Critical Illness, ICU Acquired Weakness, Microcirculation, Sepsis, Shock
Conditions
Keywords
ICU Survivors, Oxygen Delivery, Microcirculation, skeletal muscle, Exercise, near-infrared spectroscopy, cardiopulmonary exercise test, cardiovascular physiology
Brief summary
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.
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.
Interventions
None listed
Sponsors
University of Manitoba
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of enrollment | 6 months after ICU discharge | Rate of participant enrollment in the study will be recorded. Feasibility of enrollment will be one participant per month. |
| Protocol completion | Ongoing throughout 12 months after ICU discharge | 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. |
| VO2 peak oxygen uptake | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | Peak Oxygen uptake (VO2, mL/kg/min) will be measured during incremental exercise on a cycle ergometer during cardiopulmonary exercise testing (CPET). |
| oxygen on/off kinetics | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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. |
| NIRS deoxygenation during exercise (deoxy-hemoglobin) | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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. |
| NIRS deoxygenation during exercise (tissue saturation index) | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional Independence Measure (FIM) Questionnaire | Questionnaire will be conducted on up to 2 (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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 |
| Frailty Index | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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. |
| Medical Research Council (MRC) sum score | 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 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. |
| Anaerobic threshold | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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. |
| Forced Vital Capacity (FVC) | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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. |
| Forced Expiratory Volume at 1-second (FEV1) | Tests will be conducted on up to two (2) different occasions after ICU discharge: (i) 6 months, and (ii) 12 months. | 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. |
Countries
Canada
Contacts
CONTACTAsher Mendelson, MD PhD
PRINCIPAL_INVESTIGATORAsher Mendelson, MD PhD
University of Manitoba
Outcome results
None listed