The APACHE III prognostic system. Risk prediction of hospital mortality for critically ill hospitalized adults. Prevalence, etiologies and outcome of the acute respiratory distress syndrome among hypoxemic ventilated patients Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. Analysis of data from multiclinic trials. An evidence based approach to individualising treatment Low mortality rate in adult respiratory distress syndrome using low‐volume, pressure‐limited ventilation with permissive hypercapnia: A prospective study Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. Early predictive factors of survival in the acute respiratory distress syndrome. A multivariate analysis. 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. Selection of patients for randomized controlled trials: implications of wide or narrow eligibility criteria. Prospective, randomized, controlled clinical trial comparing traditional versus reduced tidal volume ventilation in acute respiratory distress syndrome patients. 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 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. Long-term follow-up of survivors of acute lung injury: lack of effect of a ventilation strategy to prevent barotrauma. Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Titration of tidal volume and induced hypercapnia in acute respiratory distress syndrome.
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 ) Objective : To evaluate the prevalence and outcome of the acute respiratory distress syndrome ( ARDS ) among patients requiring mechanical ventilation . Design : A prospect i ve , multi-institutional , initial cohort study including 28-day follow-up . Setting s : Thirty-six French intensive care units ( ICUs ) from a working group of the French Intensive Care Society ( SRLF ) . Patients : All the patients entering the ICUs during a 14-day period were screened prospect ively . Hypoxemic patients , defined as having a PaO2/FIO2 ratio ( P/F ) of 300 mmHg or less and receiving mechanical ventilation  , were classified into three groups , according to the Consensus Conference on ARDS : group 1 refers to ARDS ( P/F : 200 mmHg or less and bilateral infiltrates on the chest X-ray ) ; group 2 to acute lung injury ( ALI ) without having criteria for ARDS ( 200 < P/F ≤ 300 mmHg and bilateral infiltrates ) and group 3 to patients with P/F of 300 mmHg or less but having exclusion criteria from the previous groups . Results : Nine hundred seventy-six patients entered the ICUs during the study period , 43 % of them being mechanically ventilated and 213 ( 22 % ) meeting the criteria for one of the three groups . Among all the ICU admissions , ARDS , ALI and group 3 patients amounted , respectively , to 6.9 % ( 67 ) , 1.8 % ( 17 ) and 13.3 % ( 129 ) of the patients , and represented 31.5 % , 8.1 % and 60.2 % of the hypoxemic , ventilated patients . The overall mortality rate was 41 % and was significantly higher in ARDS patients than in the others ( 60 % vs 31 % p < 0.01 ) . In group 3 , 42 patients had P/F less than 200 mmHg associated with unilateral lung injury ; mortality was significantly lower ( 40.5 % ) than in the ARDS group . In the whole group of hypoxemic , ventilated patients , septic shock and severity indices but not oxygenation indices were significantly associated with mortality , while the association with immunosuppression revealed only a trend ( p = 0.06 ) . Conclusions : In this survey we found that very few patients fulfilled the ALI non-ARDS criteria and that the mortality of the group with ARDS was high CONTEXT Health-related quality of life ( HRQL ) is reduced in patients who survive acute respiratory distress ( ARDS ) , but whether this decline in HRQL is caused by ARDS or other aspects of the patient 's illness or injury is unknown . OBJECTIVE To determine if there are differences in the HRQL of ARDS survivors and comparably ill or injured controls without ARDS . DESIGN Prospect i ve , matched , parallel cohort study . SETTING A 411-bed municipal medical and regional level I trauma center . PATIENTS Seventy-three pairs of ARDS survivors and severity-matched controls with the clinical risk factors for ARDS of sepsis and trauma admitted between January 1 , 1994 , and July 30 , 1996 . MAIN OUTCOME MEASURES The HRQL of ARDS survivors and controls , assessed by generic and pulmonary disease-specific HRQL instruments ( Medical Outcomes Study 36-Item Short Form Health Survey , St and ard Form [ SF-36 ] and St George 's Respiratory Question naire [ SGRQ ] , respectively ) . RESULTS Clinical ly meaningful and statistically significant reductions in HRQL scores of ARDS survivors ( n = 73 ) were seen in 7 of 8 SF-36 domains and 3 of 3 SGRQ domains compared with matched controls ( P<.001 for all reductions ) . The largest decrements in the HRQL were seen in physical function and pulmonary symptoms and limitations . Analysis of trauma-matched pairs ( n = 46 ) revealed significant reductions in 7 of 8 SF-36 domains ( P < or = .02 ) and 3 of 3 SGRQ domains ( P < or = .003 ) . Analysis of sepsis-matched pairs ( n = 27 ) revealed significant reductions in 6 of 8 