Efficacy of computerized decision support for mechanical ventilation: results of a prospective multi-center randomized trial The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Low mortality rate in adult respiratory distress syndrome using low‐volume, pressure‐limited ventilation with permissive hypercapnia: A prospective study Design and analysis of randomized clinical trials requiring prolonged observation of each patient. I. Introduction and design. A high positive end-expiratory pressure, low tidal volume ventilatory strategy improves outcome in persistent acute respiratory distress syndrome: A randomized, controlled trial* Temporal hemodynamic effects of permissive hypercapnia associated with ideal PEEP in ARDS. Beneficial effects of the "open lung approach" with low distending pressures in acute respiratory distress syndrome. A prospective randomized study on mechanical ventilation. 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. Are low tidal volumes safe? Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. [Comparison of the effects of BiPAP ventilation combined with lung recruitment maneuvers and low tidal volume A/C ventilation in patients with acute respiratory distress syndrome]. [Clinical effects of low-stretch ventilation on acute respiratory distress syndrome]. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. Randomized, prospective trial of pressure‐limited versus volume‐controlled ventilation in severe respiratory failure [The application of individualized ventilation strategies in acute respiratory distress syndrome]. Computerized decision support for mechanical ventilation of trauma induced ARDS: results of a randomized clinical trial. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Effect of neuromuscular blocking agents on gas exchange in patients presenting with acute respiratory distress syndrome* Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial.
200 adult respiratory distress syndrome patients were included in a prospect i ve multicenter r and omized trial to determine the efficacy of computerized decision support . The study was done in 10 medical centers across the United States . There was no significant difference in survival between the two treatment groups ( mean 2 = 0.49 p = 0.49 ) or in ICU length of stay between the two treatment groups when controlling for survival ( F(1df ) = 0.88 , p = 0.37 . ) There was a significant reduction in morbidity as measured by multi-organ dysfunction score in the protocol group ( F(1df ) = 4.1 , p = 0.04 ) as well as significantly lower incidence and severity of overdistension lung injury ( F(1df ) = 45.2 , p < 0.001 ) . We rejected the null hypothesis . Efficacy was best for the protocol group . Protocol s were used for 32,055 hours ( 15 staff person years , 3.7 patient years or 1335 patient days ) . Protocol s were active 96 % of the time . 38,546 instructions were generated . 94 % were followed . This study indicates that care using a computerized decision support system for ventilator management can be effectively transferred to many different clinical setting s and significantly improve patient morbidity The objective of this study was to refine the APACHE ( Acute Physiology , Age , Chronic Health Evaluation ) methodology in order to more accurately predict hospital mortality risk for critically ill hospitalized adults . We prospect ively collected data on 17,440 unselected adult medical/surgical intensive care unit ( ICU ) admissions at 40 US hospitals ( 14 volunteer tertiary-care institutions and 26 hospitals r and omly chosen to represent intensive care services nationwide ) . We analyzed the relationship between the patient 's likelihood of surviving to hospital discharge and the following predictive variables : major medical and surgical disease categories , acute physiologic abnormalities , age , preexisting functional limitations , major comorbidities , and treatment location immediately prior to ICU admission . The APACHE III prognostic system consists of two options : ( 1 ) an APACHE III score , which can provide initial risk stratification for severely ill hospitalized patients within independently defined patient groups ; and ( 2 ) an APACHE III predictive equation , which uses APACHE III score and reference data on major disease categories and treatment location immediately prior to ICU admission to provide risk estimates for hospital mortality for individual ICU patients . A five-point increase in APACHE III score ( range , 0 to 299 ) is independently associated with a statistically significant increase in the relative risk of hospital death ( odds ratio , 1.10 to 1.78 ) within each of 78 major medical and surgical disease