Clinical trial NCT02367170
Conditions: Sepsis
Keywords: respiratory dysfunction chronic critical illness diaphragm weakness sepsis ventilator dependance
Sponsor: University of Florida
Start date: 2015-03-01; Completion date: 2015-07-01
Enrollment: 1 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Investigators will assess the effect of exercise on markers of inflammation and protein catabolism. This research study will further our understanding of how treating Chronic Critical illness (CCI) - related respiratory muscle weakness with strength training can not only improve muscle function, but also potentially blunt the inflammation and catabolism of Peristent Inflammation/Immunosuppression and Catabolism (PICS).

Detailed description:
In this research study, investigators will assign study participants to two groups: high intensity inspiratory muscle training and low intensity inspiratory muscle training group. This research study will last up to 28 days in 24 mechanically ventilated patients with CCI. The goal is to determine if the research participants can respond to a training program by improving weaning outcomes from the ventilator. This will be determined by measurement of breathing muscle strength with magnetic stimulation, measurement of diaphragm thickness with ultrasound, inspiratory muscle training, and blood and urine samples.

Arms: arm 1: IMST will be conducted 5 days per week by study staff using a threshold inspiratory muscle training device (Respironics model 735). Prior to training, the tracheal cuff pressure is assessed to ensure no air leakage and appropriate inflation. The IMST training takes approximately 15 minutes to complete. To perform IMST, FiO2 is increased for 2 minutes prior to each training bout to maintain oxygen saturation more than 92%. arm 2: SHAM training will also be conducted five days per week with an identical training device that has been modified by removing the valve leaflet, which essentially removes all inspiratory loading by the device. The modified SHAM device makes a whistling sound during inspiration, which enhances the sham effect. For SHAM treatment, supplemental oxygen FiO2 will be increased for two minute prior to each bout.
Interventions: intervention 1: Bilateral phrenic nerve stimulation and measurement of transdiaphragmatic pressure intervention 2: Midazolam intervention 3: Volitional Measurement of Maximal Inspiratory Pressure (MIP) intervention 4: Inspiratory Muscle Strength Training (IMST) intervention 5: SHAM Inspiratory Muscle Strength Training (IMST) intervention 6: Diaphragm thickness measurement intervention 7: Blood and Urine samples
Intervention descriptions: intervention 1: Pressure changes are recorded. The phrenic nerves are stimulated with bilateral magnetic stimulators over the neck. Measurements will be performed on day 1, every 7 days after and on last day of participation. The FiO2 will be increased (at least 20%) for at least 2 min. prior to measurement to maintain oxygen saturation \>92%. Prior to activating the stimulator, the artificial airway will be occluded with a pneumatic valve to create a quasi-isometric diaphragm contraction. The airway will be occluded for 3 seconds or less for each stimulation. The procedure will be repeated up to a maximum of 5 times per testing day. intervention 2: In the event a subject shows signs of distress during the Bilateral phrenic nerve stimulation and measurement of transdiaphragmatic pressures, a dose of Midazolam is available. IV (in the vein) dose from 0.5 mg to 2 mg. intervention 3: MIP is tested on all subjects on day 1, every 7 days after and on the last day of participation. To measure MIP, a subject will be suctioned, disconnected from the ventilator, and instructed to take a few spontaneous breaths. A 1-way exhalation valve connected to a NICO respiratory monitor will be placed on the ET/tracheotomy tube. The subject will be instructed to inhale and exhale as forcefully as possible for 20 seconds, followed by at least 2 minutes of rest on full mechanical ventilation support. MIP trials will be repeated 3 times, and the greatest negative pressure recorded with a NICO respiratory monitor connected to a laptop computer, which will digitize airway pressure, flow and volume signals at 100Hz. This allows for analysis of the individual pressure waves, facilitating pre-post comparisons of MIP at specific time points during inspiration. intervention 4: Occurs 5 days/wk using threshold IMST device-Respironics model 735. Prior to training, cuff pressure is assessed, FiO2 increased for 2 min. to keep O2 sats ≥92%. The ventilator circuit is disconnected, IMST device is attached to endotracheal or tracheotomy tube and subject is instructed to exhale then forcefully inhale for 10 breaths. The initial setting of device is set to -5cmH2O, subject must generate a negative inspiratory pressure more negative than -5cmH2O to open spring-loaded valve and receive inspiratory airflow. Pressure setting is made more negative/difficult to open by 2-5cm every few breaths until a setting is found where the patient has difficulty fully opening valve, resulting in valve flutter noise. Training pressure is then made more positive /easier by 2-4cm of H2O, so subject can fully open valve, and 4 sets of 6-10 breaths are completed. Training pressures advanced as rapidly as possible, provided the patient is able to open the valve without"valve flutter"noise. intervention 5: Training will also be conducted 5 days/wk with an identical IMST device that has been modified by removing the valve leaflet, which essentially removes all inspiratory loading by the device. The modified SHAM IMST device makes a whistling sound during inspiration, which enhances the sham effect. For SHAM treatment, supplemental oxygen FiO2 will be increased for two minute prior to each bout. The ventilator will be disconnected and a SHAM device will be attached to the endotracheal or tracheostomy tube. The subject will be instructed to take 6-10 breaths with a normal tidal volume through the SHAM device and will be reconnected to the ventilator for a 2-minute rest period. The process will be repeated 3 more times for a total of 4 sets of 6-10 breaths. intervention 6: Ultrasound will be used to obtain measurements of the thickness of the right hemidiaphragm. Ultrasonography of the diaphragm will be performed upon enrollment, every 2-4 days during hospitalization and as long as the patient is hospitalized or up to 28 days of participation. intervention 7: Peripheral blood and urine samples will be collected once upon study entry day (+/- 2 days), once every 2-4 days and once on final day of study participation (+/- 2days).

Protocol documents: