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

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

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

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).

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.

ICU acquired muscle weakness, Quadriceps muscle, Near-infrared spectroscopy, Oxygenation, EMG, Early-mobilization, Bed-cycling, Interval exercise, Continuous exercise

During Day 1, patients will be familiarized with the constant-load and interval bed-cycling exercise against no resistance. Patients will be also randomized in the two arms of the study before the determination of the appropriate exercise intensities to be subsequently use during the constant-load and interval bed-cycling protocols on Day 2 and Day 3. Exercise intensities will be determined so that the volume of training during the two protocols will be equal. During Day 2, patients randomized to arm 1 will perform the constant-load bed-cycling protocol. During Day 3, patients who executed the constant-load bed-cycling protocol on Day 1 (arm 1) will perform the interval bed-cycling protocol.

During Day 1, patients will be familiarized with the constant-load and interval bed-cycling exercise against no resistance. Patients will be also randomized in the two arms of the study before the determination of the appropriate exercise intensities to be subsequently use during the constant-load and interval bed-cycling protocols on Day 2 and Day 3. Exercise intensities will be determined so that the volume of training during the two protocols will be equal. During Day 2, patients randomized to arm 2 will perform the interval bed-cycling protocol. On Day 3 they will perform the constant-load bed-cycling protocol.

Patients will actively cycle for a minimum duration of 10 minutes and a maximum duration of 20 minutes without breaks.

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.

Differences between bed-cycling protocols in fractional oxygen saturation (StiO2,%) for each measured region of the m. quadriceps femoris

Differences between bed-cycling protocols in activation (sEMG amplitude) for each measured region of the muscle quadriceps femoris

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)

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)

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

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

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.

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.

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.

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.

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

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