High Velocity Nasal Insufflation (Hi-VNI) Use in Upper Airway Surgery
Phase: NA
Conditions: Upper Airway Surgery
Sponsor: Natasha Mirza

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High Velocity Nasal Insufflation (Hi-VNI) Use in Upper Airway Surgery 
 
Principal Investigator:  
 
 
 
 
 
 
Sub-Investigators: 
 
Natasha Mirza, M.D. 
Professor of Otolaryngology 
Department of Otorhinolaryngology-Head and Neck Surgery 
3400 Spruce St., 5th floor Silverstein, Philadelphia, PA 19104 
Natasha.Mirza@pennmedicine.upenn.edu 
(215) 662-2979  
 
Joshua H. Atkins, M.D., Ph.D. 
Associate Professor of Anesthesiology and Critical Care 
Department of Anesthesiology and Critical Care  
3400 Spruce Street, 6th Floor Dulles, Philadelphia, PA 19104 
Joshua.Atkins@pennmedicine.upenn.edu 
(215) 662-3751 
 
Jonathan R. Gavrin, M.D., Ph.D. 
Professor of Anesthesiology and Critical Care 
Department of Anesthesiology and Critical Care  
3400 Spruce Street, 6th Floor Dulles, Philadelphia, PA 19104 
Jonathan.Gavrin@pennmedicine.upenn.edu 
(215) 662-3763 
 
Diana Ayubcha, D.O., M.S.  
Assistant Professor of Anesthesiology and Critical Care 
Department of Anesthesiology and Critical Care  
3400 Spruce Street, 6th Floor Dulles, Philadelphia, PA 19104 
Diana.Ayubcha@pennmedicine.upenn.edu 
(215) 662-3751 
 
Liuba Soldatova, M.D. 
Resident Physician 
Department of Otorhinolaryngology-Head and Neck Surgery 
3400 Spruce St., 5th floor Silverstein, Philadelphia, PA 19104 
Liuba.Soldatova@pennmedicine.upenn.edu 
(215) 432-7233 
 
IRB Protocol # 834412 
 
Initial Version:    10/14/2019 
Revised:   
    12/17/2019 
Revised: 
03/17/2020 
Revised: 
05/26/2020 
Revised: 
11/02/2020 
Revised: 
11/30/2020 
Revised: 
05/20/2021 
 

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Table of Contents 
BACKGROUND AND STUDY RATIONALE .............................................................................................................5 
1 
INTRODUCTION ...............................................................................................................................................5 
1.1 
BACKGROUND AND RELEVANT LITERATURE...................................................................................................6 
2 
STUDY OBJECTIVES .......................................................................................................................................7 
2.1 
PRIMARY OBJECTIVE ...................................................................................................................................7 
2.2 
SECONDARY OBJECTIVES ............................................................................................................................8 
3 
INVESTIGATIONAL PLAN ...............................................................................................................................8 
3.1 
GENERAL DESIGN ........................................................................................................................................8 
3.2 
ALLOCATION TO INTERVENTIONAL GROUP .....................................................................................................8 
3.3 
STUDY MEASURES .......................................................................................................................................8 
3.4 
STUDY ENDPOINTS ................................................................................................................................... 12 
3.4.1 
Primary Study Endpoint ..................................................................................................................... 12 
3.4.2 
Secondary Study Endpoints .............................................................................................................. 12 
4 
STUDY POPULATION AND DURATION OF PARTICIPATION ................................................................... 12 
4.1 
DURATION OF STUDY PARTICIPATION ........................................................................................................ 12 
4.2 
TOTAL NUMBER OF SUBJECTS AND SITES .................................................................................................. 13 
4.3 
INCLUSION CRITERIA ................................................................................................................................. 13 
4.4 
EXCLUSION CRITERIA ............................................................................................................................... 13 
4.5 
SUBJECT RECRUITMENT ........................................................................................................................... 14 
4.6 
VULNERABLE POPULATIONS ...................................................................................................................... 14 
5 
STUDY PROCEDURES ................................................................................................................................. 14 
5.1 
SCREENING .............................................................................................................................................. 14 
5.2 
STUDY INTERVENTION PHASE .................................................................................................................... 14 
5.3 
DEVICE MANAGEMENT .............................................................................................................................. 15 
5.4 
SUBJECT WITHDRAWAL ............................................................................................................................. 15 
5.4.1 
Data Collection and Follow-up for Withdrawn Subjects ..................................................................... 15 
5.5 
EFFICACY EVALUATION ............................................................................................................................. 15 
6 
STATISTICAL PLAN ...................................................................................................................................... 15 
6.1 
SAMPLE SIZE AND POWER DETERMINATION ............................................................................................... 15 
6.2 
STATISTICAL METHODS ............................................................................................................................. 16 
6.3 
CONTROL OF BIAS AND CONFOUNDING ...................................................................................................... 16 
6.3.1 
Baseline Data ..................................................................................................................................... 17 
6.3.2 
Analysis of Primary Outcome of Interest ........................................................................................... 17 
7 
SAFETY AND ADVERSE EVENTS ............................................................................................................... 17 
7.1 
DEFINITIONS ............................................................................................................................................. 17 
7.1.1 
Adverse Event/Adverse Device Effect ............................................................................................... 17 
7.2 
SERIOUS ADVERSE EVENT ........................................................................................................................ 17 
7.3 
RECORDING OF ADVERSE EVENTS ............................................................................................................ 18 
7.4 
RELATIONSHIP OF AE TO STUDY ............................................................................................................... 18 
7.5 
REPORTING OF ADVERSE EVENTS AND UNANTICIPATED PROBLEMS ............................................................ 18 
7.5.1 
Follow-up Report ................................................................................................................................ 18 
7.5.2 
Data and Safety Monitoring Plan ....................................................................................................... 18 
8 
STUDY ADMINISTRATION, DATA HANDLING AND RECORD KEEPING ................................................ 19 
8.1 
CONFIDENTIALITY ..................................................................................................................................... 19 
8.2 
DATA COLLECTION AND MANAGEMENT ...................................................................................................... 19 
8.3 
RECORDS RETENTION .............................................................................................................................. 19 
9 
STUDY MONITORING, AUDITING, AND INSPECTING ............................................................................... 19 

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9.1 
STUDY MONITORING PLAN ........................................................................................................................ 19 
9.2 
AUDITING AND INSPECTING ........................................................................................................................ 20 
10 
ETHICAL CONSIDERATIONS ....................................................................................................................... 20 
10.1 
RISKS ...................................................................................................................................................... 20 
10.2 
BENEFITS ................................................................................................................................................. 22 
10.3 
RISK BENEFIT ASSESSMENT ...................................................................................................................... 22 
10.4 
INFORMED CONSENT PROCESS / HIPAA AUTHORIZATION........................................................................... 22 
11 
STUDY FINANCES ........................................................................................................................................ 23 
11.1 
FUNDING SOURCE .................................................................................................................................... 23 
11.2 
CONFLICT OF INTEREST ............................................................................................................................ 23 
11.3 
SUBJECT STIPENDS OR PAYMENTS ............................................................................................................ 23 
12 
PUBLICATION PLAN ..................................................................................................................................... 23 
13 
REFERENCES ............................................................................................................................................... 23 
 

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Study Summary 
Title 
High Velocity Nasal Insufflation (Hi-VNI) Use in Upper Airway 
Surgery 
Short Title 
Hi-VNI Use in Upper Airway Surgery 
IRB Number 
834412 
Methodology 
Prospective, interventional, pilot study 
Study Duration 
1 year 
Study Center 
Single center (University of Pennsylvania) 
Objectives 
 To establish the efficacy of Hi-VNI in upper airway surgery from 
the anesthesiologist’s and surgeon’s perspectives 
 To describe the ideal patient and the ideal pathology as well as 
suitable clinical scenarios when Hi-VNI should be selected 
Number of Subjects 
100 
Main Inclusion and 
Exclusion Criteria 
Inclusion criteria: 
Adult patients who are scheduled to undergo elective upper airway 
surgery at Penn. 
 
