Trans-nasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergency intubation (Kids THRIVE): A randomised controlled trial

When a child presents to an emergency department, or is admitted to the intensive care unit because of a life-threatening condition, they may need immediate treatment to support their breathing. The transition from spontaneous breathing when a child is awake to controlled respiration under anaesthetic via a breathing tube is called intubation. This procedure is technically challenging and is often associated with low oxygen levels in children.

New methods of intubation which reduce the risk of oxygen levels becoming low are continually developed and safely tested through clinical trials. The Trans-nasal Humidified Rapid Insufflation Ventilatory Exchange in children requiring emergency intubation (Kids THRIVE) is one of these clinical trials. By comparing the current standard practice for intubating a child in an emergency situation, we aim to demonstrate that the THRIVE method will reduce the risk for low oxygen levels in the blood and increase the likelihood that the treating doctor is able to insert the breathing tube on the first attempt.

Information for parents and guardians

What is THRIVE?

THRIVE (Transnasal Humidified Rapid-Insufflation Ventilatory Exchange) is a technique that has been used in adults to provide oxygen via a set of nasal prongs during the placement of the breathing tube. These special prongs deliver oxygen to support oxygen levels. We are doing this study to find out if the THRIVE method will prevent the periods of low oxygen or low blood pressure that can occur when the breathing tube is inserted.

Why are we conducting the Kids THRIVE trial?

When children have trouble breathing they sometimes need support from a machine to help them get enough oxygen. Before a breathing machine can be used the child will be given some medicines to make them sleep (anaesthetic). A tube will then be placed in their wind pipe to help them breathe – this is known as intubation. The tube is then connected to a breathing machine, called a ventilator which pushes air and oxygen into the child’s lungs. As a child transitions from breathing by themselves to breathing with the aid of a ventilator there is an unavoidable risk of low oxygen or low blood pressure. In emergency department settings, this happens approximately 14% of the time, and tends to drop much faster in children than in adults. We also know that treating clinicians only successfully insert a breathing tube on their first try approximately 78 per cent of the time. THRIVE (Transnasal Humidified Rapid-Insufflation Ventilatory Exchange) is a technique that has been used in adults to provide oxygen via a set of nasal prongs while the treating clinician inserts a breathing tube. We are conducting the Kids THRIVE trial to find out if the THRIVE method will prevent periods of low oxygen or low blood pressure when a child is being intubated, and whether it will also improve the first time success rate for clinicians inserting a breathing tube.

We recently performed a trail using the THRIVE method where 48 healthy children in operating rooms needed a breathing tube inserted. We found that when using the THRIVE method of giving oxygen children were able to maintain normal oxygen levels for a longer period of time. We plan to use the experience gained from this previous study to find out if the THRIVE oxygen delivery is better and safer than the standard method of inserting a breathing tube. Oxygen levels, blood pressure and the number of attempts required to successfully insert the breathing tube will be the main areas where we expect to see improvement using the THRIVE method.

Who can take part in the trial?

Your child may be eligible to take part in the Kids THRIVE trial if they,

  • are less than 16 years of age
  • attend the Emergency Department (ED) at participating hospitals
  • are admitted to the Paediatric Intensive Care Unit (PICU) at participating hospitals.

What does being part of the THRIVE trial involve?

Eligible children who need to have a breathing tube inserted are enrolled into the study by treating clinicians. The children will then be randomly sorted and be intubated using either the:

  1. Standard method
  2. THRIVE method

For the purpose of this study half (50%) of the children will receive our standard method of inserting a breathing tube, and the other half (50%) will receive the THRIVE method of having oxygen delivered while their breathing tube is being inserted. The chance of receiving each method of treatment is 50%, like tossing a coin. Every child will be carefully monitored and cared for throughout this process and then connected to a ventilator. If the child receives the THRIVE technique, a breathing tube will be placed in their windpipe as soon as their treating doctor is happy that the procedure has been successful. The THRIVE nasal prongs will then be removed and the study will be complete.

To make sure the data collected during the trial is as detailed and accurate as possible, the intubation procedure will be recorded on video. All information contained in the video is confidential and solely for the purpose of the study. The recording will be held in strict confidence and stored on a password protected storage device at the local site for 5 years after the study is complete. After this time the video will then be destroyed.


Where possible, we will talk to you before the procedure and get your consent to include your child in the trial. However, due to the nature of inserting a breathing tube in an emergency situation it may not always be practical to do this. Our Children’s Health Queensland Hospital and Health Service Human Research Ethics Committee has given this study special approval, whereby children can be included in the study before you have given consent. This is because the THRIVE method does not put your child at risk of any harm. After the breathing tube has been inserted a research team member will discuss the study with you and seek your consent to continue in the study. This process is called delayed consent.

Information for participating study centres

Background Kids THRIVE study

The success and quality of emergency intubation is dependent on both patient and operator factors. In emergency department settings, the success rate of inserting a breathing tube on the first attempt is approximately 78 per cent. Since ideal conditions and high expertise cannot be guaranteed for all emergency intubations despite best efforts, the optimisation of patient and operator related factors are paramount.

The Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) technique has been shown to prolong apnoeic oxygenation time in adult patients. This allows intubation to be performed on patients with expected difficult airways in a timely and relaxed manner. Continued post induction oxygen delivery is then made possible by using high flow nasal prongs during attempted intubation in patients with known difficult anatomical airways and compromised cardiorespiratory function. When using the traditional pre-oxygenation technique however, the oxygen reservoir is no longer renewed after the facemask is removed.

THRIVE apnoeic oxygenation
There is a gap in the current clinical literature when it comes to studies investigating the use of THRIVE apnoeic oxygenation in children. Our aim is to use the findings and experience gained from the proof of concept study – ‘Transnasal Humidified Rapid-Insufflation Ventilator Exchange (THRIVE) in children: a randomised control trial’ published the British Journal of Anaesthesia in 2016 in healthy children, and extend it to focus on children in emergency settings. By doing this we intend to demonstrate that THRIVE can improve patient and operator dependent conditions and reduce adverse events related to intubation such as desaturation, hypotension and the number of intubation attempts.

Trial aim

The aim of this trial is to assess the effectiveness of THRIVE as a method for prolonging apnoeic oxygenation during the emergency intubation of children, as well as reducing the proportion of adverse events (specifically, oxygen desaturation) and increasing the first attempt success rate for endotracheal intubation.


We hypothesise that:

  1. The use of THRIVE for apnoeic oxygenation reduces the frequency of hypoxia (patient dependent variable) and increases the first attempt success rate (operator dependent variable) during emergency intubation in children compared with standard practice.
  2. The use of THRIVE for prolonging apnoeic oxygenation during the emergency intubation of children reduces the proportion adverse events.

Trial design

This trial is a multicentre, unblinded, randomised controlled trial. Participants will be randomised to receive either THRIVE or standard clinical practice during intubations. The trial will be conducted in the selected Emergency Departments and Paediatric Intensive Care Units across Australia and New Zealand who are members of the PREDICT and/or ANZICS PSG research networks.

Sample size

The trial centres will be recruiting 820 patients who will be randomized in a 1:1 ratio stratified by age and site to receive either standard care (no apnoeic oxygen provided) or THRIVE therapy.

Outcomes, significance and innovation

Intubating a child in the emergency setting can be a very emotional experience for both the patient and their parents. Depending on their skill level and experience the treating clinician performing the procedure may also be stressed as intubation is a high-risk procedure, which needs to be performed in a timely manner. Considering this, investigating new methods for improving situational safety during intubation is an extremely worthwhile exercise for everyone involved. Many clinicians and departments have adopted airway management algorithms and checklists to improve the efficiency, safety and quality of intubations in the emergency setting. The aim of our trial is to produce tangible, high-grade evidence that the use of THRIVE apnoeic oxygenation improves success rates and minimise adverse effects in children requiring emergency intubation. Guidelines, algorithms and checklists at participating hospitals will be updated accordingly as this new data becomes available. These updates to clinical practice will then be disseminated to other Queensland and interstate emergency departments.

Inclusion criteria

Participants must:

  • be aged less than 16 years at the time of randomisation
  • require rapid sequence induction (RSI) or modified RSI (modified RSI is defined as the provision of ventilatory support by bag-mask ventilation, or other method, during the pre-oxygenation phase of induction of anaesthesia) for emergency intubation and ventilation in either the emergency department or intensive care unit
  • consent, which can be obtained from a parent or guardian.

