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].).

Arm cycle ergometry in critically ill patients: A systematic review.

BACKGROUND: Intensive care unit (ICU) survivors face functional limitations due to ICU-acquired weakness. Arm cycle ergometry (ACE) introduced in the ICU may improve physical function. To our knowledge, there is limited evidence on the effectiveness of ACE and physical function outcomes in critically ill patients. OBJECTIVE: The objective of this systematic review was to examine the impact of ICU-based ACE on physical function, safety, and other clinical outcomes. REVIEW METHOD USED: Systematic Review. DATA SOURCES: A search of seven databases was conducted from the inception to January 1, 2023: Medline Ahead of Print, Ovid MEDLINE(R), Allied and Complementary Medicine Database (AMED), Embase, Cochrane Central, Physiotherapy Evidence Database, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). REVIEW METHODS: We included two arm studies of critically ill adults admitted to the ICU who received ACE and any comparator for our primary outcome, physical function. Our secondary outcomes included severe events. We included safety studies with or without a comparator group. Screening, data abstraction, and risk-of-bias assessments were completed independently, in duplicate. We used the Grading of Recommendations, Assessment, Development, and Evaluation approach to assess the overall certainty of evidence. RESULTS: We screened 651 citations and included eight studies that enrolled 183 patients. Due to heterogeneity, meta-analysis was not performed. For our primary outcome, one randomised controlled trial found significant improvements in physical function, measured by the Barthel Index with ACE, whereas a nonrandomised study showed no difference. Out of the six studies reporting safety, none reported any severe safety events. The overall certainty of evidence was very low. CONCLUSION: ACE initiated in the ICU is a likely safe intervention. Based on the limited ACE studies and heterogeneity between studies, further research with more rigorous studies evaluating important outcomes for patients is needed.

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).

Comparator Groups in ICU-Based Studies of Physical Rehabilitation: A Scoping Review of 125 Studies.

To characterize comparator groups (CGs) in ICU-based studies of physical rehabilitation (PR), including the type, content, and reporting. DATA SOURCES: We followed a five-stage scoping review methodology, searching five databases from inception to June 30, 2022. Study selection and data extraction were completed independently, in duplicate. STUDY SELECTION: We screened studies by title and abstract, then full-text. We included prospective studies with greater than or equal to two arms enrolling mechanically ventilated adults (≥ 18 yr), with any planned PR intervention initiated in the ICU. DATA EXTRACTION: We conducted a quantitative content analysis of authors' description of CG type and content. We categorized similar CG types (e.g., usual care), classified content into unique activities (e.g., positioning), and summarized these data using counts (proportions). We assessed reporting using Consensus on Exercise Reporting Template (CERT; proportion of reported items/total applicable). DATA SYNTHESIS: One hundred twenty-five studies were included, representing 127 CGs. PR was planned in 112 CGs (88.2%; 110 studies), representing four types: usual care (n = 81, 63.8%), alternative treatment than usual care (e.g., different from intervention; n = 18, 14.2%), alternative treatment plus usual care (n = 7, 5.5%), and sham (n = 6, 4.7%). Of 112 CGs with planned PR, 90 CGs (88 studies) reported 60 unique activities, most commonly passive range of motion (n = 47, 52.2%). The remaining 22 CGs (19.6%; 22 studies) reported vague descriptions. PR was not planned in 12 CGs (9.5%; 12 studies), and three CGs (2.4%; three studies) reported no details. Studies reported a median (Q1-Q3) of 46.6% (25.0-73.3%) CERT items. Overall, 20.0% of studies reported no detail to understand planned CG activities. CONCLUSIONS: The most common type of CG was usual care. We identified heterogeneity in planned activities and CERT reporting deficiencies. Our results could help guide the selection, design, and reporting of CGs in future ICU-based PR studies.

Co-designing and pilot testing an infographic to support patients/families through the REMAP-CAP consent process: a mixed-methods study protocol.