Exclusion criteria: 
All patients with underlying medical conditions in which brief periods of 
hypoxemia or hypercarbia are not well tolerated will be excluded.  
Patients in whom delivery of air with oxygen via nasal passages is 
contraindicated will be excluded. 
 Coronary artery disease 
 Severe heart failure with EF < 40% or implanted ICD 
 Pulmonary hypertension or pulmonary fibrosis  
 History of increased intracranial pressure  
 History of skull base or intracranial surgery 
 Severe nasal obstruction 
 Extremely low or extremely high BMI (BMI <16 or >40) 
 Patients at high risk for aspiration  
 Patients taken to OR for urgent or emergent upper airway surgery 
Intervention  
 
This study will involve use of Hi-VNI device as a primary or adjunct 
method for oxygenation. 
Statistical 
Methodology 
Mann-Whitney U test or Student’s t-test and Kruskal-Wallis or ANOVA 
test will be used depending on the data distribution and the number of 
variables.   
Data and Safety 
Monitoring Plan  
The PI and sub-Is for this study will be responsible for the safety of the 
subjects enrolled into this study. 

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Background and Study Rationale 
This study will be conducted in full accordance with all applicable University of 
Pennsylvania Research Policies and Procedures and all applicable federal and state laws and 
regulations. 
1 Introduction 
The most challenging aspects of laryngeal and laryngotracheal procedures are difficulty 
of exposure and airway management.  These procedures require use of microlaryngeal 
instruments through a small lumen of a rigid laryngoscope, and are oftentimes difficult to 
perform with a standard endotracheal tube in place.  Similarly, when performing endoscopic 
evaluation of the trachea, access to the space and visualization of the entire 360-degree view 
of the trachea is crucial.   
To overcome these challenges, a number of techniques for oxygen delivery have 
evolved over time.  Among them are use of a small endotracheal tube, use of jet ventilation 
and intermittent apnea with periodic removal of the endotracheal tube.  The aforementioned 
methods of airway management carry inherent risks of airway injury,1,2 can be accompanied by 
brief periods of hypoxia or hypercarbia, and can sometimes lead to tenuous airway 
management scenarios for both the surgeon and the anesthesiologist when clear 
communication and familiarity with the airway management plan during the procedure are sub-
optimal.  For this reason, there is an ongoing search for acceptable solutions to minimize these 
risks during upper airway surgery. 
One of the newly emerging advanced oxygenation techniques, also known as Hi-VNI 
(High Velocity Nasal Insufflation), allows for delivery of humidified oxygen through a 
specialized high-flow nasal cannula at rates of up to 40 l/min.1,2  This non-invasive high flow 
respiratory support system is currently being used in the treatment of respiratory failure in both 
adult and pediatric patients.  This technique provides sustained oxygenation due to reduction 
in airway resistance, a build-up of airway pressure with oxygen-rich gas and active gas 
exchange, which lead to flushing of anatomic dead space, and delivery of oxygen into the 
lungs.3–5  This oxygenation technique can be used both in spontaneously breathing patients6 
and under apneic conditions,7,8 while providing an unobstructed surgical view with the glottis, 
subglottis and trachea fully accessible for instrumentation.  
The goal of this study is to establish the efficacy of Hi-VNI in upper airway surgery, to 
document the advantages and disadvantages of this technique from the standpoint of the 
airway surgeon and the anesthesiologist, and to provide more information about the optimal 
patient and airway pathology as well as suitable clinical scenarios when Hi-VNI device can be 
used for oxygenation during upper airway surgery.  We hypothesize that in appropriate clinical 
situations, Hi-VNI can ease airway management, shorten case duration, and provide superior 
operating conditions including space for instrumentation during upper aerodigestive tract 
procedures.  

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1.1  Background and Relevant Literature  
Upper airway surgery is performed to treat a number of laryngeal and laryngotracheal 
conditions, many of which require an unobstructed view of the glottis, the subglottis, and the 
trachea.  Various techniques of airway management have evolved over time to meet these 
requirements.  These techniques include use of a small size endotracheal tube, intermittent 
apnea (periods with no breathing or oxygenation) during periodic removal of the endotracheal 
tube, and jet ventilation.  The aforementioned methods of airway management allow for 
completion of the surgical procedures in the airway, but carry inherent risks of airway injury,7,8 
can be accompanied by periods of hypoxia or hypercarbia, and can sometimes lead to tenuous 
airway management scenarios.  
Traditionally, before endotracheal intubation during surgical procedures, pre-
oxygenation with a facemask is combined with apneic oxygenation via nasal cannula at rates 
of up to 15 mL/min.  Apneic oxygenation with nasal cannula prolongs the safe apnea time, 
defined as the apnea time before desaturation.  Recent advances in the field of anesthesia and 
oxygenation techniques introduced the Hi-VNI (High Velocity Nasal Insufflation) oxygenation 
technique.  Hi-VNI technology has been utilized in cases of spontaneously breathing6,2 or 
apneic patients.7,8  Hi-flow nasal oxygen has been advocated to improve safety in bridging 
oxygenation of high-risk patients during apnea induced for urgent or emergent intubation8–10.  
Prior studies suggest that it prolongs the safe apnea time in physiologically fragile patients who 
cannot be ventilated by facemask due to risk of aspiration or challenging airway anatomy.    
Our current approach in upper airway surgical procedures employs high-frequency jet 
ventilation (HFJV) or intubation with a small size endotracheal tube.  In upper airway surgery, 
Hi-VNI oxygenation offers the advantage of an unimpeded and more stationary surgical view, 
while avoiding the risk of barotrauma when compared to jet “ventilation”,9 and can deliver 
oxygenation in severe cases of airway obstruction such as cases of laryngotracheal stenosis 
when passage of the endotracheal tube or insertion of the jet ventilation cannula is difficult.6  
Hi-VNI may be advantageous as it produces less field motion when compared to HFJV, 
requires less technical expertise of the operator (requires a simple adjustment to titrate the rate 
of flow and oxygen content of the delivered humidified gas), does not entail instrumentation of 
the airway with a HFJV catheter or endotracheal tube, is not associated with the risk of 
barotrauma sometimes seen with HFJV, and allows for continuous oxygenation (HFJV needs 
to be paused during certain parts of the procedure to allow for a motionless field).  
Most upper airway procedures we perform are short duration procedures and can be 
completed under apneic conditions or under the conditions of intermittent apnea if the safe 
apnea time is extended.  Multiple recent case reports and small case series described 
instances where Hi-VNI-type devices extended the safe apnea time and improved patient 
safety.  Wong et al. demonstrated that use of high-flow nasal oxygenation maintained the safe 
apnea time 40% longer (mean difference of 76 sec) when compared to facemask ventilation in 
morbidly obese patients (case series of 40 patients).13  Lee and Quek described a case report 
of a morbidly obese patient (BMI of 40) undergoing a short laryngeal procedure (pan-
endoscopy and vocal cord biopsy) with Hi-VNI providing adequate oxygenation without a need 
for adjunct methods of oxygenation/ventilation.14  Hi-VNI has been recommended for use in 

