Characterizing usual-care physical rehabilitation in Canadian intensive care unit patients: a secondary analysis of the Canadian multicentre Critical Care Cycling to Improve Lower Extremity Strength pilot randomized controlled trial.

PURPOSE: Physical rehabilitation (PR) in the intensive care unit (ICU) may improve outcomes for survivors but clinical trial results have been discordant. We hypothesized that discordant results may reflect treatment heterogeneity received by "usual care" comparator groups in PR studies. Usual-care PR is typically underspecified, which is a barrier to comparing results across treatment studies. The primary objective of the present study was to describe the usual-care PR received by critically ill patients enrolled in the Canadian multicentre Critical Care Cycling to Improve Lower Extremity Strength (CYCLE) pilot randomized controlled trial (RCT) of PR. Other objectives were to help contextualize current research and provide data for international comparison. METHODS: In this secondary analysis of the CYCLE pilot RCT, patients were randomized to in-bed cycling and usual-care PR or usual-care PR alone. Physiotherapists documented usual-care PR including therapy received, type of activity, duration, adverse events and consequences, reasons for no PR, and concurrent relevant medical interventions. We characterized usual care using descriptive statistics at the cohort and patient levels. RESULTS: Across seven Canadian centres, 30 patients were randomized to usual-care PR. The median [interquartile range (IQR)] ICU stay was 10 [9-24] days and patients received PR on a median [IQR] of 5 [3-9] days for 23 [17-30] min per day. Eighteen patients (60%) stood, marched, or walked during usual care. Transient adverse events occurred in three patients on 1.5% (3/198) of days and none prompted session termination. CONCLUSIONS: In the usual-care arm of the CYCLE pilot RCT, PR was delivered on half of ICU days and over half of patients stood, marched, or walked. Adverse events during usual-care PR were uncommon. STUDY REGISTRATION: ClinicalTrials.gov ( NCT02377830 ); first posted 4 March 2015.

RéSUMé: OBJECTIF: La réadaptation physique (RP) à l'unité de soins intensifs (USI) pourrait améliorer les devenirs pour les personnes survivantes, mais les résultats des études cliniques sont contradictoires. Nous avons émis l'hypothèse que les résultats contradictoires pourraient refléter l'hétérogénéité des traitements reçus par les groupes de comparaison de « soins standards ¼ dans les études sur la RP. La RP habituelle est généralement sous-spécifiée, ce qui constitue un obstacle à la comparaison des résultats entre les études de traitement. L'objectif principal de la présente étude était de décrire les RP habituelles reçues par les patient·es gravement malades inscrit·es dans l'étude randomisée contrôlée (ERC) multicentrique canadienne pilote sur les RP intitulée CYCLE (Critical Care Cycling to Improve Lower Extremity Strength, soit Cyclisme en soins intensifs pour améliorer la force des membres inférieurs). D'autres objectifs étaient d'aider à contextualiser les recherches actuelles et de fournir des données pour une comparaison internationale. MéTHODE: Dans cette analyse secondaire de l'ERC pilote CYCLE, les patient·es ont été randomisé·es à faire du vélo au lit et de la RP habituelle ou seulement de la RP habituelle. Les physiothérapeutes ont documenté la RP habituelle, y compris la thérapie reçue, le type d'activité, la durée, les événements indésirables et les conséquences, les raisons de l'absence de RP et les interventions médicales pertinentes concomitantes. Nous avons caractérisé les soins standards à l'aide de statistiques descriptives au niveau de la cohorte et de la personne traitée. RéSULTATS: Dans sept centres canadiens, 30 patient·es ont été randomisé·es pour recevoir la RP habituelle. La durée de séjour médiane [écart interquartile (ÉIQ)] aux soins intensifs était de 10 [9-24] jours et les patient·es ont reçu de la RP sur une durée médiane [ÉIQ] de 5 [3-9] jours pendant 23 [17-30] minutes par jour. Dix-huit patient·es (60 %) se sont tenu·es debout, ont marché de façon stationnaire ou ont marché pendant les soins standards. Des effets indésirables transitoires sont survenus chez trois patient·es pendant 1,5 % (3/198) des jours et aucun n'a entraîné l'interruption de la séance. CONCLUSION: Dans le volet soins habituels de l'ERC pilote CYCLE, la réadaptation physique a été dispensée pendant la moitié des jours de soins intensifs et plus de la moitié des patient·es se sont tenu·es debout, ont marché de façon stationnaire ou ont marché. Les événements indésirables lors de la RP habituelle étaient rares. ENREGISTREMENT DE L'éTUDE: ClinicalTrials.gov ( NCT02377830 ); première mise en ligne le 4 mars 2015.

