High Flow Nasal Oxygen During Conscious Sedation in the Cardiac Catheterisation Laboratory: A Randomized Controlled Trial
Phase: NA
Conditions: Anesthesia, Cardiac Disease
Sponsor: University Health Network, Toronto

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2 INTRODUCTION
3 METHODS
4 ETHICS AND
DISSEMINATION
5 STUDY
ADMINISTRATION
REFERENCES
1 TRIAL
SUMMARY
 
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Research Protocol
High ﬂow nasal oxygen during
conscious sedation in the cardiac
catheterisation laboratory: A
randomized controlled trial
Version 5
2019.06.13
Study Principal Investigator:
Aaron Conway, RN, PhD 
RBC Chair in Cardiovascular
Nursing Research 
Peter Munk Cardiac Centre,
Toronto General Hospital,
University Health Network 
Assistant Professor
Lawrence S. Bloomberg Faculty of
Nursing, University of Toronto 
Sponsors:
Investigator-sponsored trial 
Matteo Parotto, MD, PhD 
Assistant Professor, Department of
Anesthesia and Interdepartmental
Division of Critical Care Medicine,
University of Toronto 
Staﬀ, Department of Anesthesia
and Pain Management, Toronto
General Hospital

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Protocol contributors:
Phoebe Lam, M.Ed, H.BSc, RRT,
CCAA, FCSRT 
Coordinator, Anesthesia Simulation
Centre
Educator, Anesthesia Assistant,
University Health Network
Ana Lopez Filici, MHSc (HA),
HBSc, CCAA, RRT, FCSRT 
Manager, Anaesthesia Clinical
Services,​ University Health Network
Trial identiﬁers:
CAPCR 18-6343
ABBREVIATIONS
Abbreviation
Explanation
TcCO
Transcutaneous carbon dioxide
CAPCR
Coordinated Approval Process for Clinical Research
EPR
Electronic Patient Record
HFNO
High Flow Nasal Oxygen
ISAS
Iowa Satisfaction with Anesthesia Scale
IT
Information and Technology
PHI
Personal Health Information
PI
Principal Investigator
PICF
Participant Information and Consent Form
RA
Research Assistant
REB
Research Ethics Board
UHN
University Health Network
REVISION HISTORY
2

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Version
Amendment Text
Description
2 (2019.04.08)
3.3 Interventions
3.4 Outcomes
3.7. Recruitment
3.8 Allocation
3.11. Data management
3.12 Statistical methods
4.3 Informed consent
process
4.8.3 Reproducible research
Post-initial ethics
review
3 (2019.04.30)
3.12 Statistical methods
4.3 Informed consent
process
Post ethics review
(2019.04.30)
4 (2019.05.24)
1. Introduction
3.3.2 Modiﬁcations
3.8 Allocation
3.10 Data Collection
4.3 Informed consent
process
5.2 Funders
5.3.2 Sponsor and Funder
Post full board review
(2019.05.17)
5 (2019.06.13)
3.2.1 Inclusion criteria
(clariﬁed process for AA
sedation)
3.3.1 Intervention
description
3.3.4 Concomitant Care
Post full board review
of response
(2019.06.12)
1 TRIAL SUMMARY
World Health Organization
Registration Data Set
Title
High ﬂow nasal oxygen during
conscious sedation in the cardiac
catheterisation laboratory: A
randomized controlled trial

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Primary registry and trial
identifying number
ClinicalTrials.gov NCT03858257
Secondary identifying numbers
CAPCR 18-6343
Sources of monetary or material
support
This study will be fully supported
by funds received by the PI,
Aaron Conway, for his
appointment as Chair of
Cardiovascular Nursing Research
at PMCC. This includes all work
undertaken by the Research
Coordinator and purchasing of
equipment and consumables for
the HFNO and TcCO  monitoring
devices.
Primary sponsor
Investigator-sponsored trial
Secondary sponsors (if any)
n/a
Central contact
Aaron Conway, RN, PhD
RBC Chair in Cardiovascular
Nursing Research 
Peter Munk Cardiac Centre
Toronto General Hospital
University Health Network 
Assistant Professor 
Lawrence S. Bloomberg Faculty
of Nursing, University of Toronto
Toronto General Hospital Heart &
Circulation Admin 4NU - 476 585
University Ave Toronto, ON M5G
2N2
(416) 340-4654
aaron.conway@uhn.ca
(mailto:aaron.conway@uhn.ca)
Study oﬃcials/Investigators
Aaron Conway, RN, PhD
Study Principal Investigator
Brief title
High ﬂow nasal oxygen during
sedation
Acronym
n/a
2

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Countries of recruitment
Canada
Condition(s) or focus of study
High ﬂow nasal oxygen (HFNO)
during procedural sedation.
Interventions
High ﬂow nasal oxygen
Intervention type: Device
Intervention name: High ﬂow
nasal oxygen
Intervention description: The
Optiﬂow device (Fisher and
Paykel Healthcare, Auckland,
New Zealand) will be used. The
gas temperature will commence
at the ‘High’ setting (ranges 30-
32º Celsius) and titrated
downwards if the patient
complains of irritation. The gas
ﬂow rate will commence at 30
liters per minute prior to sedation
administration and be titrated up
to 70 liters per minute as
tolerated by the patient after
sedation has been administered.
The fraction of oxygen in the gas
will be commenced at 50% (same
as that delivered from 6 liters per
minute via facemask) and can be
titrated upward according to
patient requirements
(i.e. increased if there is evidence
of hypoventilation, airway
obstruction or inadequate
oxygenation).
Facemask oxygen
supplementation (usual care)
Intervention type: Device
Intervention name: Facemask
oxygen supplementation
Intervention description:

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Supplemental oxygen through a
facemask with the ﬂow rate
chosen by the clinician
responsible for sedation as per
their standard practice. The
oxygen ﬂow rate is typically
commenced at 6 liters per minute
and can be titrated up to 15 liters
per minute.
Key eligibility criteria
Age eligibility: 16 years or older
Sex eligibility: Both
Accepts healthy volunteers: No 
Inclusion criteria: 
1. Adults undergoing an elective
cardiac implantable electronic
device procedure in the Peter
Munk Cardiac Centre Cardiac
Cath Labs with conscious
sedation administered by an
Anesthesia Assistant (de novo
and replacement/revision
procedures). 
Exclusion criteria:
1. Under 16 years of age.
2. Underlying condition requiring
chronic oxygen supplementation.
3. Diagnosed respiratory
condition with conﬁrmed current
hypercapnia.
4. Pre-existing untreated
pneumothorax.
5. Transesophageal
echocardiography planned for the
procedure.
6. Active nasal bleeding.
7. Complete nasal obstruction.
8. Recent upper airway surgery or

