Objective Survivors of severe critical illness frequently develop substantial and persistent physical complications, including muscle weakness, impaired physical function, and decreased health-related quality of life (HRQOL). Our objective was to determine the longitudinal epidemiology of muscle weakness, physical function, and HRQOL, and their associations with critical illness and intensive care unit exposures. Design A multi-site prospective study with longitudinal follow-up at 3, 6, 12, and 24 months after acute lung injury. Setting 13 intensive care units from 4 academic teaching hospitals. Patients 222 survivors of acute lung injury. Measurements and Main Results At each time point, patients underwent standardized clinical evaluations of extremity, hand grip, and respiratory muscle strength; anthropometrics (height, weight, mid-arm circumference, and triceps skin fold thickness), 6-minute walk distance, and the Medical Outcomes Short-Form 36 (SF-36) HRQOL survey. During their hospitalization, survivors also had detailed daily evaluation of critical illness and related treatment variables. Over one-third of survivors had objective evidence of muscle weakness at hospital discharge, with most improving within 12 months. This weakness was associated with substantial impairments in physical function and HRQOL that persisted at 24 months. The duration of bed rest during critical illness was consistently associated with weakness throughout 24-month follow-up. The cumulative dose of systematic corticosteroids and use of neuromuscular blockers in the intensive care unit were not associated with weakness. Conclusions Muscle weakness is common after ALI, usually recovering within 12 months. This weakness is associated with substantial impairments in physical function and HRQOL that continue beyond 24 months. These results provide valuable prognostic information regarding physical recovery after ALI. Evidence-based methods to reduce the duration of bed rest during critical illness may be important for improving these long-term impairments.

The risk of CINMA is nearly 50% in ICU patients with sepsis, multi-organ failure, or protracted mechanical ventilation. The association of CINMA with frequently cited CINMA risk factors (glucocorticoids, neuromuscular blockers) and with short-term survival is uncertain. Available data indicate glycemic control as a potential strategy to decrease CINMA risk.

Compared with the general population, ICU survivors report lower QOL prior to ICU admission. After hospital discharge, QOL in ICU survivors improves but remains lower than general population levels. Age and severity of illness are predictors of physical functioning. This systematic review provides a general understanding of QOL following critical illness and can serve as a standard of comparison for QOL studies in specific ICU subpopulations.

Objective To evaluate the association of volume limited and pressure limited (lung protective) mechanical ventilation with two year survival in patients with acute lung injury.Design Prospective cohort study.Setting 13 intensive care units at four hospitals in Baltimore, Maryland, USA.Participants 485 consecutive mechanically ventilated patients with acute lung injury.Main outcome measure Two year survival after onset of acute lung injury.Results 485 patients contributed data for 6240 eligible ventilator settings, as measured twice daily (median of eight eligible ventilator settings per patient; 41% of which adhered to lung protective ventilation). Of these patients, 311 (64%) died within two years. After adjusting for the total duration of ventilation and other relevant covariates, each additional ventilator setting adherent to lung protective ventilation was associated with a 3% decrease in the risk of mortality over two years (hazard ratio 0.97, 95% confidence interval 0.95 to 0.99, P=0.002). Compared with no adherence, the estimated absolute risk reduction in two year mortality for a prototypical patient with 50% adherence to lung protective ventilation was 4.0% (0.8% to 7.2%, P=0.012) and with 100% adherence was 7.8% (1.6% to 14.0%, P=0.011).Conclusions Lung protective mechanical ventilation was associated with a substantial long term survival benefit for patients with acute lung injury. Greater use of lung protective ventilation in routine clinical practice could reduce long term mortality in patients with acute lung injury.Trial registration Clinicaltrials.gov NCT00300248. IntroductionSurvivors of severe critical illness, such as acute lung injury, and its more severe subset, acute respiratory distress syndrome (ARDS), commonly experience increased mortality and morbidity in the months and years after hospital discharge. [1][2][3] Compared with age matched and sex matched controls, patients discharged from intensive care are two to five times more likely to die during three to 15 years' follow-up. 3 Few interventions have been evaluated for improving this increased long term mortality. 4 Randomised trials and meta-analyses have shown that use of volume limited and pressure limited mechanical ventilation (lung protective ventilation) in patients with acute lung injury substantially decreases short term mortality. [5][6][7][8][9] A randomised trial of lung protective ventilation carried out by the ARDS Network 8 found an 8.8% absolute reduction in short term mortality. This trial evaluated a ventilator tidal volume of 6 mL/kg predicted body weight (calculated on the basis of a patient's sex and height 8 ) and a plateau pressure (airway pressure measured after a 0.5 second end inspiratory pause) of ≤30 cm of water compared with a tidal volume of 12 mL/kg predicted body weight and a plateau pressure of ≤50 cm of water. Understanding the effect of lung protective ventilation on long term survival is important, 4 5 especially since critical care interventions with a mortality benefit at hospital dischar...