Early In-Bed Cycle Ergometry in Mechanically Ventilated Patients.

BACKGROUND: Critical illness requiring invasive mechanical ventilation can precipitate important functional disability, contributing to multidimensional morbidity following admission to an intensive care unit (ICU). Early in-bed cycle ergometry added to usual physiotherapy may mitigate ICU-acquired physical function impairment. METHODS: We randomly assigned 360 adult ICU patients undergoing invasive mechanical ventilation to receive 30 minutes of early in-bed Cycling + Usual physiotherapy (n=178) or Usual physiotherapy alone (n=182). The primary outcome was the Physical Function ICU Test-scored (PFIT-s) at 3 days after discharge from the ICU (the score ranges from 0 to 10, with higher scores indicating better function). RESULTS: Cycling began within a median (interquartile range) of 2 (1 to 3) days of starting mechanical ventilation; patients received 3 (2 to 5) cycling sessions for a mean (±standard deviation) of 27.2 ± 6.6 minutes. In both groups, patients started Usual physiotherapy within 2 (2 to 4) days of mechanical ventilation and received 4 (2 to 7) Usual physiotherapy sessions. The duration of Usual physiotherapy was 23.7 ± 15.1 minutes in the Cycling + Usual physiotherapy group and 29.1 ± 13.2 minutes in the Usual physiotherapy group. No serious adverse events occurred in either group. Among survivors, the PFIT-s at 3 days after discharge from the ICU was 7.7 ± 1.7 in the Cycling + Usual physiotherapy group and 7.5 ± 1.7 in the Usual physiotherapy group (absolute difference, 0.23 points; 95% confidence interval, -0.19 to 0.65; P=0.29). CONCLUSIONS: Among adults receiving mechanical ventilation in the ICU, adding early in-bed Cycling to usual physiotherapy did not improve physical function at 3 days after discharge from the ICU compared with Usual physiotherapy alone. Cycling did not cause any serious adverse events. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov numbers, NCT03471247 [full randomized clinical trial] and NCT02377830 [CYCLE Vanguard 46-patient internal pilot].).

Critical Care Cycling to Improve Lower Extremity Strength (CYCLE): protocol for an international, multicentre randomised clinical trial of early in-bed cycling for mechanically ventilated patients.

INTRODUCTION: In-bed leg cycling with critically ill patients is a promising intervention aimed at minimising immobility, thus improving physical function following intensive care unit (ICU) discharge. We previously completed a pilot randomised controlled trial (RCT) which supported the feasibility of a large RCT. In this report, we describe the protocol for an international, multicentre RCT to determine the effectiveness of early in-bed cycling versus routine physiotherapy (PT) in critically ill, mechanically ventilated adults. METHODS AND ANALYSIS: We report a parallel group RCT of 360 patients in 17 medical-surgical ICUs and three countries. We include adults (≥18 years old), who could ambulate independently before their critical illness (with or without a gait aid), ≤4 days of invasive mechanical ventilation and ≤7 days ICU length of stay, and an expected additional 2-day ICU stay, and who do not fulfil any of the exclusion criteria. After obtaining informed consent, patients are randomised using a web-based, centralised system to either 30 min of in-bed cycling in addition to routine PT, 5 days per week, up to 28 days maximum, or routine PT alone. The primary outcome is the Physical Function ICU Test-scored (PFIT-s) at 3 days post-ICU discharge measured by assessors blinded to treatment allocation. Participants, ICU clinicians and research coordinators are not blinded to group assignment. Our sample size estimate was based on the identification of a 1-point mean difference in PFIT-s between groups. ETHICS AND DISSEMINATION: Critical Care Cycling to improve Lower Extremity (CYCLE) is approved by the Research Ethics Boards of all participating centres and Clinical Trials Ontario (Project 1345). We will disseminate trial results through publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT03471247 (Full RCT); NCT02377830 (CYCLE Vanguard 46 patient internal pilot).

