Locomotor Muscle Oxygenation and Activation During Acute Interval Compared to Constant-load Bed-cycling Exercise

Critical Illness Clinical Trial

Official title:

Locomotor Muscle Oxygenation and Activation During Acute Interval Compared to Constant-load Bed-cycling Exercise: A Pilot Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05279547
• Other study ID #: S65934
• Status: Recruiting
• Phase: N/A
• Start date: February 1, 2023
• Est. completion date: December 2026

Study information

• Verified date: June 2024
• Source: KU Leuven
• Contact: Daniel Langer, Prof. Dr.
• Phone: 003216376497
• Email: daniel.langer[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Up to 60% of patients admitted to the Intensive Care Unit (ICU) with a prolonged stay in the ICU develop complications such as intensive care unit acquired weakness (ICUAW) characterized by limb and respiratory muscle weakness. ICUAW is associated with worse prognosis, longer ICU stay and increased morbidity and mortality.

Physical therapy (PT) interventions in the intensive care unit (ICU), can improve patients' outcomes.

However, improvements in muscle function achieved with standard physical activity interventions aiming at early mobilization are highly variable due to lack of consistency in definition of the interventions, lack of consideration for the complexity of exercise dose and/or insufficient stimulation of muscles during interventions. It has been suggested that modifying early mobilization and exercise protocols towards shorter intervals consisting of higher intensity exercises might result in more optimal stimulation of muscles.

In the present study the researchers therefore aim to simultaneously assess (by non-invasive technologies) locomotor muscle oxygenation and activation along with the measurements of the load imposed on respiration and circulation during two different training modalities i.e., moderate intensity continuous bed-cycling (endurance training) vs high-intensity alternated by lower intensity periods of bed-cycling (interval training).

Description:

Critical illness is related to high morbidity and mortality rates, and health-care costs. Up to 60% of patients admitted to the Intensive Care Unit (ICU) with a prolonged stay in the ICU develop complications such as intensive care unit acquired weakness (ICUAW) characterized by limb and respiratory muscle weakness. These abnormalities develop already within the first days to weeks after intensive care unit (ICU) admission and are related to immobility, sepsis, inflammatory response syndrome (SIRS), prolonged mechanical ventilation, multiple organ failure, and the use of corticosteroids. ICUAW is associated with worse prognosis, longer ICU stay and increased morbidity and mortality. Survivors of critical illness frequently report long-term physical impairments persisting up to 5 years after discharge.

Physical therapy (PT) interventions in the intensive care unit (ICU), can improve patients' outcomes. A systematic review of randomized controlled trials (RCTs) of strategies to improve physical functioning of ICU survivors identified the importance of PT interventions in the ICU. Early rehabilitation during ICU admission has the potential to result in important clinical benefits for patients. These findings highlight the importance of aiming to apply mobilization strategies early during ICU stay to maintain and improve physical functioning as good as possible.

With a projected increase in the number of critically ill patients, requiring rehabilitation in the ICU effective and efficient rehabilitation interventions are warranted. However, improvements in muscle function achieved with standard physical activity interventions aiming at early mobilization are highly variable. Therefore, there is a need for implementing more evidence-based PT interventions, as part of routine clinical practice. Variable results of current interventions may be due to lack of consistency in definition of the interventions, lack of consideration for the complexity of exercise dose and/or insufficient stimulation of muscles during interventions. It has been suggested that modifying early mobilization and exercise protocols towards shorter intervals consisting of higher intensity exercises might result in more optimal stimulation of muscles.

A recent study evaluating a cohort of 181 consecutive patients receiving 541 in-bed cycling sessions as part of routine PT interventions in ICU showed that constant-load bed-cycling appears to be both feasible and safe. In addition, recent evidence in patients with chronic lung disease shows that acute alteration of intense and less intense periods of exercise induced partial restoration of local muscle oxygen stores during the less intense periods of exercise facilitating the muscles to achieve higher exercise intensities during the intense periods, compared to constant-load submaximal exercise. Hence, in patients with chronic lung diseases, alternating intense with less intense loads during interval exercise may be physiologically more effective than constant submaximal workloads maintained during endurance type training for achieving a higher stimulation of locomotor muscles. This has not been investigated so far in intensive care unit patients.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 2026
• Est. primary completion date: December 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Full cooperatively adult patients indicated by the Adequacy Score of standardized 5 questions (SQ5) = 5/5

• Patients mechanically ventilated for longer than 48 hours during the same ICU admission

• Patients are expected to remain in the ICU for more than an additional 48 hours starting from study enrollment

• Patients able to perform active cycling for > 10 consecutive minutes

Exclusion Criteria:

• Pre-existing functional limitations

• Low limb injuries or conditions that would preclude in-bed cycling such as a body habitus unable to fit the bike