categories . The overall predictive accuracy of the first-day APACHE III equation was such that , within 24 h of ICU admission , 95 percent of ICU admissions could be given a risk estimate for hospital death that was within 3 percent of that actually observed ( r2 = 0.41 ; receiver operating characteristic = 0.90 ) . Recording changes in the  APACHE III score on each subsequent day of ICU therapy provided daily up date s in these risk estimates . When applied across the individual ICUs , the first-day APACHE III equation accounted for the majority of variation in observed death rates ( r2 = 0.90 , p less than 0.0001 ) Objectives : To evaluate the outcome in patients with severe adult respiratory distress syndrome ( ARDS ) managed with limitation of peak inspiratory pressure to 30 to 40 cm H2O , low tidal volumes ( 4 to 7 mL/kg ) , spontaneous breathing using synchronized intermittent m and atory ventilation from the start of ventilation , and permissive hypercapnia without the use of bicarbonate to buffer acidosis . Also , to compare hospital mortality rate with that predicted by the Acute Physiology and Chronic Health Evaluation ( APACHE ) II scoring system and the “ ventilator score . ” Setting : A ten‐bed general intensive care unit in a university hospital . Design : Prospect i ve , descriptive study . Patients : Fifty‐three patients with severe ARDS having a lung injury score of ≥2.5 . Interventions : Data recording . Results : The hospital mortality rate was significantly lower than that predicted by the APACHE II scores ( 26.4 % vs. 53.3 % , p = .004 ) , even after correcting the latter for the effect of hypercapnic acidosis ( 26.4 % vs. 51.1 % , p = .008 ) . The mortality rate increased with increasing number of organ failures , but was only 43 % in patients with ≥4 organ failures , 20.5 % with ≤3 organ failures , and 6.6 % with only respiratory failure . The mean maximum Paco2 was 66.5 torr ( range 38 to 158 torr [ 8.87 kPa , range 5.07 to 21.07 ] ) , and the mean arterial pH at the same time was 7.23 ( range 6.79 to 7.45 ) . There was no correlation between the maximum Paco2 or the corresponding pH and the total respiratory rate at the same time . No pneumothoraces developed during mechanical ventilation . Conclusions : These results lend further support to the hypothesis that limitation of peak inspiratory pressure and reduction of regional lung overdistention by the use of low tidal volumes with permissive hypercapnia may reduce ventilator‐induced lung injury and improve outcome in severe ARDS . This hypothesis is supported by a large body of experimental evidence , which also suggests that ventilator‐induced lung injury may result in the release of inflammatory mediators , and thus may have the potential to augment the development of multiple organ dysfunction . However , the hypothesis requires testing in a r and omized trial as acute hypercapnia could potentially have some adverse as well as beneficial effects . ( Crit Care Med 1994 ; 22:1568–1578 The Medical Research Council has for some years encouraged collaborative clinical trials in leukaemia and other cancers , reporting the results in the medical literature . One unreported result which deserves such publication is the development of the expertise to design and analyse such trials . This report was prepared by a group of British and American statisticians , but it is intended for people without any statistical expertise . Part I , which appears in this issue , discusses the design of such trials ; Part II , which will appear separately in the January 1977 issue of the Journal , gives full instructions for the statistical analysis of such trials by means of life tables and the logrank test , including a worked example , and discusses the interpretation of trial results , including brief reports of 2 particular trials . Both parts of this report are relevant to all clinical trials which study time to death , and wound be equally relevant to clinical trials which study time to other particular classes of untoward event : first stroke , perhaps , or first relapse , metastasis , disease recurrence , thrombosis , transplant rejection , or death from a particular cause . Part I , in this issue , collects together ideas that have mostly already appeared in the medical literature , but Part II , next month , is the first simple account yet published for non-statistical physicians of how to analyse efficiently data from clinical trials of survival duration . Such trials include the majority of all clinical trials of cancer therapy ; in cancer trials , however , it may be preferable to use these statistical methods to study time to local recurrence of tumour , or to study