Learning needs and perceived barriers and facilitators to end-of-life care: a survey of front-line nurses on acute medical wards.

OBJECTIVES: Caring for dying hospitalised patients is a healthcare priority. Our objective was to understand the learning needs of front-line nurses on the general internal medicine (GIM) hospital wards, and perceived barriers to, and facilitators of, optimal end-of-life care. METHODS: We developed an 85-item survey informed by the Theoretical Domains Framework and Capability-Opportunity-Motivation-Behaviour system. We included demographics and two main domains (knowledge and practice; delivering end-of-life care) with seven subsections. Nurses from four GIM wards and the nursing resource team completed this survey. We analysed and compared results overall, by Capability, Opportunity, and Motivation, and by survey domain. We considered items with median scores <4/7 barriers. We conducted an a priori subgroup analysis based on duration of practice (≤5 and >5 years). RESULTS: Our response rate was 60.5% (144/238). 51% had been practising for >5 years; most respondents were female (93.1%). Nurses had similar scores on the knowledge (mean 76.0%; SD 11.6%) and delivering care (mean 74.5% (8.6%)) domains. Scores for items associated with Capability were higher than those associated with Opportunity (median (first, third quartiles) 78.6% (67.9%, 87.5%) vs 73.9% (66.0%, 81.8%); p=0.04). Nurses practising >5 years had significantly higher scores on all analyses. Barriers included engaging with families having strong emotional reactions, managing goals of care conflicts between patients and families, and staffing challenges on the ward. Additional requested resources included formal training, information binders and more staff. Opportunities for consideration include formalised on-the-job training, access to comprehensive information, including symptom management at the end of life, and debriefing sessions. CONCLUSIONS: Front-line nurses reported an interest in learning more about end-of-life care and identified important barriers that are feasible to address. These results will inform specific knowledge translation strategies to build capacity among bedside nurses to enhance end-of-life care practices for dying patients on GIM wards.

Enhancing end of life care on general internal medical wards: the 3 Wishes Project.

BACKGROUND: Initially developed in the intensive care unit (ICU) at St. Joseph's Healthcare Hamilton (SJHH) the 3 Wishes Project (3WP) provides personalized, compassionate care to dying patients and their families. The objective of this study was to develop and evaluate 3WP expansion strategies for patients cared for on General Internal Medicine (GIM) wards in our hospital. METHODS: From January 2020-November 2021, we developed a phased, multicomponent approach for program expansion. We enrolled patients on the GIM wards who had a high probability of dying in hospital, then elicited, implemented, and documented wishes for them or their families. Data were analyzed descriptively. RESULTS: From March 2020 to November 2020, we implemented staff education and engagement activities, created an Expansion Coordinator position, held strategic consultations, and offered enabling resources. From March 2020 to November 2021, we enrolled 62 patients and elicited 281 wishes (median [1st, 3rd quartiles] 4 [4, 5] wishes/patient). The most common wish categories were personalizing the environment (67 wishes, 24%), rituals and spiritual support (42 wishes, 15%), and facilitating connections (39 wishes, 14%). The median [1st, 3rd] cost/patient was $0 [0, $10.00] (range $0 to $86); 91% of wishes incurred no cost to the program. CONCLUSIONS: The formal expansion of the 3WP on GIM wards has been successful despite COVID-19 pandemic disruptions. While there is still work ahead, these data suggest that implementing the 3WP on the GIM wards is feasible and affordable. Increased engagement of the clinical team during the pandemic suggests that it is positively received.

Multistudy Research Operations in the ICU: An Interprofessional Pandemic-Informed Approach.

