Evaluation of a Practice Change to Include The MetaNeb® System to Reduce Postoperative Pulmonary Complications
Phase: NA
Conditions: Atelectasis, Pulmonary Complications
Sponsor: Hill-Rom

Hill-Rom®
Evaluation of a practice change to include The 
MetaNeb® System to reduce postoperative 
pulmonary complications 
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Protocol #: 
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Evaluation of a practice change to include The MetaNeb® System to reduce postoperative 
pulmonary complications 
Protocol Number: 
CR-RR2015- 001 
Status:   
Rev. C 
Product: 
The MetaNeb® System
Sponsor:        
Hill-Rom Company, Inc. 
 
 
 
Study Manager: 
 
Manager, Clinical Research, 
Hill-Rom Company, Inc. 
 
 
 
 
 
 
Confidentiality Statement 
This protocol contains information that is proprietary to Hill-Rom, Company, Inc. This information is provided to you for the 
purpose of conducting a clinical study for Hill-Rom. You may disclose the contents of this protocol to your study personnel 
under your supervision and your Institutional Review Board(s) or Independent Ethics Committee(s) for the same purpose. You 
may not disclose the contents of this protocol to any other parties (unless such disclosure is required by government regulations 
or laws, in which case, Hill-Rom will be notified of the disclosure at least 5 business days prior to the disclosure) without prior 
written permission from Hill-Rom. Any supplemental information (e.g., protocol amendment) that may be added to this 
document is also proprietary to Hill-Rom and should be handled using the same disclosure procedure. 
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Investigator Agreement 
I agree to conduct this study in accordance with the design and specific provisions of this protocol.  Modifications to the study 
are acceptable only with a mutually agreed upon protocol amendment.   
I agree to await Institutional Review Board approval for the protocol before initiating the study, to obtain consent from subjects 
(unless waived) prior to their enrollment (if required) in the study, to collect and record data as required by this protocol and case 
report forms, to prepare adverse event and study reports as required by this protocol and to maintain study documentation for the 
period of time required. 
I acknowledge that I am responsible for overall study conduct. I agree to personally conduct or supervise the described study. 
I agree to ensure all associates, colleagues and employees assisting in the conduct of the study are informed about their 
obligations. Mechanisms are in place to ensure that site staff receive the appropriate information throughout the study. 
Investigator Signature: 
Date: 
Investigator Signature: 
Date: 
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Table of Contents 
Signature Page…………………………………………………………….... 
2 
Table of Contents…………………………………………………………... 
3 
List of Abbreviations……………………………………………………….. 
5 
Protocol Synopsis ..………………………………………………………… 
6 
1.0 
Introduction…………………………………………………………. 
10 
1.1 
Background and Significance ..................................................... 
10 
1.2 
Research Rationale and Supporting Evidence ............................ 
11 
1.3 
Rationale for the Proposed Study ............................................... 
12 
2.0 
Study Objectives…………………………………………………….. 
12 
3.0 
Study Design………………………………………………………... 
12 
3.1 
Overview of Study Design .......................................................... 
12 
3.2 
Study Population ......................................................................... 
15 
3.3 
Evaluation Criteria/Effectiveness ............................................... 
16 
3.4 
Study Observations Table ........................................................... 
19 
3.5 
Statistical Methods and Analysis ................................................ 
21 
4.0 
General Study Information………………………………………….. 
23 
4.1 
Technical Support ....................................................................... 
23 
4.2 
Record Retention ........................................................................ 
23 
5.0 
Study Procedures…………………………………………………. 
23 
5.1 
Informed Consent ....................................................................... 
23 
5.2 
Complaints and Adverse Events Reporting ................................ 
23 
5.3 
Deviations from the Study Protocol ........................................... 
24 
5.4 
Materials Provided by the Sponsor ............................................. 
24 
6.0 
Investigator and Sponsor Responsibilities………………………….. 
24 
6.1 
Investigator Responsibilities ....................................................... 
24 
6.2 
Sponsor Responsibilities ............................................................. 
26 
7.0 
Administrative Study Information…………………………………... 
27 
7.1 
Pre-Study Site Visit .................................................................... 
27 
7.2 
Institutional Review .................................................................... 
28 
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7.3 
Investigator Records and Reports ............................................... 
28 
7.4 
Interim Monitoring and Closeout ............................................... 
28 
8.0 
Changes Necessary after Study Initiation ............................................ 
28 
9.0 
Study Completion ................................................................................. 
28 
10.0 Confidentiality/Publication of the Study .............................................. 
28 
11.0 References .............................................................................................. 
29 
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List of Abbreviations 
AARC 
American Association for Respiratory Care 
ACT 
Airway Clearance Therapy 
ASA 
American Society of Anesthesiologists 
CF 
Cystic Fibrosis 
CHFO 
Continuous High Frequency Oscillation 
CPAP 
Continuous Positive Airway Pressure 
CPEP 
Continuous Positive Expiratory Pressure 
CPT 
Chest Physiotherapy 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIPAA 
Health Insurance Portability and Accountability Act 
ICU 
Intensive Care Unit 
IPPB 
Intermittent Positive Pressure Breathing 
IPV 
Intrapulmonary Percussive Ventilation 
IRB 
Institutional Review Board 
IV 
Intravenous 
LE 
Lung Expansion 
LOMV 
Length of Mechanical Ventilation 
LOS 
Length of Stay 
MV 
Mechanical Ventilation 
NIV 
Noninvasive Ventilation 
NSQIP 
National Surgical Quality Improvement Program 
OSA 
Obstructive Sleep Apnea 
PPC 
Postoperative Pulmonary Complication 
PRF 
Postoperative Respiratory Failure 
RCT 
Randomized Controlled Trial 
SOP 
Standard Operating Procedure 
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Protocol Synopsis 
Product Name: 
The MetaNeb® System 
Protocol Number: 
CR-RR2015-001 
Protocol Title: 
Evaluation of a practice change to include The MetaNeb® System to 
reduce postoperative pulmonary complications 
Objective(s):  
To determine if a therapy regimen including treatment with The 
MetaNeb® System has a positive impact on the rate of pulmonary 
complications that occur in high risk post-operative patients. 
Endpoints: 
Primary Endpoint: 
Significant Postoperative Pulmonary Complication (PPC): 
One or more of the following that occurs within seven (7) days of the 
post-surgical 
admission 
will 
be 
considered 
a 
Significant 
Postoperative Pulmonary Complication (PPC) 
• Patient Requires Prolonged Mechanical Ventilation (> 24 hours
from post-surgical admission).
• Patient requires prolonged respiratory support for > 24 hours from
post-surgical admission
• Diagnosis of Pneumonia Within Seven (7) Days
• Readmission to ICU for pulmonary complications within seven
(7) days of post-surgical hospital admission.