SF-36 domains ( P < or = .05 ) and 3 of 3 SGRQ domains ( P < or = .002 ) . CONCLUSIONS Survivors of ARDS have a clinical ly significant reduction in HRQL that appears to be caused exclusively by ARDS and its sequelae . Reductions were primarily noted in physical functioning and pulmonary disease-specific domains Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction To which groups of patients can the results of clinical trials be applied ? This question is often inappropriately answered by reference to the trial entry criteria . Instead , the benefit and harm ( adverse events , discomfort of treatment , etc ) of treatment could be assessed separately for individual patients . Patients at greatest risk of a disease will have the greatest net benefit as benefit to patients usually increases with risk while harm remains comparatively fixed . To assess net benefit , the relative risks should come from ( a meta- analysis of ) r and omised trials ; the risk in individual patients should come from multivariate risk equations derived from cohort studies . However , before making firm conclusions , the assumptions of fixed adverse effects and constant reduction in relative risk need to be checked 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 BACKGROUND Traditional approaches to mechanical ventilation use tidal volumes of 10 to 15 ml per kilogram of body weight and may cause stretch-induced lung injury in patients with acute lung injury and the acute respiratory distress syndrome . We therefore conducted a trial to determine whether ventilation with lower tidal volumes would improve the clinical outcomes in these patients . METHODS Patients with acute lung injury and the acute respiratory distress syndrome were enrolled in a multicenter , r and omized trial . The trial compared traditional ventilation treatment , which involved an initial tidal volume of 12 ml per kilogram of predicted body weight and an airway pressure measured after a 0.5-second pause at the end of inspiration ( plateau pressure ) of 50 cm of water or less , with ventilation with a lower tidal volume , which involved an initial tidal volume of 6 ml per kilogram of predicted body weight and a plateau pressure of 30 cm of water or less . The primary outcomes were death before a patient was discharged home and was breathing without assistance and the number of days without ventilator use from day 1 to day 28 . RESULTS The trial was stopped after the enrollment of 861 patients because  mortality was lower in the group treated with lower tidal volumes than in the group treated with traditional tidal volumes ( 31.0 percent vs. 39.8 percent , P=0.007 ) , and the number of days without ventilator use during the first 28 days after r and omization was greater in this group ( mean [ + /-SD ] , 12+/-11 vs. 10+/-11 ; P=0.007 ) . The mean tidal volumes on days 1 to 3 were 6.2+/-0.8 and 11.8+/-0.8 ml per kilogram of predicted body weight ( P<0.001 ) , respectively , and the mean plateau pressures were 25+/-6 and 33+/-8 cm of water ( P<0.001 ) , respectively . CONCLUSIONS In patients with acute lung injury and the acute respiratory distress syndrome , mechanical ventilation with a lower tidal volume than is traditionally used results in decreased mortality and increases the number of days without ventilator use To identify the potential impact of novel therapeutic approaches , we studied the early predictive factors of survival at the onset of acute respiratory distress syndrome ( ARDS ) in a 24-bed medical ICU of an academic tertiary care hospital . Over a 48-mo period , a total of 3,511 adult patients were admitted and 259 mechanically ventilated patients met ARDS criteria , as defined by American-European consensus conference , i.e. , bilateral pulmonary infiltrates and PaO2/FIO2 lower than 200 without left atrial hypertension . These patients were r and omly included in a developmental sample ( 177 patients ) and a validation sample ( 82 patients ) . Demographic variables , hemodynamic and respiratory parameters , underlying diseases , as well as several severity scores ( SAPS , SAPS-II , OSF ) and Lung Injury Score ( LIS ) were collected . These variables were compared between survivors and nonsurvivors and entered into a stepwise logistic regression model to evaluate their independent prognostic roles . The overall mortality rate was 65 % . SAPS-II , the severity of the underlying medical conditions , the oxygenation index ( mean airway pressure x FIO2 x 100/PaO2 ) , the length of mechanical ventilation prior to ARDS , the mechanism of lung injury , cirrhosis , and occurrence of right ventricular dysfunction were independently associated with an elevated risk of death . Model calibration was very good in the developmental and validation sample s ( p = 0.84 and p = 0.72 , respectively ) , as was model discrimination ( area under the ROC curves of 0.95 and 0.92 , respectively ) . Thus , the prognosis of ARDS seems to be related to the triggering risk factor , the severity of the respiratory illness , and the occurrence of a right ventricle dysfunction , after adjustment for a general severity score 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 This paper discusses the various philosophies that influence the selection of patients for entry into r and omized controlled trials .  