Rehabilitation-based Approaches to Prevent Mechanical Ventilation-induced Breathing Dysfunction

Brief periods of mechanical ventilation (MV) can degrade the function of the diaphragm, which can be a problem for older adults and people with multiple medical comorbidities. 20% of people who are placed on MV require a prolonged effort to wean back to independent breathing. The effects of MV on respiratory neural function are often unaddressed by typical clinical practices. Many aspects of clinical practice such as MV, anesthesia, opioid medication directly reduce respiratory neural drive and degrade diaphragm fiber contractile function, and these impairments can occur rapidly, persist after extubation, and increase the risk for postoperative pulmonary complications. These complications delay discharge, incur significant expenses, and place patients at risk for an incomplete recovery and significant morbidity. Thus, any rehabilitation strategies to preserve or improve phrenic/diaphragm motor function have the potential to expedite early post-operative mobilization and reduce the risk of complications.

Inspiratory muscle strength training (IST) is an effective rehabilitation method to strengthen the diaphragm muscle. Repetitive IST reinforces respiratory neuromuscular plasticity, induces diaphragm remodeling, and improves inspiratory strength. Bouts of high intensity inspiratory loading acutely increase respiratory neural drive and potentiates inspiratory motor recruitment. Additionally, in some clinical situations, IST exercise is not feasible, thus another option may be electrical stimulation of the diaphragm/phrenic motor area (C3-C6) to generate similar improvements in inspiratory drive to preserve breathing function.

The central hypothesis of this proposal is that rehabilitation to increase diaphragm excitability in advance of MV will offset post-MV inspiratory dysfunction. To test this hypothesis, a repeated-measures, blinded study of healthy adults without respiratory comorbidities will be recruited. Consenting participants will complete a familiarization session, followed by three separate, two-hour noninvasive MV sessions, one week apart. MV sessions will be preceded by: 1) a single, high-intensity IST session, and 2) transcutaneous spinal cord stimulation, and 3) sham electrical stimulation, in randomized order. Changes in respiratory drive, voluntary and evoked diaphragm strength, and dyspnea will be evaluated. The central hypothesis will be tested with the following aims:

Aim 1: Test the hypothesis that noninvasive, positive pressure ventilation acutely decreases respiratory drive and maximal diaphragm activation during a two-hour MV session and persists up to 24 hours later.

Aim 2: Test the hypothesis that even single rehabilitation sessions (IST, transcutaneous stimulation) in advance of MV will preserve evoked diaphragm recruitment and hasten early recovery from MV, when compared to sham stimulation.