Secondary Endpoints: 
• Requirement for invasive mechanical ventilation for > 48 hours
• Requirement for respiratory support for > 48 hours
• ICU Length of Stay (LOS)
• Hospital Length of Stay (LOS)
• Time on Mechanical Ventilation
• Readmissions to ICU
• 30-day Readmissions to Hospital
Study Design: 
Non-randomized facility (or hospital) level pre-post intervention study 
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Methods: 
The study will be conducted in two stages. In Stage I of the study, a 
retrospective review of medical records for post-surgical patients, who 
received STANDARD THERAPY as defined by current hospital and 
respiratory care department policies and procedures will be performed. 
In Stage II, a CHANGE IN PRACTICE will be made and patients will 
receive standard care with the addition of therapy with The MetaNeb® 
System. Demographic, clinical & outcome data will be collected for 
eligible patients during the two stages of the study. Study staff will 
collect data from the medical records, following a protocol determined 
schedule. 
Treatment 
of Subjects: 
The treatment protocol used for Respiratory Care during the 
STANDARD THERAPY period of the Study is that which was 
prescribed by the patient’s health care team in the routine standard care 
of each patient. Respiratory Care therapies include those therapies that 
were ordered and/or were delivered for the care of patients as 
determined by standard hospital and/or Respiratory Care department 
policies and procedures. The STANDARD THERAPY period is one 
year prior to initiation of the study. Data will be collected 
retrospectively. 
The treatment protocol used for Respiratory Care (excluding airway 
clearance and lung expansion interventions) during the CHANGE IN 
PRACTICE period of the Study will include care and therapy 
prescribed by the patient’s health care team in the routine standard care 
of each patient. Other components of the patients respiratory care 
regimen will remain the same as during the standard therapy period, 
however the CHANGE IN PRACTICE will incorporate the 
use/treatment with The MetaNeb® System. Use of The MetaNeb® 
System will follow the labeling of the device. During Stage II, therapy 
with The MetaNeb® System will be delivered per treatment procedures. 
Other standard airway clearance and lung expansion therapies typically 
delivered by Respiratory Therapy will not be delivered during Stage II. 
Duration of 
Participation: 
The Study will take approximately fifteen months to complete, from 
the time of study initiation through completion of data analysis. 
The duration of study participation for prospectively enrolled subjects 
will be the duration of each patient’s hospital stay with follow-up thirty 
days after discharge from the hospital. 
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Number of 
Subjects: 
The sample size will be approximately 400 patients, 200 in the 
retrospective STANDARD THERAPY group and 200 in the prospective 
CHANGE IN PRACTICE group. 
Study Population: 
The study population consists of adult post-surgical patients who have 
undergone thoracic, aortic or upper abdominal surgery who are at high 
risk for PPCs. 
Inclusion/Exclusion 
 Criteria: 
Inclusion Criteria: 
Patients who meet all of the following criteria will be included in the 
study: 
•
Age ≥ 18 years
•
Post-thoracic, -upper abdominal or -aortic surgery
•
Open surgical procedure
•
Incision at or above the umbilicus
•
High risk defined by:
•
Documented ASA class >3
OR 
•
Documented ASA class 2 AND One or more of the
following:
•
Current smoker or smoking history within past 6
months
•
History of COPD
•
Documented obesity and/or BMI > 30 kg/m2
•
Age > 75
Exclusion Criteria: 
Patients who meet any of the following criteria will be excluded (or 
will be exited) from the study: 
•
Contraindication to Continuous High Frequency Oscillation
(CHFO) therapy (e.g. untreated tension pneumothorax)
•
Minimally invasive, or “. . . scopic” procedure.
•
Spinal surgery involving a posterior approach
•
Surgery for organ transplant
•
Chronic invasive positive pressure ventilation (PPV)
 
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Statistical Methods: Descriptive summary statistics will be provided for demographics, the 
primary and secondary endpoints. Continuous data will be summarized 
with N, mean, median, standard deviation, min, and max.  Categorical 
data will be summarized with the number and percent of patients in each 
category. Time to event data (ex. Time to readmission) will be 
summarized with methods appropriate for survival data including a 
Kaplan-Meier plot. 
Ninety-five percent (95%) confidence interval will be computed for the 
primary endpoint, the incidence of significant postoperative pulmonary 
complications. Incidence rates for various demographic subsets, 
surgery types, and different population subsets may be presented as 
outlined in the statistical analysis plan document, to be published prior 
to study completion. Stage I and Stage II incident rates will be 
compared for the purpose of identifying any statistical associations that 
can be attributed to use of The MetaNeb® System. 
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1.0 
Introduction 
1.1 Background and Significance 
Post-operative pulmonary complications (PPC) are associated with significant excess 
morbidity, mortality and healthcare expenditure. The incidence of “important” PPCs, across 
all surgeries, is approximately 2-5% in the general surgical population. There are factors, 
however, that place certain patients, and patients with certain procedures, at considerably 
higher risk for PPCs. One of the key factors in development of PPCs is the type of surgery. 
Following upper abdominal and thoracic surgery, pulmonary complications are the most 
common surgical complications. Other risk factors include advanced age, American Society 
of Anesthesiologists (ASA) physical status classification score > 2, functional dependency, 
congestive heart failure and chronic obstructive pulmonary disease. Of these, ASA score > 
2 and functional dependency have consistently been associated with a higher rate of 
significant PPCs such as post-operative respiratory failure (PRF). PRF requiring prolonged 
mechanical ventilation (MV) or re-intubation accounts for the majority of poor outcomes and 
high economic costs.[1-4] Other risk factors that have been associated with increased risk of 
PPCs include history of COPD, smoking history and BMI > 30 kg/m2. [1-5] 
Although PPCs are an incompletely understood multifactorial syndrome, atelectasis is 
recognized as a critical component.[6] Evidence has shown that atelectasis is a common 
precursor and concomitant feature of PPCs. Nearly all patients undergoing major surgery 
experience some degree of transitory, clinically unimportant atelectasis, most of these 
patients do not require aggressive therapy. There is, however, a more urgent need to treat 
atelectasis in subpopulations of high-risk individuals, in order to prevent more serious 
complications including progression to PRF.[7]   
A variety of strategies have been shown to reduce the risk for development of post-operative 
atelectasis to at least some degree. These include but are not limited to pain control, 
monitoring of respiratory-depressing medications, selective use 
of nasogastric 
decompression, secretion mobilization techniques and lung expansion (LE) therapies.[6-9] 
However, the generally poor quality of clinical trials to evaluate these methods provides only 
limited, inconclusive evidence of efficacy. Among published studies, LE using continuous 
positive airway pressure (CPAP) breathing, particularly when used in hypoxemic high-risk 
patients, is the only modality to date demonstrating comparatively strong evidence.[10,11] In a 
systematic review of qualifying randomized controlled trials (RCT), Lawrence et al sought 
to evaluate interventions intended to reduce the incidence of atelectasis, pneumonia and PRF 
following non-cardiothoracic surgery.[11]  Their meta-analysis pooling all eligible studies to 
determine “strength of evidence” found that only LE therapy merited a grade of “A”. These 
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LE therapy techniques included incentive spirometry (IS), deep breathing techniques, chest 
physiotherapy (CPT), intermittent positive pressure breathing (IPPB) and continuous 
positive pressure (CPAP). Although data did not permit identification of a “best” modality, 
they did allow the conclusion that all lung expansion therapies reduced PPC by > 50% 
compared with no treatment. Well-designed studies are needed to distinguish which LE 
approach has the greatest potential to optimize patient care, clinical outcomes and cost 
savings. 
