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Trial registered on ANZCTR


Registration number
ACTRN12620000380998
Ethics application status
Approved
Date submitted
26/02/2020
Date registered
20/03/2020
Date last updated
6/04/2020
Date data sharing statement initially provided
20/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
A study in children undergoing laparoscopic appendectomy to track changes in oscillatory mechanics measured by forced oscillation technique (FOT).
Scientific title
COMET: Changes in oscillation mechanics, FOT and lung recruitment in paediatric laparoscopic appendectomy
Secondary ID [1] 300638 0
Nil
Universal Trial Number (UTN)
Trial acronym
COMET
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ventilation in children undergoing general anaesthesia for laparoscopic appendectomy 316417 0
Condition category
Condition code
Anaesthesiology 314673 314673 0 0
Anaesthetics

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The aim of this study is to track changes in oscillatory mechanics (Rrs and Xrs), measured by Forced oscillation technique (FOT), in mechanically ventilated children undergoing laparoscopic appendectomy

Following the induction of anaesthesia, the child will be intubated, and ventilation will be started. Standard monitoring will be established, including non-invasive arterial pressure, electrocardiography, pulse oximetry (SpO2), and end-tidal carbon dioxide (etCO2). Ventilation will be managed as deemed appropriate by the attending anaesthetist; however, to minimise the confounding effect of different ventilation approaches on lung mechanics, the following guidelines will be applied:
Pressure control mode;
FiO2: 0.30 – 0.45 to maintain SpO2 above 95%;
PEEP: 5 cmH2O;
Peak Inspiratory Pressure and (PIP): 10 - 25 cmH2O above PEEP to reach tidal volumes of 6-8 ml/kg;
Respiratory rate (RR): dependent on the child’s age; adjusted to maintain etCO2 between 35 - 45 mmHg.
The forced oscillation technique (FOT) equipment will be connected to the inspiratory line of the ventilator circuit and FOT data will be collected for the duration of ventilation. The following data will be recorded at relevant protocol steps:
FOT
Ventilation settings (PEEP, PIP, FiO2, RR)
SpO2
etCO2
Abdominal insufflation pressure
Train of Four (depth of muscle paralysis)

After intubation (before the beginning of the surgical procedure) and after the completion of surgery, lung volume recruitment manoeuvres will be performed manually ventilating the lungs with a peak airway pressure of 40 cm H2O and a PEEP of 15 cm H2O for 10 breaths to standardize lung volume history. We will record timing and dosing of all muscle relaxants used.

Pressure and flow will be continuously recorded allowing calculation of Rrs and Xrs throughout the period of general anaesthesia. In order to synthetize results, we will select 30-second data segments or epochs at the event points indicated below. Data will be reported as separate Rrs and Xrs values, every 15 minutes during surgery, (after induction, after recruitment, after insufflation, before and after deflation, before and after first and second recruitment manouevre) as a function of time. Any other event considered relevant to lung mechanics (e.g. changes in insufflation pressure) will be recorded

Lung mechanics will be assessed using FOT. Measurements will be carried out following the international guidelines and recommendations set by the American Thoracic Society and the European Respiratory Society.

The equipment that will be used to apply FOT during positive pressure ventilation had been developed at Politecnico di Milano University based on previously described methodology. Politecnico di Milano University owns patents on the assessment of lung volume recruitment by FOT. However, the results of this study will only partially link to that patent. The outcomes of the COMET study will primarily contribute to changing anaesthetic practice and will be openly published in an international peer reviewed journal.

The equipment consists of a small flow sensor placed close to the airway device with the other equipment inserted further away from the patient within the anaesthetic circuit. This ensures that the deadspace and extra weight on the airway device is minimal (11g). Flow will be measured using a compact commercial sensor (Florian, Acutronic Medical Systems, Hirzel, Switzerland), which has been already characterized and used for measuring FOT parameters in clinical studies and it is regularly used in commercial mechanical ventilators (e.g. Fabian, Vyaire) in both NICU and PICU. This flow sensor has 4 mL dead space and weighs about 11 g, so it will not have a significant impact on the overall equipment. This hot-wire flowmeter is not critically affected by humidity and can be placed close to the HME filter.