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critically ill patients during intubation in the ICU to prolong the safe apnea time and to help 
avoid emergent cricothyrotomy and tracheotomy.12  Other studies described the benefits of 
high-flow nasal oxygenation in patients with respiratory distress requiring emergent intubation 
in the Emergency Department4,5  This literature supports the concept that Hi-VNI devices can 
be used in apneic conditions to maintain adequate oxygenation. 
We performed eight short cases of microlaryngeal surgery using Hi-VNI device at our 
institution, and noted better access to the glottis and the subglottic area with improved 
oxygenation and delay in desaturation under apneic conditions.  These results and current 
literature on this technique call for further investigation of Hi-VNI use during upper airway 
surgery to provide additional information to the airway surgeon and the anesthesiologist 
regarding the most suitable patient and clinical scenario for its use based on the physiologic 
changes that occur when Hi-VNI is used for oxygenation. 
Preliminary investigations published thus far provide some information about the 
physiologic changes that take place during Hi-VNI oxygenation under apnea.  Ebeling et. al. 
described three cases of laryngeal and laryngotracheal surgery performed using Hi-VNI 
oxygenation with SpO2 maintained about 97% in all three cases, although their measured rise 
in pCO2 after 15 minutes of apnea, was slightly higher than previously noted.8  Other studies 
documented use of this oxygenation technique with prolonged apnea without desaturation of 
up to 65 minutes during continuous endoscopic procedures1,10 or in pediatric laryngeal 
surgery.11    Lyons et al. in their series of 28 patients undergoing laryngotracheal procedures 
with high-flow nasal oxygenation as a sole oxygenation method showed that only 4 patients 
had brief desaturations (<2 min) to the levels of SpO2 85-90% supporting use of Hi-VNI during 
laryngotracheal procedures.1  None of the studies included here reported adverse events 
related to Hi-VNI use, and in most instances the authors reported that Hi-VNI device was used 
as a sole method of oxygenation and provided adequate support.  Our study will help address 
some of the limitations in the currently available knowledge about the use of Hi-VNI in surgical 
procedures of the upper aerodigestive tract and will contribute to the growing body of literature 
in this rapidly evolving area.  Moreover, this study will help document the advantages and the 
disadvantages of Hi-VNI use from the standpoint of the upper airway surgeon and the 
anesthesiologist.   
2 Study Objectives 
The overall objectives for this study are to establish the efficacy of Hi-VNI in upper 
airway surgery from the anesthesiologist’s and surgeon’s perspectives, and to describe the 
ideal patient and the ideal pathology as well as suitable clinical scenarios when this 
oxygenation technique should be selected.  This study will not change labeling of the Hi-VNI 
Precision Flow device by the Vapotherm and is not intended to change marketing claims of the 
manufacturer pertaining to this device.   
2.1  Primary Objective 
To evaluate Hi-VNI use for airway management and oxygenation in upper airway surgery from 
the anesthesiologist’s and the surgeon’s perspective with the specific focus on:  

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 Physiologic changes during Hi-VNI use in apneic and spontaneously breathing patients 
such as maintenance of SpO2, changes in TcpCO2 (transcutaneous CO2) levels, and 
changes in vital signs, namely heart rate and blood pressure. 
2.2  Secondary Objectives 
To collect clinical information about the effect of Hi-VNI use on procedure duration with the 
specific focus on:  
 The effect of this technique on the duration of the induction phase of anesthesia, 
surgical procedure duration, and the duration of emergence from anesthesia  
 Ease of use and any intra-operative and post-operative difficulties that may arise from 
use of this oxygenation technique 
3 Investigational Plan  
3.1  General Design 
This is a prospective, interventional, pilot study that will describe the select cases of 
upper aerodigestive tract surgery performed at our institution with use of the Hi-VNI device. 
Data captured will be analyzed with a goal of determining the efficacy of this oxygenation 
technique for upper airway surgery. We will also collect useful clinical information about the 
most optimal clinical scenarios for use of this technique based on the cases in our data sample 
that will demonstrate successful case completion without a need for adjunct oxygenation 
techniques aside from Hi-VNI such as jet ventilation or endotracheal intubation.  
3.2  Allocation to Interventional Group  
All subjects included in this study will undergo the same intervention, defined as the use 
of Hi-VNI as primary or adjunct oxygenation technique.  
3.3  Study Measures 
After all of the eligibility criteria have been checked and a written informed consent has 
been signed by the patient, the recruited study participant’s records will be reviewed and 
pertinent information about the patient’s past medical/surgical history will be recorded, 
including age, sex, weight, height, BMI, and other relevant information.  
 
 
All patients will receive preoperative evaluation according to the guidelines established 
by the American Society of Anesthesia (ASA). If according to the ASA guidelines the patient 
requires a pre-operative EKG or other testing, the testing will be conducted prior to arrival in 
the preoperative area for a scheduled surgery. This is a routine sequence of events for all 
surgical patients, where they receive a preoperative physical exam and evaluation needed for 
medical clearance prior to surgery. Each patient will be evaluated by the surgical and 
anesthesia teams as part of the routine sequence of events for any surgical patient. All 
patients will have a full set of vitals taken, and will be seen by the nurse, anesthesia and 
surgical teams in the preoperative area. 
Standard anesthesia monitoring during surgery will include EKG, blood pressure, SpO2 
measured using standard anesthesia equipment used at our institution, transcutaneous pCO2 

