Outcomes after acute respiratory distress syndrome (ARDS) are similar to those of other survivors of critical illness and largely affect the nerve, muscle, and central nervous system but also include a constellation of varied physical devastations ranging from contractures and frozen joints to tooth loss and cosmesis. Compromised quality of life is related to a spectrum of impairment of physical, social, emotional, and neurocognitive function and to a much lesser extent discrete pulmonary disability. Intensive care unit-acquired weakness (ICUAW) is ubiquitous and includes contributions from both critical illness polyneuropathy and myopathy, and recovery from these lesions may be incomplete at 5 years after ICU discharge. Cognitive impairment in ARDS survivors ranges from 70 to 100 % at hospital discharge, 46 to 80 % at 1 year, and 20 % at 5 years, and mood disorders including depression and post-traumatic stress disorder (PTSD) are also sustained and prevalent. Robust multidisciplinary and longitudinal interventions that improve these outcomes are still uncertain and data in our literature are conflicting. Studies are needed in family members of ARDS survivors to better understand long-term outcomes of the post-ICU family syndrome and to evaluate how it affects patient recovery.
The original description of acute respiratory distress syndrome (ARDS) in 1967 made the seminal observation that there was a unifying process of severe lung injury among a disparate grouping of clinical diagnoses . The discovery of this syndrome promoted the characterization of its effect on pulmonary physiology function and quality of life. The observations that muscle wasting and weakness and central nervous system injury were common and consequential outcomes after an episode of ARDS stimulated a new body of work to understand if these sequelae extended to other groups of intensive care unit (ICU) survivors. What began as a study of lung inflammation has extended to a comprehensive understanding of those eloquent organ systems of nerve, muscle, and brain which are damaged during critical illness and largely determine our ability to function, to think, and to feel that our lives are worthwhile.
Outcome measures and morbidity after ARDS
ARDS survivors are a heterogeneous group precisely because they are unified through their predilection for important lung injury from a variety of inciting conditions . They may spend weeks in the ICU and therefore are vulnerable to the cumulative insults of ICU care in the context of catabolism and systemic inflammation. Estimates suggest that acute lung injury (ALI)/ARDS affects 190,600 people per year in the USA and results in 74,500 deaths and 3.6 million hospital days . Over 100,000 patients will survive ALI/ARDS each year and, with its attendant morbidity, this represents a public health priority .
Following the Lancet description of ARDS , there were many published case series which reported good lung recovery with either mild restrictive or obstructive patterns and a mild to moderate reduction in diffusion capacity [3, 4]. Early reports noted a correlation between severity of lung injury, subsequent lung volume impairment, and quality of life captured as the sickness impact profile , short-form 36 (SF-36) [6–8], and quality of well-being . Most early studies reported that the degree of pulmonary dysfunction did not explain the observed functional limitation and that patients reporting compromised physical function did not attribute their poor quality of life to breathing difficulties.
Pulmonary function outcomes may be heterogeneous after an episode of ARDS, but most patients without prior lung disease return to normal or near-normal physiology with a persistent mild reduction in diffusion capacity. Lung function appears to be stable up to 5 years after an initial episode of severe ARDS .
There have been several imaging studies to date and the most comprehensive show that fibrotic changes after ARDS occur in the non-dependent lung zones and reflect ventilator-induced lung injury [11–13] (Fig. 1). The severity of scarring, bronchiectasis, and reticular change may be associated with duration of mechanical ventilation and extracorporeal life support (ECLS).
Health-related quality of life (HRQL) and functional disability
HRQL is an important patient-centered metric of recovery from critical illness and how its sequelae relates to physical, social, emotional, and neurocognitive function.
Table 1 provides an overview of the emergence of the ARDS HRQL literature and how we have progressed from a sole focus on pulmonary function and its relationship to HRQL to extend our understanding to a spectrum of functional outcome measures that have disclosed ICU-acquired weakness (ICUAW) as a major determinant of poor long-term functional status and subsequent cost and healthcare utilization [5, 6, 8–10, 14–22].
The Toronto ARDS Outcomes study group measured multiple simultaneous outcomes to elucidate the relationships among lung injury and ICU exposures and subsequent pulmonary, exercise, quality of life, and healthcare utilization outcomes to understand the determinants of long-term disability. In-person interview and examination coupled with the 6 min walk test (6MWD) and the SF-36 generic quality of life measure showed that patients had important impairment of exercise capacity in the context of relatively preserved pulmonary function and exhibited marked and persistent muscle wasting and weakness on examination at 1 year  and which persisted to 5 years after ICU discharge  (Fig. 2).
ICUAW was described initially as a muscle wasting and weakness phenomenon  in this cohort of uniformly severe ARDS patients (median lung injury severity score of 3.7/4.0, median 25 days of mechanical ventilation, and 40 % ICU mortality) and the determinants of functional status captured as distance walked in 6 min included female sex, exposure to any systemic corticosteroids, burden of comorbid illness, and the rate of improvement of lung injury during the ICU stay. These same determinants of weakness and disability have been confirmed subsequently by the ICAP cohort and a study led by Fan and coworkers  and Needham and investigators in their ALTOS multicenter study of ARDS outcomes from ARDSNet ALTA and EDEN/OMEGA trials . They further expanded the battery of outcome tests to include arm muscle area, muscle strength using the Medical Research Council (MRC) sum score, hand grip strength, maximum inspiratory pressure, and 4 m timed walking speed. The observation that ICUAW is likely ubiquitous after critical illness and contributes to functional disability in all patients and not solely those with ARDS has continued to gain momentum as has the concern that some patients will have an irreversible decrement in their functional status.
An excellent recent review of ICUAW by Hall and Kress  outlined the pathophysiology of ICUAW and also highlighted both nonmodifiable risk factors including multiple organ failure and severity of illness and modifiable factors such as muscle immobilization, hyperglycemia, corticosteroid and neuromuscular blocker use that contribute to this muscle and nerve injury. The following section briefly outlines the muscle and nerve injury relevant to survivors of ARDS and which contributes to their disability.
Critical illness polyneuropathy (CIP)
Bolton and coworkers first reported on CIP in 1984  and described a small sample of critically ill patients who were unable to wean from mechanical ventilation and exhibited a primary axonopathy that manifested as a mixed sensorimotor neuropathy. Since this description, it is purported that CIP is common but determination of its true incidence is complicated by lack of consensus on surveillance, timing and nature of testing, and formal diagnostic criteria. Studies have reported an incidence of 25–36 % [26, 27] in those patients with demonstrable clinical weakness. A systematic review of 1421 critically ill patients reported an incidence of ICUAW of 46 % (95 % confidence interval 43–49 %)  when patients were defined as having ICUAW using diagnostic tests alone (nerve conduction velocities, needle electromyography, direct muscle stimulation, histopathology of muscle or nerve tissue) or a combination of these in the context of muscle weakness, decreased or absent deep tendon reflexes, and/or inability to wean from mechanical ventilation. Weakness can initially be absent but later demonstrate axonal degeneration of the motor neurons with subsequent injury to the sensory neural fibers which coincides with acute and chronic changes of denervation noted on muscle biopsies in affected patients .