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base of skull fracture.
9. Previous participation in the
study.
Study design
Study type: Interventional trial
Allocation: Randomized
Intervention model: Parallel group
Primary purpose: Health Services
Research 
Phase: n/a
Masking
Outcome assessors
Date of enrollment
June 2019 (anticipated)
Target sample size
150
Recruitment status
Not yet recruiting
Primary outcomes
Outcome: Peak transcutaneous
carbon dioxide (TcCO )
concentration
Timeframe: From the time
between ﬁrst sedative medication
administration to the end of the
procedure. Estimated duration of
procedures is 30 minutes to 120
minutes.
Description: Continuous
measurements will be recorded
using the Sentec Digital
Monitoring System with VSign 2
sensor.
Secondary outcomes
Outcome: Mean transcutaneous
carbon dioxide concentration
Timeframe: From the time
between ﬁrst sedative medication
administration to the end of the
procedure. Estimated duration of
procedures is 30 minutes to 120
minutes.
2

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Description:Continuous
measurements will be recorded
using the Sentec Digital
Monitoring with VSign 2 sensor
Outcome: Trajectory of
transcutaneous carbon dioxide as
a function of time 
Timeframe: From the time
between ﬁrst sedative medication
administration to the end of the
procedure. Estimated duration of
procedures is 30 minutes to 120
minutes.
Description: Continuous
measurements will be recorded
using the Sentec Digital
Monitoring with VSign 2 sensor
Outcome: Area under SpO  90%
desaturation curve 
Timeframe: From the time
between ﬁrst sedative medication
administration to the end of the
procedure. Estimated duration of
procedures is 30 minutes to 120
minutes.
Description: Diﬀerence between
the threshold (90%) and actual
oxygen saturation (SpO2)
summed every second during
which oxygen saturation was
below threshold.
Outcome: Adverse sedation
events
Timeframe: From the time
between ﬁrst sedative medication
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administration to the end of the
procedure. Estimated duration of
procedures is 30 minutes to 120
minutes.
Description: The Anaesthesia
Assistant will be asked to
complete the Tracking and
reporting outcomes of procedural
sedation (TROOPS) tool at the
end of procedures. Completion of
the tool requires identiﬁcation and
description of the adverse event,
the intervention, the outcome and
the overall severity of the adverse
event.
Outcome: Patient satisfaction
with sedation
Timeframe: After the participant
has reached phase 2 post-
anesthetic recovery. Estimated to
be 30 minutes after procedure
has ﬁnished.
Description:Iowa Satisfaction with
Anesthesia Scale
Outcome: Costs associated with
oxygen delivery
Timeframe: From the time
between ﬁrst sedative medication
administration to the end of the
procedure. Estimated duration of
procedures is 30 minutes to 120
minutes.
Description: Anesthesia
Assistants will document devices
used for supplemental oxygen
delivery and airway management

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in both groups as per their usual
practice in the anesthesia
monitoring system.
Outcome: Anesthesia Assistant
rating of diﬃculty maintaining
oxygenation status
Timeframe: To be completed as
soon as possible after the end of
the procedure (within about 5
minutes).
Description: 6-level rating scale
from “extremely diﬃcult” to
“extremely easy”
Outcome: Anesthesia Assistant
rating of diﬃculty using oxygen
delivery device
Timeframe: To be completed as
soon as possible after the end of
the procedure (within about 5
minutes)
Description: 6-level rating scale
from “extremely diﬃcult” to
“extremely easy”
Outcome: Patient comfort of
oxygen delivery
Timeframe: After the participant
has reached phase 2 post-
anesthetic recovery. Estimated to
be 30 minutes after procedure
has ﬁnished. 
Description: 6-level rating scale
from “maximal discomfort” to
“maximal comfort”

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2 INTRODUCTION
2.1 Background and rationale
High ﬂow nasal oxygen (HFNO) is increasingly regarded as a promising
technology for oxygen delivery in critical care and anesthetic
management.  It permits ﬂows of heated, humidiﬁed gas to be
delivered to the lungs via nasal prongs at up to 70 liters per minute.
Delivering oxygen at such high ﬂow rates into the lungs has multiple
physiological eﬀects that may better support the vulnerable breathing
state of patients during procedural sedation. For example, it permits
more precise titration of the amount of oxygen being administered to
the patient because the ﬂow rate exceeds normal inspiratory volumes
(about 30 liters per minute). HFNO also increases pressure in the upper
airways (which may reduce airway obstruction) and decreases the
space within the airways where gas is not able to come in contact with
blood and exchange oxygen for carbon dioxide to be exhaled.
In anticipation that the physiological eﬀects of delivering HFNO may
lead to improved clinical outcomes, multiple large-scale randomized
controlled trials were conducted to test this technology across a variety
of critical care populations including acute respiratory failure
 and
post cardiac surgery.  There have also been multiple trials testing the
eﬃcacy of integrating HFNO into anesthetic management plans,
including for pre-oxygenation prior to, and apneic oxygenation at,
anesthetic induction.
There is heightened interest in investigating the eﬀects of HFNO
therapy for procedural sedation at present. Three small randomized
controlled trials of HFNO during procedural sedation have been
published in the last year, with a further 5 trials registered at
clinicaltrials.gov. One study randomized 60 participants undergoing
bronchoscopy to receive HFNO at 50 liters per minute with 100%
oxygen or to receive oxygen at 10-15 liters per minute through a
facemask.  There was no diﬀerence observed between the treatment
groups for the primary outcome, which was the proportion of patients
who experienced oxygen desaturation (deﬁned as SpO  90%). Another
study randomized 59 morbidly obese patients undergoing endoscopy
to receive a fraction of inspired oxygen concentration of 0.36 either via
HFNO at a ﬂow rate of 60 liters per minute or via nasal cannula at 4
1
2–4
5
6,7
8
2

