Clinical trial NCT05279547: Locomotor Muscle Oxygenation and Activation During Acute Interval Compared to Constant-load Bed-cycling Exercise
Official title: Locomotor Muscle Oxygenation and Activation During Acute Interval Compared to Constant-load Bed-cycling Exercise: A Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Intensive Care Unit Acquired Weakness
Critical Illness
Keywords: ICU acquired muscle weakness
Quadriceps muscle
Near-infrared spectroscopy
Oxygenation
EMG
Early-mobilization
Bed-cycling
Interval exercise
Continuous exercise
Lead sponsor: KU Leuven
Sponsor class: OTHER
Collaborators: name: Universitaire Ziekenhuizen KU Leuven
First posted: 2022-03-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: two arms randomized cross-over trial
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Differences between bed-cycling protocols in fractional oxygen saturation (StiO2,%) for each measured region of the m. quadriceps femoris
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
measure: Differences between bed-cycling protocols in activation (sEMG amplitude) for each measured region of the muscle quadriceps femoris
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
measure: Adverse event rate during constant-load bed-cycling
timeFrame: 1 session of maximal 20 minutes of constant-load bed-cycling per patient
measure: Adverse event rate during interval bed-cycling
timeFrame: 1 session of maximal 20 minutes of interval bed-cycling per patient
measure: Percentage of completed constant-load bed-cycling sessions
timeFrame: 1 session of maximal 20 minutes of constant-load bed-cycling per patient
measure: Percentage of completed interval bed-cycling sessions
timeFrame: 1 session of maximal 20 minutes of interval bed-cycling per patient
Secondary outcomes:
measure: 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.
timeFrame: 1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
measure: 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
timeFrame: 1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
measure: Differences in Median frequency of sEMG of different regions of quadriceps femoris
timeFrame: 1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
measure: 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.
timeFrame: 1 session constant-load bed-cycling + 1 interval bed-cycling session administered in 2 different days within 1 week.
measure: Differences between bed-cycling protocols in heart rate
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
measure: Differences between bed-cycling protocols in mean arterial blood pressure
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
measure: Differences between bed-cycling protocols in respiratory frequency
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
measure: Differences between bed-cycling protocols in minute ventilation
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
measure: Differences between bed-cycling protocols in tidal volume
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
measure: Differences between bed-cycling protocols in peripheral capillary oxygen saturation
timeFrame: constant-load and interval bed-cycling protocols administered in 2 different days within 1 week
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospital Leuven
Study officials:
affiliation: KU Leuven
name: Daniel Langer, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
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.
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.
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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.
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.