Critical illness myopathy (CIM)
CIM includes critical illness myopathy, acute quadriplegic myopathy, thick filament myopathy, and necrotizing myopathy and has a variable incidence of 48–96 % in prospective studies that have included muscle biopsy . CIM is typically a non-necrotizing diffuse myopathy with associated fatty degeneration of muscle fibers, fiber atrophy, and fibrosis . This has been described in patients exposed to systemic corticosteroids, paralytics, and also in the context of sepsis and clinical features may be identical to those of CIP where only muscle biopsy facilitates differentiation between these lesions. A case series of muscle biopsies from ARDS survivors showed chronic myopathic changes up to 2 years after the episode of critical illness suggesting that residual muscle injury may correlate with functional disability observed in these patients .
Thick filament myopathy shows a selective loss of myosin filaments in association with immobility and paralytic or corticosteroid exposure , and it may represent an antecedent to acute necrotizing myopathy. This is distinguished by extensive myonecrosis with vacuolization and phagocytosis of muscle fibers and is linked to multiple organ dysfunction . The functional disabilities reported in ARDS, sepsis, and chronic critical illness have been inferred to be a consequence of ICU-acquired muscle wasting and weakness syndrome [21, 22].
Additional physical morbidities
Many physical sequelae also influence functional outcomes, HRQL, healthcare utilization and cost and have been catalogued in detail in recent ARDS publications . These include tracheal stenosis, heterotopic ossification, contractures, frozen shoulders, hoarseness and voice changes, tooth loss, sensorineural hearing loss, and tinnitus (Fig. 3). Entrapment neuropathy (peroneal and ulnar) has also been noted with a 6 % prevalence at 1-year follow-up in the Toronto ARDS Outcomes study . A 5 % prevalence of large joint heterotopic ossification, the deposition of para-articular ectopic bone, in association with polytrauma, burns, and pancreatitis  has been reported in ARDS survivors . The physical devastation of ARDS leaves a lasting legacy and recent 5-year data describe ongoing concerns about cosmesis from scars related to laparotomy, chest tube, central line, arterial line and tracheostomy insertion, burns, striae from volume overload, and facial scars from prolonged non-invasive mask ventilation. Patients reported that cosmetic concerns contributed to emotional outcomes, social isolation, and sexual dysfunction.
Reports of functional limitation extend across cohorts of ARDS to sepsis and prolonged mechanical ventilation and reinforce the ubiquitous nature of these functional consequences of critical illness. In an older patient sample (median age 77), Iwashyna and colleagues  reported persistent reduction in functional status up to 8 years after sepsis and critical illness and a high rate of new functional limitations in those who had no limitations prior to their episode of sepsis (mean 1.57 new limitations 95 % CI 0.99–2.15). In a report on outcomes in chronically critically ill patients, Unroe and colleagues  evaluated the trajectories of care and resource utilization for 126 patients with a median age of 55. At 1 year, only 11 patients (9 % of the cohort) were alive and without functional dependency and total cost for this cohort was US$38.1 million, for an estimated US$3.5 million per independently functioning survivor at 1 year .
ARDS and cognitive impairment
Cognitive impairments (prevalence, severity, domains)
A particularly devastating post-ICU morbidity for patients and families is cognitive impairment . Cognitive impairments occur in patients of all ages and across ICU etiologies as over half of all survivors develop cognitive impairments and in some subgroups such as ARDS it may be higher . Cognitive outcome studies conducted to date found that the prevalence of cognitive impairment in ARDS survivors ranges from 70 to 100 % at hospital discharge, 46–80 % at 1 year, 20–47 % at 2 years, and 20 % at 5 years (Table 2) . The cognitive impairments may be severe and are reported to be below the 6th percentile of the normal distribution of cognitive functioning for some ARDS patients . A study in a retrospective ARDS cohort found that cognitive impairment on a brief test of attention and memory was 9 % at 8 years  and a second retrospective study found 24 % of ARDS survivors had cognitive impairment after 6 years or more . Cognitive impairment may affect a wide variety of cognitive domains including attention, visual-spatial abilities, declarative memory, and executive function [10, 38, 41–44]. A prospective multicenter study in 174 ARDS patients found that 36 % at 6 months and 25 % at 12 months had significant cognitive impairments in executive function, memory, attention, and working memory and their test performance was consistently below predicated values . Memory assessment in 82 ARDS survivors using the Memory Assessment Clinics Self-Rating Scale showed 20 % scores more than 1 standard deviation below population normative data at 22 months and 15.2 % at 5 years [45, 46].
Although most studies exclude those patients with prior neurocognitive impairments it remains unclear if cognitive dysfunction is due to critical illness and its treatment or related to comorbid conditions. Differences in the prevalence of cognitive impairments across studies are due in part to the type of test used, e.g., the Mini Mental Status Examination has a lower sensitivity to detect impairments compared with comprehensive neuropsychological test batteries [47, 48]. A cross-sectional study that included data from two prospective randomized trials [ARDSNet Long Term Outcomes Study (ALTOS) and Awakening and Breathing Controlled Trial (ABC)] found that the sensitivity of the Mini Mental status Screening Test to detect cognitive impairment in ARDS survivors was 19–37 % which is substantially lower than a comprehensive neuropsychological test battery . A recent study from China study used the Montreal Cognitive Assessment (MoCA) test to assess cognitive function and found that the rate of cognitive impairment was 52 % in a mixed group of ICU survivors . The MoCA has not been evaluated in ARDS populations.
The mechanism of cognitive impairments in ARDS is likely multifactorial and current data do not support an association with illness severity scores or older age. A single-center cohort study in ARDS survivors found that a longer duration of hypoxemia was associated with cognitive impairment . This association was also noted in a prospective multicenter study . Hypoxia has been linked to brain atrophy, lateral ventricle enlargement, and concomitant impairments in memory . Duration of hypotension, lower central venous pressure, hyperglycemia, and blood glucose variability have all been associated with cognitive impairment at 12-month follow-up [38, 50, 52]. Cognitive outcome trajectories are unclear. A 2-year outcome study in ARDS survivors found improvement in cognitive function from hospital discharge to 1 year but there was no change in the rate of cognitive impairments at 2 years . There is almost no data pertaining to longitudinal functioning over time periods longer than 2 years and there are likely multiple recovery trajectories of cognitive functioning after ARDS.
