Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614001252606
Ethics application status
Approved
Date submitted
14/11/2014
Date registered
2/12/2014
Date last updated
22/04/2020
Date data sharing statement initially provided
12/04/2019
Date results information initially provided
22/04/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Development of new evidence-based ventilation guidelines for children undergoing surgery with general anaesthesia
Scientific title
To collect lung function outcomes in children undergoing surgical procedures with a general anaesthetic aged between 1 and 15 years of age and use the data with their demographic information to develop reference ranges and nomograms.
Secondary ID [1] 284924 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
None
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mechanical ventilation ranges in children undergoing general anaesthesia for a surgical procedure. 292396 0
Condition category
Condition code
Anaesthesiology 292714 292714 0 0
Other anaesthesiology
Respiratory 292715 292715 0 0
Normal development and function of the respiratory system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
All participants will be recruited at the preanaesthetic visit and will be consented voluntarily to the study after approval from the consulting anaesthetist.
Each patient will complete Lung function testing which will involve two different tests before anaesthesia induction: the measurement of respiratory mechanics using the forced oscillation technique and lung volumes using the multiple breath washout technique. These tests will take approximtaley 1 hour. The forced oscilation technique will be repeated after anaesthesia induction. This will take between 5 and 10 minutes. Patients will be monitored throughout their procedures and postoperatively in the post anaesthesia care unit (PACU). Any respiratory complications that may occur will be documented. Patients will be followed up on the ward or via telephone within 3 days following surgery incase of any complications.
Intervention code [1] 289747 0
Not applicable
Comparator / control treatment
No control. All patients recruited are undergoing a general anaesthetic for a surgical procedure
Control group
Uncontrolled

Outcomes
Primary outcome [1] 292557 0
The primary outcome is the measurement of respiratory resistance in mechanically ventilated paediatric population.
Timepoint [1] 292557 0
Measurements will be completed prior to and after anaesthesia induction by the forced oscilliation technique.
Primary outcome [2] 293632 0
The primary outcomes are the measurement of pulmonary compliance in mechanically ventilated paediatric population.
Timepoint [2] 293632 0
Measurements will be recorded by the lung function testing (Multiple Breath Washout) prior to the start of the surgery.
Secondary outcome [1] 309217 0
Creation of reference ranges for the mechanically ventilated paediatric population.
Timepoint [1] 309217 0
At the end of the study once data collection is completed all of the data will be analysed and collated to form reference ranges for the paediatric population.

Eligibility
Key inclusion criteria
Male or female
Aged 1 to 15 years
Group 1 children aged between 1 and < 6 years
Group 2 children aged between 6 and < 11 years
Group 3 children aged between 11 and < 16 years
Undergoing surgery with general anaesthesia in Princess Margaret Hospital.
Minimum age
1 Years
Maximum age
15 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children receiving a sedating premedication (e.g. midazolam, clonidine) before surgery.
Children born <37 completed weeks of gestation or having received respiratory support in the neonatal period
Children with a known difficult airway or thoracic malformation.
Children with a known lung and/or cardiopulmonary disease:
Uncorrected congenital heart disease
Primary/secondary pulmonary hypertension
Cardiac/thoracic malformations/tumours
Structural lung changes
Asthma
Cystic Fibrosis
Recurrent wheeze > 2 months or persistent cough > 3 months in past year

The above list is a non-exhaustive list. Any other less common cardiopulmonary conditions will be assessed by the anaesthetist in charge and accounted for in the exclusion criteria list.

Study design
Purpose
Screening
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
This study is the first study to establish reference values for lung function and lung mechanics in children under general anaesthesia for surgical procedures. We have thoroughly reviewed the relevant literature and were not able to find reported reference values of resistance and reactance under anaesthesia in children.

The primary aim of the study is to develop reference ranges for respiratory resistance and compliance and tidal breathing measurements in children aged 1-15 years during surgery under general anaesthesia. We acknowledge that lung function increases with growth at a varied rate during different age periods. We will develop the reference equations separately for the three age groups: 1 to<6, 6 to<11 and 11 to <16 years. Age, gender, height, weight and other potential predictors for these lung function parameters will be investigated to develop the reference equations. In the best model to predict the normal values of lung function we expect to include all predictors with a correlation coefficient >0.3 for a given lung function parameter. At the significance of 0.05 we have a power of 86% to significantly identify predictors with this strength of correlation for 100 children in each of the three age groups. There will be confounding effects between predictors. We select a variance inflation factor of 1.2 for the adjustment of multicollinearity. After the adjustment we need to recruit 120 children for each of the three age groups. We have further to account for 25% loss due to unacceptable data, subject exclusion due to clinical conditions during surgery and/or change in clinical management of airway over the three age groups. Therefore we will recruit 480 children overall for the study to develop reference equations of lung function parameters in children for the three age groups.