time to detectable metastatic spread , in addition to study ing total survival . Solid tumours can be staged at diagnosis ; if this , or any other available information in some other disease is an important determinant of outcome , it can be used to make the overall logrank test for the whole heterogeneous trial population more sensitive , and more intuitively satisfactory , for it will then only be necessary to compare like with like , and not , by chance , Stage I with Stage III Objective : It has been shown in a two-center study that high positive end-expiratory pressure ( PEEP ) and low tidal volume ( LTV ) improved outcome in ARDS . However , that study involved patients with underlying diseases unique to the study area , was conducted at only two centers , and enrolled a small number of patients . We similarly hypothesized that a ventilatory strategy based on PEEP above the lower inflection point of the pressure volume curve of the respiratory system ( Pflex ) set on day 1 with a low tidal volume would result in improved outcome in patients with severe and persistent acute respiratory distress syndrome ( ARDS ) . Design : R and omized , controlled clinical trial . Setting : Network of eight Spanish multidisciplinary intensive care units ( ICUs ) under the acronym of ARIES ( Acute Respiratory Insufficiency : España Study ) . Patients : All consecutive patients admitted into participating Spanish ICUs from March 1999 to March 2001 with a diagnosis of ARDS were considered for the study . If 24 hrs after meeting ARDS criteria , the Pao2/Fio2 remained ≤200 mm Hg on st and ard ventilator setting s , patients were r and omized into two groups : control and Pflex/LTV . Interventions : In the control group , tidal volume was 9–11 mL/kg of predicted body weight ( PBW ) and PEEP ≥5 cm H2O . In the Pflex/LTV group , tidal volume was 5–8 mL/kg PBW and PEEP was set on day 1 at Pflex + 2 cm H2O . In both groups , Fio2 was set to maintain arterial oxygen saturation > 90 % and Pao2 70–100 mm Hg , and respiratory rate was adjusted to maintain Paco2 between 35 and 50 mm Hg . Measurements and Main Results : The study was stopped early based on an efficacy stopping rule as described in the methods . Of 103 patients who were enrolled ( 50 control and 53 Pflex ) , eight patients ( five in control , three in Pflex ) were excluded from the final evaluation because the r and om group assignment was not performed in one center according to protocol . Main outcome measures were ICU and hospital mortality , ventilator-free days , and nonpulmonary organ dysfunction . ICU mortality ( 24 of 45 [ 53.3 % ] vs. 16 of 50 [ 32 % ] , p = .040 ) , hospital mortality ( 25 of 45 [ 55.5 % ] vs. 17 of 50 [ 34 % ] , p = .041 )  , and ventilator-free days at day 28 ( 6.02 ± 7.95 in control and 10.90 ± 9.45 in Pflex/LTV , p = .008 ) all favored Pflex/LTV . The mean difference in the number of additional organ failures postr and omization was higher in the control group ( p < .001 ) . Conclusions : A mechanical ventilation strategy with a PEEP level set on day 1 above Pflex and a low tidal volume compared with a strategy with a higher tidal volume and relatively low PEEP has a beneficial impact on outcome in patients with severe and persistent ARDS The associated use of permissive hypercapnia ( PHY ) and high PEEP levels ( PEEP(IDEAL ) ) has been recently indicated as part of a lung-protective-approach ( LPA ) in acute respiratory distress syndrome ( ARDS ) . However , the net hemodynamic effect produced by this association is not known . We analyzed the temporal hemodynamic effects of this combined strategy in 48 patients ( mean age 34 + /- 13 yr ) with ARDS , focusing on its immediate ( after 1 h ) , early ( first 36 h ) , and late ( 2nd-7th d ) consequences . Twenty-five patients were su bmi tted to LPA -- with the combined use of permissive hypercapnia ( PHY ) , VT < 6 ml/kg , distending pressures above PEEP < 20 cm H2O , and PEEP 2 cm H2O above the lower inflection point on the static inspiratory P-V curve ( P(FLEX))- and 23 control patients were su bmi tted to conventional mechanical ventilation .  