There is limited data regarding whether ICU interventions can prevent or improve long-term cognitive impairments in ARDS survivors. Several studies have evaluated outcomes of the Acute Respiratory Distress Syndrome Clinical Trials Network (ARDS Network) of the National Heart, Lung, and Blood Institute (NHLBI) studies. The ARDS Cognitive Outcomes Study (ACOS) that assessed cognitive outcomes of the Fluid and Catheter Treatment Trial (FACTT) study found that cognitive impairment was present in 55 % of patients at 12 months and was associated with enrollment in the conservative fluid management strategy . This study had a number of limitations including a young sample with few comorbidities and substantial loss to follow-up from the FACTT study. ALTOS assessed cognitive outcome in the EDEN trial and found that 36 % at 6 months and 25 % at 12 months had cognitive impairments, but there was no effect of initial trophic versus full enteral feeding on cognitive outcomes at 6- or 12-month outcome . ALTOS was also an ancillary multicenter study to the Statins for Acutely Injured Lungs from Sepsis (SAILS) NHLBI study that assessed mortality and ventilator-free days for rosuvastatin compared to placebo for sepsis-associated ARDS . The study assessed 272 patients from 35 hospitals for delirium and cognitive outcome. The patients in both groups experienced delirium on approximately 32 % of ICU days and overall cognitive impairment occurred in 37 % of ARDS survivors at 6 months and 29 % at 12 months. There was no difference in the rate of overall cognitive impairment for the rosuvastatin group compared to the placebo group at either 6 or 12 months .
Mood disturbances in ARDS survivors
Patients with ARDS and other critical illnesses face numerous unforeseen physical and psychic stressors, including hypoxia and respiratory failure, painful life-saving procedures, systemic inflammation, hypothalamic–pituitary–adrenal axis and sympathetic nervous system hyperactivity, acute brain dysfunction that prevents normal processing of events, and complete dependence on others with whom they have difficulty communicating [55, 56]. In addition, survivors often have long recovery periods, with physical weakness, cognitive impairments, and strained families [57, 58]. Thus, it should not be surprising that survivors often have high levels of psychological distress [59–61], especially ARDS survivors , whose critical illnesses tend to be prolonged and complex  (Table 3).
In the late 1990s, clinical researchers in Europe and the USA began investigating the correlates of diminished health-related quality of life in ARDS survivors [18, 64], including mood disturbances like post-traumatic stress disorder (PTSD), depressive, and non-specific anxiety phenomena [18, 39, 65, 66]. For example, Schelling and colleagues noted that patients who survived ARDS, while grateful to be alive, often had substantial residual angst, with vivid and distorted frightening memories of what they had experienced even after their acute brain dysfunction had resolved . At the last follow-up a median of 8 years after ARDS, the authors noted that, while the prevalence of PTSD declined over time, about one in four survivors still had PTSD; in addition, PTSD was associated with non-specific somatic concerns . In 2007, Davydow and colleagues systematically reviewed the literature on psychiatric morbidity in ARDS survivors ; ten articles [18, 38, 39, 64–66, 68–71] describing six unique cohorts were included (total n = 331). The median study prevalence of PTSD, depression, and non-specific anxiety symptoms was 28, 28, and 24 %, respectively. Since 2007, clinical researchers have conducted a number of additional relevant studies [16, 43, 45, 46, 50, 72–82]. These include four additional observational cohort studies, with longitudinal psychiatric measures on an additional 978 ARDS survivors: the Toronto study [45, 46, 83], the Improving Care of Acute lung injury Patients (ICAP) study [72, 73, 75–77, 80–82], ACOS , and ALTOS [42, 79]. Highlights from these studies are summarized in Table 3. As in the general psychiatric literature, prior psychiatric illness is a potent risk factor for psychiatric morbidity after ARDS. As in the broader critical illness literature, in-ICU sedative doses are, if anything, positively associated with post-ICU psychiatric morbidity, while in-ICU corticosteroids may prevent post-ICU PTSD.
Clinical researchers are investigating a range of in-ICU and post-ICU interventions to prevent long-term psychiatric morbidity in survivors of ARDS and encouraging examples include ICU diaries, written by clinicians and family members to critically ill patients [84–87], in-ICU psychological interventions, and post-ICU coping skills training [88, 89].
ICU interventions associated with ARDS outcome
There has been focused interest on improving the common and devastating long-term cognitive dysfunction and ICUAW in survivors of ARDS [10, 15, 23]. Cohort studies demonstrate an independent association with both onset and duration of ICU delirium and long-term cognitive impairment [44, 90, 91] and, while interventions for prevention or treatment are lacking, pharmacologic agents such as haloperidol or atypical antipsychotics may prevent or attenuate ICU delirium and improve long-term cognition of ICU survivors [92, 93]. Non-pharmacologic interventions directed at reduction of sedatives may also improve long-term cognition both by decreasing the duration of mechanical ventilation and reducing the direct toxicity of sedatives themselves [94–96].
Fluid management strategies may be associated with long-term cognitive function. Although limited by small size and loss to follow-up, a post hoc study of select survivors enrolled in the ARDS Network FACTT suggested that conservative fluid management may be associated with long-term neuropsychological impairment . Other data suggest that PTSD may be causally related to high systemic norepinephrine levels  and beta-blockers may offset these effects on the basis of observations from a modest study of cardiac surgery patients .
Critical care nutrition is an intervention that has received interest since increased caloric intake has been associated with both improved mortality and physical function outcomes in observational cohorts with critical illness . However, a large multicenter randomized controlled trial in ARDS patients (EDEN trial) failed to demonstrate any significant short-term or long-term benefit from targeting caloric intake goals compared to trophic enteral feeds during the first 6 days . Although a single-center phase II study of similar design suggested more discharges home compared to rehab with full calorie feeds , 12-month post-ICU follow-up failed to demonstrate improved physical or cognitive function in the larger multicenter EDEN trial . While this dampens enthusiasm for optimizing caloric intake, administering supplemental protein to patients with ARDS early in the acute illness may provide the needed building blocks to maintain muscle  and combining this supplementation with mobility, cycling in-bed, or electrical muscle stimulation may further attenuate the catabolism of critical illness [102, 103]. Whether the addition of anabolic agents like oxandrolone  will improve long-term physical function remains unknown.
Tight glycemic control may also improve long-term physical function. Maintaining normal or near-normal blood glucose levels in critical illness has been shown to be associated with less critical illness neuropathy . Maintaining euglycemia should be done carefully since hypoglycemia during critical illness may be associated with subsequent symptoms of depression and other mood disorders .
Although initially reported to be a risk factor for development of neuromuscular weakness post critical illness , the effect of paralytics or neuromuscular blockade on long-term outcomes remains unknown. A large randomized controlled trial showed reduction in mortality and duration of mechanical ventilation with cisatracurium for the initial 48 h of ARDS, without any increase in short-term neuromuscular weakness . However, neuromuscular weakness was assessed using an insensitive measure and long-term weakness was not evaluated.
Healthcare utilization during and after ARDS and critical illness
As a result of the need for invasive monitoring, prolonged mechanical ventilation, and extended ICU and hospital lengths of stay, acute hospitalizations for ARDS patients are costly. In a prospective cohort of 109 ARDS survivors, average total hospital costs were $128,860 (in 2002 Canadian dollars), with the vast majority due to ICU care ($97,810) [10, 16, 19, 106]. Over 75 % of these ICU costs were related to nursing care. These total hospital costs for ARDS patients are consistent with the care of other similarly ill patients such as those with septic shock or acute exacerbations of COPD [106–110].
