULTS  High-frequency oscillator ventilator setting s ( FiO2 , mean airway pressure , pressure amplitude of oscillation [ delta P ] frequency ) and hemodynamic parameters ( cardiac output , oxygen delivery [ DO2 ] ) , mean systemic and pulmonary arterial pressures , and the oxygenation index ( oxygenation index = [ FiO2 x mean airway pressure x 100]/PaO2 ) were monitored during the transition to high-frequency oscillatory ventilation and throughout the course of the high-frequency protocol . Thirteen patients demonstrated improved gas exchange and an overall improvement in PaO2/FiO2 ratio ( p < .02 ) . Reductions in the oxygenation index ( p < .01 ) and FiO2 ( p < .02 ) at 12 , 24 , and 48 hrs after starting high-frequency oscillatory ventilation were observed . No significant compromise in cardiac output or DO2 was observed , despite a significant increase in mean airway pressure ( 31.2 + /- 10.3 to 34.0 + /- 6.7 cm H2O , p < .05 ) on high-frequency oscillatory ventilation . The overall survival rate at 30 days was 47 % . A greater number of pretreatment days on conventional ventilation ( p < .009 ) and an entry oxygenation index of > 47 ( sensitivity 100 % , specificity 100 % ) were associated with mortality . CONCLUSIONS High-frequency oscillatory ventilation is both safe and effective in adult patients with severe ARDS failing conventional ventilation . A lung volume recruitment strategy during high-frequency oscillatory ventilation produced improved gas exchange without a compromise in DO2 . These results are encouraging and support the need for a prospect i ve , r and omized trial of algorithm-controlled conventional ventilation vs. high-frequency oscillatory ventilation for adults with severe ARDS Objective : Both prone position and high-frequency oscillatory ventilation ( HFOV ) have the potential to facilitate lung recruitment , and their combined use could thus be synergetic on gas exchange . Keeping the lung open could also potentially be lung protective . The aim of this study was to compare physiologic and proinflammatory effects of HFOV , prone positioning , or their combination in severe acute respiratory distress syndrome ( ARDS ) . Design : Prospect i ve , comparative r and omized study . Setting : A medical intensive care unit . Patients : Thirty-nine ARDS patients with a Pao2/Fio2 ratio < 150 mm Hg at positive end-expiratory pressure ≥5 cm H2O . Interventions : After 12 hrs on conventional lung-protective mechanical ventilation ( tidal volume 6 mL/kg of ideal body weight , plateau pressure not exceeding the upper inflection point , and a maximum of 35 cm H2O ; supine-CV ) , 39 patients were r and omized to receive one of the following 12-hr periods : conventional lung-protective mechanical ventilation in prone position ( prone-CV ) , HFOV in supine position ( supine-HFOV ) , or HFOV in prone position ( prone-HFOV ) . Measurements and Main Results : Prone-CV ( from 138 ± 58 mm Hg to 217 ± 110 mm Hg , p < .0001 ) and prone-HFOV ( from 126 ± 40 mm Hg to 227 ± 64 mm Hg , p < 0.0001 ) improved the Pao2/Fio2 ratio whereas supine-HFOV did not alter the Pao2/Fio2 ratio ( from 134 ± 57 mm Hg to 138 ± 48 mm Hg ) . The oxygenation index ( { mean airway pressure × Fio2 × 100}/Pao2 ) decreased in the prone-CV and prone-HFOV groups and was lower than in the supine-HFOV group . Interleukin-8 increased significantly in the bronchoalveolar lavage fluid ( BALF ) in supine-HFOV and prone-HFOV groups compared with prone-CV and supine-CV . Neutrophil counts were higher in the supine-HFOV group than in the prone-CV group . Conclusions : Although HFOV in the supine position does not improve oxygenation or lung inflammation , the prone position increases oxygenation and reduces lung inflammation  in ARDS patients .  Prone-HFOV produced similar improvement in oxygenation like prone-CV but was associated with higher BALF indexes of inflammation . In contrast , supine-HFOV did not improve gas exchange and was associated with enhanced lung inflammation Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising  studies  for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding .  Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the appraisal process involves a detailed assessment of the patients ( for example , high , medium , or low risk ) , the study interventions ( for example , frequency , degree , and duration ) , and the outcome measurements ( for example , definitions and degree of surveillance ) BACKGROUND In the acute respiratory distress syndrome ( ARDS ) , positive end-expiratory pressure ( PEEP ) may decrease ventilator-induced lung injury by keeping lung regions open that otherwise would be collapsed . Since the effects of PEEP probably depend on the recruitability of lung tissue , we conducted a study to examine the relationship between the percentage of potentially recruitable lung , as indicated by computed tomography ( CT ) , and the clinical and physiological effects of PEEP . METHODS Sixty-eight patients with acute lung injury or ARDS underwent whole-lung CT during breath-holding sessions at airway pressures of 5 , 15 , and 45 cm of water . The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration was restored at airway pressures between 5 and 45 cm of water . RESULTS The percentage of potentially recruitable lung varied widely in the population , accounting for a mean ( + /-SD ) of 13+/-11 percent of the lung weight , and was highly correlated with the percentage of lung tissue in which aeration was maintained after the application of PEEP ( r2=0.72 , P<0.001 ) . On average , 24 percent of the lung could not be recruited . Patients with a higher percentage of potentially recruitable lung ( greater than the median value of 9 percent ) had greater total lung weights ( P<0.001 ) , poorer oxygenation ( defined as a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen ) ( P<0.001 ) and respiratory-system compliance ( P=0.002 ) , higher levels of dead space ( P=0.002 ) , and higher rates of death ( P=0.02 ) than patients with a lower percentage of potentially recruitable lung . The combined physiological variables predicted , with a sensitivity of 71 percent and a specificity of 59 percent , whether a patient 's proportion of potentially recruitable lung was higher or lower than the median . CONCLUSIONS In ARDS , the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP Introduction To compare the safety and efficacy of high frequency oscillatory ventilation ( HFOV ) with conventional mechanical ventilation ( CV ) for early intervention in adult respiratory distress syndrome ( ARDS ) , a multi-centre r and omized trial in four intensive care units was conducted . Methods Patients with ARDS were r and omized to receive either HFOV or CV .  In both treatment arms a priority was given to maintain lung volume while minimizing peak pressures . CV ventilation strategy was aim ed at reducing tidal volumes . In the HFOV group , an open lung strategy was used . Respiratory and circulatory parameters were recorded and clinical outcome was determined at 30 days of follow up . Results The study was prematurely stopped . Thirty-seven patients received HFOV and 24 patients CV  ( average APACHE II score 21 and 20 , oxygenation index 25 and 18 and duration of mechanical ventilation prior to r and omization 2.1 and 1.5 days , respectively ) . There were no statistically significant differences in survival without supplemental oxygen or on ventilator , mortality , therapy failure , or crossover . Adjustment by a priori defined baseline characteristics showed an odds ratio of 0.80 ( 95 % CI 0.22–2.97 ) for survival without oxygen or on ventilator , and an odds ratio for mortality of 1.15 ( 95 % CI 0.43–3.10 ) for HFOV compared with CV . The response of the oxygenation index ( OI ) to treatment did not differentiate between survival and death . In the HFOV group the OI response was significantly higher than in the CV group between the first and the second day . A post hoc analysis suggested that there was a relatively better treatment effect of HFOV compared with CV in patients with a higher baseline OI . Conclusion No significant differences were observed , but this trial only had power to detect major differences in survival without oxygen or on ventilator .  In patients with ARDS and higher baseline OI , however , there might be a treatment benefit of HFOV over CV . More research is needed to establish the efficacy of HFOV in the treatment of ARDS . We suggest that future studies are design ed to allow for informative analysis in patients with higher OI 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 Soluble intercellular adhesion molecule-1 ( sICAM-1 ) , an important adhesion molecule that mediates leukocyte-endothelial interaction , has been identified as a marker for the outcome of acute respiratory tract infection . We postulate that plasma ICAM-1 may be a valuable marker for both biological and clinical severity of acute respiratory distress syndrome ( ARDS ) . Sixteen pediatric patients ( > 1 month and < 15 years of age ) diagnosed with ARDS were recruited from the Pediatric Intensive Care Unit at King Chulalongkorn Memorial University Hospital , Bangkok . The patients were r and omized to receive either  high frequency oscillatory ventilation ( HFOV ) or conventional mechanical ventilation .  