N-Acetyl-cysteine in Early Acute Respiratory Distress Syndrome

Objectives / Research Aims The overall objectives of this study are to demonstrate whether a
protocol for the early use of inhaled N-acetylcysteine improves mortality, ventilator days,
ICU days, hospital stay, as well as the need for other "rescue" modalities, such as use of
advanced ventilator modalities (such as airway pressure release ventilation [APRV]),
paralytics, and prone positioning. As this is a pilot study, we would address the feasibility
of recruiting and consenting patients as well as to ascertain the sample size that would be
needed to power the desired endpoints in a larger study.

Setting The project will be performed in the Medical Intensive Care Unit at Palmetto Health
Richland using subjects with severe acute respiratory distress syndrome that are identified
within 48 hours of their disease process.

Resources Available It is not uncommon for the patients admitted with or that develop acute
respiratory distress syndrome to receive breathing treatments of some variety, such as
bronchodilators. This study would take an existing practice and add a relatively inexpensive
medication, N-acetylcysteine.

It will be straightforward and require relatively little time to calculate the metrics for
the patients enrolled in this study as these data are typically collected for intensive care
unit patients already.

Our respiratory therapists are already very experienced and proficient at the administration
of inhaled N-acetylcysteine. Likewise, the academic intensive care team would be able to
readily classify the patients that are appropriate for this study as the partial pressure of
oxygen to fraction of inspired oxygen (P/F) ratio is typically documented for every
ventilated patient admitted to our unit.

Study Design Recruitment Methods The patients will be recruited based upon their P/F ratio
less than 150 and being mechanically ventilated with a positive end expiratory pressure of 5
or greater. These patients will be started on the protocol within 48 hours of developing
acute respiratory distress syndrome.

Inclusion and Exclusion Criteria Inclusion criteria includes adult patients admitted to the
medical intensive care unit or coronary care unit, being mechanically ventilated with a
positive end expiratory pressure greater than 5 cm H2O, with noncardiogenic pulmonary edema
on chest x-ray within 48 hours of being noted to have a P/F ratio < 150.

Exclusion criteria includes patients < 18 years of age, patients for whom no aggressive
measures are desired, patients who are already receiving "rescue methods" (prone positioning,
advanced ventilator modes, paralytics), trauma patients, vulnerable patient groups (pregnant,
prisoners), patients who have undergone a surgical operation during their time on the
ventilator, patients with end stage liver disease, patients on chronic ventilators, and
asthmatics.

Local Number of Subjects This study will seek to enroll 26 patients each in the treatment and
control arm.

Study-Wide Number of Subjects This is a single center study. Study Timelines Plans will be to
complete the study within 12 months from the time of start. Study Endpoints The patient is
liberated from the ventilator, discharged from the ICU, discharged from the hospital, or
dies.

Procedures Involved The only procedure involved would be the administration of
N-acetylcysteine via nebulization, which would be administered to the patient by respiratory
therapy in the dosage of 3 2 mL 20% solution acetylcysteine (or 6 4 mL of 10% solution) along
with inhaled albuterol via endotracheal tube every six hours for 72 hours total. The control
arm will have saline administered with the albuterol every six hours. Both arms will have
additional bronchodilators administered as indicated clinically (bronchospasm, COPD, peak
airway pressure elevation, etc.).

The patients would be monitored daily in the ICU setting with lab work, including arterial
blood gases, chemistry panels, complete blood counts. They would have all routine critical
care monitoring, such as hourly vital signs, urine output, ventilation parameters in
accordance with the nature of their critical illness.

Inclusion Criteria:

- Inclusion criteria includes adult patients admitted to the medical intensive care unit
or coronary care unit, being mechanically ventilated with a positive end expiratory
pressure greater than 5 cm H2O, with noncardiogenic pulmonary edema on chest x-ray
within 48 hours of being noted to have a P/F ratio < 150.

Exclusion Criteria:

- Exclusion criteria includes patients < 18 years of age, patients for whom no
aggressive measures are desired, patients who are already receiving "rescue methods"
(prone positioning, advanced ventilator modes, paralytics), trauma patients,
vulnerable patient groups (pregnant, prisoners), patients who have undergone a
surgical operation during their time on the ventilator, patients with end stage liver
disease, patients on chronic ventilators, and asthmatics.