Exclusion criteria

Participants must NOT:

  • undergo planned endo-tracheal tube changes or nasal intubations
  • require immediate intubation for loss of cardiac output or respiratory arrest
  • undergo intubation outside the Emergency Department or Intensive Care Unit
  • have blocked nasal airway due to anatomical abnormality (e.g. choanal atresia)
  • have blocked nasal airway due to acute injury, trauma or disease (e.g. severe facial trauma).


kids THRIVE flowchart

Outcome measures

To demonstrate that the use of THRIVE for apnoeic oxygenation reduces the frequency of hypoxia (patient dependent variable) and increases the first attempt success rate (operator dependent variable) during emergency intubation in children compared with standard practice.

Secondary outcome measures

The secondary objectives of this study include assessment of rates of adverse events categorised by:

  • Minor Adverse Events (AE)
    • Bradycardia, not requiring treatment
    • Hypotension, not requiring treatment
    • Mainstem bronchial intubation
    • Oesophageal intubation with immediate recognition
    • Emesis without aspiration
    • Epistaxis
    • Dental or lip trauma
    • Hypercapnia
  • Major Adverse Events (MAE)
    • Cardiac arrest with or without return of spontaneous circulation
    • Oesophageal intubation with delayed recognition
    • Emesis with aspiration
    • Hypotension requiring treatment
    • Bradycardia requiring treatment
    • Laryngospasm
    • Malignant hyperthermia
    • Pneumothorax or pneumomediastinum


  • Pre-oxgenation phase: The pre-oxygenation period is defined as the period in preparation for intubation where oxygen is delivered to the patient to maximise oxygen concentration in the functional residual capacity (FRC) of the lung. For this trial, pre-oxygenation can be delivered by any method at the discretion of the treating clinician. Pre-oxygenation should be provided for at least 3 minutes.
  • Apnoeic phase: The apnoeic phase begins at the time of onset of muscle paralysis, and hence apnoea. This is approximately 30 seconds after the administration of suxamethonium or 45-60 seconds after the administration of rocuronium. For the purposes of this trial, the apnoeic period will be defined as commencing at the time that the mask (or nasal prongs) used for pre-oxygenation is removed from the face. This correlates approximately with the time of onset of paralysis or the initiation of the intubation attempt if assisted ventilation is required prior to intubation. The intervention of this trial will be applied at the onset of this period.
  • Hypoxia: In line with previously published studies, hypoxia is defined as oxygen saturation of less than 90% [6, 9] or a decrease of 10% from pre-intubation oxygen saturations where 100% oxygen saturation cannot be clinically achieved during pre-oxygenation.
  • Intubation attempt: A single advanced airway manoeuvre beginning with the insertion of a device, such as a laryngoscope, into the patient’s mouth and ending when the device is removed from the patient’s mouth, or where there is a change in operator during the procedure even if the device is not removed.


REDCap is a secure, web-based application for building and managing online databases and surveys. The Kids THRIVE trial uses REDCap for electronic data collection. If you have any concerns or questions please contact the Central Trial Co-Ordinator, Tara Williams.
RECap Weblink

Participating sites

  • Gold Coast University Hospital, Queensland
  • Queensland Children’s Hospital, Queensland
  • The Townsville Hospital, Queensland
  • Royal Children’s Hospital Melbourne, Victoria
  • Starship Children’s Hospital, Auckland

Collaborators and sponsors

We are fortunate to be supported by funding grants from the Emergency Medicine Foundation.

Our collaborators include

  • The University of Queensland
  • PREDICT (Paediatric Emergency Departments International Collaborative group)
  • PSG (Paediatric Study Group)
  • ANZICS (Australia and New Zealand Intensive Care Society)