After the acute care hospitalization, ARDS survivors also utilize a significant amount of healthcare resources. At 2 years after acute hospital discharge, 39 % of ARDS survivors required at least one readmission, and overall 20 % of these patients were readmitted more than once. Post-acute care hospital costs were $28,350 by year 2 (2002 Can$) and totaled $49,572 by year 5 (2009 Can$) [10, 16, 19, 106]. The majority of these post-acute care hospitalization costs were related to subsequent hospitalizations and inpatient rehabilitation. Home care (primarily due to nursing expenses), outpatient pharmacy, and physician expenses accounted for most of the remaining healthcare utilization and costs. Post-discharge costs varied significantly depending on the number of coexisting illnesses. Patients with no more than one coexisting illness incurred less than Can$40,000 by year 5, whereas those with more than two coexisting illnesses incurred costs of over Can$80,000 .
Additional insights regarding post-discharge healthcare utilization can also be derived from other critically ill patients such as those who require prolonged mechanical ventilation. During the first year after hospitalization, patients who received prolonged ventilation (defined as ≥4 days with tracheostomy placement or ventilation for ≥21 days without tracheostomy) spent an average of 74 % of all days alive either in a hospital, post-acute care facility, or receiving home healthcare . In the subgroup of these patients who survived their acute hospitalization, 67 % of them required at least one repeat hospitalization, with an average of 2.2 readmissions. Overall, 65 % of the readmissions occurred within the first 3 months and nearly half were related to the development of sepsis. The highest mean post-acute care costs were accumulated in those patients receiving long-term acute care (US$91,277), followed by those receiving care in a skilled nursing facility ($31,892), care in an inpatient rehabilitation facility (US$21,244), and home health service care (US$6669). Of interest, annual transportation costs exceeded US$10,000 per patient. Using Medicare claims data linked to a prospective cohort study of older Americans, Prescott and colleagues examined 1-year healthcare utilization in severe sepsis survivors . Overall, 27 % of these patients were readmitted within 30 days of hospital discharge, and a total of 63 % were readmitted at some point during the first year. Of their days alive in the year after discharge, severe sepsis survivors spent a median of 16 days (9.6 %) in an inpatient healthcare facility.
Rehabilitation during and after mechanical ventilation
Bedrest is associated with muscle atrophy, weakness, and increased inflammation . Increasing physical activity during and after critical illness has been a key target for interventions designed to improve physical function. In a landmark study, Bailey and colleagues demonstrated that a progressive activity protocol for mechanically ventilated patients in the ICU was safe and feasible . At ICU discharge, 85 patients survived and 77 % were able to walk. This report led to a paradigm shift in critical care and was followed with brisk clinical and research activity. Morris and colleagues demonstrated the safety and feasibility of truly early activity in the ICU, beginning at admission of medical ICU patients on mechanical ventilation, in a quasi-experimental design using an ICU mobility team. This approach to early activity was not associated with increased complications, but was significantly associated with reductions in ICU and hospital length of stay, and with reduced hospital readmissions and mortality in the first year after discharge [114, 115].
In order to prove that early activity casually improved patient outcomes, Schweickert and colleagues randomized medical ICU patients receiving mechanical ventilation to early physical and occupational therapy versus standard care . More patients in the intervention group achieved independent functional status by hospital discharge (59 vs. 35 %, p = 0.02) as well as decreased median duration of delirium (2 vs. 4 days) and mechanical ventilation (3.4 vs. 6.1 days). Early activity protocols with bedside ergometry may improve hospital outcomes (6 min walk distance at hospital discharge) , but recent evidence suggests that intensive versus standard early activity with physical therapy does not improve longer-term physical function .
There is also great interest in improving longer-term outcomes through the provision of therapy after ICU and hospital discharge. In important foundational work published in 2003, Jones and colleagues demonstrated with a randomized trial that post-ICU provision of a self-help rehabilitation manual was associated with a significant and clinically important decrease in physical impairment at 8 weeks and 6 months . This early success was followed by four subsequent randomized trials of intensive follow-up programs (nurse or therapist-directed) designed to improve functional outcome and quality of life after critical illness, but none has shown benefit [120–123].
The current lack of evidence of outcome benefit of post-ICU programs highlights the importance of reducing immobility and promoting activity beginning early during critical illness. However, recent point prevalence studies have shown that early activity has not been incorporated into practice, as most mechanically ventilated patients may receive no out of bed activity at all . Future work is essential to identify patients with highest potential benefit, to tailor rehabilitation programs’ timing and content within the heterogeneous and growing population of survivors of critical illness, and to promote widespread implementation.
Caregiver and family burden in ARDS and critical illness
An emerging priority is the effect of critical illness on the family unit. Relatives may present with an ICU and a post-ICU syndrome from having a critically ill loved one and experiencing difficult stressors  concurrent with the need to manage uncertainty and fatigue in the complex ICU environment [126–128]. Families need to adapt while not having their needs fully met , lack a complete understanding of what is happening to their loved one [129–131], and suffer with important symptoms of anxiety and depression from day 3 of ICU admission . Although studies have shown that these symptoms improve over time, anxiety, depression, and PTSD may persist up to 1 year in a significant number of relatives [127, 133]. These symptoms tend to decrease after the first year, but no follow up studies are currently available to properly report on long-term outcomes. The impact of caregivers’ burden has been evaluated in stroke and elderly care-giving literature, suggesting that those who are challenged in these roles may compromise rehabilitation for survivors  or the ability to sustain care in the home [135, 136]. Fifty-seven percent of ICU survivors who received long-term mechanical ventilation still required the assistance of a family caregiver 1 year after their critical illness  and this may have a deleterious impact on caregivers and compromise their health-related quality of life . Ref.  concluded that caregivers experience burden due to the challenges of managing complex care in the home, lifestyle disruption, and providing high levels of care [130, 138, 140]. Further studies on caregivers of ARDS survivors are warranted since several questions remain unanswered. For instance, are families able and willing to provide complex care at home? . Identifying specific needs of these caregiving relatives is warranted to establish the framework of a multidisciplinary follow-up program. Also, studies surveying patients and relatives at the same time are needed to understand the dynamic over time of the experience of the patient–relative dyad and to help define the type of support that is needed for each of them [133, 141]. Last, preliminary programs that train and educate family members during the physical and neurocognitive rehabilitation of ARDS survivors are being developed and will need further evaluation.
ARDS patients are heterogeneous and their disability is similar to other survivors of critical illness whose outcome is dependent on underlying premorbid health status, ICU length of stay, and treatment. The morbidities of ICUAW and neuropsychological dysfunction are prevalent and debilitating and require concerted translational research efforts to elucidate their mechanism and clinical correlates to inform future interventions. The family caregivers have a parallel traumatic life event and need to be integrated into a multidisciplinary and multimodality longitudinal follow-up program.