1.2 Research Rationale and Supporting Evidence 
Among LE devices, Intrapulmonary percussive ventilation (IPV) devices have been in use 
for more than 25 years and are used widely in the acute care, post-surgical, and homecare 
setting. Such devices provide both LE and airway clearance therapy (ACT) for patients with 
obstructive and/or restrictive lung diseases and conditions. The safety and efficacy of IPV 
have been demonstrated in clinical and laboratory studies.[12-34]  
The MetaNeb® System is an LE expansion modality that incorporates all the physiological 
effects of IPV while providing additional therapeutic advantages intended primarily to more 
effectively treat or prevent pulmonary atelectasis. Equipment consists of a pneumatic 
compressor that delivers continuous high-frequency oscillation (CHFO) and positive 
expiratory pressure (CPEP) to 1) facilitate clearance of mucous from the lungs; 2) provide 
lung expansion therapy and; 3) enhance delivery of aerosol therapy. This “triple” mode 
device can provide aerosol therapy while alternating between CPEP for lung expansion and 
CHFO for airway clearance. Supplemental oxygen therapy may also be delivered when used 
with compressed oxygen. The MetaNeb® System has been cleared to market by the FDA 
based on substantial equivalence to IPV. Clinical studies of The MetaNeb® System, however, 
are limited. The only peer-reviewed publication to date is a case report concerning a patient 
who on her 17th hospital day, following an adverse medication reaction, developed severe 
atelectasis secondary to toxic epidermal necrolysis (Stevens - Johnson Syndrome). After 
initiation of therapy with The MetaNeb® System, atelectasis was completely resolved by 
hospital day 21. The patient was discharged on hospital day 25 without further pulmonary 
complications.[35] In addition to this publication, however, a number of abstracts and other 
reports have been presented or published. An abstract presented at the American Association 
for Respiratory Care (AARC) Congress in 2009, found that patients participating in a 
progressive pulmonary protocol in an oncologic intensive care unit and who received LE 
therapy with either IPV or The MetaNeb® System  had significantly better post- therapy chest 
x-ray results compared with patients treated with The Vest® System and EZ PAP.[35] An
earlier case study report presented at the AARC Congress in 2006 described an 80-year-old
post-thoracoscopic surgical patient in respiratory distress. The patient was treated with The
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MetaNeb® System, expectorated large amounts of tenacious secretions, and after only 2 
treatment sessions had improved breath sound. Chest radiographs showed improved aeration 
and there was a reduction in oxygen requirement.[37] In a long-term care treatment protocol 
with intubated or tracheostomised patients on MV, patients were treated with The MetaNeb® 
System for 10 minutes every 6 hours until decanulation or discharge. Quality improvement 
results showed improvement in the percentage of patients weaned from MV along with a 
decrease in the need for bronchoscopy.[38] Two more recent studies have been presented at 
conferences and await full-text publication. Patel et al. reported on a randomized parallel 
study comparing outcomes in 32 adult CF patients with severe pulmonary exacerbations and 
admitted for IV therapy. Patients were randomized to treatment with either The MetaNeb® 
System or The Vest® System for up to 14 days. In this setting, results were positive but 
comparable.[39] Morgan, et al. investigated the feasibility, safety and efficacy of CHFO 
administered via The MetaNeb® System to 59 invasively ventilated pediatric patients, 
between 2007-2012. A total of 528 treatments were evaluated.  Preliminary results support 
safety and feasibility and suggest that CHFO may be beneficial by improving lung 
compliance in patients with secretion-induced atelectasis.[40] 
1.3 Rationale for the Proposed Study 
Preliminary and anecdotal evidence suggests that use of The MetaNeb® System may be 
effective in postoperative patients prone to atelectasis and PPCs. The proposed study is 
intended to evaluate the effectiveness of this therapy in reducing the incidence of these 
complications in comparison to standard treatment.  
2.0 Study Objectives 
The primary objective of this study is to determine if a therapy regimen including treatment 
with The MetaNeb® System has a positive impact on the rate of pulmonary complications 
that occur in high risk post-operative patients.  
3.0 Study Design 
3.1 Overview of Study Design  
3.1.1 Design:  
This is a non-randomized facility level pre-post intervention study conducted in two 
stages for the primary purpose of evaluating the effect of The MetaNeb® System on 
postoperative pulmonary complications in high risk patients undergoing thoracic and 
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abdominal surgeries. The study will be conducted in two to four (2-4) tertiary 
academic medical facilities in the US that have not previously used The MetaNeb® 
System in post-thoracic, post-aortic, or post-upper abdominal surgery patients. After 
assessing outcomes during a baseline period, therapy with The MetaNeb® System will 
be introduced and incorporated into the respiratory care treatment regimens and 
outcomes will be assessed after the change in practice. 
3.1.2 Procedure:  
In Stage I of the study, a retrospective review of medical records for post-surgical 
patients, who received STANDARD THERAPY as defined by current hospital and 
Respiratory Care department policies and procedures. This will be a retrospective 
data collection only.   
The purpose of study Stage I is to estimate the incidence of postoperative pulmonary 
complications in post-surgical patients receiving standard of care per hospital and 
Respiratory Care department procedures and policies.  Data collected in Stage I will 
include data from the medical records of 200 randomly selected, eligible patients 
treated during the year prior to the CHANGE IN PRACTICE. This allows for 
inclusion of patients from the seasonally consistent time period as well as those from 
most recent time period, during which care practices are most similar.  
In Stage II, a CHANGE IN PRACTICE will be made and patients will receive standard 
care with the addition of therapy with The MetaNeb® System. Other standard airway 
clearance and lung expansion therapies typically delivered by Respiratory Therapy will 
not be delivered during Stage II. During Stage II, data from approximately 200 patients 
will be collected from the medical records across the 3 sites.  
Demographic, clinical & outcome data will be collected for eligible patients during 
the two stages of the study. Study staff will collect data from the medical records, 
following a protocol determined schedule. 
