Preoxygenation With High Flow Nasal Oxygenation Using Optiflow - Does Speech Have an Effect on The End Tidal Oxygen Achieved When Compared to Closed Mouth Nasal Breathing?
Phase: NA
Conditions: Unrecognized Condition
Sponsor: University Hospital Southampton NHS Foundation Trust

 
i 
  
 
  
  
This protocol has regard for the HRA guidance and order of content.  
  
  
  
  
FULL TITLE OF THE STUDY  
  
Preoxygenation with high-flow nasal oxygen using Optiflow™ - does speech have an effect on end-tidal 
oxygen achieved when compared to closed-mouth nasal breathing?  
  
SHORT STUDY TITLE   
Preoxygenation with Optiflow™ – the effect of speech on oxygenation.  
  
PROTOCOL VERSION NUMBER AND DATE  
v 0.2 26/9/2018  
  
RESEARCH REFERENCE NUMBERS  
  
IRAS Number:  
231097  
  
SPONSOR’S Number:  
RHM CR10369  
  
  
  
  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
ii  
 
  
  
SIGNATURE PAGE  
The undersigned confirm that the following protocol has been agreed and accepted and that the Chief 
Investigator agrees to conduct the study in compliance with the approved protocol and will adhere to 
the principles outlined in the Declaration of Helsinki, the Sponsor’s SOPs, and other regulatory 
requirement.  
I agree to ensure that the confidential information contained in this document will not be used for any 
other purpose other than the evaluation or conduct of the investigation without the prior written 
consent of the Sponsor  
I also confirm that I will make the findings of the study publically available through publication or other 
dissemination tools without any unnecessary delay and that an honest accurate and transparent 
account of the study will be given; and that any discrepancies from the study as planned in this 
protocol will be explained.  
  
  
  
  
  
  
  
  
  
  
  
  
Chief Investigator:  
Signature:   
  
Date: 26/9/2018  
 
  
Name: Dr Patrick Butler   
  
  
  
  
  
  
  
  
  
  
  
  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
iii  
 
LIST of CONTENTS  
GENERAL INFORMATION  
Page No.  
HRA PROTOCOL COMPLIANCE DECLARATION   
i  
TITLE PAGE   
i  
RESEARCH REFERENCE NUMBERS  
  
i  
SIGNATURE PAGE  
ii  
LIST OF CONTENTS   
iii  
KEY STUDY CONTACTS  
iv  
STUDY SUMMARY  
v  
FUNDING  
  
v  
ROLE OF SPONSOR AND FUNDER  
vi  
ROLES & RESPONSIBILITIES OF STUDY STEERING GROUPS AND INDIVIDUALS    
vi  
STUDY FLOW CHART  
  
vii  
SECTION   
1. BACKGROUND  
  
1  
2. RATIONALE  
  
1  
3. THEORETICAL FRAMEWORK  
2  
4. RESEARCH QUESTION/AIM(S)   
2  
5. STUDY DESIGN/METHODS  
3  
6. STUDY SETTING  
3  
7. SAMPLE AND RECRUITMENT  
4  
8. ETHICAL AND REGULATORY COMPLIANCE  
5  
9. DISSEMINATION  POLICY  
7  
10. REFERENCES  
8  
11. APPENDICES  
9  
  
  
KEY STUDY CONTACTS   
Chief Investigator  
Dr Patrick Butler. Tel 02381206135. patrick.butler@uhs.nhs.uk  
Study Co-ordinator  
Dr Patrick Butler. Tel 02381206135. patrick.butler@uhs.nhs.uk  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
iv  
 
Sponsor  
Dr Mikayala King  
R&D Department  
University Hospital Southampton NHS Foundation Trust   
Southampton General Hospital  
SCBR - Mailpoint 138  
Tremona Road  
Southampton  
SO16 6YD  
02381 205961  
mikayala.king@uhs.nhs.uk  
Sponsor’s co-ordinator   
Viki Rumble, Research Facilitator   
R&D Department  
Southampton General Hospital  
SCBR - Mailpoint 138  
Tremona Road  
Southampton  
SO16 6YD  
United Kingdom  
Tel: +44-(0)23-8120 5663  
E-mail: viki.rumble@uhs.nhs.uk   
  