BACKGROUND: Informed consent is critical to the ethical conduct of clinical research and requires understanding of a trial including its purpose, process, potential risks and benefits, and alternatives to participation. This can be challenging for complex trials, such as platform trials, and in high-stress environments, such as the intensive care unit (ICU). REMAP-CAP (randomized, embedded, multifactorial, adaptive platform trial for community-acquired pneumonia) is a platform trial which studies treatments for ICU patients with community-acquired pneumonia, including COVID-19. Patient/family partners (PFP) identified challenges during the REMAP-CAP consent process. METHODS: This is a patient-centred co-design study to refine and test an infographic to supplement current REMAP-CAP consent documents. Infographic prototypes were developed by patients, substitute decision-makers (SDMs), and researchers with lived experience in the ICU or with ICU research. We will apply a two-phase exploratory sequential, mixed-methods research design. In phase 1, we will conduct focus groups with ICU patients, SDMs, and research coordinators (RCs). We will use inductive content analysis to inform infographic refinement, to be pilot tested in phase 2. Phase 2 is a prospective study within a trial (SWAT) at ≤ 5 REMAP-CAP sites. We will collect self-reported data from patients/SDMs and RCs. The primary outcome is feasibility (eligible consent encounters, receipt of infographic, consent to follow-up, completion of follow-up surveys). Data will be integrated to understand if/how quantitative results build upon the qualitatively informed infographic. DISCUSSION: Phase 1 results will be used to co-design an infographic, directly informed by the perspectives of patients, SDMs, and RCs involved in ICU research consent discussions. Results from phase 2 will determine the feasibility of infographic implementation in REMAP-CAP consent encounters. These feasibility data will inform a larger SWAT to evaluate our consent infographic. If successful, use of a co-designed infographic to support REMAP-CAP consent documents may improve the experience of consent for patients, SDMs, and RCs. TRIAL REGISTRATION: The Northern Ireland Hub for Trials Methodology Research SWAT Repository (SWAT no. 176).

Research interrupted: applying the CONSERVE 2021 Statement to a randomized trial of rehabilitation during critical illness affected by the COVID-19 pandemic.

RATIONALE: The COVID-19 pandemic disrupted non-COVID critical care trials globally as intensive care units (ICUs) prioritized patient care and COVID-specific research. The international randomized controlled trial CYCLE (Critical Care Cycling to Improve Lower Extremity Strength) was forced to halt recruitment at all sites in March 2020, creating immediate challenges. We applied the CONSERVE (CONSORT and SPIRIT Extension for RCTs Revised in Extenuating Circumstance) statement as a framework to report the impact of the pandemic on CYCLE and describe our mitigation approaches. METHODS: On March 23, 2020, the CYCLE Methods Centre distributed a standardized email to determine the number of patients still in-hospital and those requiring imminent 90-day endpoint assessments. We assessed protocol fidelity by documenting attempts to provide the in-hospital randomized intervention (cycling or routine physiotherapy) and collect the primary outcome (physical function 3-days post-ICU discharge) and 90-day outcomes. We advised sites to prioritize data for the study's primary outcome. We sought feedback on pandemic barriers related to trial procedures. RESULTS: Our main Methods Centre mitigation strategies included identifying patients at risk for protocol deviations, communicating early and frequently with sites, developing standardized internal tools focused on high-risk points in the protocol for monitoring patient progress, data entry, and validation, and providing guidance to conduct some research activities remotely. For study sites, our strategies included determining how institutional pandemic research policies applied to CYCLE, communicating with the Methods Centre about capacity to continue any part of the research, and developing contingency plans to ensure the protocol was delivered as intended. From 15 active sites (12 Canada, 2 US, 1 Australia), 5 patients were still receiving the study intervention in ICUs, 6 required primary outcomes, and 17 required 90-day assessments. With these mitigation strategies, we attempted 100% of ICU interventions, 83% of primary outcomes, and 100% of 90-day assessments per our protocol. CONCLUSIONS: We retained all enrolled patients with minimal missing data using several time-sensitive strategies. Although CONSERVE recommends reporting only major modifications incurred by extenuating circumstances, we suggest that it also provides a helpful framework for reporting mitigation strategies with the goal of improving research transparency and trial management. TRIAL REGISTRATION: NCT03471247. Registered on March 20, 2018.