Pre-surgery data will be collected for eligible patients in both stages.  In both Stage I 
and Stage II, outcomes will be tracked for each day from the time of the post-surgical 
admission to the hospital unit through post-surgery day seven (7). Additionally, 
hospital length of stay (LOS) and total ICU LOS will be determined based on 
documentation of admission and discharge dates and times for all days of 
hospitalization. Length of time on mechanical ventilation (LOMV) will be determined 
based on documentation of initiation and discontinuation dates and times for all days 
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of hospitalization. LOS and LOMV data will be collected from the medical record upon 
discharge from the hospital. Hospital records will also be reviewed after 30 days to 
determine if readmission to the hospital occurred for any study patients. 
A timeline showing data procedures and collection points is included as Table 1 Study 
Observations Table. 
The estimated study enrollment is 200 patients in both stages. However, an adjustment 
in sample size may be made based on the incidence rate for post-operative pulmonary 
complications in Stage I, to allow for a robust estimate and assessment of the effect of 
therapy with The MetaNeb® System. 
3.1.3 Product Description  
The product added in Stage II, the CHANGE IN PRACTICE phase is The MetaNeb® 
System, a therapeutic device that provides airway clearance and lung expansion 
therapy. The MetaNeb® System is a marketed product, indicated for mobilization of 
secretions, lung expansion therapy, the treatment and prevention of pulmonary 
atelectasis and also has the ability to provide supplemental oxygen when used with 
compressed oxygen. The system has three therapy modes: 
•
CHFO (Continuous High Frequency Oscillation) – delivers aerosol therapy while
providing oscillating pressure pulses to the airway
•
CPEP (Continuous Positive Expiratory Pressure) – delivers aerosol therapy while
providing continuous positive pressure to help hold open and expand the airways
•
Aerosol – for delivery of aerosol only. In this mode, CHFO and CPEP are not
available
3.1.4 Treatment Protocol(s):   
Stage I:  STANDARD THERAPY period: 
In Stage I of the study, a retrospective review of medical records for post-surgical 
patients, who received STANDARD THERAPY as defined by current hospital and 
Respiratory Care department policies and procedures. This will be retrospective data 
collection only. The purpose of Stage I is to estimate the incidence of postoperative 
pulmonary complications that occur in postsurgical patients who receive standard 
therapy.  
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Respiratory Care therapies (e.g. nebulizer treatments, chest physiotherapy, etc.) that 
were delivered during the first seven (7) days following surgery, including delivered 
frequency, will be collected. 
Stage II:  CHANGE IN PRACTICE period: 
The treatment protocol used for Respiratory Care during the CHANGE IN PRACTICE 
period of the Study will be that prescribed by the patient’s health care team in the 
routine standard care of each patient. With the exception of standard airway clearance 
and lung expansion procedures, other components of the patients respiratory care 
regimen will remain the same as during the standard therapy period, however the 
CHANGE IN PRACTICE will incorporate the use/treatment with The MetaNeb® 
System as an alternative to usual airway clearance and lung expansion procedures. Use 
of The MetaNeb® System will follow the labeling of the device. 
Respiratory Care therapies, including therapy with The MetaNeb® System, that are 
delivered during the first seven (7) days of Stage II, including delivered frequency, 
will be collected. 
Exceptions to the above treatment protocols required for patient care as determined by 
the treating physician will be collected. 
3.2 Study Population  
The study population consists of adult post-surgical patients who have undergone thoracic, 
aortic or upper abdominal surgery who are at high risk for PPCs. 
3.2.1 Inclusion Criteria:   
Patients who meet all of the following criteria will be included in the study: 
•
Age ≥ 18 years
•
Post-thoracic, -upper abdominal or -aortic surgery
•
Open surgical procedure
•
Incision at or above the umbilicus
•
High risk defined by:
o
Documented ASA class >3
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OR 
o
Documented ASA class 2 AND One or more of the following:
-
Current Smoker or Smoking history within past 6 months
-
History of COPD
-
Documented Obesity and/or BMI > 30 kg/m2
-
Age > 75
3.2.2 Exclusion Criteria: 
Patients who meet any of the following criteria will be excluded (or will be exited) 
from the study: 
•
Contraindication to Continuous High Frequency Oscillation (CHFO) therapy (e.g.
untreated tension pneumothorax)
•
Minimally invasive or “…scopic” surgical procedure
•
Spinal surgery involving a posterior approach
•
Surgery for organ transplant
•
Chronic invasive Positive Pressure Ventilation (PPV) therapy
3.3  Evaluation Criteria/Effectiveness 
The CHANGE IN PRACTICE therapy regimen (which includes therapy with The MetaNeb® 
System) will be evaluated to determine if there is a decrease in the number of patients who 
experience Significant Postoperative Pulmonary Complications among the group of patients 
treated with The MetaNeb® System. Endpoints are described below: 
Primary Endpoint: 
Significant Postoperative Pulmonary Complication (PPC):  
One or more of the following that occurs within seven (7) days of the post-surgical admission 
will be considered a Significant Postoperative Pulmonary Complication (PPC) 
•
Patient Requires Prolonged Mechanical Ventilation:
Defined as patient requirement for invasive mechanical ventilation (MV) for > 24 
hours (after hour 24) post-operatively. This includes patients that require re-
intubation and MV after hour 24, regardless of length of time on MV in the first 24 
hours postoperatively. 
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•
Patient requires prolonged respiratory support for > 24 hours from post-surgical
admission
•
Requirement for non-invasive ventilation (NIV) above patient’s baseline
requirement after hour 24, or continuous positive airway pressure (CPAP) above
patient’s baseline requirement after hour 24.
•
Requirement for O2 therapy > 40 % FiO2 or > 5 LPM via NC (and above patient’s
baseline) after hour 24 postoperatively.
•
Diagnosis of Pneumonia Within Seven (7) Days
•
Physician documented pneumonia AND
•
Radiologists report indicating pneumonia / new or expanded infiltrate AND
•
Elevated or low Temperature (> 38º C or < 36 º C, or as defined by the site)
and/or elevated white count above the upper level of normal as defined by the site
•
Readmission to ICU (or transfer to an elevated level of care) for pulmonary
complications within seven (7) days of the post-surgical hospital admission
Defined as readmission to the ICU within seven days of post-surgical hospital 
admission or readmission to an elevated care unit such as special care or ICU 
step-down unit after being moved to a lower (e.g. general care) floor (e.g. patient 
discharged from ICU on day 4 at 0800 is readmitted to the ICU before day 8 at 
0800). 
Secondary Endpoints:  
•
Requirement for invasive mechanical ventilation for > 48 hours within seven (7)
days of the post-surgical hospital admission
Defined as patient requirement for invasive mechanical ventilation (MV) for > 48 
hours (after hour 48) post-operatively. This includes patients that require re-
intubation after hour 48, regardless of length of time on MV in the first 48 hours 
postoperatively. 