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levels (TcpCO2) measured using a SenTec transcutaneous monitor applied on the right or left 
upper arm prior to induction, EEG (using BIS monitor), and body temperature.  We plan to use 
propofol and remifentanil without muscle relaxation as the primary anesthetic for all study 
cases.  We do not define a maximum time for Hi-VNI use during the procedure.  We anticipate 
that most of the study cases will be done within 20 minutes of the surgeon beginning the first 
step of the procedure.  The anesthesia staff during the cases enrolled in this study will be 
limited to the sub-Is for this study (Drs. Atkins, Ayubcha, and Gavrin), who received an in-
service training by the manufacturer of Vapotherm Precision Flow device, and have clinical 
expertise in use of this device in proposed settings.  Both sub-Is are also familiar with the use 
of SenTec monitor during anesthesia, and will receive a detailed overview on how the device 
functions from a representative of SenTec before the study begins.  They will be present in the 
OR during the study cases.  Additional anesthesia team members including anesthesia 
residents, SRNAs and CRNAs will be required to read provided device manuals and study 
pathways/protocols before they participate in the care of the enrolled patients.  The entire team 
including the circulator and the scrub tech, the surgical team, the anesthesia team will go over 
the use, the contraindications and hazards of the device use for Hi-VNI Precision Flow and 
SenTec monitor, the parameters that may prompt rescue ventilation and the steps to take if 
laser or cautery will be required.  All staff members involved in the study cases will also review 
the airway fire protocol.  
 We intend to de-nitrogenate in the standard fashion with a face-mask.  All patients will 
receive preoxygenation with bag-mask to ensure mask ventilation can be performed 
successfully during the case if needed and to determine end-tidal CO2.  All patients who are 
successfully bag-masked during the induction phase will have disposable nasal cannula 
prongs placed to proceed with Hi-VNI use after the induction and the trial of bag-masking.  If 
mask ventilation during the induction phase is successful, the anesthesia team will proceed 
with oxygenation via Hi-VNI device at a maximum rate of flow of 40 L/min and FiO2 of 100%.  
The rate of flow will remain at the maximum setting of 40 L/min throughout the case, and will 
not be adjusted at any point.  If mask ventilation during the induction phase is unsuccessful, 
the anesthesia team will intubate the patient or HFJV will be initiated after exposure of the 
glottis by the airway surgeon as currently practiced, and this patient will be excluded from the 
study.   
Transcutaneous CO2 is ideal for monitoring during apneic procedures with Hi-VNI since 
it provides a continuous trend of CO2 level and does not require a closed system (such as vent 
circuit attached to the endotracheal tube or a mask device).  Prior studies reported no 
difference between transcutaneous CO2 levels and arterial CO2 levels during apneic 
procedures on the upper airway with Hi-VNI use13 and when the correlation between arterial 
and transcutaneous CO2 was measured in healthy volunteers.16  Transcutaneous CO2 
correlated with arterial CO2 irrespective of BMI or sensor position further supporting its use in 
our study.16  Since the measurement of the transcutaneous O2 is still considered experimental, 
and its correlation with the patient’s oxygenation state has not been described in the literature, 
we will not use this parameter in our study.  Based on our initial clinical experience and the 
experience of our colleagues at other institutions with TcpCO2 monitor use during general 

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anesthesia, it is evident that end-tidal CO2 deviates from the level of TcpCO2 measured by the 
TcpCO2 monitor.  We plan to establish a gradient between the value of end-tidal CO2 and the 
value of TcpCO2 in the beginning of each case, while the patient is being pre-oxygenated with 
a bag-mask.  This baseline gradient will be used to determine the level of TcpCO2 adequate 
for continuous use of Hi-VNI during the case.   
The Hi-VNI device will be used during the surgical procedure with continuous monitoring 
by anesthesia team.  If at any point the SpO2 drops below 90% or TpCO2 minus the baseline 
gradient value rises above 55 mmHg, the airway surgeon and the anesthesiologist will stop the 
procedure and immediately switch to an alternate means of oxygenation by placing an HFJV 
cannula or a small-sized endotracheal tube through the laryngoscope into the glottis/trachea (a 
step performed in the beginning of the case if HFJV or endotracheal intubation are selected as 
primary methods of oxygenation during the case). These levels of TcpCO2 were not previously 
correlated clinically with PaCO2, and therefore should be avoided when using Hi-VNI system.  
A total of 5 breaths will be administered via the endotracheal tube to determine the 
ETCO2 reading.  If the ETCO2 reading is above 60 mmHg, the patient will be ventilated via the 
endotracheal tube.  In other words, continuous monitoring will ensure that clinically significant 
hypoxia or hypercarbia (defined as SpO2 level below 90% or ETCO2 levels above 60 mm/Hg) 
that could eventually lead to adverse events if not promptly corrected will always be avoided by 
immediate switch to alternate means of oxygenation.  HFJV equipment, a small-sized 
endotracheal tube, and all standard operating room airway and resuscitation equipment will be 
available as is the current standard during each case to allow for safe use of Hi-VNI and to 
prepare for the cases in which alternate means of oxygenation may be required.  
All precautions will be taken to prevent vital sign changes that affect the accuracy of 
TcpCO2 measurements including changes in blood pressure, abnormal heart rhythm, or body 
temperature changes.  Warming blankets will be used to avoid hypothermia.  If a patient 
develops a transient arrhythmia or hypotension requiring vasopressor administration during the 
procedure, which can cause erroneous SpO2 and inaccurate TcpCO2, the patient will be 
intubated and the procedure will be completed with oxygenation/ventilation via the 
endotracheal tube.  If the procedure cannot be performed with the endotracheal tube in place, 
the procedure will be aborted.  If the arrhythmia persists, or if the nature of the arrhythmia is 
considered to warrant procedure termination, the procedure will be aborted.  Additionally, if use 
of Hi-VNI support extends beyond 20 minutes, a blood sample will be drawn to evaluate CO2 
level (PaCO2 or PvCO2).  If the blood sample collection cannot be done, the patient will be 
intubated and ETCO2 will be measured.  
If at any point during the procedure, a bleeding is encountered that requires cautery, the 
team will switch to an endotracheal tube to prevent aspiration of blood into the airway and to 
allow for appropriate hemostasis with use of cautery.  If at any point during the procedure, it 
will become evident that the laser use is necessary, the team will switch to an alternate means 
of oxygenation.  Standard practices currently in place to avoid airway fire will be used if the 
case demands use of electrocautery or laser.  These practices will be implemented 
immediately once it becomes evident that either laser or electrocautery will be used.  If laser or 
electrocautery will be used to control the bleeding during the case, following an endotracheal 