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liters per minute.  Again, there was no diﬀerence in the primary
outcome of oxygen desaturation (SpO  90%). The third study
randomized 30 participants undergoing dental sedation into three
groups to receive a fraction of inspired oxygen concentration of 0.4
either via HFNO at a ﬂow rate of 50 liters per minute, via HFNO at a
ﬂow rate of 30 liters per minute or via nasal cannula at 5 liters per
minute.
 Participants randomized to the HFNO groups had higher
nadir blood oxygen levels recorded than the low ﬂow oxygen group.
Overall, the results from the studies published to date indicate that
using HFNO may not result in a substantially improved oxygenation
status. However, only 159 participants in total were enrolled in these
studies. Therefore, further research is required to elucidate the eﬀects
of this technology on respiratory function of sedated patients.
For example, it is important to evaluate the eﬀects of this new
technology in each of the diverse contexts in which procedural
sedation is used. None of the previous or in-progress clinical trials have
enrolled patients undergoing cardiology procedures. In this regard, it is
important to note that oxygen desaturation occurs rarely in the context
of the common clinical situation where conscious sedation is
administered with prophylactic oxygen supplementation at ﬂow rates
between 6-10 liters per minute through a face mask during procedures
performed in the cardiac catheterisation laboratory.
 Results from
trials of HFNO during sedation conducted in other clinical settings,
such as bronchoscopy and gastrointestinal endoscopy, where
desaturation occurs more often, can therefore not be directly
generalised to the cardiology context.
It is also essential that all of the potentially beneﬁcial eﬀects of HFNO
on respiratory function during sedation are comprehensively evaluated.
Although oxygen desaturation is not common during cardiology
procedures, patients commonly have raised arterial carbon dioxide
levels, indicating that hypoventilation does occur. One of the proposed
physiological eﬀects of HFNO is that it facilitates active gas exchange
during times of hypoventilation due to the highly turbulent supraglottic
ﬂow vortices.
The eﬀects of the potential disadvantages of using HFNO during
sedation should also be evaluated. It is possible that potential gains
arising from delivering oxygen supplementation through the HFNO
device may be oﬀset by reduced ability to monitor ventilation from
capnography waveforms when it is being used. Capnography
9
2
10
11
12

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waveforms have not been validated for accuracy during HFNO therapy
due to exhaled carbon dioxide being “washed out” by the high ﬂows of
gas.
The impact of using high ﬂow nasal oxygen delivery systems routinely
for conscious sedation on departmental costs is also unclear. Evidence
from a pre-test post-test study of switching to routine use of HFNO in a
critical care unit actually reduced departmental costs.
In summary, although promising, further high-quality studies examining
the eﬀects of using HFNO during procedural sedation are required to
inform decision-making regarding implementation of this new
technology into practice. The 2018 guidelines from the American
Society of Anesthesiology stated that there is insuﬃcient evidence
regarding which methods of supplemental oxygen administration (e.g.,
nasal cannula, face mask, or specialized devices such as HFNO) are
more eﬀective. This trial will address this limitation in the evidence base
speciﬁcally in regard to the eﬃcacy of using HFNO during conscious
sedation in the cardiac catheterisation laboratory. Results from our
study will provide clinical evidence regarding the eﬀects of HFNO on
ventilation in sedated patients.
2.2 Objectives
The objective of this study is to test the hypothesis that using nasal
high ﬂow oxygen (HFNO) improves ventilation during cardiac
implantable electronic device procedures performed with conscious
sedation.
2.3 Trial design
A randomized controlled design will be used with participants
randomized in a 1:1 ratio to the following treatment conditions:
Oxygen supplementation through a standard facemask; or
Nasal high ﬂow oxygen.
3 METHODS
3.1 Study setting
Peter Munk Cardiac Centre Cardiac Cath Labs at Toronto General
Hospital, University Health Network.
13

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3.2 Eligibility criteria
3.2.1 Inclusion criteria
1. Adults undergoing an elective cardiac implantable electronic
device procedure in the Peter Munk Cardiac Centre Cardiac Cath
Labs with conscious sedation administered by an Anesthesia
Assistant (de novo and replacement/revision procedures). As per
the hospital’s policy for conscious sedation administered by
Anesthesia Assistants (38.40.001), these patients will have been
determined by the Anesthesiologist to be appropriate to receive
care from the Anesthesia Assistants.
3.2.2 Exclusion criteria
1. Under 16 years of age (excluded from this study as they are
considered pediatric patients).
2. Underlying condition requiring chronic oxygen supplementation.
3. Diagnosed respiratory condition with conﬁrmed current
hypercapnia. Hypercapnic COPD or obesity hypoventilation
syndrome with PaCO  during current admission over 45mmHg.
4. Pre-existing untreated pneumothorax.
5. Transesophageal echocardiography planned for the procedure.
6. Active nasal bleeding.
7. Complete nasal obstruction.
8. Recent upper airway surgery or base of skull fracture.
9. Previous participation in the study.
3.3 Interventions
3.3.1 Intervention description
All randomized participants will receive usual care in regard to the
medications used for sedation and physiological monitoring or other
interventions to support respiratory function that are considered
necessary to be initiated during the procedure by the clinicians. As per
the hospital policy for conscious sedation administered by Anesthesia
Assistants (38.40.001), oxygen therapy is administered as indicated
and prescribed to maintain oxygen saturation greater than 93%. In this
study, Anesthesia Assistants will follow this policy. Also in accordance
with this hospital policy (38.40.001), the Anesthesia Assistants
administer a combination of sedation to target the level of conscious
2

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sedation, which is deﬁned as “A drug-induced depression of
consciousness during which patients respond purposefully to verbal
commands, either alone or accompanied by light tactile stimulation.”
As such, by practicing in accordance with this hospital policy, the level
of sedation being administered by the Anesthesia Assistant for
participants included in this trial is being ‘standardized’. The hospital
policy does not stipulate any dose ranges of the diﬀerent classes of
sedative medications to be used and there will be no restrictions on the
type or dose of sedation used by Anesthesia Assistants. The actual
doses of sedation used will be recorded. Only the device used for
oxygen supplementation delivery will diﬀer between groups in the
following ways:
Facemask oxygen supplementation
Supplemental oxygen through a facemask with the ﬂow rate chosen by
the clinician responsible for sedation as per their standard practice. The
oxygen ﬂow rate is typically commenced at 6 liters per minute and can
be titrated up to 15 liters per minute.
High ﬂow nasal oxygen
The Optiﬂow device (Fisher and Paykel Healthcare, Auckland, New
Zealand), heated breathing tube and chamber, and nasal cannula will
be used. This system is a humidiﬁer with an integrated ﬂow generator,
able to humidify respiratory gases and deliver them down a heated
breathing tube and through the nasal cannula interface. The gas
temperature will commence at the ‘High’ setting (ranges 30-32º
Celsius) and titrated downwards if the patient complains of irritation.
The gas ﬂow rate will commence at 30 liters per minute prior to
sedation administration and be titrated up to 70 liters per minute as
tolerated by the patient after sedation has been administered. The
fraction of oxygen in the gas will be commenced at 50% (same as that
delivered from 6 liters per minute via facemask) and can be titrated
upward according to patient requirements (i.e. increased if there is
evidence of hypoventilation, airway obstruction or inadequate
oxygenation, decreased during use of diathermy). Anesthesia
Assistants at the site will be provided with training in the use of this
mode of oxygen delivery prior to study commencement.

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3.3.2 Modiﬁcations
The researchers may remove a potential participant that has been
enrolled in the study if:
The health care team decides that the participant will not receive
sedation during their procedure for an unforeseen reason. Under
these circumstances, the participant will not be randomized in
the study, and their data will not be included.
If a participant decides to leave the study, they will have the right to
request withdrawal of information collected about them. The
information that was collected before they left the study will still be
used in order to help answer the research question.
3.3.3 Adherence
Due to the short duration of the trial and the nature of the intervention,
strategies related to trial retention and adherence to follow-up will not
be required.
All randomized participants will receive usual care in regard to the
medications used for sedation and physiological monitoring or other
interventions to support respiratory function that are considered
necessary to be initiated during the procedure by the clinicians. As per
the hospital policy for conscious sedation administered by Anesthesia
Assistants (38.40.001), oxygen therapy is administered as indicated
and prescribed to maintain oxygen saturation greater than 93%. In this
study, Anesthesia Assistants will follow this policy. Supplemental
oxygen through a facemask with the ﬂow rate chosen by the clinician
responsible for sedation as per their standard practice. The oxygen
ﬂow rate is typically commenced at 6 liters per minute and can be
titrated up to 15 liters per minute. Percentage of hemoglobin saturated
with oxygen (SpO ) will be measured continuously throughout
procedures as part of routine clinical practice through the anesthetic
machine.
The use of high ﬂow nasal oxygen will result in no diﬀerence in the time
required for the intervention vs. routine standard of care. No additional
visits will be required following completion of the elective cardiac
implantable electronic device procedure.
3.3.4 Concomitant care
There are no restrictions on concomittant care for this trial.
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It is possible that a deeper level of sedation is deemed to be required at
some point during the procedure. This would occur only for unforeseen
reasons, which can not be anticipated ahead of time. If ‘deep’ sedation
is required for a portion of the procedure, the Anesthesiologist
overseeing the Anesthesia Assistant would be required to be present.
However, the allocated randomization for oxygen supplementation will
not need to be changed. The Anesthesiologist will be able to increase
the ﬂow rate to increase oxygen supplementation in the ‘standard’ care
group or increase the FiO2 and ﬂow rate in the HFNO group however
they deem necessary. In these circumstances, the Anesthesia Assitant
would still be involved in the procedure and document any changes in
oxygen supplementation used by the Anesthesiologist on the data
collection form.
The Research Assistant (RA) will determine if prospective participants
are already enrolled in other research trials in the Clinical Research
Record through Electronic Patient Record (EPR). If a prospective
participant is already enrolled in another trial, the RA will assess
whether that trial intervention will also be implemented during the
procedure. If not, the prospective participant will still be eligible for the
high-ﬂow nasal oxygen trial due to the short duration that this
intervention is being implemented and also because the follow-up
duration will be completed soon after the end of the procedure.
3.4 Outcomes
The selection of outcomes was informed by recommendations from the
Sedation Consortium on Endpoints and Procedures for Treatment,
Education and Research (SCEPTER) to assess diﬀerences between
groups regarding the safety and eﬃcacy of sedation.
Primary outcome: Peak transcutaneous carbon
dioxide ( TcCO ) concentration.
Continuous TcCO  measurements will be recorded using the Sentec
Digital Monitoring with VSign 2 sensor. TcCO  monitoring provides
continuous, accurate (mean bias -0.1 mmHg) and precise (95% limits
of agreement within 6 mmHg) estimates of arterial CO  (PaCO ) when
the sensor is placed on the earlobe.
 TcCO  monitoring may provide
even more precise estimates of changes in PaCO  (mean bias 0.03
mmHg, 95% limits of agreement -0.44 to 0.38 mmHg).
2
2
2
2
2
14
2
2
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We have undertaken a preliminary study to evaluate the feasibility of
using TcCO  monitoring as an outcome measure during nurse-
administered sedation in the cardiac catheterisation laboratory.
Continuous TcCO  measurements were recorded from patients
undergoing procedures with nurse-administered sedation using the
Sentec Digital Monitoring with VSign 2 sensor, starting before sedation
was induced (for measurement of baseline TcCO ) and ceasing at the
end of the procedure. Participating sites were the Wesley Hospital,
Holy Spirit Northside Private Hospital, Princess Alexandra Hospital and
John Flynn Private Hospital. The feasibility of TcCO  monitoring in this
population was conﬁrmed with continuous recordings achieved from all
participants without missing data. Changes in TcCO  concentrations
are presented in Table 1.
Table 1. Changes in TcCO  concentrations during sedation (n=123)
Mean
SD
Baseline pre-sedation TcCO
37.3
4.6
Post-sedation mean TcCO
42.3
5.8
Peak TcCO
46.8
6.9
Change from baseline to peak TcCO
9.4
5.6
Secondary outcomes
1. Mean transcutaneous carbon dioxide concentration measured
throughout the whole procedure using the VSign 2 sensor.
2. Trajectory of transcutaneous carbon dioxide concentration as a
function of time throughout the whole procedure using the VSign
2 sensor.
3. Area under the curve of oxygen desaturation: This is a composite
measure comprising the incidence, depth, and duration of
oxygen desaturation events. It is calculated as the diﬀerence
between the threshold (90%) and actual oxygen saturation
(SpO ) summed every second during which oxygen saturation
was below threshold).
4. Adverse sedation events: Adverse eﬀects of delivering gas at a
high ﬂow rate through the nasal passages will be assessed.
These include nose bleeding arising from damage to the
2
2
2
2
2
2
2
2
2
2
2

