Testing of a Valsalva Assist Device (VAD) to Assess Effects on Vagal Tone and Strain Pressures Achieved Compared to a Standard Manometer in Healthy Volunteers Performing Standard and Modified Valsalva Manoeuvres.
Phase: NA
Conditions: SVT, Vagal Bradycardia
Sponsor: University of Exeter

 
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Testing of a Valsalva Assist Device (VAD) to assess effects on vagal tone and strain 
pressures achieved compared to a standard manometer in healthy volunteers 
performing standard and modified Valsalva manoeuvres. 
 
Izzy Fitzgerald1, Professor Paul Ewings2*, Dr Iain Lang2, Dr Andy Appelboam3* 
 
1: 
University of Exeter Medical School 
2: 
University of Exeter 
3: 
Royal Devon and Exeter Foundation Trust  
(* Honorary University post) 
 
Chief Investigator: Andy Appelboam 
 
 
Protocol V4 24.08.17  
Lay Summary 
 
The Valsalva manoeuvre (VM) is a recommended initial treatment for 
supraventricular tachycardia (SVT), a common abnormal fast heart rhythm.  The VM 
is a safe physical technique involving the forced exhalation against resistance, which 
causes a physiological response that slows the heart and can correct the SVT during 
an attack (cardioversion). 
Research to date has demonstrated that a controlled strain (40mmHg pressure for 
15 seconds) combined with a postural modification gives the best chance of success 
and avoids the need for drug treatment. However, the physiological benefit of this 
posture modification has not been confirmed. There is also no standard, easy to use 
device available on the market to generate the required strain. A modified blood 
pressure gauge (sphygmomanometer) can be used but is bulky and inconvenient. 
Blowing into an empty syringe has also been used but has been shown to be 
unreliable in generating the required pressures. 
A small, easy to use device that reliably reproduces the conditions most likely to 
affect cardioversion would be advantageous as it could be used in emergency 
departments and ambulances and given to patients to take away for home use, as 
attacks can reoccur. 
A prototype for such a device, the Valsalva Assist Device (VAD), has been 
conceived by the lead applicant and developed in collaboration with Meditech. The 
device is now ready for testing in healthy volunteers. There is a need to ensure the 
device can deliver the required strain and to evaluate the physiological response 
(lowered heart rate) to its use with and without postural modification. 
Research Questions 
 
• Does postural modification to the VM induce greater vagal tone compared to a 
supine VM? 
• Does the device (VAD) used to deliver a VM in healthy volunteers reproduce 
the physiological vagal effects of a VM (slowed heart rate)? 
• Can the device (VAD) deliver the appropriate level of strain compared to a 
manometer in both a standard position and with postural modification (lying 
flat with leg elevation at end of strain) in healthy volunteers performing a VM? 

 
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Rationale and background 
The VM is an established and internationally recommended first line treatment for SVT.1 It 
causes a transient reflex physiological slowing of the heart (vagal tone) in healthy subject 
and can terminate attacks of SVT in patients. It is an extremely safe physical manoeuvre 
which mimics normal physiological responses e.g. straining at stool, child birth or when 
blowing up a balloon. 
 
However, in routine clinical practice, this physical manoeuvre has a low (5-20%) rate of 
success for treating SVT2 requiring the subsequent use of unpleasant intravenous 
treatments. Recent studies have shown that much better cardioversion rates approaching 
50% can be achieved using a postural modification to the manoeuvre together with a 
controlled strain using an adapted manometer.3 Using a manometer in routine care is not 
practical and cannot be given to patients to use out of hospital (attacks can recur and 
patients can perform their own VM).  
 
Blowing on an empty 10ml syringe has been suggested as a surrogate for the pressure 
required for the best VM.4 However, other recent studies have demonstrated syringes are 
unreliable in providing correct and consistent pressures during the VM strain.5 A prototype 
device has been developed based upon well-established anaesthetic breathing circuit 
devices which provide resistance to exhalation (positive end expiratory pressure release 
pop-off valves). These have been modified to provide the recommended VM strain pressure 
(40mmHg) resistance, are small and portable and are now ready for testing in healthy 
volunteers.  
 
The device is a small plastic tube with a standard disposable mouth piece to which can be 
fitted a standard breathing circuit (HME) filter to allow reuse of the device and connection of 
a manometer to monitor the strain without risk of cross contamination of the device (see 
figure 1). The device’s pop off valve prevents users from blowing a pressure in excess of 
40mmHg and also allows a slow leak once this pressure is achieved giving audible feedback 
to the user and researcher that the correct pressure is being achieved. This leak also 
prevents use of just mouth pressure and ensures intrathoracic pressure is appropriately 
raised a key component of the VM. 
 
By connecting this device to a manometer, its performance can be tested during the VM 
strain. As there is a normal physiological response to the VM which varies according to the 
degree of vagal tone, the effects of a VM using the device can also be compared to a strain 
using a manometer alone and with and without postural modification by assessing the fall in 
pulse rate during the manoeuvre.6 
 
Demonstrating the device is as effective as a manometer and works with a posture modified 
VM in normal volunteers would support its use in routine care and enable further evaluation 
in patients. The device, packaged with instructions for use, would be a useful piece of 
equipment for use in emergency departments and by paramedics and for patients who suffer 
from SVT. 
 
 
 

 
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Aims and objectives 
 
Aims: 
 
• 
The aim of this study is to confirm the physiological effects of a modified VM and 
evaluate the performance of a novel Valsalva assist device in healthy volunteers 
 
 
Objectives:  
 
• 
To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy 
volunteers performing a modified VM verses a standard supine VM using the VAD. 
 
• 
To evaluate whether there is a difference in vagal tone (drop in heart rate) in healthy 
volunteers performing a modified VM verses a standard supine VM using a 
manometer. 
 
• 
To measure and compare peak  strain pressure and duration produced using the 
device compared to a standard manometer in supine and modified postures  
 
 
 
 
 
Figure 1. Valsalva Assist Device (VAD). Fitted with disposable mouth piece and filter 
 
 
 

 
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Research Design 
 
We will conduct a single centre repeated measures observational study of use of the device 
to generate a Valsalva strain initially in a sample of healthy adult volunteers from the 
University of Exeter or RD&E Hospital  staff, this is not related to their role within RD&E of 
University of Exeter, but due to convenience as the study is happening at the University of 
Exeter clinical research facility on the RD&E site, this will hopefully increase the likelihood of 
people taking part. All participants will be screened for eligibility (Figure 2) and undergo 
informed written consent prior to participation. If participants fail screening due to abnormal 
clinical readings or vital signs, the chief investigator will review them, any urgent 
abnormalities (very unlikely) would be reviewed by the chief investigator or delegated 
emergency department doctor as soon as they are discovered. Depending on the severity, is 
treatment is required urgently then they will be treated in the emergency department. 
Otherwise they will be referred back to their Gp. Potential participants will be given written 
information about the study at least 24 hours prior to recruitment and interested individuals 
invited to attend screening, recruitment and testing. 
Potential participants will be invited to express an interest in taking part by responding to trial 
poster. These posters will be displayed in the student common room in the RILD, the 
medical department of St Luke’s and in the ED department noticeboard. Our main target 
population will be medical students and medical sciences students and ED department staff; 
students will be directed to the trial poster at some medical student lectures. The potential 
participant contacts the researcher leading the practical aspects of the trial by phone or 
email. Respondents will be asked how they would like to receive further information (post, 
email, and phone) and offered an appointment at the Clinical Research Facility (CRF) for 
screening and written consent if eligible, at their convenience but at least 24 hours after 
receiving the information sheet. Given the simple, safe and quick nature of the interventions, 
participants will be given the choice to take part after written consent or to return on another 
date, whichever they would prefer, to ensure minimal visits whilst giving participants further 
time to consider taking part should they wish. 
 
The VM is an extremely safe, physiological manoeuvre which is used in everyday life (eg 
straining at stool) and has been used in trial conditions and clinical practice many thousands 
of times with no serious adverse events. We will exclude participants who could conceivably 
be at any risk of harm from performing a VM or from use of the device.  
 
Screening will include 12 lead ECG and physical examination including observations of 
pulse, oxygen saturations, respiratory rate and blood pressure. Any participants with any 
detected abnormalities whether they are excluded from participation or not will be informed 
and referred to their primary care physician as appropriate.  All testing will be conducted in 
the clinical research facility (CRF) of the Royal Devon & Exeter Hospital, according to a strict 
trial protocol.  
 
 
Figure 2. Inclusion and Exclusion Criteria 
 
Inclusion Criteria: 
Adult Volunteers between 18 and 60 years old from University of Exeter or RD&E Hospital 
staff 
Sinus rhythm on initial ECG 
Self-reported good health 
 
Exclusion Criteria: 
Any regular medication other than the oral contraceptive 
Previous cardiovascular or respiratory disease 
Any contra-indication to performing a VM strain. (Eg. Known aortic stenosis, recent 
myocardial infarction, glaucoma, retinopathy)  
Pregnancy 