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intubation, appropriate washout of residual oxygen will take place per routine protocol, and the 
laser or cautery will not be used until FiO2 levels reach the values below 21%.  All standard 
fire precautions will be used and the oropharynx will be suctioned to remove any potential 
residual oxygen excess.  All cases will be screened prior to enrollment into the study to avoid 
inclusion of the cases with high risk of large-volume bleeding requiring cautery or with a need 
for laser use during the procedure.  
Any upper airway procedure we perform begins with direct laryngoscopy and the 
exposure of the glottic airway with a laryngoscope.  With the exposed view of the vocal 
cords/glottic opening, the exchange step of endotracheal intubation or placement of the HFJV 
cannula takes a few seconds.  The surgical and anesthesia staff assigned to these cases are 
familiar with the exchange from one mode of oxygenation to another since this is commonly 
performed for these cases.  After performing a portion or the entire case with HFJV, the team 
generally elects to intubate the patient for the final steps of the surgical case or for emergence 
from anesthesia.  In cases where HVNI is used, the surgeon and anesthesiologist team will 
then decide if the patient will continue to receive oxygenation through the nasal cannula, get 
mask ventilated, or get intubated.  Investigators for this study do not anticipate any additional 
risks to the patient or significant additional time needed to complete these procedures during 
this study, even in the cases where use of Hi-VNI alone is insufficient. 
All surgical aspects of the case will be captured using video recording, which is 
standard for all upper airway surgeries at our institution performed with use of an endoscope or 
a microscope. A review of the video recordings for the cases included in the study will help us 
better understand how tubeless surgical space impacts the length of the case (from the time 
laryngeal exposure is visualized to the end of the case) and to visually document the airway 
pathology treated with Hi-VNI. The duration of induction, the procedure itself and the 
emergence from anesthesia will be measured.  Post-operative recovery of each participant will 
be assessed from the standpoint of any airway related complications, prolonged drowsiness or 
other complications pertinent to this study.  Additional information about the ease of Hi-VNI use 
and any difficulties encountered during the surgical case will be recorded.  Patients will also be 
asked to rate the comfort of the procedure including sore throat and irritation, which is 
anticipated to be less with the HVNI technique. 
 
Schedule of events: 
 
 
 
 
 
 
 
 
 
 
Evaluation by the 
surgeon, anesthesia 
and RN on arrival 
Consent and procedure 
related discussion with 
both the surgeon and 
anesthesia team  
Prior to OR 

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3.4  Study Endpoints  
3.4.1 Primary Study Endpoint 
The primary endpoint for this study will be case completion rate without alternative 
mode of oxygenation.  In other words, for each case, the ability to complete the surgical 
procedure with use of only Hi-VNI device for oxygenation will be assessed. 
3.4.2 Secondary Study Endpoints 
The secondary endpoints for the study will be the total case duration (induction to end of 
surgery), the time from the end of the case to emergence from anesthesia, nadir SpO2, peak 
TcpCO2, and rate of change in TcpCO2 (transcutaneous CO2).  
4 Study Population and Duration of Participation  
4.1  Duration of Study Participation  
The subject’s participation in this study will be limited to the time of their upper airway 
surgery and the time needed for post-operative recovery.  No long-term follow-up will be 
conducted for this study.  
Preoxygenation to 
ensure oxygen can be 
administered with a 
mask to rapidly 
increase oxygen levels 
In the OR 
Application of 
monitor leads and 
nasal cannula prongs 
If successful 
Continuous monitoring to 
ensure safe oxygenation 
and vital signs  
Procedure 
completion and 
wake up from 
anesthesia  
If indicated 
Abort procedure and 
place breathing tube 
or jet ventilation 
cannula 
After Surgery 
Wake up from anesthesia 
and transport to recovery 
unit 
Evaluation by the RN, 
surgeon and anesthesia 
team  
Observation while 
recovering from 
anesthesia and discharge  

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4.2  Total Number of Subjects and Sites  
We estimate that 100 subjects will be recruited for this study.  Penn will be the only 
study site. 
4.3  Inclusion Criteria 
Our study population will include adult patients (22 years old or older) who are 
scheduled to undergo upper airway surgery at our institution with the airway pathology that will 
require surgical interventions which could potentially benefit from a tubeless surgical field. The 
airway pathology located directly at the site of the endotracheal tube placement (supraglottis, 
glottis, subglottis, and proximal trachea) will benefit from a tubeless surgical field. 
o Patients must be able to read and understand English  
o Participants must sign the informed consent form 
o The surgical case must be a scheduled elective case and not performed as an urgent 
or emergent case 
4.4  Exclusion Criteria 
All patients with underlying medical conditions in which periods of hypoxemia or 
hypercarbia are not well tolerated will be excluded.  Patients in whom delivery of air with 
oxygen via nasal passages is contraindicated will be excluded.  The manufacturer’s guidelines 
for Hi-VNI device use will be followed.  The exclusion criteria will be defined as follows: 
o Pregnancy (at our institution, all female patients of childbearing age receive a 
pregnancy test clinically prior to surgery as part of SOC) 
o Coronary artery disease or carotid/vertebral artery stenosis 
o Severe heart failure with EF < 20% or implanted ICD 
o Pulmonary hypertension or pulmonary fibrosis  
o History of increased intracranial pressure 
o History of skull base or intracranial surgery 
o Severe nasal obstruction 
o Extremely low or extremely high BMI (BMI < 16 kg/m2 or BMI > 40 kg/m2) 
o Baseline home O2 or Baseline SpO2 < 90% 
o Airway pathology requiring laser use for surgical management  
o Airway pathology requiring surgical intervention with high risk of large-volume 
bleeding 
o Airway pathology requiring use of cautery throughout the procedure 
o High risk of aspiration during the procedure as determined by the patient evaluation 
and review of prior medical history (history of gastrointestinal obstruction, prior 
esophageal procedures, esophageal cancer, hiatal hernia, incoordination of 
swallowing and respiration, class III obesity defined as BMI>40) 
o Patients who are taken to the OR for an urgent or emergent upper airway surgery 

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4.5  Subject Recruitment  
Potential study participants will be identified using the surgical schedule and/or clinic 
schedule, and will be invited to participate using a standard informed consent form. Consent 
will be obtained by an Investigator (physician).  Privacy will be ensured by discussing the study 
and the patient's disease within a private room in the clinic or in the pre-operative unit area, 
where they are unlikely to be overheard.  Patients will be given ample time to read the consent 
form, discuss the study, ask questions, consider participation, and make an informed decision. 
All potential participants will be provided with a short description of the Hi-VNI technique 
and the reasons for use of this technique during their surgical procedure.  The subjects will 
have an opportunity to ask their airway surgeon (the PI) and their anesthesiologist (the sub-Is) 
about the reasons for selection of this airway management technique and any potential 
alternatives as well as the risks and benefits of its use during their airway procedure.  The 
subjects will be enrolled into the study only after their consent is obtained and all of their 
questions about Hi-VNI have been answered.  
4.6  Vulnerable Populations 
There are no children or adolescents in this study, and all adult subjects will be 
competent to give consent.  Negative pregnancy test (administered clinically, per standard of 
care) is one of the requirements for all adult female patients of reproductive age who are 
scheduled for surgical procedure at our institution, and pregnant women will be excluded from 
this study.  Although not directly targeted, mentally disabled persons, economically or 
educationally disadvantaged persons, and/or employees or students of the University of 
Pennsylvania will not be denied enrollment and any special protections and/or additional 
safeguards will be undertaken in order to protect the rights and welfare of these subjects from 
coercion or undue influence as appropriate. 
5 Study Procedures  
Please see section 3.3. 
5.1 Screening  
The PI will identify eligible participants for this study using the surgical schedule and/or 
clinic schedule.  The subject’s eligibility will be determined based on the type of the airway 
pathology, the type of planned surgical procedure and the exclusion criteria already described 
in Section 4.4 of this protocol.  Additionally, the anesthesia team will make sure at the 
beginning of each case that adequate mask ventilation can be performed on each patient who 
consents to participate in the procedure to ensure that during the procedure the anesthesia 
team can safely switch to alternate modes of oxygenation. 
5.2  Study Intervention Phase  
All information needed for this study will be recorded during the upper airway surgical 
procedure and immediately after the surgical procedure in the post-operative recovery unit.  
Recruited subjects will not be followed long-term.  