Proliferation of COVID-19 research underscored the need for improved awareness among investigators, research staff and bedside clinicians of the operational details of clinical studies. The objective was to describe the genesis, goals, participation, procedures, and outcomes of two research operations committees in an academic ICU during the COVID-19 pandemic. DESIGN: Two-phase, single-center multistudy cohort. SETTING: University-affiliated ICU in Hamilton, ON, Canada. PATIENTS: Adult patients in the ICU, medical stepdown unit, or COVID-19 ward. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An interprofessional COVID Collaborative was convened at the pandemic onset within our department, to proactively coordinate studies, help navigate multiple authentic consent encounters by different research staff, and determine which studies would be suitable for coenrollment. From March 2020 to May 2021, five non-COVID trials continued, two were paused then restarted, and five were launched. Over 15 months, 161 patients were involved in 215 trial enrollments, 110 (51.1%) of which were into a COVID treatment trial. The overall informed consent rate (proportion agreed of those eligible and approached including a priori and deferred consent models) was 83% (215/259). The informed consent rate was lower for COVID-19 trials (110/142, 77.5%) than other trials (105/117, 89.7%; p = 0.01). Patients with COVID-19 were significantly more likely to be coenrolled in two or more studies (29/77, 37.7%) compared with other patients (13/84, 15.5%; p = 0.002). Review items for each new study were collated, refined, and evolved into a modifiable checklist template to set up each study for success. The COVID Collaborative expanded to a more formal Department of Critical Care Research Operations Committee in June 2021, supporting sustainable research operations during and beyond the pandemic. CONCLUSIONS: Structured coordination and increased communication about research operations among diverse research stakeholders cultivated a sense of shared purpose and enhanced the integrity of clinical research operations.

Clinician Perspectives on Caring for Dying Patients During the Pandemic : A Mixed-Methods Study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected the hospital experience for patients, visitors, and staff. OBJECTIVE: To understand clinician perspectives on adaptations to end-of-life care for dying patients and their families during the pandemic. DESIGN: Mixed-methods embedded study. (ClinicalTrials.gov: NCT04602520). SETTING: 3 acute care medical units in a tertiary care hospital from 16 March to 1 July 2020. PARTICIPANTS: 45 dying patients, 45 family members, and 45 clinicians. INTERVENTION: During the pandemic, clinicians continued an existing practice of collating personal information about dying patients and "what matters most," eliciting wishes, and implementing acts of compassion. MEASUREMENTS: Themes from semistructured clinician interviews that were summarized with representative quotations. RESULTS: Many barriers to end-of-life care arose because of infection control practices that mandated visiting restrictions and personal protective equipment, with attendant practical and psychological consequences. During hospitalization, family visits inside or outside the patient's room were possible for 36 patients (80.0%); 13 patients (28.9%) had virtual visits with a relative or friend. At the time of death, 20 patients (44.4%) had a family member at the bedside. Clinicians endeavored to prevent unmarked deaths by adopting advocacy roles to "fill the gap" of absent family and by initiating new and established ways to connect patients and relatives. LIMITATION: Absence of clinician symptom or wellness metrics; a single-center design. CONCLUSION: Clinicians expressed their humanity through several intentional practices to preserve personalized, compassionate end-of-life care for dying hospitalized patients during the SARS-CoV-2 pandemic. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research and Canadian Critical Care Trials Group Research Coordinator Fund.

Feasibility, Reliability, Responsiveness, and Validity of the Patient-Reported Functional Scale for the Intensive Care Unit: A Pilot Study.