The device produces small amplitude pressure oscillations (e.g. 2 cmH2O peak-to-peak), which does not cause discomfort and does not affect ventilation as the associated volume changes are very small (e.g. 1 mL). Single use anti-bacterial filters will be used to isolate the patient from the equipment and eliminate the risk of cross-contamination.

Low amplitude sinusoidal pressure oscillations (2 cmH2O peak-to-peak) at 5 Hz are generated by a loudspeaker connected to the inspiratory line of the mechanical ventilator and applied at the inlet of the tracheal tube. The rear of the loudspeaker is enclosed in a chamber and connected to the inspiratory outlet of the ventilator to equilibrate the positive pressures on both sides of the loudspeaker membrane. Pressure and flow are measured at the airway opening using a pressure transducer and a mesh-type heated pneumotachograph connected with a differential pressure transducer. Signals are sampled at 200 Hz and exported on a personal computer for offline analysis.

Intervention code [1] 316968 0
Diagnosis / Prognosis
Comparator / control treatment
An observational study without control group or randomisation - no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 323000 0
The primary outcome of the COMET study is the measurement of respiratory mechanics using the forced oscillation technique (specifically respiratory reactance (Xrs)) in mechanically ventilated children undergoing laparoscopic appendectomy. We will evaluate the changes in lung function during the procedure.
Timepoint [1] 323000 0
Specifically, we will look at differences in oscillatory mechanics at the following protocol steps:
· After intubation, muscle relaxation and induction of anaesthesia
· After a recruitment manoeuvre
· After gas insufflation into the abdomen and every 15 min thereafter
· At the completion of surgery
· After gas exsufflation
· After a recruitment manoeuvre
Primary outcome [2] 323226 0
The primary outcome of the COMET study is the measurement of respiratory mechanics using the forced oscillation technique (specifically respiratory resistance (Rrs) in mechanically ventilated children undergoing laparoscopic appendectomy. We will evaluate the changes in lung function during the procedure.
Timepoint [2] 323226 0
Specifically, we will look at differences in oscillatory mechanics at the following protocol steps:
· After intubation, muscle relaxation and induction of anaesthesia
· After a recruitment manoeuvre
· After gas insufflation into the abdomen and every 15 min thereafter
· At the completion of surgery
· After gas exsufflation
· After a recruitment manoeuvre
Secondary outcome [1] 380585 0
Nil
Timepoint [1] 380585 0
NIl

Eligibility
Key inclusion criteria
Children of any sex
Aged 2 to 16 years of age
Undergoing laparoscopic appendectomy under general anaesthesia
Minimum age
2 Years
Maximum age
16 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children with a thoracic malformation
Children with a known major lung and/or cardiopulmonary disease:
Uncorrected congenital heart disease
Primary/secondary pulmonary hypertension
Cardiac/thoracic malformations/tumours
Structural lung changes
Uncontrolled asthma
Cystic Fibrosis
Doctor diagnosed bronchiectasis
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 of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Lung mechanics (Rrs and Xrs) at different time points (after induction, after recruitment, after gas insufflation, at 15-min intervals during surgery,) will be analysed. The association between the changes in lung mechanics, age and BMI will be evaluated. A linear statistical model (essentially multiple linear regression model) will be fitted separately (that is, different models for each) to the Rrs and Xrs measurements after insufflation. The variables in the model will include the measurement before insufflation, age, BMI, and other relevant data that will be collected at each step. Separate models will be fitted to the data for each step of the protocol (intubation, recruitment, etc.). A linear model will also be fitted to the baseline respiratory mechanism to investigate if it has returned to levels prior to surgery. Other models may also be investigated depending on feasibility (for example, a longitudinal model for measurement at all stages in the protocol may be informative). Also, for gas insufflation into the abdomen every 15 minutes, a repeated measures model will be fitted.

