Patients who survive critical illness are at risk for permanent physical, functional, emotional, and neurocognitive deficits, some or all of which may contribute to a decreased health-related quality of life (HRQL). The reasons for this late morbidity after intensive care unit (ICU) care are multifactorial and include, but are not limited to, the following:
- the nature of and treatment for the inciting critical illness
- multiple organ dysfunction syndrome and hypoxemia
- physiologic and emotional stress in the ICU related to the illness itself, sleep fragmentation, psychoactive medications, and impaired drug metabolism due to simultaneous administration of multiple medications
- prolonged immobility and long ICU stay. Patients with the acute respiratory distress syndrome (ARDS) represent some of the most complex, high acuity, and long stay ICU patients.
Because of the significant potential for morbidity, ARDS patients have been the main focus of longterm outcome studies in survivors of critical illness. ARDS survivor data are some of the most complete long-term outcome data available and represent the current state-of-the-art in the critical care outcomes literature. As such, they will form the primary basis for this issue of Critical Care Rounds.
Long-term outcome measures in survivors of ARDS Pulmonary function abnormalities Many ARDS survivors have persistent pulmonary function impairments that are typically mild to moderate restrictive changes and an associated reduction in diffusion capacity.1-3 Orme and colleagues reported that ARDS survivors had abnormal pulmonary function associated with decreased HRQL one year following hospital discharge4 and Schelling recently reported no additional improvement in pulmonary function after the first year following ARDS.5 In a recent publication, Neff and colleagues reviewed 30 studies that evaluated pulmonary function in ARDS survivors.
They reported significant variability in the proportion of patients with obstructive (0%-33%) and restrictive (0%- 50%) defects, as well as compromised diffusion capacity (33%-82%). This spectrum of pulmonary dysfunction may relate to population heterogeneity with respect to evolving definitions or severity of ARDS, severity of lung injury, ICU ventilatory strategy, prior history of lung disease or smoking, and the presence of other pulmonary processes that fulfill the ARDS definition but that have a very different natural history (eg, cryptogenic organizing pneumonia). Most outcome studies found ARDS survivors are frequently unable to resume their prior lifestyle, but the degree of pulmonary dysfunction does not fully explain their functional limitation. This observation has led investigators to explore other possible contributors to physical disability.
Limitation in physical functioning The Toronto ARDS Outcomes group evaluated exercise capacity (distance walked in 6 minutes with continuous oximetry), pulmonary function, and conducted an interview, physical examination, and HRQL measure in 109 ARDS survivors at 3, 6, and 12 months after ICU discharge.7 Similar to other pulmonary function studies, the ARDS patients had mild restrictive disease and reduced diffusion capacity at 3 months following ICU discharge.
By 6 and 12 months, they had normal to near-normal lung volumes and spirometric measures with a persistent mild reduction in carbon dioxide diffusion capacity-lung impairment similar to that noted by others. The ARDS survivors had profound muscle weakness and wasting and were only able to achieve 66% of their predicted exercise capacity 1- year post-ICU discharge.
This functional disability was reflected in the HRQL assessment, in which patients reported a profound reduction in the physical functioning and role-physical domains of the SF-36. Impaired exercise capacity was related to burden of comorbid disease, exposure to systemic corticosteroid treatment during the ICU period, and the rate of resolution of lung injury, and multiple organ dysfunction during the ICU stay. The causes for the observed muscle wasting and weakness were not clear. Potential causes for weakness and functional limitation are listed in Table 1. In our cohort study, patients continued to have functional limitation from 2 to 5 years after ICU discharge.8 At 5 years, the median distance walked in 6 minutes was 427 meters for ARDS survivors, not significantly improved from the 422 meters walked at 1 year.
The proportion of patients returning to work did not increase beyond 2 years after ICU discharge. The majority of patients returned to their original work.9 Emotional outcomes – Emotional function after ARDS The prevalence and severity of mood disorders, including symptoms of depression, anxiety, and posttraumatic stress disorder (PTSD) in survivors of critical illness are quite variable among patients following ICU care.