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mucosal surface and pressure injury to skin from the device. The
RA will inspect intervention group participants' skin integrity
around the nasal region at the end of procedures to assess for
these potentially anticipated as well as unanticipated adverse
eﬀects.
5. Patient satisfaction with sedation: The Iowa Satisfaction with
Anesthesia Scale (ISAS) will be used to measure patient
satisfaction with the anesthetic used during the procedure
performed.
6. Costs associated with oxygen delivery: The amount of
consumable equipment required for oxygen delivery used during
procedures and throughout the recovery period will be measured
using a data collection form speciﬁcally designed for this study.
7. Patient comfort of oxygen delivery: Participants will be asked to
rate at the end of procedures their perceived overall comfort with
the oxygen delivery device used during the procedure using a 6-
level ratings scale.
8. Anesthesia Assistant rating of diﬃculty maintaining oxygenation
status.
9. Anesthesia Assistant rating of diﬃculty using oxygen delivery
device.
3.5 Participant timeline
Data for this study will be collected by the RA and entered into an
electronic data platform supported by REDCap
 (Research Electronic
Data Capture Vanderbilt University, Nashville, TN, USA) at three time
points: (T1) at baseline (prior to procedures); (T2) during the procedure;
and (T3) on hospital discharge.
After receiving participant consent, demographic information and
eligibility to participate will be conﬁrmed at T1. Transcutaneous carbon
dioxide ( TcCO ) monitoring and pulse oximetry will be measured
continuously at T2. Adverse sedation events, patient comfort with
sedation, diﬃculty maintaining oxygen saturation and using the device,
and cost associated with the oxygen delivery device will be assessed
at T3. Patient satisfaction with sedation will also be assessed at this
time using the Iowa Satisfaction with Anesthesia Scale (ISAS) through
REDCap
.
Pre-procedure
During
procedure
Post-
procedure
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2
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TIMEPOINT
T1
T2
T3
ENROLLMENT:
X
Eligibility screen
X
Informed consent
X
Allocation
X
INTERVENTIONS:
Facemask oxygen
supplementation
X
High ﬂow nasal
oxygen
X
ASSESSMENTS:
Demographic
information and
medical history
X
Peak TcCO
concentration
X
Mean TcCO
X
Area under the
curve of oxygen
desaturation
X
Adverse sedation
events
X
Patient
satisfaction with
sedation
X
Costs associated
with oxygen
delivery
X
Anesthesia
Assistant rating of
diﬃculty
maintaining the
patient's
oxygenation
X
2
2

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status
Anesthesia
Assistant rating of
diﬃculty using
oxygen delivery
device
X
Patient comfort of
oxygen delivery
X
3.6 Sample size
We estimate based on data from our preliminary study that the peak
TcCO  level in the control group will be 47 mmHg and standard
deviation in both groups will be 7 mmHg. Assuming a type I error rate
of 5%, a sample of 130 participants would achieve 90% power to
detect a reduction in mean TcCO  levels of 4 mmHg in the intervention
period. A diﬀerence in TcCO  levels of 4 mmHg was selected for this
sample size calculation because it was used to power previous
randomized controlled trials of the eﬀect of oxygen supplementation on
ventilation status in other populations, with the authors noting that an
eﬀect of this magnitude was of physiological signiﬁcance.
 Also,
diﬀerences in CO  levels of a similar magnitude have been detected in
previous trials evaluating the eﬃcacy of interventions to improve
sedation safety.
 To account for any missing primary outcome data
(in the event that the TcCO  monitor malfunctions) and dropouts (in the
event that a randomized patient's procedure is cancelled or anesthetic
management plan is changed prior to procedure commencement), we
plan to recruit a sample of 150 participants.
3.7 Recruitment
A Research Assistant (RA) will be engaged in this work performing the
roles of eligibility screening/participant recruitment and data collection.
3.7.1 Pre-admission clinic recruitment
process
Potential participants scheduled for a procedure in advance will be
initially approached during their attendance at the pre-admission clinic.
The RA will receive the pre-admission clinic and cardiac catheterization
2
2
2
16,17
2
18–22
2

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laboratory schedules from the electrophysiology Nurse Practitioners to
identify potential participants. Any potential participants that meet
exclusion criteria will be ﬂagged by the Nurse Practitioner at this time.
The RA will inform the pre-admissions clinic nurse or administration
assistant (i.e. someone within the patient’s circle of care) about which
patients are eligible for the study. The pre-admission clinic nurse or
administration assistant will ask the potential participant for permission
for the RA to provide additional information and invite them to
participate in the study. If the potential participant agrees, the RA will
explain the study and provide a Participant Information and Consent
Form.
3.7.2 In-patient recruitment process
The RA will review the cardiac catheterization laboratory schedules to
identify potential participants who have been admitted as in-patients.
The RA will inform either the electrophysiology Nurse Practitioner (i.e. a
healthcare professional within the patient’s circle of care) or the
patient’s allocated Registered Nurse for the shift about which patients
are potentially eligible for the study and ask them to check if they meet
any of the exclusion criteria. If the patient is eligible, the Nurse
Practitioner or Registered Nurse will ask the potential participant for
permission for the RA to provide additional information and invite them
to participate in the study. If the potential participant agrees, the RA will
explain the study and provide a Participant Information and Consent
Form the day prior to their scheduled procedure so that they can
consider their participation overnight.
3.7.3 Same-day admission recruitment
process (no attendance to pre-
admission clinic)
A small proportion of the total number of eligible participants will be
scheduled for a procedure but will not be attending the pre-admission
clinic. An example would be a stable out-patient without major
comorbidities attending for a permanent pacemaker generator change
as a day procedure. If potential participants who are to be admitted on
the day of their procedure without attending the pre-admission clinic
are identiﬁed, the electrophysiology administration assistant or Nurse
Practitioner who will be making contact with the participant to organise
their admission, will ask the participant if they are willing to be
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potential participant agrees to be contacted, The RA will use the
standardised telephone script to explain the study to the participant
and will ask if the participant would like a Participant Information and
Consent form sent to them by mail or email. On the day of admission,
the RA will conﬁrm with the potential participant if they agree to
participate and complete the consenting process.
3.7.4 Alternative process for recruitment
on day of procedure (only if potential
participants could not be contacted
using the above processes)
All eﬀorts will be made to make initial contact and explain the study to
potential participants prior to the day of their procedure using the
processes outline above. If this is not possible, in some circumstances
there may be enough time for a potential participant to consider
participating in the study on the same day as their procedure. For
example, same-day admission patients who are scheduled to have
their procedure in the afternoon still typically arrive to the hospital at
7am. In such circumstances, if an eligible participant has not been able
to be contacted, the RA will inform the same-day admission unit’s
administration assistant, the electrophysiology Nurse Practitioner or the
patient’s allocated Registered Nurse for the shift about which patients
are potentially eligible for the study and ask them if they meet any of
the exclusion criteria. If the patient is eligible, the Nurse Practitioner or
Registered Nurse will ask the potential participant for permission for
the RA to provide additional information and invite them to participate
in the study. If the potential participant agrees, the RA will explain the
study and provide a Participant Information and Consent Form.
3.8 Allocation
Consented eligible patients will be allocated randomly to intervention
and control groups. A stratiﬁed (by diagnosis of obstructive sleep
apnea and type of procedure – cardiac resynchronization therapy
device implant), block randomized sequence will be generated using
the redcapAPI package in R and uploaded to REDCap
. The RA will
retrieve the allocation for each consecutive participant in REDCap
prior to the procedure.
3.9 Blinding (masking)
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TM