•
Requirement for respiratory support for > 48 hours within seven (7) days of the
post-surgical hospital admission
Respiratory support greater than the patient’s baseline level for a period longer than 48
hours
•
Requirement for non-invasive ventilation (NIV) above patient’s baseline
requirement after hour 48 from post-surgical admission or continuous positive
airway pressure (CPAP) above patient’s baseline requirement after hour 48.
•
Requirement for O2 therapy > 40 % FiO2 or > 5 LPM pm via Nasal Cannula (and
above patient’s baseline) after hour 48 postoperatively.
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•
ICU Length of Stay (LOS)
ICU length of stay, during initial hospital stay, will be determined by calculating the
number of days/hours spent in ICU. The following will be documented:
•
Time of admission to the ICU to actual time of initial discharge from the ICU
during initial hospital stay
•
Total ICU days/hours (includes readmissions) during initial hospital stay
•
Hospital Length of Stay (LOS)
Hospital length of stay will be determined by calculating the number of days/hours
spent in hospital. The following will be documented:
•
Time of admission to time of discharge from the hospital (total days/hours)
•
Time on Mechanical Ventilation
Time on mechanical ventilation, during the initial hospital stay, will be documented
as follows:
•
Time to initial extubation from time of initial intubation, if initial intubation was
placed after surgery; or from time of post-surgical admission, if intubation was in
place prior to start of surgery
•
Total time on invasive mechanical ventilation - will be determined for each
patient by calculating the total number of days/hours intubated and mechanically
ventilated from the time of post-surgical admission until the time of initial
hospital discharge.
•
Total time on non-invasive ventilation - will be determined for each patient by
calculating the total number of days/hours ordered for non-invasive ventilation
from the time of post-surgical admission to the hospital unit until the time of
initial hospital discharge.
•
Readmission to ICU and transfers to elevated level of care for pulmonary
complications
Readmissions to ICU and transfers to an elevated level of care, during the initial
hospital stay, will be documented for each event. The following will be documented:
•
Number of readmission to ICU or elevated level of care events
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•
Number of patients requiring readmission to the ICU or to an elevated level of
care
•
Readmission to Hospital
Hospital records will be reviewed at each site, 30 days after the last patient has been
discharged from the hospital. Readmissions, for any cause, within 30 day of discharge
for any study patient will be documented.
3.4 Study Observations Table  
The study observations and documentation timeline is outlined in Table 1. 
Table 1. Study Observations Table 
* Informed consent will be obtained only for subjects in Stage II.
3.4.1 Study Observations Table Detailed Description 
Day
Pre-Surgery
Day of 
Surgery
Post Surgery
Day 1 - Day 7
Hospital 
Discharge
Early Term
Day 30 
Post 
Discharge
Selection Criteria / Enrollment
X
Informed Consent *
X
Demographic Data
X
Medical History
X
Pre-Surgery Respiratory Status 
(Patient's Baseline)
X
Post-Surgical Data (day 0) at day 
of surgery.
X
Location (7A & 7P)
X
X
Respiratory Status (Each Shift)
X
X
Respiratory Milestones
X
X
Respiratory Treatments
X
X
Hospital Discharge Summary
X
ICU Admission/Discharge 
Summary (Day 8 - Discharge)
X
Discharge Respiratory Summary 
(Day 8 - Discharge)
X
30-day Readmission
X
Study Exit Form
X
X
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Documentation of observations will be completed by study staff based on review of the 
patient’s medical records. A detailed description of documentation requirements for 
each parameter is below. 
Demographic Data:  The following data will be recorded from the patient medical 
record: Age, Height, Weight, Race, Gender, ASA score, Documented obesity and/or 
BMI > 30 kg m2. 
Medical History:  Pulmonary history will be recorded from the patient medical record 
including: Asthma, Cystic Fibrosis, Bronchiectasis, COPD,  
Neuromuscular Disease, Other Pulmonary Condition(s), Obstructive Sleep Apnea 
Pre-surgery Respiratory Status:  Pre-surgery respiratory status such as Invasive 
Mechanical Ventilation, Non-invasive Mechanical Ventilation, CPAP, Supplemental 
oxygen will be recorded. 
Post-Surgery Data (day 0):  Following surgery, the albumin level (if available in the 
medical record) and surgery type will be recorded. 
Location:  The post-surgery location of each patient upon return to the hospital unit or 
floor (ICU, General Care, etc.) will be recorded.  The patient’s location during the first 
seven days, or until the time of discharge from the hospital, whichever occurs first, will 
also be recorded at regular intervals based on entries in the medical record.  
Respiratory Status:  The respiratory status of each patient, following surgery will be 
recorded. Respiratory status during the first seven days, or until the time of discharge 
from the hospital, whichever occurs first, will also be recorded at regular intervals 
based on entries in the medical record. Respiratory status will include documentation 
of the mode of support, the device in use and the settings. 
Respiratory Milestones:  Key respiratory milestones that occur each day will be 
recorded based on entries in the medical record. These include 1) extubation, 2) re-
intubation, 3) return to baseline respiratory support, 4) Diagnosis of Pneumonia and 5) 
Readmission to the ICU or an elevated level of care. These milestones will be recorded 
for each day until discharge from the hospital, or through day seven (7) following the 
day of surgery, whichever occurs first. 
Respiratory Treatments:  Standard respiratory treatments including CPAP therapy 
(non-continuous), IPPB, Nebulizer treatments, Chest physiotherapy, and others will be 
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recorded for each day until discharge from the hospital, or through day seven (7) 
following the day of surgery, whichever occurs first. Type of therapy and the number 
of treatments received on each day will be recorded.  
During Stage II, each MetaNeb® therapy will be documented including time and 
duration of therapy and adherence to defined treatment regimen 
Hospital Discharge Summary:  A summary including date and time of discharge 
along with the location to which the patient is being discharged will be completed after 
discharge. 
ICU Admission/Discharge Summary (Day 8 – Discharge):  Dates and times of all 
ICU admissions, or admissions to a unit for an elevated level of care, along with 
discharges from those units, that occur between post-surgery day 8 and discharge from 
the hospital, will be documented.  
Discharge Respiratory Summary (Day 8 – Discharge):  Dates and times of each 
initiation and discontinuation of mechanical ventilation that occur between post-
surgery day 8 and discharge from the hospital, will be documented.  
30-day Readmission:  Hospital medical records for each patient will be evaluated after
30 days post discharge, to determine if any hospital readmissions had occurred.