 
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Any ECG abnormality  
Any contra-indication to postural modification (any reason the participant can’t lie flat and 
have both legs lifted to 45 degrees, eg prosthetic hip 
Inability or refusal to give written consent to take part 
Observations of pulse, oxygen saturations, respiratory rate or blood pressure outside the 
normal range. Specifically blood pressure less than 100 systolic 
Caffeinated drinks within 6 hours prior to testing 
The use of stimulant drugs or alcohol within 24 hours prior to testing 
 
 
 
 
 
 
 

 
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Test Valsalva Manoeuvres: 
 
Participants will undergo a total of 4 VMs of the following 4 variations in random order, 
stratified by method of strain generation to ensure balance between the order of manometer 
and device use: 
 
1. Supine VM using manometer. Supine Valsalva strain using a manometer visible to 
the participant with a target of 40mmHg for 15 seconds 
2. Supine VM using device. Supine Valsalva strain using the device connected to 
manometer invisible to the participant but visible to a researcher for 15 seconds 
3. Modified VM using manometer. Semi-recumbent (at 45 degrees) Valsalva stain using 
a manometer visible to the participant with a target of 40mmHg for 15 seconds 
followed by supine positioning and passive 45 degree leg lift immediately at the end 
of the strain for a further 15 seconds (the modified VM) 
4. Modified VM using device. Semi-recumbent (at 45 degrees) Valsalva strain using the 
device connected to manometer invisible to the participant but visible to a researcher 
for 15 seconds followed by supine positioning and passive 45 degree leg lift 
immediately at the end of the strain for a further 15 seconds (the modified VM) 
 
 
All testing will be performed on a standard hospital trolley with a manually adjustable back 
rest. A 45 degree angle template guide will be used to ensure consistent back rest and leg 
elevation angles where needed. Participant will rest for 5 minutes prior to testing to ensure 
they start with a resting heart rate. Participants will be given clear, standardised instructions 
for each manoeuvre. The strains are intuitive with feedback from the manometer or device 
noise and no practices will be allowed. A stop watch will be used to time strains and will be 
visible to participants. Participants will be instructed to stop blowing after the 15 second 
strain but no other encouragement or instruction will be allowed. No participant will be 
allowed to blow more than 50mmHg on either the manometer or device.  
 
Blowing over 40mmHg is not likely as the manometer (with target marked) will be visible to 
participants when using the manometer delivered strain and the devices are set to release at 
pressures over 40mmHg. However as a safety measure, the researcher will ensure no 
participant exceeds this level during any of the VMs. In the rare event of device malfunction 
(ie it provides no resistance or resistance is greater than 50mmHg), the VM will be 
immediately abandoned and the malfunction recorded as an adverse incident. The particular 
manoeuvre will be restarted using a new device, only if the participant is happy to continue. 
 
A new mouth piece and HME filter for the device and a new 92cm length of green oxygen 
bubble tubing, for the manometer, will be used for each participant. 
 
There will be a three minute washout period between strains including two minutes rest after 
any change in posture. Continuous 3 lead ECG monitoring on a standard print enabled 
monitor will be used to assess heart rate during the manoeuvre. ECG rhythm strip traces 
would be printed for 45 seconds (15 seconds before, during and 15 seconds after each VM). 
They will be marked at the onset of each Valsalva strain, labelled with a code and 
subsequently analysed, blind to technique according to the method described by G Smith6: 
 
Pre-manoeuvre heart rates will be determined by calculating the mean R-R interval of the 10 
beats preceding each manoeuvre before converting it to heart rate in beats/minute. The 
lowest post manoeuvre heat rate will be determined by measuring and recording the longest 
R-R interval during and up to 15 seconds post manoeuvre. This will also be converted to a 
heart rate in beats per minute. The difference between the pre and post manoeuvre heat 
rate will indicate the degree of vagal tone or slowing of heart rate induced by each 
manoeuvre. 
 

 
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Peak sustained pressures achieved as observed on the manometer and duration of longest 
strain attempt during all VMs will be recorded on a standard report card. This will allow 
comparison of the different strain techniques. 
 
Participants will be closely monitored for any adverse events. Though none are expected, if 
any participant feels unwell or develops any significant or persistent ECG abnormalities, the 
individual will be immediately withdrawn from further testing and appropriate further clinical 
assessment will be arranged. All adverse events will be recorded, graded and reported 
immediately to the CI and sponsor and reviewed by the study team. 
 
 
Data Management 
 
The data will be de-identified and stored on encrypted and password protected computers 
and laptops. Personal data such as name and e-mail address will be held separately.  All 
data will be stored on University of Exeter computers with a designated University of Exeter 
member of staff responsible for destruction. Paper copies need to be scanned and destroyed 
and electronic records kept for a period of 5 years following the completion of the study, in 
line with University guidelines.  The member of staff responsible for data storage and 
disposal will be the Chief Investigator (Andy Appelboam) or their designated deputy from the 
research team at the University of Exeter. 
 