• Extreme obesity (body mass index >35 kg/m2)

• Neurologically unstable

• Acute surgery

• Palliative goals of care

• Temperature > 40 °C

• An anticipated fatal outcome

• Evidence of coronary ischaemia, for example, chest pain or electrocardiogram changes

• Resting heart rate <40 or >120 beats per minute

• Mean arterial pressure <60 or >120 mmHg

• Peripheral capillary oxygen saturation < 90%

• Wounds, trauma or surgery of leg precluding cycle ergometry

• Wounds, trauma or surgery of pelvis precluding cycle ergometry

• Wounds, trauma or surgery of lumbar spine precluding cycle ergometry

• Coagulation disorder (international normalised ratio > 1.8, or platelets < 50,000 mcL)

• Intracranial pressure >20 mm Hg

• Femoral access other than femoral central line

• Acute deep vein thrombosis

• Pulmonary embolism

• >20 mcg/min of noradrenaline

• inotropic or vasopressor support comparable to a dose of noradrenaline >20mcg/min

• Fraction of inspired oxygen > 55%

• Arterial partial pressure of oxygen (PaO2) <65 torr (<8.66 kPa)

• Positive end-expiratory pressure > 10 cmH2O

• Respiratory rate > 30 breaths per minutes with adequate ventilatory support

• Minute ventilation >150 mL/kg body weight

Related Conditions & MeSH terms

• Critical Illness
• Intensive Care Unit Acquired Weakness

Intervention

Other:
• Constant-load bed-cycling exercise
Patients will actively cycle for a minimum duration of 10 minutes and a maximum duration of 20 minutes without breaks.
• Interval bed-cycling exercise
Patients will cycle for the same duration as during constant-load exercise. Interval bed-cycling session will consist of 30 seconds of high intensity exercise alternated by 30 seconds of passive cycling designed so that volume of training will be equal.

Locations

Country	Name	City	State
Belgium	University Hospital Leuven	Leuven

Sponsors (2)

Lead Sponsor	Collaborator
KU Leuven	Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

References & Publications (7)

Anekwe DE, Biswas S, Bussieres A, Spahija J. Early rehabilitation reduces the likelihood of developing intensive care unit-acquired weakness: a systematic review and meta-analysis. Physiotherapy. 2020 Jun;107:1-10. doi: 10.1016/j.physio.2019.12.004. Epub 2019 Dec 19. — View Citation

Clarissa C, Salisbury L, Rodgers S, Kean S. Early mobilisation in mechanically ventilated patients: a systematic integrative review of definitions and activities. J Intensive Care. 2019 Jan 17;7:3. doi: 10.1186/s40560-018-0355-z. eCollection 2019. — View Citation

Grunow JJ, Goll M, Carbon NM, Liebl ME, Weber-Carstens S, Wollersheim T. Differential contractile response of critically ill patients to neuromuscular electrical stimulation. Crit Care. 2019 Sep 10;23(1):308. doi: 10.1186/s13054-019-2540-4. — View Citation

Hoffman M, Clerckx B, Janssen K, Segers J, Demeyere I, Frickx B, Merckx E, Hermans G, Van der Meulen I, Van Lancker T, Ceulemans N, Van Hollebeke M, Langer D, Gosselink R. Early mobilization in clinical practice: the reliability and feasibility of the 'Start To Move' Protocol. Physiother Theory Pract. 2022 Jul;38(7):908-918. doi: 10.1080/09593985.2020.1805833. Epub 2020 Aug 31. — View Citation

Nickels MR, Aitken LM, Barnett AG, Walsham J, McPhail SM. Acceptability, safety, and feasibility of in-bed cycling with critically ill patients. Aust Crit Care. 2020 May;33(3):236-243. doi: 10.1016/j.aucc.2020.02.007. Epub 2020 Apr 18. — View Citation

Reid JC, Clarke F, Cook DJ, Molloy A, Rudkowski JC, Stratford P, Kho ME. Feasibility, Reliability, Responsiveness, and Validity of the Patient-Reported Functional Scale for the Intensive Care Unit: A Pilot Study. J Intensive Care Med. 2020 Dec;35(12):1396-1404. doi: 10.1177/0885066618824534. Epub 2019 Jan 22. — View Citation