Funder(s)  
Fisher & Paykel Healthcare  
Fisher & Paykel Healthcare Limited  
Unit 16, Cordwallis Park  
Clivemont Road, Maidenhead  
Berkshire SL6 7BU  
United Kingdom  
Key Protocol Contributors  
Dr Patrick Butler  
patrick.butler@uhs.nhs.uk  
STUDY SUMMARY  
  
Preoxygenation of the lungs with high-flow nasal oxygen using  
Optiflo
w 
™ - does speech have an effect on end-tidal oxygen 
Study Title  
achieved 
when 
compared 
to 
closed-mouth 
nasal
breathing? 
  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
v  
 
 
  
 
 
Short title  
Preoxygenation with Optiflow™ – the effect of speech on lung 
oxygenation.  
  
Study Design  
Randomised controlled trial  
Study Participants  
Elective booked surgical patients having a general 
anaesthetic  
Planned Size of Sample   
28  
Follow up duration   
none  
Planned Study Period  
Sept 2018 to January 2019  
Research Question/Aim(s)  
  
If a patient speaks during the process of preoxygenation with 
high-flow nasal oxygen via the Optiflow™ system, is the 
efficacy reduced as measured by end-tidal lung oxygen 
content?  
  
  
  
  
FUNDING AND SUPPORT IN KIND  
FUNDER(S)  
  
FINANCIAL AND NON FINANCIAL SUPPORT 
GIVEN  
Fisher & Paykel Healthcare Limited  
Unit 16, Cordwallis Park  
Clivemont Road, Maidenhead  
Berkshire SL6 7BU  
United Kingdom  
F&P have given free disposable equipment for 
use in this and other research studies.  
  
  
  
  
  
  
  
  
 

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
vi  
 
 
ROLE OF STUDY SPONSOR AND FUNDER  
  
PROTOCOL CONTRIBUTORS  
Dr Patrick Butler and Sophie Brindley (medical student) are responsible for the study design, conduct, 
data analysis and interpretation, manuscript writing, and dissemination of results.   
The sponsor and equipment provider do not control the final decision regarding any of these aspects 
of the study.  
  
KEY WORDS:  
Preoxygenation  
Optiflow™  
End-tidal oxygen  
  
  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
vii  
 
 STUDY FLOW CHART  
  
Patients in preassessment unit given patient information sheets  
↓  
On day of surgery patients asked by their anaesthetist if they are willing to be recruited to study  
 
↓  
  
  
  
↓  
  
  
Willing   
  
  
  
  
Not willing  
 
↓  
  
  
  
↓  
Researcher explains project, answers queries,   
  
  
Patient not included in study and 
checks inclusion/exclusion suitability  
↓  
  
  
↓  
Suitable for study   
  
Not suitable for study → Patient not included in study  
↓  
  
  
  
Researcher completes consent form with subject  
  
  
  
  
↓  
Researcher randomises subject (sealed envelopes)  
 
↓  
  
  
  
  
↓  
 
Mouth closed group  
  
  
Speech group  
 
↓  
  
  
  
  
↓  
In anaesthetic room subject has nasal  
  
  
In anaesthetic room subject has 
nasal   Optiflow™ device placed and is preoxygenated   
Optiflow™ device placed and is  
for 3 minutes with a closed mouth  
  
  
preoxygenated for 3 minutes reciting   
  
  
  
  
  
  
text from written sheet  
  
  
  
  
↓  
  
  
  
  
  
  
↓  
After 3 minutes Optiflow™ is ceased and subject exhales and then inhales through anaesthetic  
equipment with oxygen sampling to register the end-tidal oxygen content  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
viii  
 
↓  
Optiflow™ device removed and subject released from study  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
1  
STUDY PROTOCOL  
Preoxygenation with high-flow nasal oxygen using Optiflow™ - does speech have an effect on endtidal 
oxygen achieved when compared to closed-mouth nasal breathing?  
  