Ashbaugh DG, Bigelow DB, Petty TL, Levine BE (1967) Acute respiratory distress in adults. Lancet 2(7511):319–323
Rubenfeld GD, Caldwell E, Peabody E et al (2005) Incidence and outcomes of acute lung injury. N Engl J Med 353(16):1685–1693
Elliott CG, Rasmusson BY, Crapo RO, Morris AH, Jensen RL (1987) Prediction of pulmonary function abnormalities after adult respiratory distress syndrome (ARDS). Am Rev Respir Dis 135(3):634–638
Ghio AJ, Elliott CG, Crapo RO, Berlin SL, Jensen RL (1989) Impairment after adult respiratory distress syndrome. An evaluation based on American Thoracic Society recommendations. Am Rev Respir Dis 139(5):1158–1162
McHugh LG, Milberg JA, Whitcomb ME, Schoene RB, Maunder RJ, Hudson LD (1994) Recovery of function in survivors of the acute respiratory distress syndrome. Am J Respir Crit Care Med 150(1):90–94
Davidson TA, Caldwell ES, Curtis JR, Hudson LD, Steinberg KP (1999) Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. JAMA 281(4):354–360
Heyland DK, Groll D, Caeser M (2005) Survivors of acute respiratory distress syndrome: relationship between pulmonary dysfunction and long-term health-related quality of life. Crit Care Med 33(7):1549–1556
Orme J Jr, Romney JS, Hopkins RO et al (2003) Pulmonary function and health-related quality of life in survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med 167(5):690–694
Angus DC, Clermont G, Linde-Zwirble WT et al (2006) Healthcare costs and long-term outcomes after acute respiratory distress syndrome: a phase III trial of inhaled nitric oxide. Crit Care Med 34(12):2883–2890
Herridge MS, Tansey CM, Matte A et al (2011) Functional disability 5 years after acute respiratory distress syndrome. N Engl J Med 364(14):1293–1304
Desai SR, Wells AU, Suntharalingam G, Rubens MB, Evans TW, Hansell DM (2001) Acute respiratory distress syndrome caused by pulmonary and extrapulmonary injury: a comparative CT study. Radiology 218(3):689–693
Linden VB, Lidegran MK, Frisen G, Dahlgren P, Frenckner BP, Larsen F (2009) ECMO in ARDS: a long-term follow-up study regarding pulmonary morphology and function and health-related quality of life. Acta Anaesthesiol Scand 53(4):489–495
Wilcox ME, Patsios D, Murphy G, Kudlow P, Paul N, Tansey CM, Chu L, Matte A, Tomlinson G, Herridge MS (2013) Radiologic outcomes at 5 years after severe ARDS. Chest 143(4):920–926
Angus DC, Musthafa AA, Clermont G et al (2001) Quality-adjusted survival in the first year after the acute respiratory distress syndrome. Am J Respir Crit Care Med 163(6):1389–1394
Fan E, Dowdy DW, Colantuoni E et al (2014) Physical complications in acute lung injury survivors: a two-year longitudinal prospective study. Crit Care Med 42(4):849–859
Herridge MS, Cheung AM, Tansey CM et al (2003) One-year outcomes in survivors of the acute respiratory distress syndrome. N Engl J Med 348(8):683–693
Needham DM (2014) Understanding and improving clinical trial outcome measures in acute respiratory failure. Am J Respir Crit Care Med 189(8):875–877
Weinert CR, Gross CR, Kangas JR, Bury CL, Marinelli WA (1997) Health-related quality of life after acute lung injury. Am J Respir Crit Care Med 156(4 Pt 1):1120–1128
Cheung AM, Tansey CM, Tomlinson G et al (2006) Two-year outcomes, health care use, and costs of survivors of acute respiratory distress syndrome. Am J Respir Crit Care Med 174(5):538–544
Schelling G, Stoll C, Vogelmeier C et al (2000) Pulmonary function and health-related quality of life in a sample of long-term survivors of the acute respiratory distress syndrome. Intensive Care Med 26(9):1304–1311
Iwashyna TJ, Ely EW, Smith DM, Langa KM (2010) Long-term cognitive impairment and functional disability among survivors of severe sepsis. JAMA 304(16):1787–1794
Unroe M, Kahn JM, Carson SS et al (2010) One-year trajectories of care and resource utilization for recipients of prolonged mechanical ventilation: a cohort study. Ann Intern Med 153(3):167–175
Needham DM, Wozniak AW, Hough CL et al (2014) Risk factors for physical impairment after acute lung injury in a national, multicenter study. Am J Respir Crit Care Med 189(10):1214–1224
Kress JP, Hall JB (2014) ICU-acquired weakness and recovery from critical illness. N Engl J Med 371(3):287–288
Bolton CF, Gilbert JJ, Hahn AF, Sibbald WJ (1984) Polyneuropathy in critically ill patients. J Neurol Neurosurg Psychiatry 47(11):1223–1231
De Jonghe B, Sharshar T, Lefaucheur JP et al (2002) Paresis acquired in the intensive care unit: a prospective multicenter study. JAMA 288(22):2859–2867
de Letter MA, Schmitz PI, Visser LH et al (2001) Risk factors for the development of polyneuropathy and myopathy in critically ill patients. Crit Care Med 29(12):2281–2286
Stevens RD, Dowdy DW, Michaels RK, Mendez-Tellez PA, Pronovost PJ, Needham DM (2007) Neuromuscular dysfunction acquired in critical illness: a systematic review. Intensive Care Med 33(11):1876–1891
Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ (2005) Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology 64(8):1348–1353
Pandit L, Agrawal A (2006) Neuromuscular disorders in critical illness. Clin Neurol Neurosurg 108(7):621–627
Latronico N, Fenzi F, Recupero D et al (1996) Critical illness myopathy and neuropathy. Lancet 347(9015):1579–1582
Angel MJ, Bril V, Shannon P, Herridge MS (2007) Neuromuscular function in survivors of the acute respiratory distress syndrome. Can J Neurol Sci 34(4):427–432
Campellone JV, Lacomis D, Kramer DJ, Van Cott AC, Giuliani MJ (1998) Acute myopathy after liver transplantation. Neurology 50(1):46–53
Helliwell TR, Coakley JH, Wagenmakers AJ et al (1991) Necrotizing myopathy in critically-ill patients. J Pathol 164(4):307–314
Hudson SJ, Brett SJ (2006) Heterotopic ossification—a long-term consequence of prolonged immobility. Crit Care 10(6):174
Wilcox ME, Brummel NE, Archer K, Ely EW, Jackson JC, Hopkins RO (2013) Cognitive dysfunction in ICU patients: risk factors, predictors, and rehabilitation interventions. Crit Care Med 41(9 Suppl 1):S81–S98
Wolters AE, Slooter AJ, van der Kooi AW, van Dijk D (2013) Cognitive impairment after intensive care unit admission: a systematic review. Intensive Care Med 39(3):376–386
Hopkins RO, Weaver LK, Collingridge D, Parkinson RB, Chan KJ, Orme JF Jr (2005) Two-year cognitive, emotional, and quality-of-life outcomes in acute respiratory distress syndrome. Am J Respir Crit Care Med 171(4):340–347
Kapfhammer HP, Rothenhäusler HB, Krauseneck T, Stoll C, Schelling G (2004) Posttraumatic stress disorder and health-related quality of life in long-term survivors of acute respiratory distress syndrome. Am J Psychiatry 161(1):45–52