For a linear statistical model for each response, with covariates previous measurement of variable, age, BMI and sex, and using a modest correlation coefficient of 0.6, the size (using R) for a power 0f 95% gives a sample size of 34. Given that the data is longitudinal and the statistical analysis needs to account for the unknown effects of time as well person effect, we select a sample size of 60, corresponding to a conservative correlation coefficient of 0.5 and power 0.95.
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. Loss of data is standard for in theatre research measurements due to the complex theatre environment with many last minute changes to the surgical lists due to changing patient and surgical priorities, which may include changing times or days of surgery, type of surgery, which may render a patient non-eligible or move the patient to a time or date on which no study staff is available. A lesser amount of data loss (around 10%) is attributable to technical problems or other clinical issues during or prior to measurements which interfere with data collection.) This gives a sample size of 90. We take a sample size of 100 for an extra safety margin.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 15979 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 29469 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 305062 0
Hospital
Name [1] 305062 0
Perth Children's Hospital
Address [1] 305062 0
Department of Anaesthesia and Pain Medicine
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country [1] 305062 0
Australia
Primary sponsor type
Hospital
Name
Perth Children's Hospital
Address
15 Hospital Avenue
Nedlands
WA 6009
Country
Australia
Secondary sponsor category [1] 305427 0
None
Name [1] 305427 0
Address [1] 305427 0
Country [1] 305427 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305448 0
Child and Adolescent Health Services Ethics Committee
Ethics committee address [1] 305448 0
Level 5
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Ethics committee country [1] 305448 0
Australia
Date submitted for ethics approval [1] 305448 0
22/10/2019
Approval date [1] 305448 0
27/11/2019
Ethics approval number [1] 305448 0
RGS0000003281

Summary
Brief summary
Laparoscopy is the preferred surgical approach in several abdominal procedures as it provides several advantages compared to open surgery, including: minimal incision, shorter hospital stay, less pain after the operation, and early mobilization . However, gas insufflation into the abdomen increases abdominal pressure with consequent changes in respiratory mechanics and lung volume de-recruitment. During an operation an anaesthetist will typically use what are called recruitment manoeuvres, e.g. sustained inflation or multiple manual breaths, to re-open collapsed lung areas.

Patients undergoing laparoscopic surgery are normally anaesthetised, muscle paralysed, receive a breathing tube and will need to be on a ventilator. The ventilator must generate (positive) pressure to blow oxygen into the lung and inflate them. Prolonged positive pressure ventilation, particularly requiring higher pressures, is damaging to the delicate lining of the lung. The continual opening and closing and/or over-distention of the alveoli caused by the ventilator seem to be the most important trigger for damage. The younger and smaller the children the more susceptible the airway, but also the lower safety margin with the pressures that are safe to use.


The forced oscillation technique (FOT) is a non-invasive method for the assessment of lung mechanics, which has been successfully applied in patients with breathing tubes in. Briefly, it applies small pressure waves down into the airway and detects the reflected/returning waves allowing assessment of the airway. While intermittent assessments have been performed in the past, our study proposes a novel continuous technique not previously used in the anaesthetic setting.

he aim of this study is therefore to assess the feasibility of this novel continuous assessment of respiratory mechanics in theatre and to track their changes, as measured by FOT, in children undergoing laparoscopic appendectomy. If this study demonstrates the feasibility of this new technique of tracking lung function during laparoscopic surgery, it will allow paediatric anaesthetists to use real time data to continually optimise the ventilator settings required for a child. It could then allow formulation of new evidence-based ventilation guidelines and policies to optimize and personalize the ventilation strategy in children undergoing laparoscopic surgery.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 100422 0
Prof Britta Regli-von Ungern-Sternberg
Address 100422 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 100422 0
Australia
Phone 100422 0
+61 420790101
Fax 100422 0
Email 100422 0
Britta.Regli-VonUngern@health.wa.gov.au
Contact person for public queries
Name 100423 0
Prof Britta Regli-von Ungern-Sternberg
Address 100423 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 100423 0
Australia
Phone 100423 0
+61 420790101
Fax 100423 0
Email 100423 0
Britta.Regli-VonUngern@health.wa.gov.au
Contact person for scientific queries
Name 100424 0
Prof Britta Regli-von Ungern-Sternberg
Address 100424 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands
WA 6009
Country 100424 0
Australia
Phone 100424 0
+61 420790101
Fax 100424 0
Email 100424 0
Britta.Regli-VonUngern@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Investigators for the study are still deciding upon how to proceed with this.
What supporting documents are/will be available?
No other documents available
Summary results
No Results