LPA was initiated at once , result ing in an immediate increase in heart rate ( p = 0.0002 ) , cardiac output ( p = 0.0002 ) , oxygen delivery ( DO2l , p = 0.0003 ) , and mixed venous Po2 ( p = 0.0006 ) , with a maintained systemic oxygen consumption ( p = 0.52 ) . The mean pulmonary arterial pressure markedly increased ( mean increment 8.8 mm Hg ; p < 0.0001 ) , but the pulmonary vascular resistance did not change ( p = 0.32 ) . Cardiac filling pressures increased ( p < 0.001 ) and the systemic vascular resistance fell ( p = 0.003 ) . All these alterations were progressively attenuated in the course of the first 36 h , despite persisting hypercapnia . Plasma lactate suffered a progressive decrement along the early period in LPA but not in control patients ( p < 0.0001 ) . No hemodynamic consequences of LPA were noticed in the late period and renal function was preserved . A multivariate analysis suggested that these acute hyperdynamic effects were related to respiratory acidosis , with no depressant effects ascribed to high PEEP levels . In contrast , high plateau pressures were associated with cardiovascular depression . Thus , as long as sufficiently low distending pressures are concomitantly applied , the sudden installation of PHY plus PEEP(IDEAL ) induces a transitory hyperdynamic state and pulmonary hypertension without harmful consequences to this young ARDS population Alveolar overdistention and cyclic reopening of collapsed alveoli have been implicated in the lung damage found in animals su bmi tted to  artificial ventilation  . To test whether these phenomena are impairing the recovery of patients with acute respiratory distress syndrome ( ARDS ) su bmi tted to conventional mechanical ventilation ( MV ) , we evaluated the impact of a new ventilatory strategy directed at minimizing " cyclic parenchymal stretch . " After receiving pre-established levels of hemodynamic , infectious , and general care , 28 patients with early ARDS were r and omly assigned to receive either MV based on a new approach ( NA , consisting of maintenance of end-expiratory pressures above the lower inflection point of the P x V curve , VT < 6 ml/kg , peak pressures < 40 cm H2O , permissive hypercapnia , and stepwise utilization of pressure-limited modes ) or a conventional approach ( C = conventional volume-cycled ventilation , VT = 12 ml/kg , minimum PEEP guided by FIO2 and hemodynamics and normal PaCO2 levels ) . Fifteen patients were selected to receive NA , exhibiting a better evolution of the PaO2/FIO2 ratio ( p < 0.0001 ) and of compliance ( p = 0.0018 ) , requiring shorter periods under FIO2 > 50 % ( p = 0.001 ) and a lower FIO2 at the day of death ( p = 0.0002 ) . After correcting for baseline imbalances in APACHE II , we observed a higher weaning rate in NA ( p = 0.014 ) but not a significantly improved survival ( overall mortality : 5/15 in NA versus 7/13 in C , p = 0.45 ) . We concluded that the NA ventilatory strategy can markedly improve the lung function  in patients with ARDS , increasing the chances of early weaning and lung recovery during mechanical ventilation 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 High airway pressure may be injurious to lung parenchyma , but lowering airway pressure using conventional mechanical ventilation necessitates lowering tidal volume ( VT ) . Intubated patients in the surgical intensive care unit ( SICU ) were r and omly assigned to group 1 ( VT = 12 ml/kg , n = 56 ) or group 2 ( VT = 6 ml/kg , n = 47 ) . Variables recorded included acute physiology and chronic health evaluation ( APACHE II ) score , mean peak airway pressure ( MPAP ) , mean PaO2/FIO2 , incidence of pulmonary infectious complications ( PIC ) , duration of intubation ( DOI ) , and duration of SICU stay ( DOS ) . Results in the table are means + /- SE . ( table ; see text ) The incidence of pulmonary infection tended to be lower and DOI and DOS tended to be shorter for nonneurosurgical and noncardiac surgical patients r and omized to low VT , suggesting that morbidity may be decreased . The use of low VT was associated with a statistically significant but clinical ly irrelevant decrease in oxygenation . The routine use of low VT appeared to be safe in a selected population of patients in the SICU OBJECTIVE To assess the safety and potential efficacy of a mechanical ventilation strategy design ed to reduce stretch-induced lung injury in acute respiratory distress syndrome . DESIGN Prospect i ve , r and omized , controlled clinical trial . SETTING Eight intensive care units in four teaching hospitals . PATIENTS Fifty-two patients with acute respiratory distress syndrome . INTERVENTIONS Traditional tidal volume patients : tidal volume 10 - 12 mL/kg ideal body weight , reduced if inspiratory plateau pressure was > 55 cm H2O ( 7.3 kPa ) . Small tidal volume patients : tidal volume 5 - 8 mL/kg ideal body weight , to keep plateau pressure < 30 cm H2O ( 4.0 kPa ) . MEASUREMENTS AND MAIN RESULTS Mean tidal volumes during the first 5 days in traditional and small tidal volume patients were 10.2 and 7.3 mL/kg , respectively ( p < .001 ) , with mean plateau pressure = 30.6 and 24.9 cm H2O ( 3.3 kPa ) , respectively ( p < .001 ) . There were no significant differences in requirements for positive end-expiratory