Rothenhausler HB, Ehrentraut S, Stoll C, Schelling G, Kapfhammer HP (2001) The relationship between cognitive performance and employment and health status in long-term survivors of the acute respiratory distress syndrome: results of an exploratory study. Gen Hosp Psychiatry 23(2):90–96
Jackson JC, Girard TD, Gordon SM et al (2010) Long-term cognitive and psychological outcomes in the awakening and breathing controlled trial. Am J Respir Crit Care Med 182(2):183–191
Needham DM, Dinglas VD, Bienvenu OJ et al (2013) One year outcomes in patients with acute lung injury randomised to initial trophic or full enteral feeding: prospective follow-up of EDEN randomised trial. BMJ 346:f1532
Needham DM, Dinglas VD, Morris PE et al (2013) Physical and cognitive performance of patients with acute lung injury 1 year after initial trophic versus full enteral feeding. EDEN trial follow-up. Am J Respir Crit Care Med 188(5):567–576
Pandharipande PP, Girard TD, Jackson JC et al (2013) Long-term cognitive impairment after critical illness. N Engl J Med 369(14):1306–1316
Adhikari NK, McAndrews MP, Tansey CM et al (2009) Self-reported symptoms of depression and memory dysfunction in survivors of ARDS. Chest 135(3):678–687
Adhikari NK, Tansey CM, McAndrews MP et al (2011) Self-reported depressive symptoms and memory complaints in survivors five years after ARDS. Chest 140(6):1484–1493
Pfoh ER, Chan KS, Dinglas VD et al (2015) Cognitive screening among acute respiratory failure survivors: a cross-sectional evaluation of the mini-mental state examination. Crit Care 19:220
Woon FL, Dunn CB, Hopkins RO (2012) Predicting cognitive sequelae in survivors of critical illness with cognitive screening tests. Am J Respir Crit Care Med 186(4):333–340
Zhao J, Yao L, Wang C, Sun Y, Sun Z (2015) The effects of cognitive intervention on cognitive impairments after intensive care unit admission. Neuropsychol Rehabil 27:1–17
Mikkelsen ME, Christie JD, Lanken PN et al (2012) The adult respiratory distress syndrome cognitive outcomes study: long-term neuropsychological function in survivors of acute lung injury. Am J Respir Crit Care Med 185(12):1307–1315
Bigler ED, Blatter DD, Anderson CV et al (1997) Hippocampal volume in normal aging and traumatic brain injury. AJNR Am J Neuroradiol 18(1):11–23
Hopkins RO, Suchyta MR, Snow GL, Jephson A, Weaver LK, Orme JF (2010) Blood glucose dysregulation and cognitive outcome in ARDS survivors. Brain Inj 24(12):1478–1484
Mikkelsen ME LP, Biester R, Gallop R, Bellamy S, Localio AR, Hopkins RO, Angus DC, Christie JD (2008) Conservative fluid strategy is associated with neurocognitive deficits in survivors of acute lung injury. Am J Respir Crit Care Med 177:A819
Needham DM, Colantuoni E, Dinglas VD et al (2016) Rosuvastatin versus placebo for delirium in intensive care and subsequent cognitive impairment in patients with sepsis-associated acute respiratory distress syndrome: an ancillary study to a randomised controlled trial. Lancet Respir Med. doi:10.1016/S2213-2600(16)00005-9
Bienvenu OJ, Neufeld KJ (2011) Post-traumatic stress disorder in medical settings: focus on the critically ill. Curr Psychiatry Rep 13(1):3–9
Bienvenu OJ (2014) Depressive mood states following critical illness. In: Stevens RD, Hart N, Herridge M (eds) The legacy of critical illness—a textbook of post-ICU medicine. Oxford University Press, New York, pp 216–231
Needham DM, Davidson J, Cohen H et al (2012) Improving long-term outcomes after discharge from intensive care unit: report from a stakeholders’ conference. Crit Care Med 40(2):502–509
Davidson JE, Jones C, Bienvenu OJ (2012) Family response to critical illness: post-intensive care syndrome—family. Crit Care Med 40(2):618–624
Davydow DS, Gifford JM, Desai SV, Bienvenu OJ, Needham DM (2009) Depression in general intensive care unit survivors: a systematic review. Intensive Care Med 35(5):796–809
Davydow DS, Gifford JM, Desai SV, Needham DM, Bienvenu OJ (2008) Posttraumatic stress disorder in general intensive care unit survivors: a systematic review. Gen Hosp Psychiatry 30(5):421–434
Parker AM, Sricharoenchai T, Raparla S, Schneck KW, Bienvenu OJ, Needham DM (2015) Posttraumatic stress disorder in critical illness survivors: a metaanalysis. Crit Care Med 43(5):1121–1129
Davydow DS, Desai SV, Needham DM, Bienvenu OJ (2008) Psychiatric morbidity in survivors of the acute respiratory distress syndrome: a systematic review. Psychosom Med 70(4):512–519
Herridge MS, Angus DC (2005) Acute lung injury: affecting many lives. New Engl J Med 353(16):1736–1738
Schelling G, Stoll C, Haller M et al (1998) Health-related quality of life and posttraumatic stress disorder in survivors of the acute respiratory distress syndrome. Crit Care Med 26(4):651–659
Deja M, Denke C, Weber-Carstens S et al (2006) Social support during intensive care unit stay might improve mental impairment and consequently health-related quality of life in survivors of severe acute respiratory distress syndrome. Crit Care 10(5):R147
Hopkins RO, Weaver LK, Chan KJ, Orme JF Jr (2004) Quality of life, emotional, and cognitive function following acute respiratory distress syndrome. J Int Neuropsychol Soc 10(7):1005–1017
Schelling G, Kapfhammer HP (2013) Surviving the ICU does not mean that the war is over. Chest 144(1):1–3
Christie JD, Biester RC, Taichman DB et al (2006) Formation and validation of a telephone battery to assess cognitive function in acute respiratory distress syndrome survivors. J Crit Care 21(2):125–132
Nelson JE, Cox CE, Hope AA, Carson SS (2010) Chronic critical illness. Am J Respir Crit Care Med 182(4):446–454
Shaw RJ, Harvey JE, Nelson KL, Gunary R, Kruk H, Steiner H (2001) Linguistic analysis to assess medically related posttraumatic stress symptoms. Psychosomatics 42(1):35–40
Stoll C, Kapfhammer HP, Rothenhausler HB et al (1999) Sensitivity and specificity of a screening test to document traumatic experiences and to diagnose post-traumatic stress disorder in ARDS patients after intensive care treatment. Intensive Care Med 25(7):697–704
Bienvenu OJ, Colantuoni E, Mendez-Tellez PA et al (2012) Depressive symptoms and impaired physical function after acute lung injury: a 2-year longitudinal study. Am J Respir Crit Care Med 185(5):517–524
Bienvenu OJ, Colantuoni E, Mendez-Tellez PA et al (2015) Cooccurrence of and remission from general anxiety, depression, and posttraumatic stress disorder symptoms after acute lung injury: a 2-year longitudinal study. Crit Care Med 43(3):642–653
Bienvenu OJ, Gellar J, Althouse BM et al (2013) Post-traumatic stress disorder symptoms after acute lung injury: a 2-year prospective longitudinal study. Psychol Med 43(12):2657–2671