Software 
 
Data will be stored on Excel and analysed using STATA.   
 
Statistical Analysis (Revised 
 
The heart rates measured under each of the four testing scenarios will be summarised 
appropriately, e.g. mean and SD, or median and IQR if necessary; it is expected that heart 
rate will be approximately normally distributed. 
 
The contrasts of interest are to compare heart rate for: 
 
1. Supine VM vs modified VM (recognising that this comparison may or may not be 
different according to which instrument is used – manometer or device) 
2. Manometer vs device (recognising that this comparison may or may not be different 
according to the posture adopted – supine or modified) 
 
The analysis will be based on mixed effects linear regression (with appropriate prior 
assessment of assumptions, e.g. Normality), with individual as a random effect, position 
(supine/modified) as a fixed effect and instrument (manometer/device) as a fixed effect.  An 
interaction term (position x instrument) will be examined to consider whether there is any 
evidence of a differential effect (of device according to position, or equivalently position 
according to device), but will be dropped from the model if p>0.1.  If the interaction term is 
retained then comparison 1 between postures will be presented separately by device, and 
comparison 2 between devices will be presented separately by posture type; otherwise the 
two comparisons will be presented overall. 
 
Sample size calculations are based on a simple paired t-test.  There is no obvious way to 
determine a “smallest clinically important difference”, but we have used 4 beats per minute 
as a reasonably small difference, below which is unlikely to be important clinically.  The SD 
reported in G Smith et al is about 12 (similar for individual measures and for differences 
between measures).  With these parameters, a sample size of at least 73 participants 
provides 80% power at the 5% level of significance.  
 
 

 
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Project management 
 
The programme team consists of a multidisciplinary team with complementary skills and 
expertise as follows: 
Dr Andy Appelboam is the Chief Investigator and will lead the project and provide clinical 
expertise and advice. 
Prof Paul Ewing is a statistician and director of the research design service. He will advise 
on design and statistical aspects of the project. 
Izzy Fitzgerald will run the day to day practical aspects of the study as part of her 
Intercalated Master by Research Project 
Iain Lang will act as academic supervisor and provide academic support to the project. 
The project team will meet regularly for the duration of the study.  
 
 
 

 
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Dissemination 
 
The results will be presented at UK Emergency Medicine conferences (RCEM Scientific 
Meeting), the National Clinical Studies Group Meeting and South West Emergency 
Academic Team (SWEAT) Meeting.  If the results are sufficiently strong, then a paper will be 
written for publication in an appropriate emergency medicine journal.   
 
 
Patient involvement 
 
The initial study will be conducted in healthy student volunteers, however if the device 
performs as expected, there will be a need for it to be tested in a wider population and there 
may be an opportunity to involve patients in the design and conduct of this stage of research 
through the Exeter 10,000 project. We have had feedback on our information sheet from 
lay representatives of the Exeter 10,000, and have re-worded the information sheet in light of 
these comments Should this be the case, volunteers from this scheme will be involved in 
designing a modified protocol and information aimed at patients. In addition, the Arrhythmia 
Alliance, a patient support charity, who were partners in the original research underpinning 
this project and can provide further help with dissemination of results or findings relevant for 
patients. We will also be showing actual SVT patients the device and informally be asking for 
patient opinions during the lifetime of the project to prepare for the next stages if the 
evaluation is successful in volunteers. 
 
 
 
Timelines 
 
 
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References 
 
 
                                                            
1 Resuscitation Council (UK) Resuscitation Guidelines 2005. 
http://www.resus.org.uk/pages/guide.htm 
2 Smith G, Morgans, Boyle M. Use of the valsalva manoeuvre in the prehospital setting: a review of 
the literature. Emerg Med J. 2009;26:8-10 
3 Appelboam A, Reuben A, Mann C, et al; REVERT Trial Collaborators. Postural modification to the 
standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a 
randomised controlled trial. Lancet 201531.;386:1747–53. 
4 Smith G, Boyle M. The 10ml syringe is useful in generating the recommended standard of 40mmHg 
intrathoracic pressure for the Valsalva manoeuvre. Emerg Med Aust 2009;21:449-454 
5 Thornton HS, Elwan MH, Reynolds JA, et al Valsalva using a syringe: pressure and variation Emerg 
Med J 2016;33:748-749. 
6 Smith G, Broek A, Taylor DM, et al Identification of the optimum vagal manoeuvre technique for 
maximising vagal tone Emerg Med J 2015;32:51-54.