Critical Illness
Conditions
Keywords
protein, exercise, muscle
Brief summary
This is a 2-arm, parallel-group, randomized controlled trial that investigates the effect of combined high protein and early resistance exercise versus usual care on muscle mass, quality and strength, clinical outcomes, functional outcomes and quality of life in mechanically ventilated critically ill patients
Detailed description
With the advancement of critical care, about 80% of ICU patients are surviving critical illness. However, ICU survivors often experience significant post-ICU morbidities including muscle weakness and impairments in physical functioning that can persist for years. We hypothesized that early intervention with two of the most basic features of critical care: nutrition (feeding high protein) together with mobility (early resistance exercise) may help to attenuate muscle loss, thereby reducing the severity of ICU-acquired weakness and its associated physical impairments. A 2-arm, parallel-group, randomized controlled trial is proposed to investigate the effect of the combined interventions. The intervention will be conducted for up to 28 days in the ICU. Outcome measurements will be conducted by a blinded assessor at baseline (within 24 hours of randomization), Day 10 post-randomization, before hospital discharge and at 6-month post-randomization. Ultrasound and bioelectrical impedance analysis will be conducted to measure muscle mass and quality. Manual muscle testing, handgrip and knee extension strength will also be measured. Physical function will be assessed by a series of test including the six minutes walk test. Telephone interview will be conducted to administer quality of life questionnaires at 6 months. These combined simple and non-invasive interventions, if proven effective, may potentially revolutionize critical care.
Interventions
OTHERHigh protein and early exercise
High protein is defined as protein prescription of ≥2.2 gram/kg body weight and early exercise is defined as starting cycle ergometry intervention within 24 hours of randomization
OTHERUsual Care
Usual care group has protein prescription of ≤1.2 gram/kg body weight and exercise at the discretion of attending clinicians
Sponsors
University of Malaya
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 years old and above 2. Mechanically ventilated and expected to remain mechanically ventilated for an additional 48 hours from screening 3. High nutritional risk (at least one of the following): * BMI ≤ 25 or ≥ 35 * Moderate to severe malnutrition as defined by Subjective Global Assessment (SGA) * Frailty (Clinical Frailty Scale ≥ 5 from proxy) * SARC-F (note: 'sarc-f' is the full name, not an abbreviation) questionnaire ≥ 4 * From point of screening, projected duration of mechanical ventilation of \>4 days
Exclusion criteria
1. \>96 continuous hours of mechanical ventilation before screening 2. Expected death or withdrawal of life-sustaining treatments within 7 days from screening 3. Pregnant (Note: post-partum and lactating patients are not excluded from the trial) 4. The responsible clinician feels that the patient either needs low or high protein 5. Patient requires parenteral nutrition only and site does not have products to reach the high protein dose group. 6. Not ambulating independently prior to illness that lead to ICU admission (use of gait aid permitted) 7. Lower extremity injury or impairments that prevents them walking prior to hospital discharge (e.g. amputation, knee/hip injury) 8. Pre-existing cognitive impairment or language barrier that prohibits outcomes assessment 9. Pre-existing primary severe systemic neuromuscular disease resulting in severe weakness pre-ICU (e.g., Guillain Barre) 10. Intracranial or spinal process affecting motor function 11. Patients in hospital \>5 days prior to ICU admission 12. Not expected to stay ≥4 days after enrollment 13. Neuromuscular blocker infusion (eligible once infusion discontinued if other inclusion criteria met) 14. Lower extremity injury or impairments that prevents cycling (e.g. amputation, knee/hip injury) 15. Weight ≥150 kg 16. Physician declines enrolment for Exercise
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rectus femoris cross-sectional area (RFCSA) | Change in RFCSA between Day 1 and Day 10 of randomization | RFCSA measured by ultrasonography |
| Rectus femoris linear depth (RF LD) | Change in RF LD between Day 1 and Day 10 of randomization | RF LD measured by ultrasonography |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quadriceps muscle echogenicity | Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital | Quadriceps muscle echogenicity measured by ultrasonography |
| Quadriceps muscle pennation angle | Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital | Quadriceps muscle pennation angle measured by ultrasonography |
| Quadriceps muscle fascicle length | Day 1 and Day 10 of randomization, and within 72 hours before discharge from the hospital | Quadriceps muscle fascicle length measured by ultrasonography |
| Functional Status Score for the Intensive Care Unit (FSS-ICU) | Day 1 of randomization (surrogate interview), within 72 hours before discharge from the ICU and hospital (by trained physiotherapist) | An assessment that consist of rolling, transfer from supine to sit, sitting at the edge of bed, transfer from sit to stand and walking |
| Short Physical Performance Batteries (SPPB) | Within 72 hours before discharge from the ICU and hospital | An assessment that consist of balance test, gait speed test and chair stand test |
| Handgrip strength | Within 72 hours before discharge from the ICU and hospital | Handgrip strength of both hands by using handgrip dynamometer |
| 6 minutes walk test | Within 72 hours before discharge from the hospital | To evaluate how far the subject can walk in 6 minutes time |
| Manual muscle testing | Within 72 hours before discharge from the hospital | Bilateral muscle strength for shoulder abduction, elbow flexion, wrist extension, hip flexion, knee extension and ankle dorsiflexion |
| Knee extension strength | Within 72 hours before discharge from the hospital | Knee extension strength measured by Handheld Dynamometer |
| Mortality | Percentage of Patient who died within this ICU or hospital admission, at day 60 and 6 months post-randomization | Percentage of patient who died |
| Time-to-discharge alive from the hospital | Time elapsed from randomization to hospital discharge (for a maximum of 6 months from randomization) | Time-to-discharge alive from the hospital |
| Length of mechanical ventilation | Total time from start to end of mechanical ventilation for a maximum of 6 months from randomization | Duration of mechanical ventilation |
| Health-related Quality of life by 36-item short form survey (SF-36) | 6 months after randomization | SF-36 is a questionnaire that will be administered by telephone interview |
| Health-related Quality of life by Euro Quality of Life 5 Dimension 5 level (EQ-5D-5L) | 6 months after randomization | EQ-5D-5L is a questionnaire that will be administered by telephone interview |
| Katz Activities of Daily Living (ADL) | Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview) | Katz ADL is a questionnaire that will be administered by either surrogate or telephone interview |
| Lawton Instrumental Activities of Daily Living (IADL) | Day 1 of randomization (surrogate interview) and 6 months after randomization (telephone interview) | Lawton IADL is a questionnaire that will be administered by either surrogate or telephone interview |
Countries
Malaysia
Contacts
PRINCIPAL_INVESTIGATORZheng Yii Lee
University of Malaya
Outcome results
None listed