Education and resources

  1. Kids THRIVE instructional video (authorised access only – password required, please email study coordinator

Key references

  1. Frei, F.J. and W. Ummenhofer, Difficult intubation in paediatrics. Paediatr Anaesth, 1996. 6(4): p. 251-63.
  2. Patel, A. and S.A. Nouraei, Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE): a physiological method of increasing apnoea time in patients with difficult airways. Anaesthesia, 2015. 70(3): p. 323-9.
  3. Bartlett, R.G., Jr., H.F. Brubach, and H. Specht, Demonstration of aventilatory mass flow during ventilation and apnea in man. J Appl Physiol, 1959. 14(1): p. 97-101.
  4. Erb, T., et al., Teaching the use of fiberoptic intubation for children older than two years of age. Anesth Analg, 1997. 85(5): p. 1037-41.
  5. Humphreys, S., et al., Transnasal humidified rapid-insufflation ventilatory exchange (THRIVE) in children: a randomized controlled trial. Br J Anaesth, 2017. 118(2): p. 232-238.
  6. Long, E., S. Sabato, and F.E. Babl, Endotracheal intubation in the pediatric emergency department. Paediatr Anaesth, 2014. 24(12): p. 1204-11.
  7. Miguel-Montanes, R., et al., Use of high-flow nasal cannula oxygen therapy to prevent desaturation during tracheal intubation of intensive care patients with mild-to-moderate hypoxemia. Crit Care Med, 2015. 43(3): p. 574-83.
  8. Vourc’h, M., et al., High-flow nasal cannula oxygen during endotracheal intubation in hypoxemic patients: a randomized controlled clinical trial. Intensive Care Med, 2015. 41(9): p. 1538-48.
  9. Bhatt, M., et al., Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children. Ann Emerg Med, 2009. 53(4): p. 426-435 e4.
  10. Fiadjoe, J.E., et al., Airway management complications in children with difficult tracheal intubation from the Pediatric Difficult Intubation (PeDI) registry: a prospective cohort analysis. Lancet Respir Med, 2016. 4(1): p. 37-48.
  11. Nishisaki, A., et al., Characterization of tracheal intubation process of care and safety outcomes in a tertiary pediatric intensive care unit. Pediatr Crit Care Med, 2012. 13(1): p. e5-10.
  12. Lee, J.H., et al., The number of tracheal intubation attempts matters! A prospective multi-institutional pediatric observational study. BMC Pediatr, 2016. 16: p. 58.
  13. National Health and Medical Research Council, A.R.C., Australian Vice-Chancellors’ Committee,, National Statement in Ethical Conduct in Human Research, N.H.a.M.R. Council, Editor. 2007.
  14. United Kingdom Government, Medications for Human Use (Clinical Trials). 2006.
  15. World Medical Association, World Medical Association Declaration of Helskini; Ethical Principles for Medical Research Involving Human Subjects. 2008.
  16. Chan, A.W., et al., SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med, 2013. 158(3): p. 200-7.
  17. Zaritsky AL, S.S., Berg RA, et al., Circularion, in PALS Course Guide, H.M. Ralston M, Zaritsky AL, et al., Editor. 2006, American Heart Association: Dallas TX.
  18. Zaritsky AL, S.S., Woelfel SK, et al., Bradyarrthymias and tachyarrhytmias, in PALS Course Guide, H.M. Ralston M, Zaritsky AL, et al., Editor. 2006, American Heart Association: Dallas, TX.
  19. US Department of Health and Human Services, Common Terminology Criteria for Adverse Events (CTCAE) v4.0. 2009, National Institutes of Health.
  20. Oliveira, S. et al., Effectiveness of Apneic Oxygenation During Intubation: A Systematic Review and Meta-analysis. Annals of Emergency Medicine, 2017.
  21. Deane, H. et al., PREDICT prioritisation study:establishing the research priorities of paediatric emergency medicine physicians in Australia and New Zealand. Emeregency Medicine Journal, 2017.


Centre for Children’s Health Research
Queensland Children’s Hospital Precinct
Paediatric Critical Care Research Group
Level 7, 62 Graham Street
South Brisbane, Qld, 4101

Central team (CCHR – Brisbane)

For study queries contact

Study Coordinator

Tara Williams
p: 07 3069 7480

Chief Investigator

Dr Shane George

Chief Investigator

Dr Susan Humpherys

Chief Investigator

Dr Ben Gelbart

Participating sites

Gold Coast University Hospital, Queensland
Queensland Children’s Hospital, Queensland
The Townsville Hospital, Queensland
Royal Children’s Hospital Melbourne, Victoria
Starship Children’s Hospital, Auckland