3.5 Statistical Methods and Analysis 
3.5.1 Sample Size Estimation: 
This study is designed to provide information on the benefits of the addition of the 
MetaNeb® System in reducing the incidence of postoperative pulmonary complications 
(PPCs) in high-risk subjects undergoing high-risk surgical procedures (upper 
abdominal, thoracic, aortic).  The study will be conducted in 2 stages: 
•
Stage I: To update/confirm the estimate of the current incidence of PPC’s with
current Standard of Care Practice. Recent published articles suggest incidence rates
between 5%-15%, depending on the patient population and type of surgery. This
stage of the study will be a retrospective pre-intervention observational period,
conducted at 2 - 4 hospitals/sites, with no intervention in the patients’ post-surgical
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management.  Data from approximately 200 subjects will be collected.  The 
incidence rate will be calculated, along with a 95% confidence interval.  
•
Stage II: To assess the impact of the MetaNeb® System on the incidence of PPC’s.
This stage of the study will be a prospective post-intervention period conducted in
the same 2 - 4 hospital sites with an intervention involving use of the MetaNeb®
System in addition to Standard of Care Practice.
3.5.2 Statistical Analysis:  
•
Summary statistics and data listings will be provided.
•
Demographic data will be summarized.  For continuous type data (e. g. Age),
descriptive summary statistics (N, mean, median, standard deviation, min, and
max) will be presented. For categorical variables (gender, race, etc.) the number
and percent of patients in each category will be provided.
Primary Endpoints: 
The incidence of significant postoperative pulmonary complications (as defined in 
section 3.3) along with 95% confidence interval will be generated.  Additionally, the 
incidence rates will be summarized for various demographic subsets, by surgery type, 
and for different population subsets.  The descriptive summary statistics for the subsets 
may be presented side-by-side for ease of comparison.  The specific subsets to be 
summarized will be described in a separate document (the statistical analysis plan). 
Secondary Endpoints: 
The secondary endpoints as listed in section 3.3 will be summarized with descriptive 
summary statistics appropriate for continuous or categorical data, depending on the 
outcome being summarized: 
1. Requirement for invasive mechanical ventilation for more than 48 hours.
2. Requirement for respiratory support for more than 48 hours
3. Length of ICU stay (ILOS)
4. Length of hospital stay (HLOS)
5. Time on mechanical ventilation
6. Readmission to ICU
7. Readmission to hospital
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Stage I and Stage II results will be compared for the purpose of identifying any 
statistical associations that can be attributed to use of The MetaNeb® System. 
4.0 General Study Information 
4.1 Technical Support  
Technical product support will be performed by Hill-Rom following routine service 
practices (contact details will be provided). 
4.2 Record Retention 
Records must be maintained for a period of up to three years after the latter of the 
following dates:  the date the study is completed/terminated, or the date of the last 
regulatory approval.  The Investigators or Institutions shall notify the Sponsor at least 
thirty (30) days prior to any planned destruction of records from this study. 
All records will be kept confidential and the patient’s name will not be released at any 
time. Code numbers will be used to de-identify patient information on the CRFs and 
other study-related documents. 
5.0 Study Procedures 
5.1 Informed Consent:  
A waiver of informed consent will be requested for patients enrolled in the study in 
Stage I (retrospective review of data). Informed consent must be obtained from all 
subjects in Stage II prior to participation as per Federal Regulations and/or the 
qualifying Institutional Review Board (IRB).  A blank copy of the IRB-approved form 
must be kept on-site and by the sponsor.  The signed original for each subject must be 
kept in the study files. 
5.2   Complaints and Adverse Events Reporting 
During the study, any adverse device effect, device-related complaint or allegation of 
injury (of any type) must be reported to the Sponsor within 24 hours. Please contact 
  
 
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A complaint is defined as any written, electronic or verbal communication that 
alleges deficiencies related to the identity, design, quality, durability, reliability, 
safety, effectiveness or performance of the device. A serious injury is defined as an 
injury or illness that is life-threatening; results in permanent impairment of a body 
function or permanent damage to a body structure; or necessitates medical or surgical 
intervention to preclude permanent impairment of a body function or permanent 
damage to a body structure. 
Any device complaint and/or allegation of injury shall be reviewed, evaluated, and 
investigated by Hill-Rom Post Market Surveillance and reported to the appropriate 
Health Authority per current regulations. The Investigators are responsible for 
informing the Institutional Review Boards, as per their guidelines. 
5.3 Deviations from the Study Protocol 
A change (other than administrative) to any part of the study protocol must be mutually 
agreed upon by the Sponsor and the Investigator(s). The Investigator(s) will then 
submit an amendment to his/her/their institution’s local IRB. Until the new protocol is 
approved, new patients will be included under the current protocol. 
5.4 Materials Provided by the Sponsor 
The Sponsor will supply all The MetaNeb® System devices to the institutions.  
6.0 
Investigator and Sponsor Responsibilities 
6.1 Investigator’s Responsibilities 
The Investigator will comply with Good Clinical Practices (GCPs) and applicable 
regulatory requirements, as itemized below. 
•
The Investigator should be familiar with the appropriate use of The MetaNeb®
System Device and any other information provided by the Sponsor.
•
The Investigator should provide adequate staff to conduct and complete the
study within the agreed study time period. The Investigator should ensure that
all persons assisting with the study are adequately informed about the protocol,
The MetaNeb® System Device and their study related duties.
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•
A qualified physician delegated as an investigator or sub-investigator will be
responsible for all study related duties and functions. During a patients’
participation, the Investigator/Institution should ensure that adequate medical
care is provided to the patient for any adverse event.
•
The Investigator should have written and dated approval from the IRB for the
protocol, IC forms or waiver of informed consent, HIPAA authorization, patient
recruitment procedures and any other written information for the conduct of the
study and/or to be provided to patients.
•
The Investigator/Institution should conduct the study in compliance with the
protocol agreed to by the Sponsor. The Investigator should sign the protocol or
alternative contract to confirm agreement. The Investigator should not
implement any deviation or changes to the protocol without agreement with the
Sponsor and prior review and agreement from the IRB, unless the deviation or
change is to eliminate an immediate hazard to study patients.
•
The Investigator/Institution is responsible for all MetaNeb® System Devices
that are placed with the Investigator/Institution. When it is allowed, the
Investigator may assign Device accountability to another appropriate
individual. The Investigator or responsible individual shall maintain records of
the Device delivery to the site, inventory at the site, the use by each patient, and
the return to the Sponsor of unused Device or equipment. The MetaNeb®
System Device should be stored as specified by the Sponsor and applicable
regulatory requirements. The Investigator should ensure that the individual
Device is demonstrated and/or used in accordance with the approved protocol.
If appropriate and applicable, the Investigator or designee should explain the
correct use of The MetaNeb® System Device to each patient.
•
In obtaining and documenting informed consent (unless waived), the
Investigator should comply with the applicable regulatory requirements and
should adhere to GCP and the ethical principles that have their origin in the
Declaration of Helsinki.