Rincon et al10 noted symptoms of depression and anxiety in 14% and 24%, respectively, in survivors of critical illness. Similar prevalence rates of anxiety and depression have been reported by Scragg11 and Orme and co-workers.4 In contrast, Weinert and colleagues found that 43% of patients with acute lung injury reported symptoms of depression12 and Angus and coworkers reported a 50% prevalence of depression and anxiety at 1 year in ARDS patients.13 The Toronto ARDS outcomes group found that 58% of ARDS survivors reported depressive symptoms almost 2 years after ICU discharge.
More severe symptoms of 100% of ARDS survivors had cognitive impairments, including memory, attention, concentration, and decreased intellectual function at the time of hospital discharge. At 1-year follow-up, 30% of the survivors had decreased intellectual function and 78% had impaired memory, attention, concentration, and/or mental processing speed. ARDS survivors had signifi- cantly lower IQ than their estimated premorbid IQ (p < 0.05) and their measured IQ 1 year later. In this cohort, the degree of hypoxia significantly correlated with neurocognitive sequelae (r2 = 0.25 to 0.45, all p<0.01).
Other groups have confirmed these findings. In a retrospective study of 33 ARDS survivors, Marquis and co-workers reported impaired attention, visual processing, psychomotor speed, and cognitive flexibility compared to critically-ill control subjects.20 Rothenhäusler retrospectively evaluated 46 ARDS survivors and found that 24% had cognitive impairments and 41% were disabled and could not return to work.19 A study of self-reported memory problems in the Toronto ARDS cohort found that 20% of ARDS survivors rated their memory as “poor” 18 months following their ICU discharge.14 Forty percent of survivors fell below 1 standard deviation of an ageadjusted sample mean on the ability and frequency scale of the Memory Self-rating Scale. Cognitive impairments may persist to 2 years after hospital discharge.
In their recent prospective, 2-year, follow-up study, Hopkins and colleagues assessed cognitive outcome in 71 consecutive ARDS survivors treated with higher and lower tidal volume strategies. Fifty-nine percent and 43% of patients had evidence of cognitive dysfunction (>1.5 SD below the mean) in at least 2 cognitive domains at 1- and 2-year follow-up, respectively. There were no significant differences between 1- and 2-year cognitive outcomes except improvement in performance IQ. Cognitive impairments at 1- and 2- years correlated with duration of hypoxemia.21 Hopkins has also shown that ARDS survivors have brain atrophy, significantly enlarged ventricles, and an increased ventricle-to-brain ratio (another measure of generalized atrophy and an indirect index of white matter integrity) compared to matched controls and this was associated with cognitive dysfunction.
In 1994, McHugh and colleagues prospectively evaluated pulmonary function and quality of life to assess the relationship between pulmonary dysfunction and functional disability. 23 These authors found that the Sickness Impact Profile (generic quality of life measure of the subject’s self-perceived physical and psychological condition) scores were very low at extubation, rose substantially in the first 3 months, and then exhibited only slight improvement to 1 year. When quality of life.tioning, physical ability to maintain their roles (role-physical), bodily pain, general health, and vitality (energy) on the SF-36. The pulmonary function abnormalities correlated with decreased HRQL for domains reflecting physical function.
Not only is the observation of impaired physical functioning robust across studies and investigators, it also appears to persist for long periods of time following ICU or hospital discharge. The Davidson paper25 discussed the above reported outcomes at 23 months after discharge. We have also reported persistent physical dysfunction at 2 years after ICU discharge.8 In the Toronto ARDs Outcomes Group cohort, HRQL improved each year after discharge from the ICU, but continued to be lower than an age- and sex-matched normal population at 5 years.9 The improvement in quality of life is discordant with the lack of ongoing improvement in functional status measured as distance walked in 6 minutes. This is consistent with irreversible functional morbidity to which ARDS survivors accommodate over time.
Hopkins and colleagues were the first to rigorously evaluate cognitive dysfunction in ARDS survivors and report the significant impact this had on reported HRQL outcomes.15 Fifty-five consecutive ARDS survivors completed detailed neuropsychological testing and questionnaires relating to health status, cognitive and psychological function at hospital discharge and at 1 year after ARDS onset. In this study, decreased HRQL was related to cognitive dysfunction and, in a subsequent report, the cognitive changes persisted to 2 years after hospital discharge.21 Impaired long-term cognitive function following ARDS has also been reported by others.