Prolonged acute care and post-acute care admission and recovery of physical function in survivors of acute respiratory failure: a secondary analysis of a randomized controlled trial

With advances in intensive care, survival of patients with acute respiratory failure has improved. Functional impairments in these survivors are common and persist up to 5 years after the initial episode of illness [1]. As a result, there is a growing proportion of patients who do not fully recover and remain dependent on hospital resources. These chronically critically ill patients have high mortality, and those who survive have functional and cognitive disabilities [2‐4]. The rate of post-acute care admission in survivors of acute respiratory failure continues to rise, with a greater proportion of patients requiring extended treatment in a long-term acute care facility, rehabilitation facility, or skilled nursing facility and fewer patients returning directly home [5, 6]. Unfortunately, interventions to treat and improve physical function have had variable efficacy, and to date, randomized controlled studies of both intensive inpatient and outpatient physical therapy interventions as well as multidisciplinary approaches designed to increase physical function have not improved long-term physical function [7‐12].

Although prolonged admission is common in patients with chronic critical illness, little is known about the long-term trajectory of functional recovery for those patients who survive. Understanding how their recovery unfolds over time and the factors that influence this recovery could inform the timing and intensity of future therapeutic physical interventions; help in the design of unique therapies for specific patient populations; and provide prognostic information to inform patients and their families about the likelihood, rate, and anticipated course of functional recovery. Prior efforts to identify predictors of functional recovery have been focused on patient characteristics prior to acute illness or on intensive care unit (ICU)-related factors [13, 14]. Although equally important, to date, there has been limited evaluation of patient predictors of long-term functional recovery based on functional status after acute illness. Furthermore, because older patients are more likely to have loss of physical function after hospital discharge [13‐15], understanding how age influences the trajectory of recovery could highlight a group at particularly high risk of poor outcomes.

To further understand functional recovery over time in patients who require prolonged admission, we performed a secondary analysis of a previously published exercise intervention study [12]. We defined prolonged admission as requiring ongoing admission at 1 month after critical illness in an acute or post-acute care facility, such as a long-term acute care hospital, skilled nursing facility, or rehabilitation facility. Because the availability of post-acute care facilities such as long-term acute care facilities and skilled nursing facilities is variable across national and international healthcare systems, many of the patients in this U.S. population cohort would otherwise remain hospitalized and therefore were included in the prolonged admission group. We sought to determine whether the magnitude of the association between time and physical function varied on the basis of whether a patient required prolonged admission or returned home. Furthermore, we sought to determine whether older patients recover physical function at a lower rate. Understanding the association between functional recovery and age could identify groups who require more intensive and long-term therapeutic interventions to improve functional outcomes.

Of the 120 patients enrolled in the clinical trial, 28 died during the 6-month follow-up period. A total of 89 patients were included in the secondary analysis (Fig. 1). At 1 month, 86% (89 of 104) of survivors had follow-up. At 3 and 6 months, 76% (73 of 96) and 60% (55 of 92) of survivors, respectively, had follow-up. At 1 month, functional outcome testing and CS-PFP-10 testing were not assessed in 56% (50 of 89) of survivors, owing to prolonged admission in an acute or post-acute care facility. At 3 and 6 months, functional outcomes were not assessed in 20% (15 of 73), and 7% (4 of 55), respectively, owing to ongoing admission in an acute or post-acute care facility.

The mean age was 52 ± 15 years, 59% were male, and the mean APACHE II score was 17.6 ± 5.7. Common diagnoses were acute respiratory distress syndrome (32%), nonpulmonary sepsis (22%), and pneumonia (21%). The mean total CS-PFP-10 score at 1 month was 20 ± 26 (n = 89). At 3- and 6-month follow-up, the mean total CS-PFP-10 scores were 35 ± 26 (n = 73) and 42 ± 24 (n = 55), respectively. Patients who required prolonged admission at 1 month compared with those who returned home were older (mean age 55 vs. 49 years; p = 0.04) and were more likely to require ongoing admission in a post-acute care facility at 3 and 6 months (Table 1). In comparison of baseline demographics, we observed that compared with those patients who were included in the secondary analysis, patients who were lost to follow-up at 1 month had lower APACHE II scores (14.6 ± 4.6 vs. 17.5 ± 5.8; p = 0.04) and those who were lost to follow-up at 6 months were younger (48 ± 14 vs. 54 ± 14 years; p = 0.05) (Table 2).

