ICU Combined Assessment of Cardio-Respiratory Exercise (ICU-CARE)

Exercise Testing in ICU Survivors to Evaluate ICU-acquired Weakness

This study aims to investigate how sepsis and critical illness can impair the cardiovascular system and microcirculation in intensive care unit (ICU) patients, which can lead to long-lasting muscle weakness/dysfunction or ICU-Acquired Weakness (ICU-AW) and exercise limitations.

Study Overview

• Status: Recruiting
• Conditions: Sepsis; Shock; Critical Illness; ICU Acquired Weakness; Microcirculation

Detailed Description

This longitudinal study will assess cardiovascular fitness and microvascular function through two (2) follow-ups after ICU discharge: at (i) 6 months, and (ii) 12 months. The first timepoint will be at 6 months will be required, and the second timepoint at 12 months will be optional based on participant availability. The goal is to understand how microvascular dysfunction contributes to ICU-AW and long-term exercise limitation in ICU survivors.

Specific goals are:

1. Determine the feasibility of study enrollment and protocol completion.
2. Evaluate peak oxygen uptake and oxygen on/off kinetics in ICU survivors using a standardized cardiopulmonary exercise test (CPET) protocol. This protocol has been adapted from Santana et. al. (2025) for the ICU population.
3. Characterize skeletal muscle microvascular function in ICU survivors using high-resolution NIRS during CPET protocol.
4. Determine the association between impairments in skeletal muscle microvascular oxygen delivery and cardiovascular blood flow regulation in ICU survivors.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Asher Mendelson, MD PhD; Phone Number: 204-787-1634; Email: asher.mendelson@umanitoba.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2H 2A6
      • Recruiting
      • St. Boniface General Hospital
      • Contact: Asher Mendelson, MD PhD; Phone Number: 204-787-1634; Email: asher.mendelson@umanitoba.ca
    • Winnipeg, Manitoba, Canada, R3A 1R9
      • Recruiting
      • Health Sciences Centre Winnipeg
      • Contact: Asher Mendelson, MD PhD; Phone Number: 204-787-1634; Email: asher.mendelson@umanitoba.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

ICU survivor: Patients who have received mechanical ventilation for at least 7 days in the intensive care unit (ICU) and have subsequently been discharged from hospital

Description

Inclusion Criteria:

• Patients who have received mechanical ventilation for at least 7 days in the intensive care unit (ICU) and have subsequently been discharged from hospital.

Exclusion Criteria:

• Unable to provide consent
• Trajectory of health expected to be significantly limited in the upcoming 12 months
• those who self-report that they cannot climb at least one flight of stairs due to limited exercise capacity
• have significant orthopedic or musculoskeletal impairment affecting mobility
• have a medical history of neuromuscular disease
• ongoing respiratory limitations (i.e., supplemental oxygen)
• significant heart disease (i.e. ejection fraction less than 30%, unstable ischemic heart disease, severe valvular heart disease)
• a body mass index (BMI) of ≥ 40 kg/m2 (impacting NIRS signal due to adipose tissue thickness)
• if participant's primary residence is a significant distance from the participating study site