1  
BACKGROUND  
Before anaesthetists commence anaesthetising patients it is common practice in many cases to ask 
the patient to breathe 100% oxygen for a few minutes (this is called preoxygenation). The reason for 
this is that the percentage of oxygen in the lungs can be raised from about 21% to 90%. If / when 
patients stop breathing as the anaesthetic drugs are injected, the oxygen in the lungs acts as a 
reservoir to keep them well oxygenated whilst the anaesthetist inserts a breathing tube into the airway. 
If this process of intubating the airway proves to be difficult and prolonged (e.g. due to anatomical 
problems) the preoxygenation will have given a larger reservoir of oxygen in the lungs and the patient 
will be less likely to become poorly oxygenated and come to harm.  
Preoxygenation can be done with a normal anaesthetic circuit or with other oxygen delivery equipment 
such as high-flow nasal oxygenation with the Optiflow™ device. The latter is commonly used to 
support awake patients with breathing difficulties but is increasingly used in anaesthesia to maintain a 
high flow of oxygen via a patient's nasal airway and may be useful to prevent falls in oxygen levels 
during difficult intubation of the airway.   
The amount of oxygen in the lungs after a period of preoxygenation can readily be measured with 
standard anaesthetic monitoring equipment.  
Preoxygenation is commonly done with the patient breathing through their nose with a closed mouth. 
However, people often tend to talk during this process and this may result in less efficient 
preoxygenation if they breathe in room air whilst doing so.  
This study aims to investigate whether there is a measurable difference in the efficiency of Optiflow™ 
preoxygenation (as measured by expired oxygen content) when the patient either breaths only through 
their nose or when they talk during the process. Talking will be standardised by reading aloud a poem.  
  
2  
RATIONALE   
During induction of anaesthesia, one of the primary aims of the anaesthetist is to continue to keep the 
patient well oxygenated whilst the patient passes from the situation of breathing for them self to being 
anaesthetised and having their breathing controlled or supported by the anaesthetist. This will often 
entail a period of time when from when the patient stops breathing (an apnoeic period) until an airway 
device is inserted and the anaesthetist can oxygenate the lungs. If that apnoeic period is prolonged, 
the amount of oxygen remaining in the lungs will start to fall and this will result in a fall in the amount of 
oxygen in the bloodstream and then the oxygenation of vital organs. To try to prevent this happening it 
is common practice to increase the oxygen content in the lungs before the patient is anaesthetised by 
asking them to breathe 100% oxygen for a short period of time (about 3 minutes) before the start of 
the anaesthetic. Research has shown that the amount of oxygen in the lungs can be raised to 85-90% 
by this process – an increase to over 4 times the usual amount – which will allow the patient to remain 
well oxygenated for several minutes without breathing.  
An alternative technique which can be used alongside preoxygenation is to use high-flow nasal 
oxygenation (in which a high flow of warmed, humidified oxygen is provided from nasal prongs) to 
keep oxygenating the lungs during a period of apnoea. It has been possible to continue oxygenating 