The sit-to-stand test as a patient-centered functional outcome for critical care research: a pooled analysis of five international rehabilitation studies.

BACKGROUND: With ICU mortality rates decreasing, it is increasingly important to identify interventions to minimize functional impairments and improve outcomes for survivors. Simultaneously, we must identify robust patient-centered functional outcomes for our trials. Our objective was to investigate the clinimetric properties of a progression of three outcome measures, from strength to function. METHODS: Adults (≥ 18 years) enrolled in five international ICU rehabilitation studies. Participants required ICU admission were mechanically ventilated and previously independent. Outcomes included two components of the Physical Function in ICU Test-scored (PFIT-s): knee extensor strength and assistance required to move from sit to stand (STS); the 30-s STS (30 s STS) test was the third outcome. We analyzed survivors at ICU and hospital discharge. We report participant demographics, baseline characteristics, and outcome data using descriptive statistics. Floor effects represented ≥ 15% of participants with minimum score and ceiling effects ≥ 15% with maximum score. We calculated the overall group difference score (hospital discharge score minus ICU discharge) for participants with paired assessments. RESULTS: Of 451 participants, most were male (n = 278, 61.6%) with a median age between 60 and 66 years, a mean APACHE II score between 19 and 24, a median duration of mechanical ventilation between 4 and 8 days, ICU length of stay (LOS) between 7 and 11 days, and hospital LOS between 22 and 31 days. For knee extension, we observed a ceiling effect in 48.5% (160/330) of participants at ICU discharge and in 74.7% (115/154) at hospital discharge; the median [1st, 3rd quartile] PFIT-s difference score (n = 139) was 0 [0,1] (p < 0.05). For STS assistance, we observed a ceiling effect in 45.9% (150/327) at ICU discharge and in 77.5% (79/102) at hospital discharge; the median PFIT-s difference score (n = 87) was 1 [0, 2] (p < 0.05). For 30 s STS, we observed a floor effect in 15.0% (12/80) at ICU discharge but did not observe a floor or ceiling effect at hospital discharge. The median 30 s STS difference score (n = 54) was 3 [1, 6] (p < 0.05). CONCLUSION: Among three progressive outcome measures evaluated in this study, the 30 s STS test appears to have the most favorable clinimetric properties to assess function at ICU and hospital discharge in moderate to severely ill participants.

Enabling Healthy Aging to AVOID Frailty in Community Dwelling Older Canadians.

The Canadian population is aging. With aging, biological and social changes occur increasing the risk of developing chronic conditions and functional loss leading to frailty. Older adults living with frailty are more vulnerable to minor stressors, take longer to recover from illness, and have difficulty participating in daily activities. The Canadian Frailty Network's (CFN) mission is to improve the lives of older adults living with frailty. In September 2019, CFN launched the Activity & Exercise, Vaccination, Optimization of medications, Interaction & Socialization, and Diet & Nutrition (AVOID) Frailty public health campaign to promote assessing and reducing risk factors leading to the development of frailty. As part of the campaign, CFN held an Enabling Healthy Aging Symposium with 36 stakeholders from across Canada. Stakeholders identified individual and community-level opportunities and challenges for the enablement of healthy aging and frailty mitigation, as part of a focused consultative process. Stakeholders ranked the three most important challenges and opportunities at the individual and community levels for implementing AVOID Frailty recommendations. Concrete actions, further research areas, policy changes, and existing resources/programs to enhance the AVOID Frailty campaign were identified. The results will help inform future priorities and behaviour change strategies for healthy aging in Canada.

Retention in RCTs of physical rehabilitation for adults with frailty: a systematic review and meta-analysis.

