Project 4A: Inspiratory Muscle Training and Diaphragm Strength

University of Florida

Status and phase: Terminated; Phase 2; Phase 1

Conditions: Sepsis

Treatments: Other: Blood and Urine samples; Procedure: Volitional Measurement of Maximal Inspiratory Pressure (MIP); Drug: Midazolam; Procedure: Bilateral phrenic nerve stimulation and measurement of transdiaphragmatic pressure; Procedure: Diaphragm thickness measurement; Device: SHAM Inspiratory Muscle Strength Training (IMST); Device: Inspiratory Muscle Strength Training (IMST)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02367170

IRB201400889-N

GM111152 (Other Grant/Funding Number)

Details and patient eligibility

About

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).

Full 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.

Enrollment: 1 patient

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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1 participants in 2 patient groups

IMST Intervention group

Experimental group

Description:

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%.

Treatment:

Device: Inspiratory Muscle Strength Training (IMST)

Drug: Midazolam

Other: Blood and Urine samples

Procedure: Diaphragm thickness measurement

Procedure: Volitional Measurement of Maximal Inspiratory Pressure (MIP)

Procedure: Bilateral phrenic nerve stimulation and measurement of transdiaphragmatic pressure

SHAM group

Sham Comparator group

Description:

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.

Treatment:

Device: SHAM Inspiratory Muscle Strength Training (IMST)

Drug: Midazolam

Other: Blood and Urine samples

Procedure: Diaphragm thickness measurement

Procedure: Volitional Measurement of Maximal Inspiratory Pressure (MIP)

Procedure: Bilateral phrenic nerve stimulation and measurement of transdiaphragmatic pressure