Plasma sICAM-1 was measured by enzyme linked immunosorbent assay ( ELISA ) on days 1 , 3 , 5 and 7 of ARDS . Plasma sICAM-1 levels in survivors and non-survivors of the HFOV and conventional treatment groups were compared . Nine and 7 patients constituted the control group receiving conventional treatment and HFOV group , respectively . Overall nine patients survived . The patients in the HFOV group had a better chance of survival compared to the controls ( 71 % versus 31.5 % ) , but it was not statistically significant ( p = 0.2 ) . The overall mortality was 45.7 % . The mean plasma sICAM-1 levels ( n = 13/16 ) were significantly elevated among non-survival patients as compared to survival patients at all time points , which indicates that an unfavorable outcome in ARDS is related to the degree of epithelial and endothelial alveolar cell injury . The elevation of plasma slCAM-1 on day 3 provided the best predictor of mortality ( likelihood ratio 11.9 , p < 0.001 ) . It was concluded that HFOV facilitated a potentially better outcome compared to conventional treatment and it was associated with less lung injuries evidence d by lower plasma sICAM-1 Because animal studies have demonstrated that mechanical ventilation at high volume and pressure can be deleterious to the lungs , limitation of airway pressure , allowing hypercapnia if necessary , is already used for ventilation of acute respiratory distress syndrome ( ARDS ) . Whether a systematic and more drastic reduction is necessary is debatable . A multicenter r and omized study was undertaken to compare a strategy aim ed at limiting the end-inspiratory plateau pressure to 25 cm H2O , using tidal volume ( VT ) below 10 ml/kg of body weight , versus a more conventional ventilatory approach ( with regard to current practice ) using VT at 10 ml/kg or above and close to normal PaCO2 . Both arms used a similar level of positive end-expiratory pressure . A total of 116 patients with ARDS and no organ failure other than the lung were enrolled over 32 mo in 25 centers . The two groups were similar at inclusion . Patients in the two arms were ventilated with different VT ( 7.1 + /- 1.3 versus 10.3 + /- 1.7 ml/kg at Day 1 , p < 0.001 ) and plateau pressures ( 25.7 + /- 5 . 0 versus 31.7 + /- 6.6 cm H2O at Day 1 , p < 0.001 ) , result ing in different PaCO2 ( 59.5 + /- 15.0 versus 41.3 + /- 7.6 mm Hg , p < 0.001 ) and pH ( 7.28 + /- 0.09 versus 7.4 + /- 0.09 , p < 0.001 ) , but a similar level of oxygenation . The new approach did not reduce mortality at Day 60 ( 46.6 % versus 37.9 % in control subjects , p = 0.38 ) , the duration of mechanical ventilation ( 23.1 + /- 20.2 versus 21.4 + /- 16 . 3 d , p = 0.85 ) , the incidence of pneumothorax ( 14 % versus 12 % , p = 0 . 78 ) , or the secondary occurrence of multiple organ failure ( 41 % versus 41 % , p = 1 ) . We conclude that no benefit could be observed with reduced VT titrated to reach plateau pressures around 25 cm H2O compared with a more conventional approach in which normocapnia was achieved with plateau pressures already below 35 cm H2O Before we can agree ( or disagree ) on whether high-frequency ventilation is the optimal physiological approach for ventilating patients with acute respiratory distress syndrome ( ARDS ) , we must first define exactly what we mean by an optimal physiological approach . In this regard , we are not talking about restoring a “ normal ” physiological pattern of breathing nor even necessarily achieving “ normal ” blood gases . The goals of mechanical ventilation in ARDS have changed markedly over the last 10–15 years ; we now define an optimal physiological approach as that which preserves “ acceptable ” gas exchange while simultaneously minimizing further lung injury caused by the ventilator , termed ventilator-induced lung injury ( VILI ; Ref . 4 ) . This focus on VILI avoidance is justified by a wealth of pre clinical data ( briefly discussed below ) , along with several clinical trials demonstrating decreased mortality with lung-protective ventilation strategies ( 24 , 28 ) . VILI occurs through various mechanisms , including oxygen toxicity , volutrauma , atelectrauma , and biotrauma ( 4 , 27 ) . Relatively early research documented oxygen toxicity — the deleterious effects of high levels of oxygen on lung tissue ( 14 ) . Volutrauma refers to lung injury arising from pulmonary overdistension ( 5 ) . ARDS is a heterogeneous disease ; the least damaged ( most compliant ) regions of lung receive a disproportionate fraction of the inspired volume and are at particularly high risk of volutrauma . There is surfactant deficiency and alveolar instability result ing in repetitive alveolar collapse ( atelectasis ) and reopening , which generates shear forces that accentuate lung injury : so-called atelectrauma ( 20 ) . Limiting alveolar collapse ( by adequate positive end-expiratory pressure [ PEEP ] ) can mitigate atelectrauma ( 13 , 23 , 25 , 27 , 30 ) . These three mechanisms of ventilator-induced lung injury can all contribute to biotrauma with release of inflammatory mediators [ e.g. , interleukins , tumor necrosis factor ( TNF ) , . . . ; Refs . 4 , 26 ] . These mediators can translocate into the circulation ( 15 , 25–27 ) , potentially contributing to multi-organ dysfunction , the major cause of ARDS mortality . As demonstrated below , high-frequency oscillation ( HFO ) addresses all of these major mechanisms of injury while providing adequate gas exchange ; hence , from a physiological perspective , it is the ideal way to ventilate patients with ARDS . HFO is a subtype of high-frequency ventilation that provides pressure oscillations around a relatively constant mean airway pressure , delivering very small tidal volumes ( VT ) at high respiratory rates ( frequencies ) of 3–15 Hz . The key to the lung protective potential of HFO are these very small VT . Not only will they directly limit tidal overdistension and volutrauma , but equally importantly they facilitate the safe use of higher mean airway pressures to mitigate atelectrauma . With minimal tidal excursions , the mean airway pressure on HFO can be thought of as being similar to positive-end expiratory pressure ( PEEP ) on conventional ventilation . CO2 removal is achieved through a number of mechanisms including bulk convection , convective streaming , pendelluft , cardiogenic mixing , and diffusion ( 21 ) . Because cyclic alveolar stretch is minimal , volutrauma can be avoided even when the mean airway pressure is set to higher levels than can be reasonably set with PEEP on conventional ventilation . Indeed , to the extent that these higher mean airway pressures are able to recruit previously atelectatic lung , the potential for volutrauma may be further decreased by increasing the size of the “ baby lung , ” ( 7 ) and the potential for oxygen toxicity may be reduced as lower FIO2s are required . This lung-protective potential of HFO has been examined in numerous animal studies . In addition to older studies that demonstrated benefits of HFO versus traditional ventilation ( i.e. , with higher VT than currently used ) , the majority of more recent studies that have compared HFO with a lung-protective conventional strategy have continued to demonstrate the superiority of HFO on physiological ( e.g. , oxygenation , compliance ) , inflammatory ( e.g. , TNF , IL-6 , neutrophil counts in broncho-alveolar lavage ) , and pathological evidence of lung injury ( 11 , 12 , 17 , 19 , 29 ) . Thus there are strong animal data supporting the concept that HFO is better than conventional lung-protective ventilation . These physiological advantages of HFO would be meaningless if HFO were not effective in humans . Clinical ly , HFO was first introduced in the neonatal ICU ; whereas there are important differences in characteristics , pathology , and management between neonates with respiratory distress syndrome and adults with ARDS , some important inferences can still be drawn from this population . In general , r and omized controlled trials ( RCTs ) that have employed a lung recruitment strategy in the HFO arm have shown better oxygenation and lung mechanics in the  HFO  group , with some showing significant improvement in outcomes ( e.g. , chronic lung disease ; Ref . 10 ) . Even with all the advances made in the care of neonatal respiratory distress in the last two decades , a cumulative meta- analysis continues to demonstrate benefit with HFO ( 1 ) . Adult HFO has been commercially available for only 10 years , so this body of literature is underst and ably smaller . The largest of two published RCTs comparing HFO with conventional ventilation showed an impressive trend toward decreased mortality with HFO ( absolute risk difference 16 % ; R-R 0.72 ; 95 % confidence interval 0.50–1.04 ; Ref . 