BACKGROUND: Although many performance-based measures assess patients' physical function in intensive care unit (ICU) survivors, to our knowledge, there are no patient-reported ICU rehabilitation-specific measures assessing function. We developed the Patient-Reported Functional Scale-ICU (PRFS-ICU), which measures patients' perceptions of their ability to perform 6 activities (rolling, sitting edge of bed, sit-to-stand and bed-to-chair transfers, ambulation, and stair climbing). Each item is scored from 0 (unable) to 10 (able to perform at pre-ICU level) to a maximum of 60. OBJECTIVES: Estimate the feasibility, reliability, responsiveness, and validity of the PRFS-ICU. METHODS: This was a substudy of TryCYCLE, a single-center, prospective cohort examining the safety and feasibility of early in-bed cycling with mechanically ventilated patients (NCT01885442). To determine feasibility, we calculated the number of patients with at least 1 PRFS-ICU assessment during their hospital stay. To assess reliability, 2 raters blinded to each other's assessments administered the PRFS-ICU within 24-hours of each other. We calculated the intraclass correlation coefficient (ICC; 95% confidence interval [CI]), standard error of measurement (SEM, 95% CI), and minimal detectable change (MDC90). To assess validity, we estimated convergent validity of the PRFS-ICU with the Functional Status Score for ICU (FSS-ICU), Medical Research Council Sum Score (MRC-SS), Physical Function Test for ICU (PFIT-s), Katz Index of Independence in Activities of Daily Living (Katz ADLs), and a pooled index using Pearson's correlation coefficient (r, 95% CI). RESULTS: Feasibility: 20 patients completed a PRFS-ICU assessment. Reliability and responsiveness: 16 patients contributed data. The ICC, SEM, and MDC90 were 0.91 (0.76, 0.97), 4.75 (3.51, 7.35), and 11.04 points, respectively. Validity: 19 patients contributed data and correlations were (r [95% CI]): FSS-ICU (0.40 [-0.14, 0.76]), MRC-SS (0.51 [0.02, 0.80]), PFIT-s (0.43 [-0.13, 0.78]), Katz ADLs (0.53 [0.10, 0.79]), and pooled index (0.48 [-0.14, 0.82]). CONCLUSIONS: Our pilot work suggests the PRFS-ICU may be a useful tool to assess and monitor patients' perceptions of function over time.

Correction to: Project management lessons learned from the multicentre CYCLE pilot randomized controlled trial.

Following publication of the original article [1], we have been notified that one of the authors' names is spelled incorrectly. In this Correction the incorrect and correct author name are shown.

Project management lessons learned from the multicentre CYCLE pilot randomized controlled trial.

BACKGROUND: Clinical trials management can be studied using project management theory. The CYCLE pilot randomized controlled trial (RCT) was conducted to determine the feasibility of a future rehabilitation trial of early in-bed cycling in the intensive care unit (ICU). In-bed cycling is a novel intervention, not typically available in ICUs. Implementation of this intervention requires personnel with specialized clinical expertise caring for critically ill patients and use of the in-bed cycle. Our objective was to describe the implementation and conduct of our pilot RCT using a project management approach. METHODS: We retrospectively reviewed activities, timelines, and personnel involved in the trial. We organized activities into four project management phases: initiation, planning, execution, and monitoring and controlling. Data sources included Methods Centre documents used for trial coordination and conduct, and the trial data set. We report descriptive statistics as counts and proportions and also medians and quartiles, and we summarize the lessons learned. RESULTS: Seven ICUs in Canada participated in the trial. Time from research ethics board and contracts submission to first enrolment was a median (first quartile, third quartile) of 185 (146, 209) and 162 (114, 181) days, respectively. We trained 128 personnel on the CYCLE pilot RCT protocol, and 80 (63%) completed trial-related activities. Four sites required additional training after start-up due to staff turnover and leaves of absence. Over 15 months, we screened 864 patients: 256 were eligible and 66 were enrolled. Despite an 85% consent rate, 74% (190/256) of eligible patients were not randomized, largely (80% [152/190]) due to physiotherapist availability. Thirteen percent of recruitment weeks were lost due to physiotherapist staffing shortages. We highlight five key lessons learned: (1) prepare and anticipate site needs; (2) communicate regularly; (3) proactively analyse and act on process measure data; (4) develop contingency plans; (5) express appreciation to participating sites. CONCLUSIONS: Our analysis highlights the scope of relevant activities, rigorous training and monitoring, number and types of required personnel, and time required to conduct a multicentre ICU rehabilitation intervention trial. Our lessons learned can help others interested in implementing complex intervention trials, such as rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02377830 . Registered prospectively on 4 March 2015.

Determinants of Depressive Symptoms at 1 Year Following ICU Discharge in Survivors of ≥ 7 Days of Mechanical Ventilation: Results From the RECOVER Program, a Secondary Analysis of a Prospective Multicenter Cohort Study.