In both groups, significant physical function limitations were present 6 months after recovery (mean CS-PFP-10 = 43 [CI 36–49]). Compared with patients who had returned home, patients who required prolonged admission had significantly lower physical function at 3 months (mean total CS-PFP-10 = 22 vs. 47; p < 0.0001) and 6 months (mean total CS-PFP-10 = 32 vs. 52; p < 0.002) (Fig. 2). When we examined the subscales of the CS-PFP-10 over time, we observed significant differences in functional scores for all functional domains (Table 2). A higher proportion of patients who required prolonged admission at 1 month had died at 6 months than among those who had returned home (22% vs. 2.5%; p = 0.007).

Adjusting for age, sex, and APACHE II score, we observed no difference in the rate at which physical function improved from 3 to 6 months for patients who required prolonged admission at 1 month compared with those who were discharged to home (p = 0.24 for interaction between time and prolonged admission). On average, patients with prolonged admission had CS-PFP-10 scores that were 20.1 (CI 10.4–29.8) points lower (p < 0.0001) than those of patients who had been discharged to home at 1 month (Table 3). Both groups had CS-PFP-10 scores that were 8.2 (CI 4.5–12.0) points higher at 6 months than at 3 months (p < 0.0001). Male patients had CS-PFP-10 scores that were 7.25 (CI 2.4–12.1) points higher than females. The results were similar with identical multivariable regression models using the five subscales of CS-PFP-10 as the outcome variable. The results of the sensitivity analysis excluding patients with CS-PFP-10 scores of 0 at 3 and 6 months were similar without a significant change in parametric estimates (Additional files 1 and 2).

The age of the patient was associated with a slower rate of improvement in physical function with a change in CS-PFP-10 of −0.36 for every increasing year age (CI −0.61 to −0.12; p = 0.004 for age × time interaction) (Table 4).

This secondary analysis demonstrates that in patients recovering from respiratory failure requiring mechanical ventilation, physical functional limitations are common. Prior to illness, all patients were living independently; yet, by 6 months, few had regained such function. The mean CS-PFP-10 score achieved by patients at 6 months was only 42, well below the threshold score of 57 that is associated with the ability to live independently [16, 17]. Compared with patients who returned home, patients who required prolonged admission had significantly lower physical function even by 6 months of recovery after an episode of acute respiratory failure (CS-PFP-10 = 32 vs. 55). Despite likely receiving higher-intensity rehabilitative services, patients who required prolonged admission were unable to achieve physical function levels of those patients who had returned home. Interestingly, both groups demonstrated parallel trajectories of recovery to those of patients who required prolonged admission and demonstrated improvement in physical function between 3 and 6 months of recovery at a rate similar to those who had returned home.

Our results suggest that patient heterogeneity may influence functional recovery after critical illness and that risk stratification based on ongoing need for admission in an acute or post-acute care setting at 1 month after an episode of acute respiratory failure may feasibly predict long-term physical functional recovery and guide rehabilitation interventions. Because patients respond differently to physical therapy, a single prescriptive approach for all patients may be ineffective and may contribute to findings from the numerous clinical trials of intensive physical therapy that have not demonstrated benefit in improving long-term functional recovery [7, 9, 11]. Instead, a targeted rehabilitation approach directed at patient subgroups that is based on patient-specific predictors has been hypothesized to be more effective. In a recent secondary analysis, Puthucheary and Denehy demonstrated that patient characteristics, specifically the presence or absence of preexisting chronic disease, were associated with trajectory of functional recovery [14]. Our secondary analysis suggests that age as well as prolonged admission after an episode of acute respiratory failure may also serve as predictors of future long-term recovery. Because younger age has been shown on the basis of observational data to be associated with a greater rate of functional recovery [1], it seems likely that age influences response to therapy. Recently, Ferrante and colleagues demonstrated that, in older adults aged 70 years and older who survived an ICU hospitalization, only 52.3% had recovery of pre-ICU function [15]. Therefore, older patients may need a different intensity or form of therapy to achieve rates of recovery similar to those of younger age groups. Additionally, in our model, there was an association between male sex and greater functional recovery. Gender differences in mobility have previously been observed; women have been shown to have greater levels of disability in their mobility [18, 19]. The reasons for this are not well understood but are an important area of further study. Furthermore, if gender is a patient characteristic potentially influential on physical functional recovery, this characteristic would be important in guiding targeted future interventions to promote post-ICU recovery.