For the investigated predictors we will perform a set of regression analyses with respiratory resistance and compliance and tidal breathing measurements as dependent variables. Diagnostic tests for outliers and influential cases will be utilised to identify outliers. Linear, logarithmic, power and exponential regression techniques will be employed to determine the best relationship between every measured lung function parameter and the investigated predictors. The best-fitting regression model will be selected according to the likelihood ratio test.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
The investigator team thought we may have sufficient participant numbers.
Date of first participant enrolment
Anticipated
15/12/2014
Actual
26/03/2015
Date of last participant enrolment
Anticipated
31/05/2019
Actual
22/08/2017
Date of last data collection
Anticipated
Actual
23/08/2017
Sample size
Target
480
Accrual to date
Final
418
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 2705 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 8418 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 289551 0
Hospital
Name [1] 289551 0
Princess Margaret Hospital
Country [1] 289551 0
Australia
Primary sponsor type
Individual
Name
Prof Britta Regli-von Ungern-Sternberg
Address
Department of Anaesthesia and Pain Management
Princess Margaret Hospital
Roberts Road
Subiaco
WA 6008
Country
Australia
Secondary sponsor category [1] 288234 0
Charities/Societies/Foundations
Name [1] 288234 0
Australian and New Zealand College of Anaesthetists,
Address [1] 288234 0
ANZCA House, 630 St Kilda Road, Melbourne, Victoria 3004.
Country [1] 288234 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291292 0
Princess Margaret Hospital for Children Ethics Committee
Ethics committee address [1] 291292 0
Level 1, Children's Clinical Research Facility
Princess Margaret Hospital
Roberts Road, Subiaco
Perth
WA 6008
Ethics committee country [1] 291292 0
Australia
Date submitted for ethics approval [1] 291292 0
02/06/2014
Approval date [1] 291292 0
06/11/2014
Ethics approval number [1] 291292 0
EP 2014064

Summary
Brief summary
Paediatric patients undergoing elective or emergency surgery, or who have been admitted to the Neonatal/Paediatric Intensive Care Unit (NICU/PICU), often require mechanical ventilation. During the perioperative period, these patients are at risk of several types of lung injury, including atelectasis (collapse of lung tissue), pneumonia (disease marked by inflammation of the lungs), pneumothorax (presence of air within the pleural cavity leading to lung collapse), Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS).
Anaesthetic management can contribute to these injuries, exacerbate any underlying lung conditions or even improve outcomes, depending on the specific situation. Moreover, several studies have shown that pulmonary complications, more specifically respiratory failure requiring ventilation, are associated with high morbidity and mortality along with increased health-related costs and greater length of hospital stay.
Ventilation mode (volume, pressure or dual), modality (controlled, assisted, support ventilation) and respiratory parameters (e.g. tidal volume and respiratory rate) are the most important factors of mechanical ventilation. An important aspect of ventilation strategies is to optimise respiratory mechanics. A critical part of this process is knowing the normal range of respiratory mechanics during ventilation. This allows clinicians to define ventilation such that the respiratory mechanics can be maintained at a level expected for that particular patient and therefore protect against over- or under ventilation and thus minimise potential harm. While the normal ranges of a variety of respiratory outcomes during mechanical ventilation have been assessed in adults, there are no normal reference ranges of values available for the paediatric population. This precludes the formulation of clear evidence-based ventilation guidelines in children.
Measurable mechanical and physiological parameters such as pulmonary compliance (ease of expansion of the lungs and thorax), respiratory resistance (resistance to flow of gases during ventilation), tidal volume (volume of air moved in and out during quiet/normal breathing) can be used to effectively monitor the effect of changes in mechanical ventilation and limit the risk of Ventilator-Induced Lung Injury VILI. Furthermore, the lack of precise data on these essential parameters as well as the implications relating to the lack of this important data, have been highlighted by experts from the recent American Thoracic Society workshop on the evaluation of respiratory mechanics and function in patients being cared for in paediatric and neonatal ICU settings (personal communication from Dr Carmichael-Peterson, Chair of the American Thoracic Society Task Force for the measurement of respiratory function in the ICU). Better ventilation strategies are also of particular importance in children with cardiac and/or respiratory co-morbidities undergoing anaesthesia as well as children with prolonged surgeries impacting on respiratory function, e.g. pneumoperitoneum, extensive abdominal surgery.

This study aims at measuring lung function outcomes in children aged between 1 and 15 years old who are undergoing surgery under general anaesthesia and require mechanical ventilation.

We hypothesise that by measuring the respiratory resistance and pulmonary compliance of children undergoing surgery before and after anaesthesia induction, we will be able to develop robust prediction equations and nomograms that define the values of physiological parameters to be programmed in mechanical ventilators for optimal lung function in anaesthetised children having surgery.
Trial website
None
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48462 0
Prof Britta Regli-von Ungern-Sternberg
Address 48462 0
Department of Anaesthesia and Pain Management, Princess Margaret Hospital for Children, Roberts Road, Subiaco WA 6008
Country 48462 0
Australia
Phone 48462 0
+61893408109
Fax 48462 0
Email 48462 0
[email protected]
Contact person for public queries
Name 48463 0
Prof Britta Regli-von Ungern-Sternberg
Address 48463 0
Department of Anaesthesia and Pain Management, Princess Margaret Hospital for Children, Roberts Road, Subiaco WA 6008
Country 48463 0
Australia
Phone 48463 0
+61893408109
Fax 48463 0
Email 48463 0
[email protected]
Contact person for scientific queries
Name 48464 0
Prof Britta Regli-von Ungern-Sternberg
Address 48464 0
Department of Anaesthesia and Pain Management Princess Margaret Hospital for Children Roberts Road, Subiaco WA 6008
Country 48464 0
Australia
Phone 48464 0
+61893408109
Fax 48464 0
Email 48464 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment


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.