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3.9.1 Blinding mechanism
Due to the nature of the intervention, participants or personnel involved
in the trial cannot be blinded to the treatment conditions. Data will be
collected in a fashion such that the primary outcome assessment for
comparisons between groups will be made without knowledge of the
assigned treatment allocation.
3.9.2 Emergency unblinding
Due to the nature of the intervention, participants or personnel involved
in the trial cannot be blinded to the treatment conditions.
3.10 Data collection
3.10.1 Trial procedures and evaluations
Instruments used to measure outcomes
Transcutaneous carbon dioxide concentrations: PI Conway will provide
training to the RA in use of the transcutaneous carbon dioxide
monitoring device and other data collection procedures. The RA will
attach the Sentec VSign 2 sensor to the participant's forehead using a
multi-site attachment ring. Once the Sentec Digital Monitoring System
displays a stabilized TcCO  level, the monitor will be covered with a
drape so that it is not visible to research staﬀ or clinicians during the
procedure. The monitor will not be used by the clinicians to guide
treatment. Data will be downloaded to a computer using the USB port
on the monitor. TcCO  monitoring provides continuous, accurate (mean
bias within 2 mmHg) and precise (95% limits of agreement within 6
mmHg) estimates of arterial CO  (PaCO ) in sedated patients.
Pulse oximetry: Percentage of hemoglobin saturated with oxygen
(SpO ) will be measured continuously throughout procedures as part of
routine clinical practice through the anaesthetic machine. We will
access the DREAM (Drug Reconciliation and Electronic Anesthesia
Monitoring) system to download this data. Unreliable SpO
measurements will be ﬁltered out if a pulse rate is not detectable.
Tracking and reporting outcomes of procedural sedation tool.
 This
tool was developed, using a consensus process, by members of a
multidisciplinary society who had demonstrated capacity, dedication
and competence in research and/or clinical experience in procedural
sedation. Completion of the tool requires identiﬁcation and description
2
2
2
2
14
2
2
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of the adverse event, the intervention, the outcome and the overall
severity of the adverse event. The Anaesthesia Assistant will be asked
to complete this tool at the end of procedures. It takes approximately 2
minutes to complete.
Iowa Satisfaction with Anesthesia Scale (ISAS): The ISAS is a
questionnaire that can be used to measure patient satisfaction with the
anesthetic used during a procedure performed with sedation.
Completion of the 11 items takes 4-5 minutes. This scale reliably
measures the construct of satisfaction with the anesthetic, with a
Cronbach alpha of .84 found in a 24-center, 315 patient placebo-
controlled trial of dexmedetomidine.
 In this study, the utility of the
ISAS as an outcome measure for sedation trials was demonstrated, as
it was able to diﬀerentiate patient satisfaction among patients. There
were 47 diﬀerent scores among the 315 participants. In addition,
whereas 73% of patients responded with the minimum or maximum
score for the single question “I was satisﬁed with my anesthetic”, only
14% of the sample scored the minimum or maximum for the ISAS.
Adverse eﬀects: Adverse eﬀects of delivering gas at a high ﬂow rate
through the nasal passages will be assessed. These include nose
bleeding arising from damage to the mucosal surface and pressure
injury to skin from the device. The RA will inspect intervention group
participants' skin integrity around the nasal region at the end of
procedures to assess for these potentially anticipated as well as
unanticipated adverse eﬀects.
Costs: Anesthesia Assistants will document devices used for
supplemental oxygen delivery and airway management in both groups
as per their usual practice in the DREAM anesthesia monitoring
system. This data will be accessed for the study by downloading the
report from the DREAM anaesthesia monitoring system, permitting the
per-patient costs for oxygen delivery and airway management to be
calculated and compared between groups.
Anesthesia Assistant rating of perceived level of diﬃculty in maintaining
oxygenation: The Anaesthesia Assistant will be asked to rate their
perceived level of diﬃculty in maintaining oxygenation using a 6-level
rating scale with ratings of “extremely diﬃcult”, “very diﬃcult”,
“diﬃcult”, “easy”, “very easy”, “extremely easy”.
Anesthesia Assistant rating of perceived level of diﬃculty using the
oxygen delivery device: The Anaesthesia Assistant will be asked to rate
their perceived level of diﬃculty using the oxygen delivery device using
24,25
25
25