pressure or FIO2 , fluid intakes/outputs , requirements for vasopressors , sedatives , or neuromuscular blocking agents , percentage of patients that achieved unassisted breathing , ventilator days , or mortality . CONCLUSIONS The reduced tidal volume strategy used in this study was safe . Failure to observe beneficial effects of small tidal volume ventilation treatment in important clinical outcome variables may have occurred because a ) the sample size was too small to discern small treatment effects ; b ) the differences in tidal volumes and plateau pressures were modest ; or c ) reduced tidal volume ventilation is not beneficial OBJECTIVE To compare the effects of BiPAP ventilation combined with lung recruitment maneuvers ( LRM ) with low tidal volume A/C ventilation in patients with acute respiratory distress syndrome ( ARDS ) . METHODS A prospect i ve , r and omized comparison of BiPAP mechanical ventilation combined with lung recruitment maneuvers ( test group ) with low tidal volume A/C ventilation ( control group ) was conducted in 28 patients with ARDS .  FiO2/PaO2 ratio , respiratory system compliance ( Cs ) , central venous pressure ( CVP ) , duration of ventilation support were recorded at 0 h , 48 h and 72 h separately . The ventilation associated lung injury and mortality at 28 d were also recorded . RESULTS The FiO2/PaO2 ratio were ( 298+/-16 ) and ( 309+/-16 ) cm H2O , Cs were ( 38.4+/-2.2 ) and ( 42.0+/-1.3 ) ml/cm H2O , CVP were ( 13.8+/-0.8 ) and ( 11.6+/-0.7 ) cm H2O in the test group at 48 h and 72 h separately . In the control group , FiO2/PaO2 ratio were ( 212+/-12 ) and ( 246+/-17 ) cm H2O , Cs were ( 29.5+/-1.3 ) and ( 29.0+/-1.0 ) ml/cm H2O , CVP were 18.6+/-1.1 and ( 16.8+/-1.0 ) cm H2O . The results were better in the test group as compared with the control group ( t=10.03 - 29.68 , all P<0.01 ) . The duration of ventilation support in the test group was shorter than the control group [ ( 14+/-3 ) d vs ( 19+/-3 ) d , t=4.80 , P<0.01 ] . The mortality in 28 d and ventilation associated lung injury were similar in the two groups . CONCLUSION The results show that combination of LRM with BiPAP mode ventilation , as compared with the control group , contributes to improved FiO2/PaO2 ratio , pulmonary compliance , stable hemodynamic and shorter duration of ventilation support in patients with ARDS OBJECTIVE To investigate the effectiveness of low-stretch as compared with low-tidal-volume strategy in the treatment of acute respiratory distress syndrome ( ARDS ) . METHODS Eighty-five cases of ARDS patients were r and omly divided into low-stretch group ( 42 cases ) and low-tidal-volume group ( 43 cases ) . The former group of patient received pressure assist control mode with not higher than 35 cm H(2)O ( 1 cm H(2)O=0.098 kPa ) of peak pressure or pressure support mode ventilation with not higher than 30 cm H(2)O of Pplateau , while in low-tidal-volume group tidal volume of no more than 6 ml/kg of predicted body weight was given . The mortality rate within 28 days , the incidence of hypercapnia , the duration of using sedatives and neuromuscular blockade agents , the time of ventilation and the length of intensive care unit ( ICU ) stay were compared between two groups . According to the monitored expiratory tidal volume ( V(T)e ) , the low-stretch group was divided into low-tidal-volume subgroup ( V(T)e < or = 6 ml/kg , 11 cases ) and non-low-tidal-volume subgroup ( V(T)e > 6 ml/kg , 31 cases ) . The mortality within 28 days and the incidence of hypercapnia were compared between two subgroups . RESULTS There was no significant difference in the 28-day mortality rate between two groups ( 34.0 % vs. 37.0 % , P>0.05 ) , but patients of low-stretch group had lower incidence of hypercapnia than low-tidal-volume group ( 10.6 % vs. 40.7 % , P<0.05 ) , and also the duration of using sedatives [ ( 4.5+/-1.2 ) days vs. ( 8.7+/-2.3 ) days ] and neuromuscular blockade agents [ ( 8.4+/-2.1 ) days vs. ( 10.7+/-1.2 ) days ] , and the length of ventilation and ICU stay [ ( 10.2+/-2.2 ) days vs. ( 13.7+/-3.1 ) days , all P<0.05 ] were less . Low tidal volume occurred in 26.2 % of low-stretch group , and the low-tidal-volume subgroup had higher 28-day mortality rate ( 40.8 % ) and incidence of hypercapnia ( 65.7 % ) than non-low-tidal-volume subgroup ( 13.2 % and 8.6 % , both P<0.05 ) . CONCLUSION Compared with low-tidal-volume strategy , low-stretch strategy can reduce the incidence of hypercapnia , the length of ventilation and ICU stay for ARDS patients , but have similar mortality rate . When low-stretch strategy is exercised , an inappropriate low tidal volume may be associated with poor outcome of ARDS BACKGROUND In