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.

Objective To evaluate the effect of initial low energy permissive underfeeding ("trophic feeding") versus full energy enteral feeding ("full feeding") on physical function and secondary outcomes in patients with acute lung injury. Design Prospective longitudinal follow-up evaluation of the NHLBI ARDS Clinical Trials Network's EDEN trialSetting 41hospitals in the United States.Participants 525 patients with acute lung injury.Interventions Randomised assignment to trophic or full feeding for up to six days; thereafter, all patients still receiving mechanical ventilation received full feeding. MeasurementsBlinded assessment of the age and sex adjusted physical function domain of the SF-36 instrument at 12 months after acute lung injury. Secondary outcome measures included survival; physical, psychological, and cognitive functioning; quality of life; and employment status at six and 12 months.Results After acute lung injury, patients had substantial physical, psychological, and cognitive impairments, reduced quality of life, and impaired return to work. Initial trophic versus full feeding did not affect mean SF-36 physical function at 12 months (55 (SD 33) v 55 (31), P=0.54), survival to 12 months (65% v 63%, P=0.63), or nearly all of the secondary outcomes. ConclusionIn survivors of acute lung injury, there was no difference in physical function, survival, or multiple secondary outcomes at 6 and 12 month follow-up after initial trophic or full enteral feeding. Trial Registration NCT No 00719446 IntroductionOptimal nutritional strategies for mechanically ventilated patients in the intensive care unit are uncertain. There is some evidence and recommendations to support both initial full energy enteral feeding ("full feeding") and low energy permissive underfeeding ("trophic feeding") with different risks and benefits described. [1][2][3][4][5][6][7] The Acute Respiratory Distress Syndrome Clinical Trials Network of the National Heart, Lung and Blood Institute published a large, multicentre randomised open label trial of initial trophic compared with full enteral feeding for up to six days in patients with acute lung injury (the "EDEN trial"). 8 This trial found no significant difference in short term outcomes, including mortality and days without ventilation. Because nutritional interventions have the potential for longer term effects, 9 and because longer term outcomes of patients in intensive care units might differ from short term results, study outcomes also should be assessed over a longer time frame. 10-15Evaluation of longer term functional outcomes is especially important in patients with acute lung injury because trophic feeding can exacerbate protein limitations in the intensive care unit, 16 and such malnutrition might underlie important muscle loss, 17 persistent muscle weakness, and functional impairment in these patients. [18][19][20][21][22] Moreover, post hoc data analyses from a previous phase II randomised trial in mechanically ventilated patients in intensive care showed that they were more...

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) ...

Rationale: Existing studies of risk factors for physical impairments in acute lung injury (ALI) survivors were potentially limited by single-center design or relatively small sample size.Objectives: To evaluate risk factors for three measures of physical impairments commonly experienced by survivors of ALI in the first year after hospitalization.Methods: A prospective, longitudinal study of 6-and 12-month physical outcomes (muscle strength, 6-minute-walk distance, and Short Form [SF]-36 Physical Function score) for 203 survivors of ALI enrolled from 12 hospitals participating in the ARDS Network randomized trials. Multivariable regression analyses evaluated the independent association of critical illness-related variables and intensive care interventions with impairments in each physical outcome measure, after adjusting for patient demographics, comorbidities, and baseline functional status.Measurements and Main Results: At 6 and 12 months, respectively, mean (6 SD) values for strength (presented as proportion of maximum strength score evaluated using manual muscle testing) was 92% (6 8%) and 93% (6 9%), 6-minute-walk distance (as percent-predicted) was 64% (6 22%) and 67% (6 26%), and SF-36 Physical Function score (as percent-predicted) was 61% (6 36%) and 67% (6 37%). After accounting for patient baseline status, there was significant association and statistical interaction of mean daily dose of corticosteroids and intensive care unit length of stay with impairments in physical outcomes.Conclusions: Patients had substantial impairments, from predicted values, for 6-minute-walk distance and SF-36 Physical Function outcome measures. Minimizing corticosteroid dose and implementing existing evidence-based methods to reduce duration of intensive care unit stay and associated patient immobilization may be important interventions for improving ALI survivors' physical outcomes.