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a 6-level rating scale with ratings of “extremely diﬃcult”, “very diﬃcult”,
“diﬃcult”, “easy”, “very easy”, “extremely easy”.
Comfort associated with oxygen delivery: Participants will be asked to
rate at the end of procedures their perceived overall comfort with the
oxygen delivery device used during the procedure using a 6-level rating
scale with ratings of ‘maximal discomfort’, ‘very uncomfortable’,
‘uncomfortable’, ‘comfortable’, ‘very comfortable’ and ‘maximal
comfort’.
Supplemental oxygen use and ﬂow settings: Anesthesia Assistants will
document their use of oxygen therapy in a case report form provided to
them by the Research Assistant. Information on the FiO2 setting, ﬂow
rate and temperature will be recorded in the HFNO group. The oxygen
ﬂow rate will be recorded in the control group.
Sedative medications: The Anesthesia Assistant will record the total
doses of sedative medications used during procedures.
3.10.2 Retention
Due to the design and short duration of the trial, no plans for
participation retention will be required.
3.11 Data management
Data Forms and Data Entry
In the High ﬂow nasal oxygen (HFNO) during sedation trial, all data will
be entered electronically using REDCap. No identifying information will
be included in the database. A study ID will be assigned for each study
participant and only this will be entered into the REDCap database. A
majority of this will occur on site where the data originated at the Peter
Munk Cardiac Cath cardiac cath labs, however some instances may
occur at the PI's oﬃce located in the Peter Munk Cardiac Centre,
Toronto General Hospital. Original study forms will be entered and kept
on ﬁle at the participating hospital site.
All personal information such as the patient's name, date of birth,
health information, and UHN MRN will be removed from the data and
will be replaced with a participant ID number. A list linking the
participant ID number with patient names will be stored in an electronic
ﬁle by the study team on a secure UHN Network in compliance with
UHN's policy and procedural manual on storage, transport and
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Data Transmission and Editing
Using REDCap
, range checks will be applied to minimize errors in
data entry.
Security and Back-Up of Data
All forms related to study data will be kept in locked cabinets. Access
to the study data will be restricted. A password system will be utilized
to control access to electronic ﬁles related to the study on a secure
UHN Network in compliance with UHN's policy and procedural manual
on storage, transport and destruction of conﬁdential information. These
passwords will be changed on a regular basis. In compliance with
UHN's policy & procedure manual on “Research: Data Ownership,
Stewardship & Security of Health Information”, the institution will be
responsible for providing hard data backs ups of all UHN Information
and Technology (IT) systems for disaster recovery purposes.
Data Storage In accordance with the UHN Administrative -
Management, Retention & Disposal of Administrative Record policy
1.30.007, the study data will be retained for 10 years.
3.12 Statistical methods
3.12.1 Outcomes
For the primary outcome, peak TcCO  will be compared between the
intervention and control groups using a Bayesian hierarchical model
with baseline TcCO  concentration included in the model as a covariate
as is recommended for this type of design.
 Bayesian models will also
be used to compare secondary outcomes among the randomization
groups. Prior distributions for all model parameters will initially be
chosen to be non-informative and will be adjusted as necessary to
improve model ﬁt. The posterior distributions of parameters and
quantities of interest will be presented as well as their medians and
95% highest-density intervals (HDI). Subgroup analyses will be
conducted to compare the eﬀects of HFNO with standard care in
patients who have a diagnosis of sleep apnea and those who have a
cardiac resynchronization therapy device implant (the variables used
for stratiﬁcation) by including these variables in the model as
interaction terms.
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In addition to comparing the peak TcCO , per-second TcCO  levels will
be compared between randomization groups using methods of
functional data analysis. Functional observations will be estimated by
ﬁtting a B-spline basis to the TcCO  data, subject to a roughness
penalty on the second derivative of the estimated function. Common
features of these estimated functions will be examined using functional
principal component analysis (FPCA). A formal comparison of TcCO
levels between randomization groups will be performed using
functional analysis of variance (FANOVA). Results of this functional
analysis will be compared to those obtained in the bayesian analysis on
just the peak TcCO  levels.
3.12.2 Additional analyses
No additional analyses will be conducted.
3.12.3 Analysis population and missing
data
The primary analysis will be performed on an intention-to-treat basis.
Participants included in the intention to treat analysis will be those who
provided consent and then underwent a procedure with sedation, even
if they do not receive the assigned treatment.
3.13 Data monitoring
3.13.1 Formal committee
A Data Monitoring Committee is not needed for this trial as it will be
conducted within a short duration of time with known minimal risks.
3.13.2 Interim analysis
As participants for this trial are not anticipated to be recruited over an
extended period of time and the safety of high ﬂow nasal oxygen has
already been established in critical care and anesthesia settings,
interim analyses for safety or eﬃcacy will not be conducted.
3.14 Safety/harms
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2
2
2
2

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Any adverse events that arise, whether related to the study intervention
or not, will in the ﬁrst instance be reported to the Nurse Manager of the
Cardiac Catheter Laboratories and to the Principal Investigator who will
then submit a report of the event to UHN's REB. The standard
reporting system for Toronto General Hospital will be followed.
It is not anticipated that this project will need to be ceased prematurely
due to concerns about safety as the intervention is already extensively
used and recommended for diﬀerent population in anesthetic and
critical care medicine. Any adverse events that do occur will be
reported to UHN's REB in compliance with the UHN and CAREB's
guidelines for reporting adverse events (unanticipated problems).
3.15 Auditing
REDCap
 retains an audit trail by logging user activity and pages
viewed or accessed. Activities documented include data entry and
modiﬁcations, exporting data, and generating reports.
The study team will request the Research Quality Integration
department at UHN to conduct a pre-study audit. The objective of this
audit is to determine whether eﬀective processes are in place to
achieve the study objectives and compliance with the applicable
regulations and guidelines.
4 ETHICS AND
DISSEMINATION
4.1 Research ethics approval
This protocol and the participant informed consent forms (PICF) will be
reviewed and approved by the sponsor and entered into the
Coordinated Approval Process for Clinical Research (CAPCR) to
receive approval from UHN's Research Ethics Board (REB) and
Institutional Authorization with respect to scientiﬁc content and
compliance with applicable research and human subjects regulations.
The protocol, PICFs, participant education and recruitment materials,
and other requested documents — and any subsequent modiﬁcations
— will also be submitted through CAPCR to be reviewed by UHN's
REB for ethics approval, and the Executive Vice President of Science
and Research or designate for institutional authorization.
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Subsequent to initial review and approval, an annual study renewal will
be submitted to CAPCR for the UHN's REB to review at least 14-30
days before the study's REB expiry date. The Investigator will make
safety and progress reports to the REB at least annually and within
three months of study termination or completion at the study site.
4.2 Protocol amendments
Any modiﬁcations to the protocol which may impact on the conduct of
the study, potential beneﬁt of the patient or may aﬀect patient safety,
including changes of study objectives, study design, patient
population, sample sizes, study procedures, or signiﬁcant
administrative aspects will require a formal amendment to the protocol.
Such amendment will be agreed upon by the High-Flow Nasal Oxygen
(HFNO) study team, and approved by UHN's Research Ethics Board
(REB) prior to implementation.
4.3 Informed consent process
The Research Assistant (RA) will review the cardiac catheterization
laboratory schedule to identify potential participants. As per the Health
Care Consent Act, individuals who are capable and are 16 years of age
or more have the capacity to provide consent regarding their own care.
Potential participants will have the study explained to them by the RA
and also receive a Participant Information and Consent Form to
consider their participation in the study.
Potential participants will be asked for permission to obtain relevant
clinical and demographic information from their records for use only in
this study. Potential participants scheduled for a procedure in advance
will be initially approached during their attendance at the pre-admission
clinic. The cardiac catheterization laboratory schedule will be checked
each day to identify potentially eligible participants who have not
attended the pre-admission clinic. Potential participants who have
been admitted to hospital will have the study explained to them and will
be given a PICF the day prior to their scheduled procedure so that they
can consider their participation overnight. Potential participants who
are to be admitted on the day of their procedure without attending the
pre-admission clinic, will receive a phone call from the RA prior to their
admission to maximize the time for consideration of participation.