3 ) . The smaller RCT did not demonstrate a mortality trend in either direction , but these results are confounded by an almost 20 % crossover rate and by large baseline differences favoring the control group ( 2 ) . We readily admit that data from these trials are not definitive . There are method ological issues : small sample sizes and the use of now date d , potentially injurious conventional ventilation strategies in the control arms ; they do , however , provide supporting data that are consistent with our physiological framework supporting HFO . It is important to point out that the purpose of this debate is not to demonstrate that HFO is better clinical ly , but rather that it represents the “ optimal physiological ” ventilatory approach that is currently available . Of course , the most important issue for patients is clinical outcomes , but unfortunately there are insufficient data in the literature to adequately address this point ( if these existed , there would be no debate ) . We stated earlier that the very small VTs on HFO are the cornerstone of this physiological framework . It is true , however , that VT is not routinely measured with currently available oscilJ Appl Physiol 104 : 1230–1235 , 2008 ; doi:10.1152/japplphysiol.01226.2007 There is little information on long-term outcome after acute respiratory distress syndrome ( ARDS ) . We measured quality -adjusted survival in the first year after ARDS in a prospect i ve cohort ( n = 200 ) . All patients met traditional criteria for ARDS . Patients with sepsis and acute nonpulmonary organ dysfunction at presentation were excluded . The cohort was healthy before onset of ARDS as evidence d by high functional status ( mean Karnofsky Performance Status index : 82.2/100 where > /= 80 = able to perform normal activities independently ) and minimal comorbid illness ( mean Charlson-Deyo comorbidity score : 0.32/17 where 0 = absence of chronic illness ) . We determined quality -adjusted life-years ( QALYs ) using the Quality of Well-being ( QWB ) scale ( 0 to 1 scale where 1 = optimal well-being ) , measured at 6 and 12 mo . Survival was 69.5 + /- 5.0 % at 1 month , fell to 55.7 + /- 3.7 % at 6 mo , and did not change at 12 mo , yielding a survival of 59 life-years in the first year per 100 patients with ARDS . QWB was low at 6 and 12 mo ( 0.59 + /- 0.015 and 0.60 + /- 0.015 ) , yielding a quality -adjusted survival of 36 QALYs per 100 patients ( sensitivity range : 21 to 46 QALYs ) . We conclude that ARDS developing in previously healthy patients is associated with poor quality -adjusted survival . These data are important for cost-effectiveness analyses and long-term care 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 RATIONALE Little is known about the long-term outcomes and costs of survivors of acute respiratory distress syndrome ( ARDS ) . OBJECTIVES To describe functional and quality of life outcomes , health care use , and costs of survivors of ARDS 2 yr after intensive care unit ( ICU ) discharge . METHODS We recruited a cohort of ARDS survivors from four academic tertiary care ICUs in Toronto , Canada , and prospect ively monitored them from ICU admission to 2 yr after ICU discharge .  MEASUREMENTS Clinical and functional outcomes , health care use , and direct medical costs . RESULTS Eighty-five percent of patients with ARDS discharged from the ICU survived to 2 yr ; overall 2-yr mortality was 49 % . At 2 yr , survivors continued to have exercise limitation although 65 % had returned to work . There was no statistically significant improvement in health-related quality of life as measured by Short-Form General Health Survey between 1 and 2 yr , although there was a trend toward better physical role at 2 yr ( p = 0.0586 ) . Apart from emotional role and mental health , all other domains remained below that of the normal population . From ICU admission to 2 yr after ICU discharge , the largest portion of health care costs for a survivor of ARDS was the initial hospital stay , with ICU costs accounting for 76 % of these costs . After the initial hospital stay , health care costs were related to hospital readmissions and inpatient rehabilitation . CONCLUSIONS Survivors of ARDS continued to have functional impairment and compromised health-related quality of life 2 yr after discharge from the ICU . Health care use and costs after the initial hospitalization were driven by hospital readmissions and inpatient rehabilitation BACKGROUND In patients with the acute respiratory distress syndrome , massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury . We determined whether a ventilatory strategy design ed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome . METHODS We r and omly assigned 53 patients with early acute respiratory distress syndrome ( including 28 described previously ) , all of whom were receiving identical hemodynamic and general support , to conventional or protective mechanical ventilation . Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure ( PEEP ) for acceptable oxygenation , with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels ( 35 to 38 mm Hg ) . Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve , a tidal volume of less than 6 ml per kilogram , driving pressures of less than 20 cm of water above the PEEP value , permissive hypercapnia , and preferential use of pressure-limited ventilatory modes . RESULTS After 28 days , 11 of 29 patients ( 38 percent ) in the protective-ventilation group had died , as compared with 17 of 24 ( 71 percent ) in the conventional-ventilation group ( P<0.001 ) . The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group ( P=0.005 ) : the rates of clinical barotrauma were 7 percent and 42 percent , respectively ( P=0.02 ) , despite the use of higher PEEP and mean airway pressures in the protective-ventilation group . The difference in survival to hospital discharge was not significant ; 13 of 29 patients ( 45 percent ) in the protective-ventilation group died in the hospital , as compared with 17 of 24 in the conventional-ventilation group ( 71 percent , P=0.37 ) . CONCLUSIONS As compared with conventional ventilation , the protective strategy was associated with improved survival at 28 days , a higher rate of weaning from mechanical ventilation , and a lower rate of barotrauma in patients with the acute respiratory distress syndrome .  Protective ventilation was not associated with a higher rate of survival to hospital discharge 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 Objective : To compare the effectiveness of high‐frequency oscillatory ventilation with conventional mechanical ventilation in pediatric patients with respiratory failure . Setting : Five tertiary care pediatric intensive care units . Design : A prospect i ve , r and omized , clinical study with crossover . Patients : Seventy patients with either diffuse alveolar disease and /or airleak syndrome were r and omized to receive high‐frequency oscillatory ventilation or conventional mechanical ventilation .  Interventions : Patients r and omized to receive high‐frequency oscillatory ventilation  were managed , using a strategy that consisted of aggressive increases in mean airway pressure to attain the “ ideal ” lung volume and to achieve an arterial oxygen saturation of ≥90 % , with an Fio2 of ≤0.6 . Patients who were r and omized to receive conventional mechanical ventilation  were treated with a strategy that utilized increases in end‐expiratory pressure and inspiratory time to increase mean airway pressure and to limit increases in peak inspiratory pressure . Target blood gas values were the same for both groups . Crossover to the alternate ventilator was required if the patient met defined criteria for treatment failure . Measurements and Main Results : Physiologic data and ventilatory parameters were collected prospect ively at predetermined intervals after r and omization . Airleak Scores were derived daily , based on the chest radiograph and the patient 's clinical condition . In the high‐frequency oscillatory ventilation group , the Pao2/Pao2 ratio increased significantly and the oxygenation index ( mean airway pressure × Fio2 × 100/Pao2 ) decreased significantly over time . There were no differences between the groups in duration of mechanical ventilation , frequency of airleak , Airleak Scores , or 30‐day survival rates . Significantly fewer patients treated with high‐frequency oscillatory ventilation  required supplemental oxygenation at 30 days compared with patients managed with conventional ventilation . When ventilatory subgroups were compared , the patients managed with high‐frequency oscillation only had significantly better ranked outcomes than patients managed with conventional ventilation only . Conclusions : Our results indicate that high‐frequency oscillatory ventilation , utilizing an aggressive volume recruitment strategy , results in significant improvement in oxygenation compared with a conventional ventilatory strategy design ed to limit increases in peak airway pressures . Furthermore , despite the use of higher mean airway pressures , the optimal lung volume strategy used in this study was associated with a lower frequency of barotrauma , as indicated by requirement for supplemental oxygen at 30 days , and improved outcome compared