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5.3 Device Management 
There are two Precision Flow Hi-VNI devices in the PCAM equipment storage room.  
The surgical procedures planned for this study will be performed at PCAM.  These devices will 
be stored according to the manufacturer's requirements and in compliance with the Penn peri-
op policies for storage of standard anesthesia and peri-op equipment.  No special storage or 
processing will be required when these devices are used for our research study.  The devices 
will be used by fully-trained personnel, as the PI, co-Is, and research staff, as well as 
anesthesia support staff, had an in-service with the manufacturer's representative to learn how 
to use these devices.  Disposable parts needed for the devices will be discarded after one use.  
All disposables will be provided by the manufacturer, Vapotherm, Inc.  
5.4  Subject Withdrawal  
All study subjects may withdraw from the study at any time without impact to their care.  
They may also be discontinued from the study at the discretion of the PI and co-Is if it is 
determined that they are not good candidates for Hi-VNI use immediately prior to surgical 
procedure or during the surgical procedure.  This decision will be made based on a joint 
discussion between the airway surgeon and the anesthesiologist.   
5.4.1 Data Collection and Follow-up for Withdrawn Subjects 
Subjects who choose to withdraw from the study or will be withdrawn from the study at 
the discretion of the PI or co-I will not require any additional follow-up data collection for this 
study.   
5.5  Efficacy Evaluation 
The ability of the Hi-VNI device to provide adequate oxygenation has already been 
demonstrated based on existing literature and a small number of cases performed at our 
institution.  However, further evaluation of the efficacy for this oxygenation technique during 
upper airway surgery is one of the primary objectives for this study.  All information captured 
during this study will contribute to our present knowledge about the ideal clinical cases and 
patient characteristics when Hi-VNI should be selected for upper airway procedures performed 
under general anesthesia.  
6 Statistical Plan  
6.1  Sample Size and Power Determination 
The subjects will be recruited prospectively based on the eligibility criteria for this study. 
The investigators anticipate that 100 subjects will be recruited for this study between January 
2020 and January 2021.  This sample size is determined based on the previously noted 
caseload for our practice and the fact that this study duration will be limited to one year only.  
No comparison or control group will be used for this study.  The calculation of statistical power 
will not be required. Patel et al showed that a rate of rise in pCO2 was 0.15 kPa/min with Hi-
VNI oxygenation while measuring end tidal CO2 transcutaneously, which translates into 1.125 
mmHg/min.3 Another study by Gustaffson et al cited average apnea duration during elective 

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laryngeal surgery of 22.5+4.5 min.13 Based on these values of the rate of rise for pCO2 and 
the average apnea duration for elective laryngeal surgery, assuming normal data distribution, 
the range of TcpCO2 change for procedure length within one standard deviation of the mean 
value (22.5 min) will be [20.25; 30.38].  
Using a normal end-tidal CO2 value of 37.5 mmHg and adding this value to the limits of 
the range of change in TcpCO2 listed above will give us a range of the values for TcpCO2 at 
the end of the procedure assuming the average duration of the procedure is 22.5+4.5 min.  
This range of the TcpCO2 at the end of the procedure would be [57.75; 67.88].  Our cutoff of 
TcpCO2 minus the baseline gradient between TcpCO2 and end-tidal CO2 > 55 mmHg is when 
the mode of oxygenation will be changed from Hi-VNI to an alternate method (endotracheal 
intubation or HFJV).  The baseline gradient will be measured as the TcpCO2 minus the end-
tidal CO2 during routine pre-oxygenation with a facemask.  Based on the normal distribution 
assumption, one can deduce that only procedures with the duration one standard deviation 
away from the mean duration value of 22.5 min will not reach this level of TcpCO2.  In other 
words, approximately 16% of patients will not require alternate means of ventilation (population 
which falls to the left of the line through a value of (22.5-4.5) on the normal distribution curve or 
15.85%).  Based on the author’s prior experience and operative volume, there are 2-3 elective 
cases per week performed by the PIs that may qualify based on the inclusion/exclusion criteria 
to be included in the study.  If 3 cases per week is used will equal to 144 qualified cases per 
year.  For the confidence interval of 95% and the margin of error of 5% with the rate of 16%, 
the calculated sample size will equal to 86 individuals who might have a good chance of 
having their procedure completed with Hi-VNI without a need to switch to alternate mode of 
oxygenation.  To account for the fact that some patients may not consent to be in the study or 
may require alternate means of oxygenation after Hi-VNI is used for other reasons, we added 
14 patients to the sample size.  This would lead to an estimated sample size of 100 individuals. 
6.2  Statistical Methods 
Descriptive statistics will be used to characterize the data distribution with normally 
distributed data presented as means and standard deviation, otherwise median and 
interquartile range will be used.  Proportions will be presented in numbers and percentages.  
All data analyses will be performed using a statistical tool (SPSS, version 15.0, SPSS).  Mann-
Whitney U test or Student’s t-test and Kruskal-Wallis or ANOVA test will be used depending on 
the data distribution and the number of variables.  All statistical analyses will use a p<0.05 as 
statistically significant.  Any additional statistical analyses will be determined during secondary 
data analysis with help from a statistician.  
6.3  Control of Bias and Confounding  
This is an interventional study that will involve recruitment of subjects who are 
scheduled to undergo an upper airway surgery and are good candidates for use of Hi-VNI 
during their procedure.  The investigators for this study expect some degree of bias during the 
subject recruitment phase, but this selection bias will help exclude patients who will not tolerate 
use of Hi-VNI for oxygenation during surgery due to their co-morbidities.  Please see Section 
4.4 for exclusion criteria defined for this study.  

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6.3.1 Baseline Data 
Baseline and demographic characteristics will be summarized by standard descriptive 
statistics (including mean and standard deviation for continuous variables such as age and 
standard percentages for categorical variables such as gender). 
6.3.2 Analysis of Primary Outcome of Interest 
The primary outcomes of interest will be analyzed based on the data distribution with a 
goal of determining the averages and the standard deviations within the dataset.  
7 Safety and Adverse Events 
7.1  Definitions 
7.1.1 Adverse Event/Adverse Device Effect 
An adverse event (AE)/adverse device effect (ADE) is any symptom, sign, illness or 
experience that develops or worsens in severity during the course of the study.  Intercurrent 
illnesses or injuries should be regarded as adverse events.  Abnormal results of diagnostic 
procedures are considered to be adverse events if the abnormality: 
 results in study withdrawal 
 Is associated with a serious adverse event 
 is associated with clinical signs or symptoms 
 leads to additional treatment or to further diagnostic tests 
 is considered by the investigator to be of clinical significance 
7.2 Serious Adverse Event 
Adverse events are classified as serious or non-serious.  A serious AE is any AE that is:  
 fatal 
 life-threatening 
 requires or prolongs hospital stay 
 results in persistent or significant disability or incapacity 
 required intervention to prevent permanent impairment or damage 
 a congenital anomaly or birth defect 
 an important medical event 
 
Important medical events are those that may not be immediately life threatening, but are 
clearly of major clinical significance.  They may jeopardize the subject, and may require 
intervention to prevent one of the other serious outcomes noted above.  For example, drug 
overdose or abuse, a seizure that did not result in in-patient hospitalization, or intensive 
treatment of bronchospasm in an emergency department would typically be considered 
serious.  
All adverse events that do not meet any of the criteria for serious should be regarded as 
non-serious adverse events.  