patients with the acute respiratory distress syndrome , massive alveolar collapse and cyclic lung reopening and overdistention during mechanical ventilation may perpetuate alveolar injury . We determined whether a ventilatory strategy design ed to minimize such lung injuries could reduce not only pulmonary complications but also mortality at 28 days in patients with the acute respiratory distress syndrome . METHODS We r and omly assigned 53 patients with early acute respiratory distress syndrome ( including 28 described previously ) , all of whom were receiving identical hemodynamic and general support , to conventional or protective mechanical ventilation . Conventional ventilation was based on the strategy of maintaining the lowest positive end-expiratory pressure ( PEEP ) for acceptable oxygenation , with a tidal volume of 12 ml per kilogram of body weight and normal arterial carbon dioxide levels ( 35 to 38 mm Hg ) . Protective ventilation involved end-expiratory pressures above the lower inflection point on the static pressure-volume curve , a tidal volume of less than 6 ml per kilogram , driving pressures of less than 20 cm of water above the PEEP value , permissive hypercapnia , and preferential use of pressure-limited ventilatory modes . RESULTS After 28 days , 11 of 29 patients ( 38 percent ) in the protective-ventilation group had died , as compared with 17 of 24 ( 71 percent ) in the conventional-ventilation group ( P<0.001 ) . The rates of weaning from mechanical ventilation were 66 percent in the protective-ventilation group and 29 percent in the conventional-ventilation group ( P=0.005 ) : the rates of clinical barotrauma were 7 percent and 42 percent , respectively ( P=0.02 ) , despite the use of higher PEEP and mean airway pressures in the protective-ventilation group . The difference in survival to hospital discharge was not significant ; 13 of 29 patients ( 45 percent ) in the protective-ventilation group died in the hospital , as compared with 17 of 24 in the conventional-ventilation group ( 71 percent , P=0.37 ) . CONCLUSIONS As compared with conventional ventilation , the protective strategy was associated with improved survival at 28 days , a higher rate of weaning from mechanical ventilation , and a lower rate of barotrauma in patients with the acute respiratory distress syndrome .  Protective ventilation was not associated with a higher rate of survival to hospital discharge 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 OBJECTIVE To explore better ventilation strategies above lower-tidal-volume ( LTV ) strategy to protect lung function and improve outcome in acute respiratory distress syndrome ( ARDS ) . METHODS Thirty ARDS patients were enrolled in Department of Critical Care Medicine of Peking Union Medical College Hospital from July , 2004 to June , 2005 . They were r and omly allocated into two groups , LTV group and individual ventilation ( IV ) group . Patients received 6 ml/kg tidal volume ( V(T ) ) and high positive end-expiratory pressure ( PEEP ) in LTV group . In IV group , static pressure-volume ( P-V ) curve was measured daily , and PEEP and V(T ) were set based on P-V variation , and the open-lung potential was evaluated before recruitment maneuvers . The clinical effect , the degree of lung injury and other outcome indicators in two groups were assessed . RESULTS The mortality rate in 28 days of IV group ( 35.7 % ) was lower than that of LVT group ( 57.2 % , chi(2 ) = 1.265 , P > 0.05 ) . The serum surfactant-associated protein D ( SP-D ) expression in the third and the seventh day of IV group [ 154 ( 91 - 217 ) , 149 ( 91 - 206 ) mg/L ] were higher than those before enrollment [ 140 ( 80 - 200 ) mg/L ] ; and the IL-8 expression in the third and the seventh day of IV group [ 179 ( 122 - 236 ) , 210 ( 100 - 321 ) ng/L ] were higher than those before enrollment [ 210 ( 132 - 289 ) ng/L ] ; but all showed no significant difference [ chi(2 ) = 1.265 , Z = 1.079 , 1.741 , -0.879 , 0.471 , respectively , all P > 0.05 ] . The free-ICU days in 28 days and free-organ-dysfunction days of IV group [ 11 ( 5 - 16 ) d , 13 ( 6 - 18 ) d ] were significantly higher than that of LTV group [ 3 ( 0 - 8) d , 3 ( 0 - 7 ) d , Z = -2.277 , -2.372 respectively , all P < 0.05 ] . The PEEP , V(T ) , partial pressure of carbon dioxide in arterial blood ( PaCO2 ) , the plateau pressure ( Pplat ) of initial 3 days after enrollment in IV group [ ( 11 + /- 2 ) cm H2O ( 1 cm H2O = 0.098 kPa ) , ( 511 + /- 66 ) ml , ( 37 + /- 5 ) mm Hg ( 1 mm Hg = 0.133 kPa ) , ( 21 + /- 5 ) cm H2O ] were significant different with those of LTV group [ ( 16 + /- 3 ) cm H2O , ( 407 + /- 58 ) ml , ( 47 + /- 8) mm Hg , ( 26 + /- 4 ) cm