•
The Investigator, per Title 21 Code of Federal Regulations Part 54, should
disclose any financial interests that could affect the reliability of the data.
•
The Investigator should ensure the accuracy, completeness, legibility and
timeliness of the data reported to the Sponsor in the CRFs and required reports.
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•
The Investigator should maintain the study documents as required by the
applicable regulatory requirements. Records must be maintained for a period of
three years after the latter of the following dates:  the date the study is
completed/terminated or the date of the last regulatory approval based on the
study data. The Investigator or Institution shall notify the Sponsor at least thirty
(30) days prior to any planned destruction of records from this study.
•
The Investigator should submit written summaries of the status of the study to
the IRB annually, or as requested by the IRB, and upon completion of the Study.
•
All serious adverse device effects should be reported immediately to the
Sponsor, per the local IRB’s reporting policy at that site. The initial reports
should be followed by more detailed reports if more information becomes
available. If the study is terminated prematurely or suspended for any reason,
the Investigator should promptly inform the study patients and ensure
appropriate therapy and follow-up is scheduled or documented for each patient.
6.2 Sponsor’s Responsibilities 
The Sponsor of the program is Hill-Rom Company, Inc. The Sponsor’s, responsibilities 
are itemized below. 
•
The Sponsor is responsible for implementing and maintaining quality assurance
and quality control systems with written standard operating procedures (SOPs)
to ensure that studies are conducted and that the data are generated,
documented, and reported in compliance with the protocol, GCPs and
applicable regulatory requirements. The Sponsor is responsible for securing an
agreement from all involved parties to ensure direct access to all study-related
sites, source documents, and reports for the purpose of monitoring and auditing.
•
The Sponsor may transfer any or all of the study-related duties and functions to
a Contract Research Organization (CRO), but the ultimate responsibility for the
quality and integrity of the data resides with the Sponsor.
•
The Sponsor should use an unambiguous patient identification code that allows
for de-identification of all the data reported for each patient.
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•
The Sponsor should retain the essential documents as required by the applicable
regulatory requirements. Records must be maintained for a period of three years
after the latter of the following dates:  the date the study is completed/terminated
or the date of the last regulatory approval.
•
The Sponsor should ensure the Investigator(s) selected for the study have the
proper qualifications, training, and resources to perform the study adequately.
•
The Sponsor shall provide the Investigator(s) with a protocol and an
Investigator Brochure (or equivalent documentation) and allow sufficient time
for the Investigator to review the information provided.
•
The Sponsor should ensure timely delivery of the Device(s) to the
Investigator(s); maintain records that document shipment, receipt, disposition,
return and destruction (if applicable) of the Devices; maintain a system for
retrieving Devices and documenting this retrieval; maintain a system for the
disposition of unused Device(s) and for the documentation of this disposition.
•
The Sponsor should ensure that it is specified in the protocol or other written
agreement that the Investigator(s)/Institution(s) provide direct access to source
documents for study-related monitoring, audits, IRB review, and regulatory
inspection. The Sponsor should verify that each patient has consented in
writing, to direct access to his/her original medical records for study-related
monitoring, audit, IRB review and regulatory inspection, or that informed
consent has been waived.
•
The Sponsor is responsible for submitting reports of all recalls and device
disposition to the IRB and the FDA.
7.0 Administrative Study Information 
7.1 Pre-Study Site Visit 
The Sponsor will visit the site and meet with the Investigator(s) to assess and confirm 
the site’s ability to perform the study, store study equipment, and recruit patients.    
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7.2 Institutional Review 
Prior to study initiation, the appropriate IRB must approve the observational study.  It 
is the responsibility of the Investigators, in collaboration with the Sponsor, to provide 
the IRB with all necessary information to satisfy the individual Institution’s 
requirements. 
7.3 Investigator Records and Reports 
Where required by applicable regulatory requirements, an investigator signatory will 
be obtained for the acceptance of the clinical study report. The Investigator(s) will be 
provided reasonable access to statistical results and tables and will be provided a 
summary of the study results. 
7.4  Interim Monitoring and Closeout 
Interim monitoring and close-out visits may be conducted by the Sponsor for quality 
assurance. 
8.0 Changes Necessary after Study Initiation  
If there are changes to the study plan or protocol, these changes will be agreed upon by the 
Sponsor, its acting representative (if appropriate), the Investigator(s), and the IRB before the 
changes are implemented.  All changes must be documented. 
9.0 Study Completion 
See section 3.4 for timeline details.  Upon completion of the study, a study exit form will be 
completed for each patient. 
10.0 Confidentiality/Publication of the Study 
Any information shared by the Sponsor regarding this clinical study is the property of the 
Sponsor. This protocol is considered proprietary information and should be kept confidential. 
The data generated by this clinical study are the property of the Sponsor. These data may 
be used by the Sponsor, now and in the future, for presentation or publication at the Sponsor’s 
discretion or for submission to regulatory agencies.  
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11.0 
References 
1 Gupta H, Gupta PK, Fang X, et al. Development and validation of a risk calculator predicting 
postoperative respiratory failure. Chest 2011; 140:1207-1215. 
2 Dimick JB, Chen SL, Taheri PA, et al. Hospital costs associated with surgical complications: a 
report from the private-sector National Surgical Quality Improvement Program. J Am 
Coll Surg 2004; 199:531-537. 
3 Zilberberg MD, Shorr AF. Prolonged acute mechanical ventilation and hospital bed utilization 
in 2020 in the United States: implications for budgets, plant and personnel planning. 
BMC Health Serv Res 2008; 8:242. 
4 Khuri SF, Henderson WG, DePalma RG, et al. Determinants of long-term survival after major 
surgery and the adverse effect of postoperative complications. Ann Surg 2005; 242:326-
341; discussion 341-323. 
5 Agostini P, Cieslik H, Rathinam S, et al. Postoperative pulmonary complications following 
thoracic surgery:  are there any modifiable risk factors? Thorax 2010; 65:815-818. 