with conventional mechanical ventilation . ( Crit Care Med 1994 ; 22:1530–1539 Background Pressure control ventilation ( PCV ) , high-frequency oscillation ( HFO ) , and intratracheal pulmonary ventilation ( ITPV ) may all be used to provide lung protective ventilation in acute respiratory distress syndrome , but the specific approach that is optimal remains controversial . Methods Saline lavage was used to produce acute respiratory distress syndrome in 21 sheep r and omly assigned to receive  PCV , HFO , or  ITPV as follows : positive end-expiratory pressure ( PCV and ITPV ) and mean airway pressure ( HFO ) were set in a pressure-decreasing manner after lung recruitment that achieved a ratio of Pao2/Fio2 > 400 mmHg . Respiratory rates were 30 breaths/min , 120 breaths/min , and 8 Hz , respectively , for PCV , ITPV , and HFO . Eucapnia was targeted with peak carinal pressure of no more than 35 cm H2O . Animals were then ventilated for 4 h. Results There were no differences among groups in gas exchange , lung mechanics , or hemodynamics . Tidal volume  ( PCV , 8.9 ± 2.1 ml/kg ; ITPV , 2.7 ± 0.8 ml/kg ; HFO , approximately 2.0 ml/kg ) and peak carinal pressure ( PCV , 30.6 ± 2.6 cm H2O ; ITPV , 22.3 ± 4.8 cm H2O ; HFO , approximately 24.3 cm H2O ) were higher in PCV . Pilot histologic data showed greater interstitial hemorrhage and alveolar septal expansion  in PCV than in HFO or ITPV . Conclusion These data indicate that HFO , ITPV , and PCV when applied with an open-lung protective ventilatory strategy results in the same gas exchange , lung mechanics , and hemodynamic response , but pilot data indicate that lung injury may be greater with PCV BACKGROUND Some r and omised controlled trials ( RCTs ) done in German-speaking Europe are published in international English- language journals and others in national German- language journals . We assessed whether authors are more likely to report trials with statistically significant results in English than in German . METHODS We studied pairs of RCT reports , matched for first author and time of publication , with one report published in German and the other in English . Pairs were identified from reports round in a manual search of five leading German- language journals and from reports published by the same authors in English found on Medline .  Quality of methods and reporting were assessed with two different scales by two investigators who were unaware of authors ' identities , affiliations , and other characteristics of trial reports . Main study endpoints were selected by two investigators who were unaware of trial results . Our main outcome was the number of pairs of studies in which the levels of significance ( shown by p values ) were discordant . FINDINGS 62 eligible pairs of reports were identified but 19 ( 31 % ) were excluded because they were duplicate publications . A further three pairs ( 5 % ) were excluded because no p values were given . The remaining 40 pairs were analysed . Design characteristics and quality features were similar for reports in both language s. Only 35 % of German- language articles , compared with 62 % of English- language articles , reported significant ( p < 0.05 ) differences in the main endpoint between study and control groups ( p = 0.002 by McNemar 's test ) . Logistic regression showed that the only characteristic that predicted publication in an English- language journal was a significant result . The odds ratio for publication of trials with significant results in English was 3.75 ( 95 % CI 1.25 - 11.3 ) . INTERPRETATION Authors were more likely to publish RCTs in an English- language journal if the results were statistically significant . English language bias may , therefore , be introduced in review s and meta-analyses if they include only trials reported in English . The effort of the Cochrane Collaboration to identify as many controlled trials as possible , through the manual search of many medical journals published in different language s will help to reduce such bias Observational studies of high-frequency oscillatory ventilation in adults with the acute respiratory distress syndrome have demonstrated improvements in oxygenation . We design ed a multicenter , r and omized , controlled trial comparing the safety and effectiveness of high-frequency oscillatory ventilation with conventional ventilation in adults with acute respiratory distress syndrome ; 148 adults with acute respiratory distress syndrome ( Pa(O2)/fraction of inspired oxygen < or= 200 mm Hg on 10 or more cm H2O positive end-expiratory pressure ) were