ARDS survivors in different clinical settings experience similar decrements in QOL. The precise magnitude of these decrements helps clarify the long-term prognosis for ARDS survivors.

Rationale: Reducing tidal volume decreases mortality in acute respiratory distress syndrome (ARDS). However, the effect of the timing of low tidal volume ventilation is not well understood.Objectives: To evaluate the association of intensive care unit (ICU) mortality with initial tidal volume and with tidal volume change over time.Methods: Multivariable, time-varying Cox regression analysis of a multisite, prospective study of 482 patients with ARDS with 11,558 twice-daily tidal volume assessments (evaluated in milliliter per kilogram of predicted body weight [PBW]) and daily assessment of other mortality predictors.Measurements and Main Results: An increase of 1 ml/kg PBW in initial tidal volume was associated with a 23% increase in ICU mortality risk (adjusted hazard ratio, 1.23; 95% confidence interval [CI], 1.06-1.44; P = 0.008). Moreover, a 1 ml/kg PBW increase in subsequent tidal volumes compared with the initial tidal volume was associated with a 15% increase in mortality risk (adjusted hazard ratio, 1.15; 95% CI, 1.02-1.29; P = 0.019). Compared with a prototypical patient receiving 8 days with a tidal volume of 6 ml/kg PBW, the absolute increase in ICU mortality (95% CI) of receiving 10 and 8 ml/kg PBW, respectively, across all 8 days was 7.2% (3.0-13.0%) and 2.7% (1.2-4.6%). In scenarios with variation in tidal volume over the 8-day period, mortality was higher when a larger volume was used earlier.Conclusions: Higher tidal volumes shortly after ARDS onset were associated with a greater risk of ICU mortality compared with subsequent tidal volumes. Timely recognition of ARDS and adherence to low tidal volume ventilation is important for reducing mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00300248).