Although a number of different and often competing issues have to be considered depending upon the trial , keeping entry criteria simple , wide and at times even flexible is usually preferable . Such a strategy can be a positive virtue by helping to attain the large numbers of patients that are usually needed to reliably detect the sorts of moderate benefits that are plausible , at a reasonable cost and by providing answers that are relevant to many different categories of patients with a particular condition 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 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 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 OBJECTIVES To determine the effect of a ventilation strategy to prevent barotrauma on long-term outcome in survivors of acute lung injury . DESIGN Prospect i ve blinded cohort analysis . SETTING Three university-affiliated medical-surgical intensive care units . PATIENTS A total of 28 survivors of acute lung injury , 1 - 2 yrs after diagnosis , from a multicenter prospect i ve r and omized controlled trial comparing pressure ( peak inflation pressure < or = 30 cm H2O ) and volume ( tidal volume < or = 8 mL/kg ) limited ventilation to a conventional ( peak inflation pressure < or = 50 cm H2O , tidal volume 10 - 15 mL/kg ) ventilation strategy . MEASUREMENTS AND MAIN RESULTS Physicians blinded as to treatment group evaluated 20 of 28 survivors ( treatment group , 7 ; control group , 13 ) . Exercise tolerance in the 6-minute walk test was comparable to patients with chronic respiratory disease and equivalent between groups ( treatment group , 373+/-171 m vs. control group , 375+/-129 m ; p = .84 ) . Pulmonary function testing showed reduced diffusing capacity ( treatment group , 64+/-29 % predicted vs. control group , 74+/-14 % predicted ; p = .68 ) and normal volumes , flows , and blood gases . Two domains of disease-specific Health Related Quality of Life assessed by the Chronic Respiratory Question naire were worse for patients in the treatment group compared with the control group ( Emotional Function 3.8+/-1.4 vs. 5.1+/-0.08 ; p = .05 , Mastery 4.7+/-1.7 vs. 6.2+/-0.8 ; p = .03 ) . There were no between-group differences in the scores of the Spitzer Quality of Life Index ( a generic Health Related Quality of Life instrument ) , although they were reduced ( 7.5+/-1.9 ) and comparable to patients with chronic disease . CONCLUSIONS We found that 1 - 2 yrs after the onset of their illness , survivors of acute lung injury have reductions in quality of life and exercise tolerance which are similar to patients with chronic diseases . We were unable to show that a limited ventilation strategy improves either long-term pulmonary function or quality of life in survivors of acute lung injury 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 Mechanical ventilation may promote overdistension-induced pulmonary lesions in patients with acute respiratory distress syndrome ( ARDS ) . The static pressure-volume ( P-V ) curve of the respiratory system can be used to determine the lung volume and corresponding static airway pressure at which lung compliance begins to diminish ( the upper inflection point , or UIP ) . This fall in compliance may indicate overdistension of lung units . We prospect ively studied 42 patients receiving mechanical ventilation with an FIO2 of 0.5 or more for at least 24 h. According to the Lung Injury Score ( LIS ) , 25 patients were classified as having ARDS ( LIS > 2.5 ) , while 17 patients constituted a non-ARDS control group . The P-V curve was obtained every 2 d. Mechanical ventilation initially used st and ard setting s ( volume-control mode , a positive end-expiratory pressure [ PEEP ] adjusted to the lower inflection point on the P-V curve , and a tidal volume [ VT ] of 10 ml/kg ) . The end-inspiratory plateau pressure ( Pplat ) was compared to the UIP , and VT was lowered when the Pplat was above the UIP . In the range of lung volume studied on the P-V curves ( up to 1600 ml ) , a UIP could be shown in only one control patient ( at 23 cm H2O ) . By contrast , a UIP was present on the P-V curve obtained from all patients with ARDS , corresponding to a mean airway pressure of 26 + /- 6 cm H2O , a lung volume of 850 + /- 200 ml above functional residual capacity and 610 + /- 235 ml above PEEP . ( ABSTRACT TRUNCATED AT 250 WORDS
BACKGROUND Patients with acute respiratory distress syndrome ( ARDS ) and acute lung injury ( ALI ) require mechanical ventilatory support .
ALI/ARDS is further complicated by ventilator-induced lung injury .
Lung-protective ventilation strategies may lead to improved survival .
OBJECTIVES To assess the effects of ventilation with lower tidal volume ( Vt ) on morbidity and mortality in adults patients affected by ALI/ARDS .
A secondary objective was to determine whether the comparison between low and conventional Vt is different if a plateau airway pressure of greater than 30 to 35 cm H20 was used .