Using Ultrasound to Study Respiratory Muscle Function in Critically Ill Patients

This is a prospective observational study designed to assess serial changes in quantitative
respiratory parameters in patients on different modes of MV e.g. synchronized intermittent
mandatory ventilation, controlled mechanical ventilation and pressure support ventilation.
This strategy will compare serial changes in diaphragm muscle parameters in ventilator
strategies that provide different level of spontaneous respiratory effort and targets for MV.
The study will be carried out at Wake Forest Baptist Medical Center. The protocol has been
approved by the Institutional Review Board. All adult (>18 years) patients admitted to an ICU
will be screened. Written informed consent will be obtained from each patient or their
surrogate.

Daily ultrasound studies will be done on the diaphragm muscle. The first study will be
conducted within 48 hours of ICU admission. Serial exams will be repeated daily until the
patients are extubated or transferred out of the ICU. A maximum of 7 ultrasound studies will
be performed since the focus is to demonstrate the utility of early serial changes in
measurable parameters on ultrasound. Images will be acquired on both sides during quiet
breathing with the patient's arms relaxed by the side in a neutral position while lying with
the head of bed at 30 degrees. Most ICU patients are in this position. Diaphragm muscle image
at end expiration on each side will be acquired in B mode with a 6-13 MHz transducer in the
mid axillary line using the intercostal approach. Diaphragm excursion will be measured
bilaterally through anterior subcostal approach in the M mode through a 2-5 MHz transducer.
Images will be acquired in accordance with the guidelines set forth in the AANEM position
statement. Each ultrasound examination will be done at a time when it does not interfere with
concurrent ongoing nursing & medical care.

To determine the effect of the serial changes that occur in respiratory muscle thickness and
echodensity on MV, linear regression models will be applied. The distribution of the outcome
variables and the need for any transformation to approximate normality will be checked. The
outcome variables are serial changes between first and last visit diaphragm muscle thickness
and echodensity. The covariate of interest is the mode of MV. The confounding variables are
neurological disease, acute lung injury, cumulative fluid balance, age, BMI, history of
smoking, duration between the first and last ultrasound examination and the nutritional
status (albumin, cumulative calorie intake and type of tube feeds). Since serial changes are
the outcome variables, besides the potential confounders, baseline outcome measures will be
also adjusted in the regression models. Model selection approaches will be used to select the
confounding variables adjusted in the models. Furthermore, to consider the changes across
different ultrasound visits, first the individual trajectories of the outcome variables will
be displayed graphically. Then, the mixed effects model will be used to examine the
associations. This model can handle repeated measures over time by modeling the covariance
structure. The covariates will be the same as described previously for the linear regression
model. Logistic regression models will then be used to determine if the serial changes in
diaphragm muscle thickness and echodensity predict the total number of days on MV, success at
SBTs and successful extubation.

Diaphragm ultrasound is a promising new method for evaluating the diaphragm during MV. The
investigators feel that the study proposal is extremely relevant in its ability to explore a
novel approach to assess the risk of extubation failure, very early on, in the course of MV
based on change in muscle echotexture using a noninvasive bedside tool. The investigators
propose that changes in diaphragm configuration associated with MV correlate to clinical
outcomes as measured by days on MV and extubation failure. The early serial changes detected
by ultrasound suggest a potential benefit of proactive early therapies designed to preserve
respiratory muscle architecture to reduce days on MV and prevent extubation failure. The
investigators further hypothesize that different ventilator modes may affect these changes
differentially and these changes might be prevented by titrating ventilatory support to
maintain normal levels of respiratory effort. If spontaneously breathing patients and
patients on low level of ventilatory support show differential changes on diaphragm muscle
parameters compared to patients on controlled modes and higher ventilatory support, clinical
protocols might need to emphasize alternate strategies that focus on "muscle protective" or
"muscle restorative" ventilation. Ultrasound can also be used to develop clinical paradigms
that involve inspiratory muscle training in helping patients who have failed extubation in
getting liberated from MV.

The goals are to use the pilot data generated through this grant to power and design a
randomized controlled trial of a "muscle protective" or "muscle restorative" ventilation
strategy and assess its effectiveness in reducing days on MV and extubation failure compared
to current medical practice. This team approach will involve a novel collaboration of key
members with expertise in muscle ultrasound, mechanical ventilation, mechanisms of muscle
wasting related to acute lung injury and physiological effects of exercise on respiratory
muscle hence representing critical input into developing clinical strategies to assess and
reduce the burden of extubation failure. The investigators believe this approach is
innovative in aiming to use a non-invasive bedside clinical tool to develop "muscle
protective" and "muscle restorative" ventilator strategies with a focus on early respiratory
rehabilitation in critically ill patients on MV.

Inclusion Criteria

- Patients will be included if first ultrasound measurement can be performed within 48
hours of ICU admission and informed consent can be obtained from patient or designated
health care representative.

- Adult patients (≥ 18 years of age) in any intensive care unit.

- Patients who are expected to have the need for prolonged mechanical ventilation
(treating physician's assessments that patient will likely need mechanical ventilation
for >48 hours; 2 days) and have been on mechanical ventilation for <48 hours at the
time of enrollment.

Exclusion Criteria

- Patients in any ICU who is expected to be on mechanical ventilation for <48 hours
based on treating physicians judgment.

- Patients that were on MV for more than 48 hours prior to transfer to the ICU.

- Patients who are expected to be extubated, transferred out of the ICU or discharged
from the intensive care unit in the next 48 hours based on treating physicians
judgment.

- Patients who are transitioning to palliative care or expected to die in the next 48
hours based on treating physicians judgment.

- Any patient where access to chest to study intercostal muscle and diaphragm is limited
due to skin /subcutaneous lesions.

- Patients with a history of or current chest tubes, chest trauma or anterior rib
fractures.

- Patients with a history of prior MV >48 hours or prior history of tracheostomy.

- Patients with a history of chest or abdominal surgery.

- Patients that have a tracheotomy or require non-standard modes of ventilation
including airway pressure release ventilation or high frequency oscillatory
ventilation.

- Patients with physician orders for positioning of the patient is different from head
of the bed at 30 degree. E.g. patients with recent lumbar spinal surgery are laid flat
to reduce spinal fluid pressure in lumbar area.

- Patients with a known allergy to ultrasound gel

- Pregnant women