Supinski GS, Valentine EN, Netzel PF, Schroder EA, Wang L, Callahan LA. Does Standard Physical Therapy Increase Quadriceps Strength in Chronically Ventilated Patients? A Pilot Study. Crit Care Med. 2020 Nov;48(11):1595-1603. doi: 10.1097/CCM.0000000000004544. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences between bed-cycling protocols in fractional oxygen saturation (StiO2,%) for each measured region of the m. quadriceps femoris	Assessed by near-infrared spectroscopy	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Primary	Differences between bed-cycling protocols in activation (sEMG amplitude) for each measured region of the muscle quadriceps femoris	Assessed by surface electromyography	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Primary	Adverse event rate during constant-load bed-cycling	Constant-load bed-cycling protocol will be considered as a safe intervention in case the adverse event rate will be less than 2.6%; adverse events: catheter/tube removal, increase in vasoactive medications >5mcg/min, increase in systolic blood pressure > 200 mmHg for > 2min, decrease in mean arterial pressure < 60 mmHg for > 2 min, decrease in heart rate < 50 bpm for > 2 min, increase in heart rate > 140 beats per minute for > 2 min, increase in respiratory rate and sustained > 5 min after session, decrease in peripheral capillary oxygen saturation < 88% for > 1 min requiring an increase in fraction of inspired oxygen > 0.1 sustained > 5 min)	1 session of maximal 20 minutes of constant-load bed-cycling per patient
Primary	Adverse event rate during interval bed-cycling	Interval bed-cycling protocol will be considered as a safe intervention in case the adverse event rate will be less than 2.6%; adverse events: catheter/tube removal, increase in vasoactive medications >5mcg/min, increase in systolic blood pressure > 200 mmHg for > 2min, decrease in mean arterial pressure < 60 mmHg for > 2 min, decrease in heart rate < 50 bpm for > 2 min, increase in heart rate > 140 beats per minute for > 2 min, increase in respiratory rate and sustained > 5 min after session, decrease in peripheral capillary oxygen saturation < 88% for > 1 min requiring an increase in fraction of inspired oxygen > 0.1 sustained > 5 min)	1 session of maximal 20 minutes of interval bed-cycling per patient
Primary	Percentage of completed constant-load bed-cycling sessions	The constant-load bed-cycling is deemed to be feasible if at least 80% of planned constant-load sessions were able to be commenced and 80% of commenced sessions can be completed	1 session of maximal 20 minutes of constant-load bed-cycling per patient
Primary	Percentage of completed interval bed-cycling sessions	The interval bed-cycling is deemed to be feasible if at least 80% of planned interval sessions were able to be commenced and 80% of commenced sessions can be completed	1 session of maximal 20 minutes of interval bed-cycling per patient
Secondary	Differences in Relative dispersion (RD) of fractional oxygen saturation (StiO2,%) among the different regions of quadriceps femoris as indicator of heterogeneity of fractional oxygen extraction among different regions of quadriceps femoris muscle.	Differences between exercise protocols in Relative dispersion (RD) of fractional oxygen saturation (StiO2,%) among the different regions of quadriceps femoris (i.e., vastus lateralis, vastus medialis, rectus femoris upper part and rectus femoris lower part) as indicator of heterogeneity of fractional oxygen extraction among different regions of quadriceps femoris muscle.	1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
Secondary	Differences between exercise protocols in oxygenated hemoglobin/myoglobin (OxyHb/Mb), deoxygenated hemoglobin/myoglobin (DeoxyHb/Mb) and total hemoglobin/myoglobin concentration (TotHb/Mb) for each measured region of quadriceps femoris	Differences between exercise protocols in oxygenated hemoglobin/myoglobin (OxyHb/Mb), deoxygenated hemoglobin/myoglobin (DeoxyHb/Mb) and total hemoglobin/myoglobin concentration (TotHb/Mb) for each measured region of quadriceps femoris (i.e., vastus lateralis, vastus medialis, rectus femoris upper part and rectus femoris lower part)	1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
Secondary	Differences in Median frequency of sEMG of different regions of quadriceps femoris	Differences in Median frequency of sEMG of different regions of quadriceps femoris (i.e., vastus lateralis, vastus medialis, rectus femoris upper part and rectus femoris lower part) between exercise protocols	1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
Secondary	Differences in relative dispersion (RD) of sEMG values among the different regions of quadriceps femoris as indicator of heterogeneity of activation among different regions of quadriceps femoris muscle.	Differences between exercise protocols in relative dispersion (RD) of sEMG values among the different regions of quadriceps femoris as indicator of heterogeneity of activation among different regions of quadriceps femoris muscle.	1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
Secondary	Differences between bed-cycling protocols in heart rate	Assessed by monitoring vital signs	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Secondary	Differences between bed-cycling protocols in mean arterial blood pressure	Assessed by monitoring vital signs	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Secondary	Differences between bed-cycling protocols in respiratory frequency	Assessed by monitoring vital signs	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Secondary	Differences between bed-cycling protocols in minute ventilation	In case of mechanically ventilated patients	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Secondary	Differences between bed-cycling protocols in tidal volume	In case of mechanically ventilated patients	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Secondary	Differences between bed-cycling protocols in peripheral capillary oxygen saturation	Assessed by monitoring vital signs	constant-load and interval bed-cycling protocols administered in 2 different days within 1 week