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
2  
apnoeic patients for up to 30 minutes during airway surgery using such a technique but this can only 
happen if the airway from nose/mouth through the larynx and into the trachea remain open and patent.  
It is therefore becoming common practice to use a device such as Optiflow™ to perform both 
preoxygenation and apnoeic oxygenation since the device can remain in place from the start of 
preoxygenation until the airway has been secured and hopefully extend the safe apnoeic period in 
those cases where the anaesthetist has either expected or unexpected difficulty in passing an 
endotracheal tube.  
Despite the value of high-flow nasal oxygenation during apnoea, preoxygenation remains important 
because, if the airway become not fully patent (a not uncommon situation in anaesthesia) the highflow 
nasal oxygenation becomes ineffective and then we become reliant on the oxygen stores already 
produced by preoxygenation to prevent falls in systemic oxygenation and potential patient harm.  
 In circumstances when we are using Optiflow™ to provide preoxygenation it is important that the 
patient breathes 100% oxygen into their lungs. If they start to speak during the process there is the 
possibility that they might breath in some room air through their mouth despite the high flow of oxygen 
via their nose. If they dilute the inspired oxygen in this manner it may be that the lung oxygen content 
at the end of preoxygenation is not as high as it might otherwise be and the safe apnoeic period will 
therefore be shorter.  
By measuring the expired lung oxygen content after Optiflow™ preoxygenation in groups with either 
solely nasal breathing or with speech encouraged we hope to quantify any difference in efficacy. 
Publication of this information may help to guide clinical practice especially if a large difference in 
mean values between the 2 groups is demonstrated.  
  
3  
THEORETICAL FRAMEWORK  
  
Previous studies including those involving the principal investigator have shown that the end tidal 
oxygen content of the lungs can be reliably measured by asking a subject to exhale and then breathe 
normally via a mouthpiece which has a side sampling port connected to a standard gas monitor (as 
used during anaesthesia) which will measure and display the expired oxygen percentage.  
We have also shown that Optiflow™ can preoxygenate volunteer females to a comparable level to 
traditional facemask oxygenate within 3 minutes. In that trial all subjects breathed through their nose 
with a closed mouth and no vocalisation.  
The planned study moves on from previous studies by comparing 2 groups of subjects (patients not 
volunteer medical students) who either breathe with a closed mouth or recite a standardised text, 
reading from a sheet. The study is designed to address the gap in knowledge about whether speech 
adversely affects the efficacy of this preoxygenation technique.  
  
4  
RESEARCH QUESTION  
The research question being addressed is: Does speaking during preoxygenation with Optiflow™ have 
an effect on the expired oxygen fraction in the lungs at the end of 3 minutes preoxygenation.  
  
4.1  
Objectives  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
3  
The objective is to quantify the end-tidal oxygen after 3 minutes of Optiflow™ preoxygenation in 
groups of either closed-mouth, nasal breathers or ones who speak throughout the process.  
  
4.2  
Outcome  
The outcome will be that we will produce a mean (range/SD) value for the end-tidal oxygen content of 
the lungs after 2 styles of Optiflow™ preoxygenation. We can give guidance to the practical use of 
high-flow nasal oxygen for preoxygenation particularly with respect to whether efficacy is improved if 
patients are instructed to refrain from talking during the process.  
  
5  
STUDY DESIGN and METHODS of DATA COLLECTION AND DATA ANALYSIS  
For each subject demographic data will be collected: age, gender, height, weight, body mass index.  
For both study group arms, the end tidal oxygen fraction of the first expired breath after 3 minutes of 
preoxygenation will be recorded.  
Demographic data will be analysed with descriptive statistics.  
The findings generated (mean end-tidal oxygen levels) will be quantitative/parametric data and a t-test 
will be used to compare the groups.  
Data will be anonymised and stored on password protected NHS computers.   
Access to the study data will only be available to the researchers.  
  
6  
STUDY SETTING  
The study will be a single centre study at University Hospital Southampton.   
The study will be conducted in the operating theatre anaesthetic room prior to anaesthesia and 
surgery.  
Participants will have been recruited from the patients booked on the elective surgical list who have 
been to the preassessment clinic in advance of the operating day.    
7  
SAMPLE AND RECRUITMENT  
7.1   
Eligibility Criteria  
  
The study population will be from booked, elective surgical patients who have been preassessed and 
given a patient participation sheet to read in advance.  
  
7.1.1 Inclusion criteria   
Age 18 to 65  
ASA category 1 and 2 for cardiorespiratory fitness  
BMI 18 to 35  
Able to understand instructions and read aloud in English  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
4  
7.1.2 Exclusion criteria   
ASA 3 or above for cardiorespiratory fitness  
Outside age or BMI range  
Unable to understand and follow detailed instructions from the researcher.   
Inability to read aloud the standardised poem.  
Prescribed a sedative premedication. 
  