Rationale: We hypothesized that providing patients with acute lung injury two different protein/calorie nutritional strategies in the intensive care unit may affect longer-term physical and cognitive performance. Objectives: To assess physical and cognitive performance 6 and 12 months after acute lung injury, and to evaluate the effect of trophic versus full enteral feeding, provided for the first 6 days of mechanical ventilation, on 6-minute-walk distance, cognitive impairment, and secondary outcomes. Methods: A prospective, longitudinal ancillary study of the ARDS Network EDEN trial evaluating 174 consecutive survivors from 5 of 12 centers. Blinded assessments of patients' arm anthropometrics, strength, pulmonary function, 6-minute-walk distance, and cognitive status (executive function, language, memory, verbal reasoning/ concept formation, and attention) were performed. Measurements and Main Results: At 6 and 12 months, respectively, the mean (SD) percent predicted for 6-minute-walk distance was 64% (22%) and 66% (25%) (P ¼ 0.011 for difference between assessments), and 36 and 25% of survivors had cognitive impairment (P ¼ 0.001). Patients performed below predicted values for secondary physical tests with small improvement from 6 to 12 months. There was no significant effect of initial trophic versus full feeding for the first 6 days after randomization on survivors' percent predicted for 6-minutewalk distance, cognitive impairment status, and all secondary outcomes. Conclusions: EDEN trial survivors performed below predicted values for physical and cognitive performance at 6 and 12 months, with some improvement over time. Initial trophic versus full enteral feeding for the first 6 days after randomization did not affect physical and cognitive performance.Keywords: follow-up studies; exercise tests; muscle strength; neuropsychological tests; cognition disorders ized trial (the EDEN trial), there was no effect of initial trophic versus full enteral feeding in the intensive care unit on the short-term mortality and ventilator-free days of patients with acute lung injury (ALI), or on patient-reported physical, psychological, and cognitive outcomes 6 and 12 months after ALI.d Given differences in protein and total caloric intake between these two feeding strategies, understanding the effect on the longer-term physical and cognitive performance of patients is important and novel.What This Study Adds to the Field d In studying 174 patients from the EDEN trial, recruited from 12 hospitals at 5 ARDS Network study centers, these ALI survivors consistently performed below predicted values across a battery of physical and cognitive tests, with some improvements observed between 6 and 12 months.d At both 6 and 12 months, initial trophic versus full enteral feeding had no effect on either physical performance outcomes (upper arm anthropometrics, muscle strength, pulmonary function, 6-min-walk distance) or cognitive impairment (based on tests of executive function, language, memory, verbal reasoning/concept formation, and...

Rationale: Survivors of acute lung injury (ALI) frequently have substantial depressive symptoms and physical impairment, but the longitudinal epidemiology of these conditions remains unclear. Objectives: To evaluate the 2-year incidence and duration of depressive symptoms and physical impairment after ALI, as well as risk factors for these conditions. Methods: This prospective, longitudinal cohort study recruited patients from 13 intensive care units (ICUs) in four hospitals, with follow-up 3, 6, 12, and 24 months after ALI. The outcomes were Hospital Anxiety and Depression Scale depression score greater than or equal to 8 ("depressive symptoms") in patients without a history of depression before ALI, and two or more dependencies in instrumental activities of daily living ("impaired physical function") in patients without baseline impairment. Measurements and Main Results: During 2-year follow-up of 186 ALI survivors, the cumulative incidences of depressive symptoms and impaired physical function were 40 and 66%, respectively, with greatest incidence by 3-month follow-up; modal durations were greater than 21 months for each outcome. Risk factors for incident depressive symptoms were education 12 years or less, baseline disability or unemployment, higher baseline medical comorbidity, and lower blood glucose in the ICU. Risk factors for incident impaired physical function were longer ICU stay and prior depressive symptoms. Conclusions: Incident depressive symptoms and impaired physical function are common and long-lasting during the first 2 years after ALI. Interventions targeting potentially modifiable risk factors (e.g., substantial depressive symptoms in early recovery) should be evaluated to improve ALI survivors' long-term outcomes.Keywords: depression; recovery of function; critical illness; critical care; acute lung injury Survivors of acute lung injury/acute respiratory distress syndrome (ALI) and other critical illnesses frequently have substantial depressive symptoms and impaired physical functioning, with associated decrements in quality of life (1-9). At present, there are gaps in knowledge regarding the incidence and duration of these conditions in ALI survivors, as well as their risk factors.Our objective was to longitudinally examine the incidence and duration of depressive symptoms and impaired physical functioning in the first 2 years after ALI. We also sought to determine risk factors for each of these conditions, to help inform future prevention and treatment efforts. Some of the results of this study have been reported previously in the form of an abstract (10). METHODS Study PopulationMechanically ventilated patients with ALI (11) were enrolled consecutively in a prospective cohort study involving 13 intensive care units (ICUs) at four hospitals in Baltimore, Maryland, between October 2004 and October 2007 (12). To avoid inclusion of patients with primary neurologic disease or head trauma, neurologic specialty ICUs at the participating hospitals were excluded. Key exclusion criteria were (1) ...