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Unanticipated Adverse Device Effect (UADE) 
A UADE is any serious adverse effect on health or safety, or any life-threatening 
problem or death caused by, or associated with, a device, if that effect, problem, or death was 
not previously identified in nature, severity, or degree of incidence in the investigational plan or 
application, or any other unanticipated serious problem associated with a device that relates to 
the rights, safety, or welfare of subjects. 
7.3  Recording of Adverse Events 
All adverse events occurring during the study period will be recorded.  The clinical 
course of each event will be followed until resolution, stabilization, or until it has been 
determined that the study intervention or participation is not the cause.  Serious adverse 
events that are still ongoing at the end of the study period will be followed up to determine the 
final outcome.  Any serious adverse event that occurs after the study period and is considered 
to be possibly related to the study intervention or study participation will be recorded and 
reported. 
7.4  Relationship of AE to Study  
The PI will determine the relationship of each adverse event to the study procedures.  
Relationship will be classified as definitely related, probably related, possibly related, or not 
related. 
7.5  Reporting of Adverse Events and Unanticipated Problems 
The Investigator will promptly notify the Penn IRB of all on-site unanticipated, Adverse 
Events that are related to the research activity.  Other unanticipated problems related to the 
research involving risk to subjects or others will also be reported promptly.  Written reports will 
be filed using the HS-ERA and in accordance with the Penn IRB timeline of 10 working days.  
7.5.1 Follow-up Report 
If an AE has not resolved at the time of the initial report and new information arises that 
changes the investigator’s assessment of the event, a follow-up report including all relevant 
new or reassessed information (e.g., concomitant medication, medical history) should be 
submitted to the IRB.  The investigator is responsible for ensuring that all SAEs are followed 
until either resolved or stable.  
7.5.2 Data and Safety Monitoring Plan 
The PI and the co-Is for this study will be responsible for data and safety monitoring.  
No formal data safety monitoring committee will be designated for this study since the PI and 
the sub-Is will closely monitor data safety for this study. 

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8 Study Administration, Data Handling and Record Keeping 
8.1  Confidentiality 
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA).  
Those regulations require a signed subject authorization informing the subject of the following:  
 What protected health information (PHI) will be collected 
 Who will have access to that information and why 
 Who will use or disclose that information 
 The rights of a research subject to revoke their authorization for use of their PHI.  
In the event that a subject revokes authorization to collect or use PHI, the investigator, 
by regulation, retains the ability to use all information collected prior to the revocation of 
subject authorization. 
8.2  Data Collection and Management  
The primary source of data collection for this study will be the current electronic medical 
record (EMR) system used at the University of Pennsylvania Health System (UPHS) and intra-
operative/post-operative findings and observations recorded by the study personnel.  During 
the selection of potential study participants, the electronic medical records will be reviewed by 
the PI/Co-Is, who will confirm eligibility based on the inclusion and exclusion criteria.  If the 
case meets eligibility, the research team will proceed with informed consent either prior to or 
on the day of the scheduled surgical procedure.  
Qualified patients will be assigned a unique study identification number (UID).  Data will 
be abstracted electronically in a comma separated variable format for a statistical software 
package.  The databases will be maintained on an institutionally secured and managed 
network drive.  Only members of this research study team will have access to the data.  Birth 
date will only be used to calculate an exact age in years and months.  Upon completion of data 
collection, the age will replace the birth date.  A master data sheet will include the relevant 
personal health information (PHI) for the study with the matching UID numbers.  A separate 
data sheet used for statistical analyses will have only the UID numbers with de-identified 
information.  
8.3  Records Retention 
The electronic data as well as paper and digital records collected during this study will 
be destroyed within five years following publishing.  
9 Study Monitoring, Auditing, and Inspecting 
9.1  Study Monitoring Plan 
The study PI and sub-Is will be responsible for ensuring the ongoing quality and integrity 
of the research study.  

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9.2  Auditing and Inspecting 
The investigator will permit study-related monitoring, audits, and inspections by the IRB, 
government regulatory bodies, and University compliance and quality assurance groups of all 
study-related documents.  The investigator will ensure the capability for inspections of 
applicable study-related facilities. 
Participation as an investigator in this study implies acceptance of potential inspection 
by government regulatory authorities and applicable University compliance and quality 
assurance offices. 
10 Ethical Considerations 
All study team members have experience/training in clinical research and have 
completed their CITI human subjects training.  All study team members will be asked to 
document their role on the study delegation log.  Ongoing training will take place as needed.  
The investigators will maintain open communication with study staff and IRB, and will submit 
protocol changes to IRB for approval prior to implementing them. 
10.1 Risks 
All subjects included in this study will be informed about potential risks associated with 
the use of the Hi-VNI device during surgery based on the previously published studies and the 
safety information reported by the Hi-VNI device manufacturer.  These risks include nasal 
discomfort and/or rhinorrhea.  To our knowledge, no other risks have been previously directly 
linked to Hi-VNI use.  These side effects of Hi-VNI use could be related to dry nasal mucosa 
after use of high-flow nasal insufflation, and will prescribe nasal saline sprays and recommend 
Tylenol or other mild over the counter analgesics in cases when patients report symptoms of 
nasal pain and/or rhinorrhea.   
To minimize the risk of inadequate oxygenation and other complications, careful 
continuous monitoring will be maintained throughout the case.  All patients will receive 
preoxygenation with a bag-mask to ensure that mask ventilation can be performed 
successfully during the case if needed and to determine the baseline gradient between end-
tidal CO2 and TcpCO2.  If mask ventilation during the induction phase is unsuccessful, the 
anesthesia team will intubate the patient or HFJV will be initiated after exposure of the glottis 
by the airway surgeon, and the patient will be withdrawn from the study.  
The Hi-VNI device will be used during the surgical procedure with continuous monitoring 
by anesthesia team.  If at any point the SpO2 drops below 90% or the value of  TcpCO2 minus 
the baseline gradient rises above 55 mmHg, the airway surgeon and the anesthesiologist will 
stop the procedure and will switch to an alternate means of oxygenation immediately by 
placing an HFJV cannula or a small sized endotracheal tube through the laryngoscope into the 
glottis/trachea (a step performed in the beginning of the case if HFJV or endotracheal 
intubation are selected as primary methods of oxygenation during the case).  Continuous 
monitoring in the OR will help us avoid TcpCO2 minus the baseline gradient levels above 55 
mmHg (levels of TcpCO2 not previously correlated clinically with PaCO2). As soon as this 
threshold value is reached, the surgeon will place an endotracheal tube through the 