r and omized to high-frequency oscillatory ventilation  ( n = 75 ) or conventional ventilation ( n = 73 ) . Applied mean airway pressure was significantly higher in the high-frequency oscillation group compared with the conventional ventilation group throughout the first 72 hours ( p = 0.0001 ) . The high-frequency oscillation group showed early ( less than 16 hours ) improvement in Pa(O2)/fraction of inspired oxygen compared with the conventional ventilation group ( p = 0.008 ) ; however , this difference did not persist beyond 24 hours . Oxygenation index decreased similarly over the first 72 hours in both groups . Thirty-day mortality was 37 % in the high-frequency oscillation group and was 52 % in the conventional ventilation group ( p = 0.102 ) . The percentage of patients alive without mechanical ventilation at Day 30 was 36 % and 31 % in the high-frequency oscillation and conventional ventilation groups , respectively ( p = 0.686 ) . There were no significant differences in hemodynamic variables , oxygenation failure , ventilation failure , barotraumas , or mucus plugging between treatment groups . We conclude that high-frequency oscillation is a safe and effective mode of ventilation for the treatment of acute respiratory distress syndrome in adults CONTEXT Studies have shown that an inflammatory response may be elicited by mechanical ventilation used for recruitment or derecruitment of collapsed lung units or to overdistend alveolar regions , and that a lung-protective strategy may reduce this response . OBJECTIVE To test the hypothesis that mechanical ventilation induces a pulmonary and systemic cytokine response that can be minimized by limiting recruitment or derecruitment and overdistention . DESIGN AND SETTING R and omized controlled trial in the intensive care units of 2 European hospitals from November 1995 to February 1998 , with a 28-day follow-up . PATIENTS Forty-four patients ( mean [ SD ] age , 50 [ 18 ] years ) with acute respiratory distress syndrome were enrolled , 7 of whom were withdrawn due to adverse events . INTERVENTIONS After admission , volume-pressure curves were measured and bronchoalveolar lavage and blood sample s were obtained . Patients were r and omized to either the control group ( n = 19 ) : tidal volume to obtain normal values of arterial carbon dioxide tension ( 35 - 40 mm Hg ) and positive end-expiratory pressure ( PEEP ) producing the greatest improvement in arterial oxygen saturation without worsening hemodynamics ; or the lung-protective strategy group ( n = 18 ) : tidal volume and PEEP based on the volume-pressure curve . Measurements were repeated 24 to 30 and 36 to 40 hours after r and omization . MAIN OUTCOME MEASURES Pulmonary and systemic concentrations of inflammatory mediators approximately 36 hours after r and omization . RESULTS Physiological characteristics and cytokine concentrations were similar in both groups at r and omization . There were significant differences ( mean [ SD ] ) between the control and lung-protective strategy groups in tidal volume ( 11.1 [ 1.3 ] vs 7.6 [ 1.1 ] mL/kg ) , end-inspiratory plateau pressures ( 31.0 [ 4.5 ] vs 24.6 [ 2.4 ] cm H2O ) , and PEEP ( 6.5 [ 1.7 ] vs 14.8 [ 2.7 ] cm H2O ) ( P<.001 ) . Patients in the control group had an increase in bronchoalveolar lavage concentrations of interleukin ( IL ) 1beta , IL-6 , and IL-1 receptor agonist and in both bronchoalveolar lavage and plasma concentrations of tumor necrosis factor ( TNF ) alpha , IL-6 , and TNF-alpha , receptors over 36 hours ( P<.05 for all ) . Patients in the lung-protective strategy group had a reduction in bronchoalveolar lavage concentrations of polymorphonuclear cells , TNF-alpha , IL-1beta , soluble TNF-alpha receptor 55 , and IL-8 , and in plasma and bronchoalveolar lavage concentrations of IL-6 , soluble TNF-alpha receptor 75 , and IL-1 receptor antagonist ( P<.05 ) . The concentration of the inflammatory mediators 36 hours after r and omization was significantly lower in the lung-protective strategy group than in the control group ( P<.05 ) . CONCLUSIONS Mechanical ventilation can induce a cytokine response that may be attenuated by a strategy to minimize overdistention and recruitment/derecruitment of the lung . Whether these physiological improvements are associated with improvements in clinical end points should be determined in future studies
OBJECTIVE To determine clinical and physiological effects of high frequency oscillation compared with conventional ventilation in patients with acute lung injury/acute respiratory distress syndrome ( ARDS ) .