BACKGROUND: Physical rehabilitation (PR) interventions can improve physical function for adults with frailty; however, participant retention rates in randomized controlled trials (RCTs) are unknown. Objective is to summarize participant retention rates in RCTs of PR for adults with frailty. Design is a systematic review and meta-analysis (DOI:10.17605/OSF.IO/G6XR2). Participants are adults ≥ 18 years with frailty. Setting consists of inpatient, outpatient and community-based interventions. Intervention includes any PR intervention. METHODS: We searched 7 electronic databases from inception to April 15, 2020 for published RCTs. Our primary outcome was participant retention rate to primary outcome measurement. Secondary outcomes included retention by study group, participant retention to intervention completion, reported reasons for attrition and reported strategies for maximizing retention. We completed screening, data extraction and risk of bias (ROB) assessments independently and in duplicate. We conducted a meta-analysis, calculating retention rates and 95% confidence intervals (CIs) using fixed or random-effects models, as appropriate. RESULTS: We included 21 RCTs, enrolling 1685 adults with frailty (median age 82.5 years (79.0, 82.2), 59.8% female (57.5, 69.8)). Twenty RCTs reported retention data, of which 90.0% (n = 18) had high ROB. The pooled participant retention rate to primary outcome measurement was 85.0% [95%CI (80.0, 90.0), I2 = 83.9%, p < 0.05]. There were no differences by group for retention to the primary outcome [intervention 87.0% (83.0, 91.0), p < 0.05, comparator 85.0% (79.0, 90.0), p < 0.05] or in retention to intervention completion [83.0% (95.0% CI (78.0-87.0), p < 0.05]. Of the 18 studies reporting 24 reasons for attrition, 51.3% were categorized as potentially modifiable by the research team (e.g. low motivation). Only 20.0% (n = 4) of studies reported strategies for maximizing retention. CONCLUSIONS: In this review of 21 RCTs of PR, we identified acceptable rates of retention for adults with frailty. High retention in PR interventions appears to be feasible in this population; however, our results are limited by a high ROB and heterogeneity.

Characteristics and outcomes of patients with COVID-19 admitted to hospital and intensive care in the first phase of the pandemic in Canada: a national cohort study.

BACKGROUND: Clinical data on patients admitted to hospital with coronavirus disease 2019 (COVID-19) provide clinicians and public health officials with information to guide practice and policy. The aims of this study were to describe patients with COVID-19 admitted to hospital and intensive care, and to investigate predictors of outcome to characterize severe acute respiratory infection. METHODS: This observational cohort study used Canadian data from 32 selected hospitals included in a global multisite cohort between Jan. 24 and July 7, 2020. Adult and pediatric patients with a confirmed diagnosis of COVID-19 who received care in an intensive care unit (ICU) and a sampling of up to the first 60 patients receiving care on hospital wards were included. We performed descriptive analyses of characteristics, interventions and outcomes. The primary analyses examined in-hospital mortality, with secondary analyses of the length of hospital and ICU stay. RESULTS: Between January and July 2020, among 811 patients admitted to hospital with a diagnosis of COVID-19, the median age was 64 (interquartile range [IQR] 53-75) years, 495 (61.0%) were men, 46 (5.7%) were health care workers, 9 (1.1%) were pregnant, 26 (3.2%) were younger than 18 years and 9 (1.1%) were younger than 5 years. The median time from symptom onset to hospital admission was 7 (IQR 3-10) days. The most common symptoms on admission were fever, shortness of breath, cough and malaise. Diabetes, hypertension and cardiac, kidney and respiratory disease were the most common comorbidities. Among all patients, 328 received care in an ICU, admitted a median of 0 (IQR 0-1) days after hospital admission. Critically ill patients received treatment with invasive mechanical ventilation (88.8%), renal replacement therapy (14.9%) and extracorporeal membrane oxygenation (4.0%); 26.2% died. Among those receiving mechanical ventilation, 31.2% died. Age was an influential predictor of mortality (odds ratio per additional year of life 1.06, 95% confidence interval 1.03-1.09). INTERPRETATION: Patients admitted to hospital with COVID-19 commonly had fever, respiratory symptoms and comorbid conditions. Increasing age was associated with the development of critical illness and death; however, most critically ill patients in Canada, including those requiring mechanical ventilation, survived and were discharged from hospital.