Bienvenu OJ, Williams JB, Yang A, Hopkins RO, Needham DM (2013) Posttraumatic stress disorder in survivors of acute lung injury: evaluating the impact of event scale-revised. Chest 144(1):24–31
Dowdy DW, Bienvenu OJ, Dinglas VD et al (2009) Are intensive care factors associated with depressive symptoms 6 months after acute lung injury? Crit Care Med 37(5):1702–1707
Dowdy DW, Dinglas V, Mendez-Tellez PA et al (2008) Intensive care unit hypoglycemia predicts depression during early recovery from acute lung injury. Crit Care Med 36(10):2726–2733
Hopkins RO, Key CW, Suchyta MR, Weaver LK, Orme JF Jr (2010) Risk factors for depression and anxiety in survivors of acute respiratory distress syndrome. Gen Hosp Psychiatry 32(2):147–155
Huang M, Parker AM, Bienvenu OJ et al (2016) Psychiatric symptoms in acute respiratory distress syndrome survivors: a 1-year national multicenter study. Crit Care Med (in press)
Jutte JE, Needham DM, Pfoh ER, Bienvenu OJ (2015) Psychometric evaluation of the hospital anxiety and depression scale 3 months after acute lung injury. J Crit Care 30(4):793–798
Stevenson JE, Colantuoni E, Bienvenu OJ et al (2013) General anxiety symptoms after acute lung injury: predictors and correlates. J Psychosom Res 75(3):287–293
Needham DM, Dennison CR, Dowdy DW et al (2006) Study protocol: the improving care of acute lung injury patients (ICAP) study. Crit Care 10(1):R9
Herridge M, Cameron JI (2013) Disability after critical illness. N Engl J Med 369(14):1367–1369
Garrouste-Orgeas M, Coquet I, Périer A et al (2012) Impact of an intensive care unit diary on psychological distress in patients and relatives. Crit Care Med 40:2033–2040
Jones C, Bäckman C, Capuzzo M et al (2010) Intensive care diaries reduce new-onset post-traumatic stress disorder following critical illness: a randomised, controlled trial. Crit Care 14:R168
Aitken LM, Rattray A, Hull A, Kenardy JA, Le Brocque R, Ullman AJ (2013) The use of diaries in psychological recovery from intensive care. Crit Care 17:253
Ullman AJ, Aitken LM, Rattray J et al (2014) Diaries for recovery from critical illness. Cochrane Database Syst Rev 12:CD010468
Cox CE, Porter LS, Hough CL et al (2012) Development and preliminary evaluation of a telephone-based coping skills training intervention for survivors of acute lung injury and their informal caregivers. Intensive Care Med 38(8):1289–1297
Peris A, Bonizzoli M, Iozzelli D et al (2011) Early intra-intensive care unit psychological intervention promotes recovery from post traumatic stress disorders, anxiety and depression symptoms in critically ill patients. Crit Care 15(1):R41
Girard TD, Jackson JC, Pandharipande PP et al (2010) Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 38(7):1513–1520
Jackson JC, Pandharipande PP, Girard TD et al (2014) Depression, post-traumatic stress disorder, and functional disability in survivors of critical illness in the BRAIN-ICU study: a longitudinal cohort study. Lancet Respir Med 2(5):369–379
Devlin JW, Garpestad E, Hill NS (2010) Neuromuscular blockers and ARDS. N Engl J Med 363(26):2562 (author reply 2563–2564)
Girard TD, Pandharipande PP, Carson SS et al (2010) Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 38(2):428–437
Girard TD, Kress JP, Fuchs BD et al (2008) Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (awakening and breathing controlled trial): a randomised controlled trial. Lancet 371(9607):126–134
Kress JP, Pohlman AS, O’Connor MF, Hall JB (2000) Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. N Engl J Med 342(20):1471–1477
Strom T, Martinussen T, Toft P (2010) A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 375(9713):475–480
Strawn JR, Geracioti TD Jr (2008) Noradrenergic dysfunction and the psychopharmacology of posttraumatic stress disorder. Depress Anxiety 25(3):260–271
Krauseneck T, Padberg F, Roozendaal B et al (2010) A beta-adrenergic antagonist reduces traumatic memories and PTSD symptoms in female but not in male patients after cardiac surgery. Psychol Med 40(5):861–869
Wei X, Day AG, Ouellette-Kuntz H, Heyland DK (2015) The association between nutritional adequacy and long-term outcomes in critically ill patients requiring prolonged mechanical ventilation: a multicenter cohort study. Crit Care Med 43(8):1569–1579
Rice TW, Wheeler AP, Thompson BT et al (2012) Initial trophic vs full enteral feeding in patients with acute lung injury: the EDEN randomized trial. JAMA 307(8):795–803
Rice TW, Mogan S, Hays MA, Bernard GR, Jensen GL, Wheeler AP (2011) Randomized trial of initial trophic versus full-energy enteral nutrition in mechanically ventilated patients with acute respiratory failure. Crit Care Med 39(5):967–974
Brummel NE, Girard TD, Ely EW et al (2014) Feasibility and safety of early combined cognitive and physical therapy for critically ill medical and surgical patients: the activity and cognitive therapy in ICU (ACT-ICU) trial. Intensive Care Med 40(3):370–379
Heyland DK, Stapleton RD, Mourtzakis M et al (2015) Combining nutrition and exercise to optimize survival and recovery from critical illness: conceptual and methodological issues. Clin Nutr. doi:10.1016/j.clnu.2015.07.003
Wischmeyer PE, San-Millan I (2015) Winning the war against ICU-acquired weakness: new innovations in nutrition and exercise physiology. Crit Care 19(Suppl 3):S6
Papazian L, Forel JM, Gacouin A et al (2010) Neuromuscular blockers in early acute respiratory distress syndrome. N Engl J Med 363(12):1107–1116
Bice T, Cox CE, Carson SS (2013) Cost and health care utilization in ARDS—different from other critical illness? Semin Respir Crit Care Med 34(4):529–536
The Veterans Affairs Total Parenteral Nutrition Cooperative Study Group (1991) Perioperative total parenteral nutrition in surgical patients. N Engl J Med 325(8):525–532
Hamel MB, Phillips RS, Davis RB et al (2000) Outcomes and cost-effectiveness of ventilator support and aggressive care for patients with acute respiratory failure due to pneumonia or acute respiratory distress syndrome. Am J Med 109(8):614–620
Sznajder M, Aegerter P, Launois R, Merliere Y, Guidet B (2001) CubRea. A cost-effectiveness analysis of stays in intensive care units. Intensive Care Med 27(1):146–153
Talmor D, Greenberg D, Howell MD, Lisbon A, Novack V, Shapiro N (2008) The costs and cost-effectiveness of an integrated sepsis treatment protocol. Crit Care Med 36(4):1168–1174
Prescott HC, Langa KM, Liu V, Escobar GJ, Iwashyna TJ (2014) Increased 1-year healthcare use in survivors of severe sepsis. Am J Respir Crit Care Med 190(1):62–69