Prolonged admission in an acute or post-acute care setting after an episode of respiratory failure may serve as a predictor of recovery or, alternatively, may be associated with the intensity of rehabilitation services received. In the original study, patients who were persistently admitted at 1 month resided either in an acute care facility or in a post-acute care facility (long-term care, skilled nursing, or rehabilitation facility). It is likely that during that 1 month, these patients received a higher intensity of rehabilitative therapy than those who returned home; however, their rate of recovery between 3 and 6 months postillness was similar to that of patients who returned home. This finding raises the possibility that physical functional recovery may be influenced not only by intensity of therapy but also perhaps by timing of physical therapy interventions. Because the majority of patients in both groups continued to have functional limitations even at 6 months postillness, it appears that physical functional recovery plateaus. One possible explanation for this includes that, upon returning home, survivors of acute respiratory failure receive limited physical functional rehabilitation services. Patients likely need a longer duration of therapy beyond what is provided in the hospital, and ongoing rehabilitation at home may similarly need to be intensified.

Our study has several strengths. By use of a performance-based outcome measure of physical function, the functional limitations of these survivors can be objectively measured. With the CS-PFP-10 assessment, we were able to define functional limitations in terms of a survivor’s ability to perform activities of daily living, quantify the severity of their impairments, and objectively describe their functional recovery over time. Furthermore, in this relatively young cohort, our demonstration that age influences functional recovery is an important finding. Last, we demonstrate that although prolonged admission is associated with lower physical functional performance, these patients do recover physical function over time. Stratification based on prolonged admission could be used as a potential predictor of long-term functional recovery.

The results of this secondary analysis are limited by those lost to follow-up as well as those unable to complete functional outcome assessments. Patients who were lost to follow-up at 1 month had higher baseline APACHE II scores than those included in the cohort, but by 6 months the baseline APACHE II scores were not different. By 6 months, those lost to follow-up were slightly younger than the entire cohort. Therefore, it is possible that if younger, healthier patients were lost to follow-up, the functional recovery in this cohort would be underestimated. Our analysis is also limited by those patients who did have functional outcome assessments because of ongoing admission in an acute or post-acute care facility. Because many patients required prolonged admission at 1 month and were therefore assigned a CS-PFP-10 score of 0, the 1-month functional outcome analysis was excluded. Thus, the initial early change in function between 1 and 3 months cannot be fully characterized. Additionally, this also may underpower the overall analysis. Additionally, we could not adjust for unmeasured confounding variables such as intensity of physical therapy received outside the clinical trial, which may have influenced changes in functional performance testing.

Our results suggest that physical functional limitations in survivors of acute respiratory failure requiring mechanical ventilation are common. This analysis is unique in that the level of physical functional recovery was quantified over time using the CS-PFP-10, a robust, performance-based measure of physical functional ability in multiple domains, as opposed to single-domain physical function assessments or questionnaire-based data. Furthermore, the results offer additional insight into physical functional recovery of patients who require prolonged admission in an acute or post-acute care setting. Although both groups recover, those who remain hospitalized 1 month after critical illness do not achieve similar levels of physical function by 6 months, and neither group achieves physical function associated with functional independence. Age negatively influences this trajectory of recovery. Further research is needed to intensify and individualize therapy to promote functional recovery as patients transition from the hospital and from the post-acute care setting to home.