BACKGROUND: Moderate to severe depressive symptoms occur in up to one-third of patients at 1 year following ICU discharge, negatively affecting patient outcomes. This study evaluated patient and caregiver factors associated with the development of these symptoms. METHODS: This study used the Rehabilitation and Recovery in Patients after Critical Illness and Their Family Caregivers (RECOVER) Program (Phase 1) cohort of 391 patients from 10 medical/surgical university-affiliated ICUs across Canada. We determined the association between patient depressive symptoms (captured by using the Beck Depression Inventory II [BDI-II]), patient characteristics (age, sex, socioeconomic status, Charlson score, and ICU length of stay [LOS]), functional independence measure (FIM) motor subscale score, and caregiver characteristics (Caregiver Assistance Scale and Center for Epidemiologic Studies-Depression Scale) by using linear mixed models at time points 3, 6, and 12 months. RESULTS: BDI-II data were available for 246 patients. Median age at ICU admission was 56 years (interquartile range, 45-65 years), 143 (58%) were male, and median ICU LOS was 19 days (interquartile range, 13-32 days). During the 12-month follow-up, 67 of 246 (27.2%) patients had a BDI-II score ≥ 20, indicating moderate to severe depressive symptoms. Mixed models showed worse depressive symptoms in patients with lower FIM motor subscale scores (1.1 BDI-II points per 10 FIM points), lower income status (by 3.7 BDI-II points; P = .007), and incomplete secondary education (by 3.8 BDI-II points; P = .009); a curvilinear relation with age (P = .001) was also reported, with highest BDI-II at ages 45 to 50 years. No associations were found between patient BDI-II and comorbidities (P = .92), sex (P = .25), ICU LOS (P = .51), or caregiver variables (Caregiver Assistance Scale [P = .28] and Center for Epidemiologic Studies Depression Scale [P = .74]). CONCLUSIONS: Increased functional dependence, lower income, and lower education are associated with increased severity of post-ICU depressive symptoms, whereas age has a curvilinear relation with symptom severity. Knowledge of risk factors may inform surveillance and targeted mental health follow-up. Early mobilization and rehabilitation aiming to improve function may serve to modify mood disorders.

Multicentre pilot randomised clinical trial of early in-bed cycle ergometry with ventilated patients.

Introduction: Acute rehabilitation in critically ill patients can improve post-intensive care unit (post-ICU) physical function. In-bed cycling early in a patient's ICU stay is a promising intervention. The objective of this study was to determine the feasibility of recruitment, intervention delivery and retention in a multi centre randomised clinical trial (RCT) of early in-bed cycling with mechanically ventilated (MV) patients. Methods: We conducted a pilot RCT conducted in seven Canadian medical-surgical ICUs. We enrolled adults who could ambulate independently before ICU admission, within the first 4 days of invasive MV and first 7 days of ICU admission. Following informed consent, patients underwent concealed randomisation to either 30 min/day of in-bed cycling and routine physiotherapy (Cycling) or routine physiotherapy alone (Routine) for 5 days/week, until ICU discharge. Our feasibility outcome targets included: accrual of 1-2 patients/month/site; >80% cycling protocol delivery; >80% outcomes measured and >80% blinded outcome measures at hospital discharge. We report ascertainment rates for our primary outcome for the main trial (Physical Function ICU Test-scored (PFIT-s) at hospital discharge). Results: Between 3/2015 and 6/2016, we randomised 66 patients (36 Cycling, 30 Routine). Our consent rate was 84.6 % (66/78). Patient accrual was (mean (SD)) 1.1 (0.3) patients/month/site. Cycling occurred in 79.3% (146/184) of eligible sessions, with a median (IQR) session duration of 30.5 (30.0, 30.7) min. We recorded 43 (97.7%) PFIT-s scores at hospital discharge and 37 (86.0%) of these assessments were blinded. Discussion: Our pilot RCT suggests that a future multicentre RCT of early in-bed cycling for MV patients in the ICU is feasible. Trial registration number: NCT02377830.

One-Year Outcomes in Caregivers of Critically Ill Patients.