7.2   
Sampling  
  
7.2.1  Size of sample  
A power calculation has been performed which gives a sample size of 28 (estimated mean for control 
group 0.85, estimated mean for test group 0.75 {SD 0.1}, p=0.05, power 0.8 [actual power 0.824]).  
  
The control group value comes from a previous volunteer study using the same technique. The lower 
mean value for the speech group is a conservative estimate based on experience with mask 
preoxygenation by the chief investigator.  
  
7.2.2  Sampling technique  
The selection of participants will be at random from the population of preassessed elective surgical 
patients on any particular day that the research team is available to conduct the study in any particular 
theatre location. Any patient who reaches the inclusion criteria and is willing will be included.  
  
7.3  
 Recruitment  
  
7.3.1 Sample identification  
  
Potential subjects will be identified by asking the nurses in preassessment clinic to give patient 
participation sheets to all patients booked on certain operating lists (from a diary/list provided by the 
researcher for when she is available to conduct the study). There will be no recruitment by publicity, 
posters, leaflets, adverts or websites.  
On the day of surgery the routine anaesthetist for that operating session will ask patients who have 
been given participation sheets if they are willing to be spoken to about the research by the researcher 
and if they are willing to be screened by them to check eligibility.  
If they are willing, the researcher will approach them; discuss the study in more detail, answering any 
questions. She will also screen them for (in)eligibility.  
  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
5  
7.3.2 Consent  
  
If, after discussion with the researcher, they are still willing to participate and are eligible to do so, the 
researcher will ask them to read and sign the consent form, again providing further explanation when 
needed.  
  
  
8.1  
Assessment and management of risk  
Preoxygenation is a standard safety technique, commonly employed before many general 
anaesthetics. Optiflow™ is a commonly used alternative to traditional facemask preoxygenation. The 
technique can therefore be considered a safe one with no additional risks for a patient about to 
undergo a general anaesthetic.  
There are no additional risks to the researcher or other hospital staff.  
Subjects will not directly benefit from participation in the study  
  
8.2    Research Ethics Committee (REC) and other Regulatory review & reports  
Before the start of the study, a favourable opinion will be sought from a REC for the study protocol, 
informed consent forms and other relevant documents.  
Substantial amendments that require review by NHS REC will not be implemented until that review is 
in place and other mechanisms are in place to implement at site.    
All correspondence with the REC will be retained.  
It is the Chief Investigator’s responsibility to produce the annual reports as required.  
The Chief Investigator will notify the REC of the end of the study.  
An annual progress report (APR) will be submitted to the REC within 30 days of the anniversary date 
on which the favourable opinion was given, and annually until the study is declared ended.  
If the study is ended prematurely, the Chief Investigator will notify the REC, including the reasons for 
the premature termination.  
Within one year after the end of the study, the Chief Investigator will submit a final report with the 
results, including any publications/abstracts, to the REC.  
  
Regulatory Review & Compliance   
Before any patients are enrolled into the study, the Chief Investigator/Principal Investigator or 
designee will ensure that appropriate approvals from participating organisations are in place. For any 
amendment to the study, the Chief Investigator or designee, in agreement with the sponsor will submit 
information to the appropriate body in order for them to issue approval for the amendment. The Chief 
Investigator or designee will work with sites (R&D departments at NHS sites as well as the study 
delivery team) so they can put the necessary arrangements in place to implement the amendment to 
confirm their support for the study as amended.  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
6  
Amendments   
Any amendments that might need to be made to the study will be made via the REC by the principal 
investigator who will also be responsible for amending the protocol and other paperwork. If the 
sponsor wishes to make a substantial amendment to the REC application or the supporting 
documents, the sponsor must submit a valid notice of amendment to the REC for consideration. It is 
the sponsor’s responsibility to decide whether an amendment is substantial or non-substantial for the 
purposes of submission to the REC.  
  