6 Restrepo RD, Braverman J. Current challenges in the recognition, prevention and treatment of 
perioperative pulmonary atelectasis. Expert Rev Respir Med 2015; 9:97-107 
7 Rama-Maceiras P. [Peri-operative atelectasis and alveolar recruitment manoeuvres]. Arch 
Bronconeumol 2010; 46:317-324 
8 Hans GA, Sottiaux TM, Lamy ML, et al. Ventilatory management during routine general 
anaesthesia. Eur J Anaesthesiol 2009; 26:1-8 
9 Sabate S, Mazo V, Canet J. Predicting postoperative pulmonary complications: implications 
for outcomes and costs. Curr Opin Anaesthesiol 2014; 27:201-209 
10 Branson RD. The scientific basis for postoperative respiratory care. Respir Care 2013; 
58:1974-1984 
11 Qaseem A, Snow V, Fitterman N, et al. Risk assessment for and strategies to reduce 
perioperative pulmonary complications for patients undergoing noncardiothoracic 
surgery: a guideline from the American College of Physicians. Ann Intern Med 2006; 
144:575-580 
12 Berlinski A, Willis JR. Albuterol delivery via intrapulmonary percussive ventilator and jet 
nebulizer in a pediatric ventilator model. Respir Care 2010; 55:1699-1704 
13 Birnkrant DJ, Pope JF, Lewarski J, et al. Persistent pulmonary consolidation treated with 
intrapulmonary percussive ventilation: a preliminary report. Pediatr Pulmonol 1996; 
21:246-249 
14 Clini EM, Antoni FD, Vitacca M, et al. Intrapulmonary percussive ventilation in 
tracheostomized patients: a randomized controlled trial. Intensive Care Med 2006; 
32:1994-2001 
CBI

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15 Dimassi S, Vargas F, Lyazidi A, et al. Intrapulmonary percussive ventilation superimposed on 
spontaneous breathing: a physiological study in patients at risk for extubation failure. 
Intensive Care Med 2011; 37:1269-1276 
16 Fornasa E, Ajcevic M, Accardo A. Characterization of the mechanical behavior of 
intrapulmonary percussive ventilation. Physiol Meas 2013; 34:1583-1592 
17 Gatani T, Martucci N, La Rocca A, et al. Management of localized pneumothoraces after 
pulmonary resection with intrapulmonary percussive ventilation. Ann Thorac Surg 2010; 
90:1658-1661 
18 Ides K, Vos W, De Backer L, et al. Acute effects of intrapulmonary percussive ventilation in 
COPD patients assessed by using conventional outcome parameters and a novel 
computational fluid dynamics technique. Int J Chron Obstruct Pulmon Dis 2012; 7:667-
671 
19 Natale JE, Pfeifle J, Homnick DN. Comparison of intrapulmonary percussive ventilation and 
chest physiotherapy. A pilot study in patients with cystic fibrosis. Chest 1994; 105:1789-
1793 
20 Nava S, Barbarito N, Piaggi G, et al. Physiological response to intrapulmonary percussive 
ventilation in stable COPD patients. Respir Med 2006; 100:1526-1533 
21 Newhouse PA, White F, Marks JH, et al. The intrapulmonary percussive ventilator and flutter 
device compared to standard chest physiotherapy in patients with cystic fibrosis. Clin 
Pediatr (Phila) 1998; 37:427-432 
22 Nicolini A, Mollar E, Grecchi B, et al. Comparison of intermittent positive pressure breathing 
and temporary positive expiratory pressure in patients with severe chronic obstructive 
pulmonary disease. Arch Bronconeumol 2014; 50:18-24 
23 Paneroni M, Clini E, Simonelli C, et al. Safety and efficacy of short-term intrapulmonary 
percussive ventilation in patients with bronchiectasis. Respir Care 2011; 56:984-988 
24 Reper P, van Looy K. Chest physiotherapy using intrapulmonary percussive ventilation to 
treat persistent atelectasis in hypoxic patients after smoke inhalation. Burns 2013; 
39:192-193 
25 Reychler G, Keyeux A, Cremers C, et al. Comparison of lung deposition in two types of 
nebulization: intrapulmonary percussive ventilation vs jet nebulization. Chest 2004; 
125:502-508 
26 Riffard G, Buzenet J, Guerin C. Intrapulmonary percussive ventilation superimposed on 
conventional mechanical ventilation: comparison of volume controlled and pressure 
controlled modes. Respir Care 2014; 59:1116-1122 
27 Toussaint M, De Win H, Steens M, et al. Effect of intrapulmonary percussive ventilation on 
mucus clearance in duchenne muscular dystrophy patients: a preliminary report. Respir 
Care 2003; 48:940-947 
28 Toussaint M, Guillet MC, Paternotte S, et al. Intrapulmonary effects of setting parameters in 
portable intrapulmonary percussive ventilation devices. Respir Care 2012; 57:735-742 
CBI

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29 Tsuruta R, Kasaoka S, Okabayashi K, et al. Efficacy and safety of intrapulmonary percussive 
ventilation superimposed on conventional ventilation in obese patients with compression 
atelectasis. J Crit Care 2006; 21:328-332 
30 Vargas F, Boyer A, Bui HN, et al. Effect of intrapulmonary percussive ventilation on 
expiratory flow limitation in chronic obstructive pulmonary disease patients. J Crit Care 
2009; 24:212-219 
31 Yen Ha TK, Bui TD, Tran AT, et al. Atelectatic children treated with intrapulmonary 
percussive ventilation via a face mask: clinical trial and literature overview. Pediatr Int 
2007; 49:502-507 
32 Vargas F, Bui HN, Boyer A, et al. Intrapulmonary percussive ventilation in acute 
exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled 
trial [ISRCTN17802078]. Crit Care 2005; 9:R382-389 
33 Nino G, McNally P, Miske LJ, et al. Use of intrapulmonary percussive ventilation (IPV) in 
the management of pulmonary complications of an infant with osteogenesis imperfecta. 
Pediatr Pulmonol 2009; 44:1151-1154 
34 Testa A, Galeri S, Villafane JH, et al. Efficacy of short-term intrapulmonary percussive 
ventilation in patients with chronic obstructive pulmonary disease. Disabil Rehabil 
2014:1-5 
35 Ortiz-Pujols S BL, Klatt-Cromwell C, et al. Chest high-frequency oscillatory treatment for 
severe atelectasis in a patient with toxic epidermal necrolysis. . J Burn Care Res 2013; 
34:e112-115 
36 Withers L FC, Price KJ, Nguyen QM. Use of a progressive pulmonary protocol in an 
oncology intensive care unit. In: Care R, ed. Resp Care Open Forum 2009 
37 Bocci M GJ, Timons B, et al. A case study: The use of MetaNeb to improve secretion 
removal and reverse atelectasis. In: AARC, ed. AARC Open Forum. 
http://www.rcjournal.com/abstracts/2006/?id=of-06-113, 2006 
38 Coleman E BB. Aggressive pulmonary secretion clearance intervention in long term care 
(LTC): A treatment protocol using the MetaNeb System. Advance for Long Term Care 
Management 2011 
39 Patel P FL, Balekian A, et al. Is MetaNeb comparable to high frequency chest compression in 
the setting of a severe pulmonary exacerbation in adults with cystic fibrosis? North 
American Cystic Fibrosis Conference 2013: Pediatr Pulmonol, 2013; 359 
40 Morgan S HC, Willford L, Turner D, Cheifetz IM. Continuous high frequency oscillation 
therapy in mechanically ventilated patients in the pediatric intensive care unit. AARC 
Congress 2014. Las Vegas, NV, 2014 
CBI