H2O , t = -8.019 , 6.501 , -4.311 , -4.823 , all P < 0.01 ] . CONCLUSIONS Compared with LTV and high PEEP therapy , IV strategies are feasible for decreasing PEEP and Pplat , increasing tidal compliance and V(T ) , and avoiding CO2 retention . It also increased free-ICU days and free-organ-dysfunction days BACKGROUND Variability and logistic complexity of mechanical ventilatory support of acute respiratory distress syndrome , and need to st and ardize care among all clinicians and patients , led University of Utah/LDS Hospital physicians , nurses , and engineers to develop a comprehensive computerized protocol . This bedside decision support system was the basis of a multicenter clinical trial ( 1993 - 1998 ) that showed ability to export a computerized protocol to other sites and improved efficacy with computer- versus physician-directed ventilatory support . The Memorial Hermann Hospital Shock Trauma intensive care unit ( ICU ) ( Houston , TX ; a Level I trauma center and teaching affiliate of The University of Texas Houston Medical School ) served as one of the 10 trial sites and recruited two thirds of the trauma patients . Results from the trauma patient subgroup at this site are reported to answer three questions : Can a computerized protocol be successfully exported to a trauma ICU ? Was ventilator management different between study groups ? Was patient outcome affected ? METHODS Sixty-seven trauma patients were r and omized at the Memorial Hermann Shock Trauma ICU site . " Protocol " assigned patients had  ventilatory support directed by the bedside respiratory therapist using the computerized protocol . " Non protocol " patients were managed by physician orders . RESULTS Of the 67 trauma patients r and omized , 33 were protocol ( age 40 + /- 3 ; Injury Severity Score [ ISS ] 26 + /- 3 ; 73 % blunt ) and 34 were non protocol ( age 38 + /- 2 ; ISS 25 + /- 2 ; 76 % blunt ) . For the protocol group , the computerized protocol was used 96 % of the time of ventilatory support and 95 % of computer-generated instructions were followed by the bedside respiratory therapist . Outcome measures ( i.e. , survival , ICU length of stay , morbidity , and barotrauma ) were not significantly different between groups . Fio2 > or = 0.6 and Pplateau > or = 35 cm H2O exposures were less for the protocol group . CONCLUSION A computerized protocol for bedside decision support was successfully exported to a trauma center , and effectively st and ardized mechanical ventilatory support of trauma-induced acute respiratory distress syndrome without adverse effect on patient outcome Although survival rates for acute respiratory distress syndrome have increased , there is only limited information regarding the quality of life and the relationship between quality of life and pulmonary function after survival . We prospect ively measured pulmonary function , emotional function , and health-related quality of life in a cohort of acute respiratory distress syndrome survivors recruited from patients who were enrolled in a r and omized clinical trial of high versus low tidal volume mechanical ventilation at 1 year after their recovery . No significant differences were found between the patients treated with high and low tidal volumes on any pulmonary function measure . Approximately 80 % of the patients in both groups demonstrated reduced diffusing capacity ; 20 % had airflow obstruction , and 20 % had chest restriction . Scores on measures of depression and anxiety were within the normal ranges , suggesting that they did not have significant affective symptoms . However , both groups reported decreased health-related quality of life in physical functioning , physical ability to maintain their roles ( role-physical ) , bodily pain , general health , and vitality ( energy ) on the Medical Outcome Study Short Form Health Survey with similar physical limitations reported on the Sickness Impact Profile question naire . The pulmonary function abnormalities correlated with decreased health-related quality of life for domains reflecting physical function . Acute respiratory distress syndrome survivors treated with high and low tidal volumes have abnormal pulmonary function that was related to decreased health-related quality of life 1 year after hospital discharge 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 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
BACKGROUND Acute lung injury ( ALI ) and acute respiratory distress syndrome ( ARDS ) are life threatening clinical conditions seen in critically ill patients with diverse underlying illnesses .
Lung injury may be perpetuated by ventilation strategies that do not limit lung volumes and airway pressures .