Needham DM (2008) Mobilizing patients in the intensive care unit: improving neuromuscular weakness and physical function. JAMA 300(14):1685–1690
Bailey P, Thomsen GE, Spuhler VJ et al (2007) Early activity is feasible and safe in respiratory failure patients. Crit Care Med 35(1):139–145
Morris PE (2007) Moving our critically ill patients: mobility barriers and benefits. Crit Care Clin 23(1):1–20
Morris PE, Griffin L, Berry M et al (2011) Receiving early mobility during an intensive care unit admission is a predictor of improved outcomes in acute respiratory failure. Am J Med Sci 341(5):373–377
Schweickert WD, Pohlman MC, Pohlman AS et al (2009) Early physical and occupational therapy in mechanically ventilated, critically ill patients: a randomised controlled trial. Lancet 373(9678):1874–1882
Burtin C, Clerckx B, Robbeets C et al (2009) Early exercise in critically ill patients enhances short-term functional recovery. Crit Care Med 37(9):2499–2505
Moss M, Nordon-Craft A, Malone D et al (2015) A randomized trial of an intensive physical therapy program for acute respiratory failure patients. Am J Respir Crit Care Med. doi:10.1164/rccm.201505-1039OC
Jones C, Skirrow P, Griffiths RD et al (2003) Rehabilitation after critical illness: a randomized, controlled trial. Crit Care Med 31(10):2456–2461
Cuthbertson BH, Rattray J, Campbell MK et al (2009) The PRaCTICaL study of nurse led, intensive care follow-up programmes for improving long term outcomes from critical illness: a pragmatic randomised controlled trial. BMJ 339:b3723
Elliott D, McKinley S, Alison J et al (2011) Health-related quality of life and physical recovery after a critical illness: a multi-centre randomised controlled trial of a home-based physical rehabilitation program. Crit Care 15(3):R142
Denehy L, Skinner EH, Edbrooke L et al (2013) Exercise rehabilitation for patients with critical illness: a randomized controlled trial with 12 months of follow-up. Crit Care 17(4):R156
Walsh TS, Salisbury LG, Merriweather JL et al (2015) Increased hospital-based physical rehabilitation and information provision after intensive care unit discharge: the recover randomized clinical trial. JAMA Intern Med 175(6):901–910
Harrold ME, Salisbury LG, Webb SA, Allison GT, Australia and Scotland ICU Physiotherapy Collaboration (2015) Australia, Scotland ICUPC. Early mobilisation in intensive care units in Australia and Scotland: a prospective, observational cohort study examining mobilisation practises and barriers. Crit Care 19:336
Puntillo K, Nelson JE, Weissman D et al (2014) Palliative care in the ICU: relief of pain, dyspnea, and thirst—a report from the IPAL-ICU Advisory Board. Intensive Care Med 40(2):235–248
Azoulay E, Citerio G, Bakker J et al (2014) Year in review in Intensive Care Medicine 2013: II. Sedation, invasive and noninvasive ventilation, airways, ARDS, ECMO, family satisfaction, end-of-life care, organ donation, informed consent, safety, hematological issues in critically ill patients. Intensive Care Med 40(3):305–319
Jabre P, Tazarourte K, Azoulay E et al (2014) Offering the opportunity for family to be present during cardiopulmonary resuscitation: 1-year assessment. Intensive Care Med 40(7):981–987
Verceles AC, Corwin DS, Afshar M et al (2014) Half of the family members of critically ill patients experience excessive daytime sleepiness. Intensive Care Med 40(8):1124–1131
Bouju P, Tadie JM, Uhel F et al (2014) Internet use by family members of intensive care unit patients: a pilot study. Intensive Care Med 40(8):1175–1176
Curtis JR, Sprung CL, Azoulay E (2014) The importance of word choice in the care of critically ill patients and their families. Intensive Care Med 40(4):606–608
Debaty G, Ageron FX, Minguet L et al (2015) More than half the families of mobile intensive care unit patients experience inadequate communication with physicians. Intensive Care Med 41(7):1291–1298
Pochard F, Darmon M, Fassier T et al (2005) Symptoms of anxiety and depression in family members of intensive care unit patients before discharge or death. A prospective multicenter study. J Crit Care 20(1):90–96
Long AC, Kross EK, Davydow DS, Curtis JR (2014) Posttraumatic stress disorder among survivors of critical illness: creation of a conceptual model addressing identification, prevention, and management. Intensive Care Med 40(6):820–829
Cox CE, Docherty SL, Brandon DH et al (2009) Surviving critical illness: acute respiratory distress syndrome as experienced by patients and their caregivers. Crit Care Med 37(10):2702–2708
Evans RL, Bishop DS, Haselkorn JK (1991) Factors predicting satisfactory home care after stroke. Arch Phys Med Rehabil 72(2):144–147
Kao HF, McHugh ML (2004) The role of caregiver gender and caregiver burden in nursing home placements for elderly Taiwanese survivors of stroke. Res Nurs Health 27(2):121–134
Chelluri L, Im KA, Belle SH et al (2004) Long-term mortality and quality of life after prolonged mechanical ventilation. Crit Care Med 32(1):61–69
Cameron JI, Herridge MS, Tansey CM, McAndrews MP, Cheung AM (2006) Well-being in informal caregivers of survivors of acute respiratory distress syndrome. Crit Care Med 34(1):81–86
Johnson P, Chaboyer W, Foster M, van der Vooren R (2001) Caregivers of ICU patients discharged home: what burden do they face? Intensive Crit Care Nurs 17(4):219–227
Van Pelt DC, Milbrandt EB, Qin L et al (2007) Informal caregiver burden among survivors of prolonged mechanical ventilation. Am J Respir Crit Care Med 175(2):167–173
Rier DA (2014) From three sides now: reflections on an ICU journey as patient, parent, and researcher. Intensive Care Med 40(8):1162–1163
Hopkins RO, Weaver LK, Pope D, Orme JF, Bigler ED, Larson LV (1999) Neuropsychological sequelae and impaired health status in survivors of severe acute respiratory distress syndrome. Am J Respir Crit Care Med 160(1):50–56
Mikkelsen ME, Shull WH, Biester RC, et al (2009) Cognitive, mood and quality of life impairments in a select population of ARDS survivors. Respirology 14(1):76–82
Jackson JC, Hopkins RO, Miller RR, Gordon SM, Wheeler AP, Ely EW (2009) Acute respiratory distress syndrome, sepsis, and cognitive decline: a review and case study. South Med J 102(11):1150–1157
Conflicts of interest
The authors have nothing to disclose.
About this article
Cite this article
Herridge, M.S., Moss, M., Hough, C.L. et al. Recovery and outcomes after the acute respiratory distress syndrome (ARDS) in patients and their family caregivers. Intensive Care Med 42, 725–738 (2016). https://doi.org/10.1007/s00134-016-4321-8
- Acute respiratory distress syndrome (ARDS)
- ICU acquired weakness
- Healthcare utilization