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Trial registered on ANZCTR

Registration number

ACTRN12620001268932

Ethics application status

Approved

Date submitted

22/10/2020

Date registered

25/11/2020

Date last updated

25/11/2020

Date data sharing statement initially provided

25/11/2020

Type of registration

Prospectively registered

Titles & IDs

Public title

A comparison of the rate of rise of transcutaneous carbon dioxide during apnoeic oxygenation in microlaryngoscopy using transnasal humidified rapid insufflation ventilatory exchange (THRIVE) versus low flow tracheal insufflation: a randomised control trial

Scientific title

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1260-0086

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

laryngeal pathology

carbon dioxide rate of rise

Condition category

Condition code

Anaesthesiology

Anaesthetics

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This study will involve patients undergoing elective microlaryngoscopy procedures under care of ENT and anaesthetics. These patients will be randomised on day of surgery using simple randomisation, assigning patients to one of two anaesthetic techniques;

ARM 1: Trans-nasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE)
Those patients enrolled into the THRIVE arm will be induced with high flow nasal cannula attached but not yet turned on. As surgery begins, they will have their face masks removed and high flow O2 at 100% 70L started via Optiflow THRIVETM apparatus (Fisher and Paykel Healthcare Ltd, Auckland, New Zealand).
OR
ARM 2: Low Flow Intra-tracheal Oxygen Insufflation (Lo-Flo)
Those patients enrolled into the Lo-Flo arm will be induced. After face mask ventilation and waiting suitable time for paralysis, a low flow oxygen catheter will be passed through the glottic opening to sit mid tracheal level using standard intubating equipment (direct or indirect laryngoscopy). After this oxygen catheter has been place, the patient will be ventilated using face mask ventilation until the surgical start point. At this point, face mask will be removed and oxygen catheter attached to oxygen wall outlet will be started at 0.5L/min.

The maximal allowable time for either apnoea technique will have a 30 minute cut off point.

There will be 45 patients will be randomised into each trial arm.
As the patient arrives in the holding bay prior to their operation, the transcutaneous carbon dioxide (TcCO2) monitor will be connected to the patient. Upon entering the operating room, routine anaesthetic monitoring will be established. The patient will be pre-oxygenated using an appropriately size face mask until the end tidal oxygen (EtO2) > 70 mmHg. The patient will be induced with propofol 1-2mg/kg and/or propofol infusion (target controlled infusion or mg/hr), 0.1mcg-0.4mcg/kg/min remifentanil infusion and paralysed using a muscle relaxant.

Ventilation of the patient will occur using face mask technique until appropriate degree of paralysis and up to immediate commencement of surgery.

This study will be powered to show a true “no difference” in the rate of rise of TcCO2 between the two anaesthetic techniques.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

ARM 1: Trans-nasal Humidified Rapid Insufflation Ventilatory Exchange (THRIVE)

Control group

Active

Outcomes

Primary outcome [1]

Rate of rise of TcCO2 per unit time

Timepoint [1]

Time zero will be the moment that the surgical laryngoscope first enters the patient’s oral cavity. TcCO2 is recorded continuously and electronically by the Sentec TcCO2 device. The TcCO2 will be measured every minute. The rate of CO2 rise will be calculated over the operative time period.

Secondary outcome [1]

Maintenance of oxygenation

Timepoint [1]

Oxygen saturation (SpO2) at time zero; and at the completion of surgery will be recorded. The times at which SpO2 falls to 95% and 92% will also be recorded, should these events occur.

Secondary outcome [2]

Surgical conditions - this will seek the opinion of the surgical conditions from our otolaryngologist performing the microlaryngoscopy. This will be recorded immediately after surgery on a proforma describing quality surgical field as poor, adequate or excellent, with a free text comments section.

Timepoint [2]

To be documented by consultant surgeon immediately after procedure

Secondary outcome [3]

Oral, nose or throat discomfort as reported by patient

Timepoint [3]

Discomfort defined by patient complaining of mucosal dryness or pain immediately post operatively and at day 3 -5 post operatively by telephone will be recorded on a scale of none, mild, moderate or severe.

Eligibility

Key inclusion criteria

All patients over the age of 18 years undergoing microlaryngoscopy procedure

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

BMI > 40
Pregnancy
Expected > 30 minutes procedure time
Resting saturations on air < 92%

Study design

Purpose of the study

Treatment

Allocation to intervention

Randomised controlled trial

Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)

central randomisation by computer

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

simple randomisation using computer software

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s

Intervention assignment

Parallel

Other design features

Phase

Not Applicable

Type of endpoint/s

Efficacy

Statistical methods / analysis

Our aim is to show that our Lo-Flo catheter technique is non-inferior to THRIVE with regard to CO2 rise, with a non-inferiority margin of 15%. We have chosen 15% because a difference less than this would be insignificant in clinical practice. In a study similar to the one we are proposing, arterial CO2 rose by 0.24kPa/min with THRIVE; with a standard deviation (0.05). The rate of rise was close to linear over a period of up to 30 minutes.