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
ICU survivors; Patients who have received prolonged mechanical ventilation (7 days or more) in the intensive care unit (ICU), and have been discharged from hospital.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VO2 peak oxygen uptake	Peak Oxygen uptake (VO2, mL/kg/min) will be measured during incremental exercise on a cycle ergometer during cardiopulmonary exercise testing (CPET).	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
oxygen on/off kinetics	time constant (seconds) of oxygen uptake will be assessed at the transition to constant work rate exercise at the beginning of CPET; time constant (seconds) of oxygen uptake will also be assessed at the transition to rest at the end of CPET after reaching VO2 peak.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
NIRS deoxygenation during exercise (deoxy-hemoglobin)	NIRS will be applied to the vastus lateralis during exercise testing. Deoxygenation profile, as measured by increase in deoxy-hemoglobin will be recorded throughout exercise. Higher values indicate impaired oxygen delivery to tissue.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
NIRS deoxygenation during exercise (tissue saturation index)	NIRS will be applied to the vastus lateralis during exercise testing. Deoxygenation profile, as measured by decrease in tissue saturation index will be recorded throughout exercise. Lower values indicate impaired oxygen delivery to tissue.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
Rate of enrollment	Rate of participant enrollment in the study will be recorded. Feasibility of enrollment will be one participant per month.	6 months after ICU discharge
Protocol completion	The number of completed sessions within 12 months for each eligible patient will be recorded. Feasibility target will be ≥ 80% completion of the protocol at 6 month time point for all participants.	Ongoing throughout 12 months after ICU discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Independence Measure (FIM) Questionnaire	will assess functional capacity, and will be administered by research staff. Response will be sought directly from the patient. FIM is scored with motor (13-91) and cognitive (5-35). Lower scores indicate lower functional independence	Questionnaire will be conducted on up to 2 (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
Frailty Index	The frailty index identifies 42 deficits, each coded as 0 (absent), 1 (present), or 0.5 (where intermediate values were possible). It was calculated as the cumulative proportion of deficits present (minimum score 0; maximum score 1.0), and then graded as mild (0 and 0.2), moderate (0.2 and 0.4) or severe frailty (>0.4). See references for studies where Index is derived.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
Medical Research Council (MRC) sum score	Medical Research Council (MRC) sum score tests power in muscle groups for upper and lower extremities and score is tallied as the sum of all tested muscles. Value ranges from complete paralysis (0/60) to full strength (60/60). Score less than 48/60 denotes clinically significant weakness.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
Anaerobic threshold	Work rate at anaerobic threshold (AT), represented at percentage of VO2 peak will be quantified with CPET. This corresponds to the time where oxygen (O2) utilization and carbon dioxide (CO2) production curves begin to diverge.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
Forced Vital Capacity (FVC)	Standard spirometry techniques are used to quantify the maximum volume of expired breath (Litres), and represented as a %predicted compared to reference values. All tests are performed in accordance with standard ATS guidelines.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.
Forced Expiratory Volume at 1-second (FEV1)	Standard spirometry techniques are used to quantify the volume of expired breath (Litres) in 1 second, and represented as a %predicted compared to reference values. All tests are performed in accordance with standard ATS guidelines.	Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months.

Collaborators and Investigators

• Sponsor: University of Manitoba
• Investigators: Principal Investigator: Asher Mendelson, MD PhD, University of Manitoba

Publications and helpful links

General Publications

• Heyland DK, Garland A, Bagshaw SM, Cook D, Rockwood K, Stelfox HT, Dodek P, Fowler RA, Turgeon AF, Burns K, Muscedere J, Kutsogiannis J, Albert M, Mehta S, Jiang X, Day AG. Recovery after critical illness in patients aged 80 years or older: a multi-center prospective observational cohort study. Intensive Care Med. 2015 Nov;41(11):1911-20. doi: 10.1007/s00134-015-4028-2. Epub 2015 Aug 26.
• Mendelson AA, Erickson D, Villar R. The role of the microcirculation and integrative cardiovascular physiology in the pathogenesis of ICU-acquired weakness. Front Physiol. 2023 May 10;14:1170429. doi: 10.3389/fphys.2023.1170429. eCollection 2023.
• Muscedere J, Bagshaw SM, Boyd G, Sibley S, Norman P, Day A, Hunt M, Rolfson D. The frailty, outcomes, recovery and care steps of critically ill patients (FORECAST) study: pilot study results. Intensive Care Med Exp. 2022 Jun 10;10(1):23. doi: 10.1186/s40635-022-00446-7.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: December 8, 2023
• First Submitted That Met QC Criteria: January 3, 2024
• First Posted (Actual): January 8, 2024

Study Record Updates

• Last Update Posted (Actual): June 15, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; near-infrared spectroscopy; Microcirculation; skeletal muscle; cardiopulmonary exercise test; Oxygen Delivery; cardiovascular physiology; ICU Survivors
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathological Conditions, Signs and Symptoms; Behavior; Critical Illness; Sepsis; Shock; Motor Activity
• Other Study ID Numbers: HS25592

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No