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laryngoscope.  A total of 5 breaths will be administered via the endotracheal tube to determine 
the ETCO2 reading.  If the ETCO2 reading is above 60 mmHg, the patient will be ventilated via 
the endotracheal tube. In other words, continuous monitoring will ensure that clinically 
significant hypoxia or hypercarbia (defined as SpO2 level below 90% or ETCO2 levels above 
60 mmHg) that could eventually lead to adverse events if not promptly corrected will always be 
avoided by immediate switch to alternate means of oxygenation.  HFJV equipment, a small 
sized endotracheal tube, and all standard operating room airway and resuscitation equipment 
will be available as is the current standard during each case to allow for safe use of Hi-VNI and 
to prepare for the cases in which alternate means of oxygenation may be required.  
All precautions will be taken to prevent vital sign changes that affect the accuracy of 
TcpCO2 measurements including changes in blood pressure, abnormal heart rhythm or body 
temperature changes. Warming blankets will be used to avoid hypothermia. If a patient 
develops a transient arrhythmia or hypotension requiring vasopressor administration during the 
procedure, which can cause erroneous SpO2 and inaccurate TcpCO2, the patient will be 
intubated and the procedure will be completed with oxygenation/ventilation via the 
endotracheal tube.  If the procedure cannot be performed with the endotracheal tube in place, 
the procedure will be aborted.  If the arrhythmia persists, or if the nature of the arrhythmia is 
considered to warrant procedure termination, the procedure will be aborted.  Additionally, if use 
of Hi-VNI support extends beyond 20 minutes, a blood sample will be drawn to evaluate CO2 
level (PaCO2 or PvCO2).  If the blood sample collection cannot be done, the patient will be 
intubated and ETCO2 will be measured.  
If at any point during the procedure, a bleeding is encountered that requires cautery, the 
team will switch to an endotracheal tube to prevent aspiration of blood into the airway and to 
allow for appropriate hemostasis with use of cautery.  If at any point during the procedure, it 
will become evident that the laser use is necessary, the team will switch to an alternate means 
of oxygenation.  Standard practices currently in place to avoid airway fire will be used if the 
case demands use of electrocautery or laser.  These practices will be implemented 
immediately once it becomes evident that either laser or electrocautery will be used.  If laser or 
electrocautery will be used to control the bleeding during the case, following an endotracheal 
intubation, appropriate washout of residual oxygen will take place per routine protocol, and the 
laser or cautery will not be used until FiO2 levels reach the values below 21%.  All standard 
fire precautions will be used and the oropharynx will be suctioned to remove any potential 
residual oxygen excess.  All cases will be screened prior to enrollment into the study to avoid 
inclusion of the cases with high risk of large-volume bleeding requiring cautery or with a need 
for laser use during the procedure.  
Any upper airway procedure we perform begins with direct laryngoscopy and the 
exposure of the glottic airway with a laryngoscope.  With the exposed view of the vocal 
cords/glottic opening, the exchange step of endotracheal intubation or placement of the HFJV 
cannula takes a few seconds.  The surgical and anesthesia staff assigned to these cases are 
familiar with the exchange from one mode of oxygenation to another since this is commonly 
performed for these cases.  After performing a portion or the entire case with HFJV, the team 
then elect to intubate the patient for the final steps of the surgical case or for emergence from 

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anesthesia.  In cases where HVNI is used the surgeon and anesthesiologist team will then 
decide if the patient will continue to receive oxygenation through the nasal cannula, get mask 
ventilated or get intubated.  Investigators for this study do not anticipate any additional risks to 
the patient or significant additional time needed to complete these procedures during this 
study, even in the cases where use of Hi-VNI alone is insufficient. 
Patients who are not candidates for Hi-VNI use will be excluded from this study.  These 
patients include those with underlying medical conditions in which brief periods of hypoxemia 
or hypercarbia are not well-tolerated, such as pregnant patients, patients with coronary artery 
disease or carotid/vertebral artery stenosis, patients with severe heart failure or implanted ICD, 
patients with extremely low or extremely high BMI or patients with baseline hypoxia and 
oxygen requirement at home.  Additionally, patients in whom use of high-flow oxygenation is 
contraindicated, such as patients with increased intracranial pressure or history of skull base 
surgery, will be excluded.  Patients at high risk for aspiration and patients scheduled for 
emergent or urgent interventions will also be excluded. 
10.2 Benefits 
The potential direct benefits to the subjects who will consent to participate in this study 
are a chance of shorter surgical case duration, potential avoidance of intubation, and lower risk 
of barotrauma and airway trauma if Hi-VNI is used without a need for intubation or HVJV use 
during the procedure.  This study also offers indirect benefits to the society and the future 
patients by attempting to further evaluate the efficacy of the Hi-VNI as a primary or adjunct 
oxygenation technique during upper airway surgery.  This study will not change labeling of the 
Hi-VNI Precision Flow device by the Vapotherm and is not intended to change marketing 
claims of the manufacturer. 
10.3 Risk Benefit Assessment 
The Risk Benefit Assessment will be done for each individual subject before proceeding 
with the enrollment to ensure that use of Hi-VNI during upper airway surgery does not 
predispose the potential subject to any foreseeable harm or risk of complications.  This 
assessment will involve a joint discussion between the airway surgeon (the PI) and the 
anesthesiologist (the sub-Is).  
10.4 Informed Consent Process / HIPAA Authorization  
All subjects for this study will be provided a combined consent/HIPAA authorization form 
(attached) describing this study providing sufficient information for subjects to make an 
informed decision about their participation in this study.  This consent form will be submitted 
with the protocol for review and approval by the IRB.  The formal consent of a subject, using 
the IRB-approved consent form, will be obtained before that subject undergoes any study 
procedure.  The subject and the investigator-designated research professional obtaining the 
consent will sign the consent form.  Subjects will be consented by the study Principal 
Investigator, or appropriate designee, in a private room where their discussions are unlikely to 
be overheard and their privacy is priority.  Potential subjects will review the consent form in 

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detail with the person designated to consent and will have the ability to take the consent home 
for further review.  
11 Study Finances 
11.1 Funding Source 
None.  The manufacturer of the device, Hi-VNI Precision Flow, will provide the devices 
needed for this study (Hi-VNI Precision Flow and SenTec monitor) and the disposables 
needed for their use.  No additional funding will be provided.  
11.2 Conflict of Interest 
All University of Pennsylvania Investigators will follow the University of Pennsylvania 
Policy on Conflicts of Interest Related to Research. 
11.3 Subject Stipends or Payments 
None  
12 Publication Plan 
The Principal Investigator intends to present the results at a national conference and 
publish the study results in a peer-reviewed medical journal.  
13 References 
 
1.  
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