BACKGROUND: Few resources are available to support caregivers of patients who have survived critical illness; consequently, the caregivers' own health may suffer. We studied caregiver and patient characteristics to determine which characteristics were associated with caregivers' health outcomes during the first year after patient discharge from an intensive care unit (ICU). METHODS: We prospectively enrolled 280 caregivers of patients who had received 7 or more days of mechanical ventilation in an ICU. Using hospital data and self-administered questionnaires, we collected information on caregiver and patient characteristics, including caregiver depressive symptoms, psychological well-being, health-related quality of life, sense of control over life, and effect of providing care on other activities. Assessments occurred 7 days and 3, 6, and 12 months after ICU discharge. RESULTS: The caregivers' mean age was 53 years, 70% were women, and 61% were caring for a spouse. A large percentage of caregivers (67% initially and 43% at 1 year) reported high levels of depressive symptoms. Depressive symptoms decreased at least partially with time in 84% of the caregivers but did not in 16%. Variables that were significantly associated with worse mental health outcomes in caregivers were younger age, greater effect of patient care on other activities, less social support, less sense of control over life, and less personal growth. No patient variables were consistently associated with caregiver outcomes over time. CONCLUSIONS: In this study, most caregivers of critically ill patients reported high levels of depressive symptoms, which commonly persisted up to 1 year and did not decrease in some caregivers. (Funded by the Canadian Institutes of Health Research and others; ClinicalTrials.gov number, NCT00896220.).

The RECOVER Program: Disability Risk Groups and 1-Year Outcome after 7 or More Days of Mechanical Ventilation.

RATIONALE: Disability risk groups and 1-year outcome after greater than or equal to 7 days of mechanical ventilation (MV) in medical/surgical intensive care unit (ICU) patients are unknown and may inform education, prognostication, rehabilitation, and study design. OBJECTIVES: To stratify patients for post-ICU disability and recovery to 1 year after critical illness. METHODS: We evaluated a multicenter cohort of 391 medical/surgical ICU patients who received greater than or equal to 1 week of MV at 7 days and 3, 6, and 12 months after ICU discharge. Disability risk groups were identified using recursive partitioning modeling. MEASUREMENTS AND MAIN RESULTS: The 7-day post-ICU Functional Independence Measure (FIM) determined the recovery trajectory to 1-year after ICU discharge and was an independent risk factor for 1-year mortality. The 7-day post-ICU FIM was predicted by age and ICU length of stay. By 2 weeks of MV, ICU patients could be stratified into four disability groups characterized by increasing risk for post ICU disability, ICU and post-ICU healthcare use, and disposition. Patients less than 42 years with ICU length of stay less than 2 weeks had the best function and fewest deaths at 1 year compared with patients greater than 66 years with ICU length of stay greater than 2 weeks who sustained the worst disability and 40% 1-year mortality. Depressive symptoms (17%) and post-traumatic stress disorder (18%) persisted at 1 year. CONCLUSIONS: ICU survivors of greater than or equal to 1 week of MV may be stratified into four disability groups based on age and ICU length of stay. These groups determine 1-year recovery and healthcare use and are independent of admitting diagnosis and illness severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00896220).

Roles of iNOS and nNOS in sepsis-induced pulmonary apoptosis.

Apoptosis(programmed cell death) is induced in pulmonary cells and contributes to the pathogenesis of acute lung injury in septic humans. Previous studies have shown that nitric oxide (NO) is an important modulator of apoptosis; however, the functional role of NO derived from inducible NO synthase (iNOS) in sepsis-induced pulmonary apoptosis remains unknown. We measured pulmonary apoptosis in a rat model of Escherichia coli lipopolysaccharide (LPS)-induced sepsis in the absence and presence of the selective iNOS inhibitor 1400W. Four groups were studied 24 h after saline (control) or LPS injection in the absence and presence of 1400W pretreatment. Apoptosis was evaluated using DNA fragmentation, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining, and caspase activation. LPS administration significantly augmented pulmonary cell apoptosis and caspase-3 activity in airway and alveolar epithelial cells. Pretreatment with 1400W significantly enhanced LPS-induced pulmonary apoptosis and increased caspase-3 and -7 activation. The antiapoptotic effect of iNOS was confirmed in iNOS-/- mice, which developed a greater degree of pulmonary apoptosis both under control conditions and in response to LPS compared with wild-type mice. By comparison, genetic deletion of the neuronal NOS had no effect on LPS-induced pulmonary apoptosis. We conclude that NO derived from iNOS plays an important protective role against sepsis-induced pulmonary apoptosis.