We are assuming the numbers will be similar with the Lo-Flo catheter technique. We then assume that the average gradient is normally distributed and that it is valid to construct a 95% confidence interval for the mean gradient in each group. For a margin of 15% greater rate of rise of CO2 with cannula cf THRIVE, we then have (delta equal to 0.24 multiplied by 0.15, equals 0.036kPa/min)

Under these assumptions, we would need 41 per group to show non-inferiority with 90% power and alpha equal to 2.5%. We have therefore chosen to enrol 45 per group to allow for some failure dropouts.

Note that if it turns out that the cannula technique is better, we will know because the 95% CI for the difference between groups will exclude zero.

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

1/01/2021

Actual

Date of last participant enrolment

Anticipated

1/12/2021

Actual

Date of last data collection

Anticipated

6/12/2021

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

Monash Medical Centre - Moorabbin campus - East Bentleigh

Recruitment postcode(s) [1]

3165 - East Bentleigh

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

Monash Health

Address [1]

823-865 Centre Road, Bentleigh East, VIC 3165

Country [1]

Australia

Primary sponsor type

Hospital

Name

Monash Health Anaesthetic Department

Address

823-865 Centre Road, Bentleigh East, VIC 3165

Country

Australia

Secondary sponsor category [1]

Hospital

Name [1]

Monash Health ENT Department

Address [1]

823-865 Centre Road, Bentleigh East, VIC 3165

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Monash Health Human Research Ethics Committee

Ethics committee address [1]

Monash Health, 246 Clayton Road
Clayton Vic 3168

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

05/08/2020

Approval date [1]

02/10/2020

Ethics approval number [1]

61519

Summary

Brief summary

Trans-nasal humidified rapid insufflation ventilatory exchange (THRIVE) has been widely taken up by anaesthetic and ear, nose and throat (ENT) departments worldwide for airway management. THRIVE is a technique that uses rapidly insufflated, heated and humidified oxygen administered via nasal cannula to maintain oxygenation during periods of apnoea.  

It is regularly used for ENT procedures, in particular microlaryngoscopy. It allows for maintenance of oxygenation and unobscured surgical field by anaesthetic endotracheal tubes. 

The mechanism by which THRIVE and other apnoeic techniques (such as low flow intra-tracheal oxygen insufflation) maintain oxygenation is well understood, i.e. bulk flow of oxygen from the upper airway to replace the volume of oxygen taken up from the alveoli. However, a concern with all apnoeic techniques is the rise of blood and tissue carbon dioxide (CO2) levels in the absence of ventilation. Much of the support for THRIVE has centred on claims that unlike other apnoeic techniques, it is effective at eliminating CO2..

Recently, however, a study (1) of THRIVE in ENT microlaryngoscopy patients has suggested that when arterial CO2 levels are measured, the rate of rise of CO2 is actually as much as would be expected with other apnoeic techniques. 

In our anaesthetic department, we have considerable experience of apneoic oxygenation by low flow intra-tracheal oxygen insufflation (Lo-Flo). An oxygen catheter is directly passed under vision using a laryngoscope through the glottic opening to sit at mid tracheal level. This is then attached to oxygen supply at 0.5-1L/min.

Transcutaenous carbon dioxide (TcCO2) can be easily measured with a transcutaneous probe that attaches to the patient’s skin in a non painful, non invasive manner. It is applied a few minutes prior to the start of the procedure. 

This study would build on the previous departmental experience with apnoeic oxygenation research. We plan to compare the two techniques of apnoeic oxygenation for ENT microlaryngoscopy, focusing particularly on the rate of rise of  TcCO2. We believe it is likely that we will disprove the now widely held belief that CO2 rises less quickly with THRIVE than with other apnoeic techniques. 



(1) Gustafsson IM, Lodenius A, Tunelli J, Ullman J, Jonsson-Fagerlund M. Apnoeic oxygenation in adults under general anaesthesia using transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) – a physiological study. British Journal of Anaesthesia 2017; 118: 610–7

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Richard Barnes

Address

Monash Health Anaesthetic Department, 246 Clayton Road, Clayton, Victoria, 3168

Country

Australia

Phone

+61 0395946666

Fax

richard.barnes@monashhealth.org

Contact person for public queries

Name

Katie Fitzsimons

Address

Monash Health Anaesthetic Department, 246 Clayton Road, Clayton, Victoria, 3168

Country

Australia

Phone

+61 0395946666

Fax

katie.fitzsimons@monashhealth.org

Contact person for scientific queries

Name

Richard Barnes

Address

Monash Health Anaesthetic Department, 246 Clayton Road, Clayton, Victoria, 3168

Country

Australia

Phone

+61 0395946666

Fax

richard.barnes@monashhealth.org

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

Individual participant data will not be available during the trial.

What supporting documents are/will be available?

No Supporting Document Provided

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

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