8.3   
Peer review  
Peer review will be undertaken in line with the University of Southampton guidance for Medical 
Student research projects and include 2 reviewers who have relevant knowledge of the field of 
research, have experience in research including that involving medical student researchers and are 
suitably independent of the conduct of the study.   
  
8.4   
Patient & Public Involvement  
A similar related study on the use of high-flow nasal oxygen for preoxygenation of term pregnant 
subjects is underway at the same study site. Prior to starting that study patient feedback about the 
design of the patient information sheet was obtained from patients who had undergone caesarean 
section and would have been suitable for enrolment. Knowledge of that feedback has guided the 
design of the present study.  
  
  
  
8.5  
Protocol compliance   
Accidental deviations from the protocol will be recorded and reported to the CI.   
  
8.6  
Data protection and patient confidentiality   
Only members of the patient’s routine care team will see the participant before the day of surgery. 
Only information used as part of the routine process for assessing patients pre-operatively would be 
used to identify them as suitable for inclusion in the study. The researcher will only approach subjects 
who have indicated to their anaesthetist a willingness to participate in the study. The consent form will 
explain that the researcher has access to certain demographic data from patient notes (e.g. name, 
age) but personal identifiable information will not be stored for the study.  
To protect personal data, hospital identification numbers will be anonymised. A list of hospital 
identification numbers with cross reference to their research ID numbers will be kept in a locked NHS 
office.  
All investigators and study site staff will comply with the requirements of the Data Protection Act 1998 
with regards to the collection, storage, processing and disclosure of personal information and will 
uphold the Act’s core principles.  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
7  
Data generated by the study, which will be anonymised, will be kept on NHS password protected 
computers. This data will be retained for 5 years by the CI.  
  
8.7  
Indemnity  
  
As an NHS organisation has agreed to act as sponsor and as researchers with substantive NHS 
employment contracts have designed the research, indemnity is provided through NHS schemes.  
  
  
8.8  
Access to the final study dataset  
The full anonymised data set will be accessed only by the research team.  
  
9  
DISSEMINATION POLICY  
9.1   
Dissemination policy  
At the end of the study the researcher will produce a full written report which will be submitted to the 
University of Southampton as part of her BM degree work. An abstract and presentation at an annual 
medical student conference will be made.  
Further publication of the study may be made in peer reviewed publications or at conferences as a 
poster or oral presentation.  
  
Fisher and Paykel, as providers of the disposable equipment, will be provided with copies of reports 
and potential publications but will not have rights to review or edit publications.  
  
Participants who are interested will be sent a copy of the researcher’s report.  
  
9.2   
Authorship eligibility guidelines and any intended use of professional writers  
Authorship of reports and publications will be limited to the researcher and principal/chief investigator. 
10  
REFERENCES  
  
Mir F, Patel A, Iqbal R, Cecconi M, Nouraei S. A randomised controlled trial comparing transnasal 
humidified rapid insufflations ventilator exchange (THRIVE) with facemask pre-oxygenation in patients 
undergoing rapid sequence induction of anaesthesia. Anaesthesia 2016; 72: 439 – 43  
Ang KS, Green A, Ramaswamy KK, Frerk C. Preoxygenation using the OptiflowTM system. British 
Journal of Anaesthesia 2017; 118: 463 – 4  
Tan PCF, Dennis AT. High-flow nasal pre-oxygenation in pregnant women. Anaesthesia  2016; 71: 
851 - 2  
  

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
8  
  
 

Preoxygenation with Optiflow – the effect of speech on lung oxygenation.  
  
    
  
9  
 
11.   
APPENDICES  
Text chosen for reading aloud is the opening pages from The Chronicles of Narnia by CS Lewis  
  
  
  
  
13.3  
Appendix 3 – Amendment History  
Amendment  
No.  
Protocol 
version no.  
Date issued  Author(s) of 
changes  
Details of changes made  
 1 
 0.2 
 26/9/18 
 p butler 
Subject exclusion criteria to include 
those having a sedative premedication