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The Anesthesia Assistant team fully supports this study. All Anesthesia
Assistants will be required to deliver oxygen supplementation using the
device assigned per randomization (i.e. either standard face mask or
high ﬂow nasal cannula). The Anesthesia Assistants will be provided
with education sessions about the study and use of HFNO, to be led by
the PI Aaron Conway, supported by Co-Investigator Phoebe Lam
(Anesthesia Assistant Educator) and Co-Investigator Ana Lopez-Filici.
Completion of the data collection form, where Anesthesia Assistants
are asked to anonymously rate their experience of using the oxygen
supplementation device, will be voluntary. All Anesthesia Assistants will
be provided with an Information Sheet explaining these details (to be
distributed by Co-Investigator Ana Lopez-Filici, Anesthesia Assistant
Manager) prior to study commencement. Implied consent will be
gained from Anesthesia Assistants using the ‘opt-in’ form of consent,
which will be indicated ‘by conduct’. Completion of the data collection
form will indicate that they consented to provide this information for the
study. The data collected from Anesthesia Assistants is non-
identiﬁable, but they will required to enter a unique identiﬁer so that
their responses can be linked together but not to the individual
Anesthesia Assistant.
4.3.1 Ancillary studies
No biological specimens will be collected in this trial. Data collected in
this trial will not be used in ancillary studies.
Participant data collected from this study will be recorded in their
medical records at Toronto General Hospital and in the UHN computer
system. This is for clinical safety purposes. The UHN shares the patient
information stored on its computers with other hospitals and health
care providers in Ontario so they can access the information if it is
needed for clinical care. The study team will inform participants about
what will be stored electronically and may be shared outside of the
UHN.
4.4 Conﬁdentiality
All study-related information will be stored securely in compliance with
UHN's “Storage, Transport & Destruction of Conﬁdential Information”
policy. All participant information will be stored in locked ﬁle cabinets in
areas with limited access. The types of Participant Health Information
(PHI) that will be collected for this study have been limited to that which

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is necessary for the purposes of the research study, and will be de-
identiﬁed. PHI will not be used or disclosed for purposes other than
those which it was collected, except with the express consent of the
individual or as required by law. All personal information such as the
patient's name, date of birth, health information, and UHN MRN will be
removed from the data and will be replaced with a participant ID
number. A list linking the participant ID number with patient names will
be stored in an electronic ﬁle by the study team on a secure UHN
Network. Thus, all reports, data collection, process, and administrative
forms will be de-identiﬁed.
All information collected during this study, including PHI, will be kept
conﬁdential and will not be shared with anyone outside the study
unless required by law. Participants will not be named in any reports,
publications, or presentations that may come from this study.
Participant de-identiﬁed data from this study may be used for other
research purposes. If the study data is shared with other researchers,
information that links study data directly to the participant will not be
shared.
4.5 Declaration of interests
There are no conﬂict of interests to declare.
4.6 Access to data
All members of the study team will be given access to the cleaned data
sets. The study data sets will be housed on the UHN computer system,
and all data sets will be password protected. To ensure conﬁdentiality,
data dispersed to the study team members will not contain any
identifying participant information.
4.7 Ancillary and post-trial care
If a participant is harmed as a direct result of taking part in this study,
all necessary medical treatment will be made available to them by the
UHN.
4.8 Dissemination policy
4.8.1 Trial results

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The study results will be reported in publications and presentations.
4.8.2 Authorship
The study's investigators will be authors on the reporting and
presentation of the trial's results. Topics suggested for presentation or
publication will be circulated among the High-Flow Nasal Oxygen
(HFNO) study team.
4.8.3 Reproducible research
In accordance with the Tri-Agency Statement of Principles on Digital
Data Management and the Tri-Agency Open Access Policy on
Publication, study data such as participant-level data sets (without
identifying information) and code for statistical analyses will be shared
in a publicly accessible repository at the time of publication.
5 STUDY ADMINISTRATION
5.1 Key contacts
Study Principal Investigator
Aaron Conway, RN, PhD
RBC Chair in Cardiovascular Nursing Research Peter Munk Cardiac
Centre Toronto General Hospital University Health Network Assistant
Professor Lawrence S. Bloomberg Faculty of Nursing University of
Toronto
Toronto General Hospital Heart & Circulation Admin 4NU - 476 585
University Ave Toronto, ON M5G 2N2
416. 340-4654
aaron.conway@uhn.ca (mailto:aaron.conway@uhn.ca)
Central contact
Aaron Conway, RN, PhD
RBC Chair in Cardiovascular Nursing Research Peter Munk Cardiac
Centre Toronto General Hospital University Health Network Assistant
Professor Lawrence S. Bloomberg Faculty of Nursing University of
Toronto

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Toronto General Hospital Heart & Circulation Admin 4NU - 476 585
University Ave Toronto, ON M5G 2N2
416. 340-4654
aaron.conway@uhn.ca (mailto:aaron.conway@uhn.ca)
Sponsor
Investigator-sponsored trial
5.2 Funders
This is an Investigator-sponsored trial. This study will be fully supported
by funds received by the PI, Aaron Conway, for his appointment as
Chair of Cardiovascular Nursing Research at PMCC. This includes all
work undertaken by the Research Coordinator and purchasing of
equipment and consumables for the HFNO and TcCO  monitoring
devices. The funding source for the Chair had no role in the design of
the study and will not have any role during its execution, analyses,
interpretation of the data, or decision to submit results.
5.3 Roles and responsibilities
5.3.1 Protocol contributors
AC conceived of the study. AC, MP, PL, ALF contributed to the study
design. All authors contributed to reﬁnement of the study protocol and
will approve the ﬁnal manuscripts of results.
5.3.2 Sponsor and funder
This is an Investigator-sponsored trial. The funding source (resources
made available from PI Conway’s Research Chair appointment) will not
have any role during its execution, analyses, interpretation of the data,
or decision to submit results.
5.3.3 Trial committees
N/A
REFERENCES
2

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1. Drake, M. G. High-Flow Nasal Cannula Oxygen in Adults: An
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Created by Aaron Conway (https://www.aaronconway.info)
Aaron.Conway@uhn.ca