Project 4A: Inspiratory Muscle Training and Diaphragm Strength

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).

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.

Eligibility Criteria:
Inclusion Criteria:

* presence in the surgical or trauma ICU
* age of ≥18 years
* received mechanical ventilation (MV) for 3 days and expected to survive ICU stay
* ability to obtain informed consent from patient or proxy

Exclusion Criteria:

* Inability to speak and understand English
* Uncontrollable source of sepsis with imminent death (e.g., irreversible disease state, unresectable dead bowel)
* Receiving "comfort care only" or have advanced care directives limiting resuscitative efforts
* Known HIV infection with CD4 count \< 200 cells/mm
* Organ transplant recipients on immunosuppressive agent(s),
* Known pregnancy
* Unable to follow simple, one-step commands, such as "breathe in as hard as you can!"
* Prior arrangements to be transferred to other facilities before 28 days of treatment
* Contraindications to being disconnected from MV for sham or inspiratory muscle strength training treatment
* Unstable or "difficult airway" at 3 days of ICU care defined by ICU protocol, predicted to last for more than 72 hours
* Ongoing use of vasopressor or vasodilatatory agents for unstable blood pressure. (beyond minimal intermittent amount or "renal perfusion dose,"
* Severe cardiac dysrhythmias
* Esophageal varices or recent esophageal or gastric surgery,
* Upper-airway issues that would be aggravated by inserting esophageal pressure transducers
* Unstable neck/cervical anatomy that might be adversely impacted by bilateral magnetic stimulation of phrenic nerves at the neck
* Acute coronary syndrome
* Pulmonary contraindications (pneumon/hemothorax not drained, flail chest)
* Cardiac pacemakers and/or implanted defibrillator or other implanted electronic devices interfering with magnetic stimulation
* Implanted metal in the chest, neck or head, making magnetic stimulation contraindicated (dental fillings are permitted)
* Postoperative severe surgical problems interfering with the respiratory training (serious postoperative bleeding, wound dehiscence, etc.) - when and if these problems resolve and the patient meets other entry criteria, they will be eligible to be recruited for participation
* Active neuromuscular diseases that would prevent or interfere with responding to strength training (e.g. amyotrophic lateral sclerosis, multiple sclerosis, myasthenia gravis, polymyositis, muscular dystrophy or other dystrophies and myopathies)
* Any other factor that in the investigators' opinions would prevent response to training or create an unsafe condition for the patient.