ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12612000626864

Ethics application status

Approved

Date submitted

6/06/2012

Date registered

12/06/2012

Date last updated

30/01/2023

Date data sharing statement initially provided

30/01/2023

Date results information initially provided

30/01/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Does inhaled salbutamol decrease the incidence of perioperative respiratory adverse events in children at high risk for respiratory complications?

Scientific title

Does inhaled salbutamol decrease the incidence of perioperative respiratory adverse events in children at high risk for respiratory complications?

Secondary ID [1]

none

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

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

The impact of salbutamol vs placebo on the incidence of respiratory complications in children at a particular high risk for respiratory complications

Condition category

Condition code

Anaesthesiology

Anaesthetics

Respiratory

Other respiratory disorders / diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

All participants will be recruited at the pre-anaesthetic visit and randomised to receive either an inhaled placebo or inhaled salbutamol (200 mg; Ventolin, GSK) via a Metered Dose Inhaler (pMDI) and spacer approx 30 min prior to surgery. The attending anaesthetists, the surgeon, recovery staff, as well as the research staff undertaking lung function assessments will be blinded to the group allocation.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

All participants will be recruited at the pre-anaesthetic visit and randomised to receive either an inhaled placebo (identical to salbutamol puffer but without salbutmol) or inhaled salbutamol (200 mg; Ventolin, GSK) via a Metered Dose Inhaler (pMDI) and spacer approx 30 min prior to surgery. The propellant used in both puffers is hydrofluoroalkane. The attending anaesthetists, the surgeon, recovery staff, as well as the research staff undertaking lung function assessments will be blinded to the group allocation.

Control group

Placebo

Outcomes

Primary outcome [1]

The incidence of perioperative respiratory complications until the patient is discharge from the postanaesthetic care unit will be assessed via clinical assessments

Timepoint [1]

Perioperative period until patient is discharged from the postanaesthetic care unit.

Secondary outcome [1]

Lung function changes before and after the administration of salbutamol or placebo

Lung Function will be measured prior to surgery using the forced oscillation technique, as described below prior to and 15 minutes following administration of salbutamol or placebo. Mean Zrs from 3-5 acceptable measurements will be obtained as per international guidelines and respiratory resistance, reactance, frequency dependence and area under the reactance curve reported. Baseline values will be expressed as standardised deviation (z) scores using locally derived reference values and bronchodilator response reported as the relative (%) change from baseline. Lung volumes will be assessed at the same time.
Forced oscillation:
The mechanical impedance of the respiratory system (Zrs) will be measured with the modification of the Forced Oscillation Technique (FOT). Briefly, a small-amplitude signal between 4-64 Hz will be delivered to the subject through a mouthpiece and/or LMA (as appropriate) via a low-deadspace wave tube. The averaged Zrs data between 4 and 40 Hz will be evaluated to obtain total respiratory resistance (Rrs) and reactance (Xrs) in line with international guidelines. In addition to the average values the within-breath variations of these parameters as functions of tidal volume and flow will also be determined.
Lung volumes:
Functional residual capacity (FRC) and ventilation distribution (lung clearance index and moment ratios) will be measured using an ultrasonic flow meter (Exhalyzer D with ICU insert, Eco Medics, Duernten, Switzerland) using the multiple breath nitrogen wash-out (MBW). Children will breathe via a mouthpiece (or LMA as appropriate) -with a nose clip in place. Once a stable breathing pattern has been established, 100% O2 is introduced and continued until the exhaled nitrogen concentration is stable and decreased to <1.5%. Washout data are analysed off-line for FRC and global indices of ventilation distribution and will include the lung clearance index, alveolar-based mean dilution numbers and the mixing ratio. An increase in markers of ventilation distribution reflects more inhomogeneous ventilation.

Timepoint [1]

prior to and 15 min following the administration of salbutamol or placebo

Eligibility

Key inclusion criteria

Children, aged 6-16 years, male or female, undergoing elective surgery with a laryngeal mask airway. All children have to have 2 or more risk factors for respiratory complications:
1) Upper respiratory tract infection < 2 weeks prior to surgery
2) eczema at present or in the past
3) wheezing in the last 12 months
4) previous asthma (if wheezing in the past year is negative)
5) dry night cough
6) respiratory symptoms with exercise
7) family history of asthma (mother, father and/or siblings)
8) family history of eczema (mother, father and/or siblings)
9) family history of hayfever(mother, father and/or siblings)
10) passive smoke exposure (mother, father, caregiver)

Minimum age

6 Years

Maximum age

16 Years

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Known cardiac disease, airway or thoracic malformations, syndrome, neurological disorder, need for premedication, contraindication for LMA use as assessed by an anaesthetist independent of the study team. Any surgery involving the upper airway, chest or abdomen.

Study design

Purpose of the study

Prevention

Allocation to intervention

Randomised controlled trial

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

All patients will be recruited at the pre-anaesthetic visit. Only patients who meet the inclusion criteria for the study will be enrolled and only after informed consent is given voluntarily by the guardian and by the patient if appropriate. The patients will be randomised by computer generated block randomisation. The next available participant number will be assigned to the patient.
The drug randomisation will be performed by pharmacy at Princess Margaret Hospital. The patient will receive the study drug corresponding with his/her Participant Number. The study drug is in boxes with patient numbers detailed on the outside. The participant number will be used to identify the patient for the duration of the study.
All staff involved with the care of the patient and the data recording and entering will be blinded to the group allocation.

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

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data

Intervention assignment

Parallel

Other design features

Phase

Phase 4

Type of endpoint/s

Safety/efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Completed

Date of first participant enrolment

Anticipated

1/10/2012

Actual

12/12/2012

Date of last participant enrolment

Anticipated

12/12/2014

Actual

6/10/2015

Date of last data collection

Anticipated

7/10/2015

Actual

9/10/2015

Sample size

Target

470

Accrual to date

Final

470

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Australia

Primary sponsor type

Hospital

Name

Princess Margaret Hospital for Children

Address

Roberts Road
Subiaco, WA 6008

Country

Australia

Secondary sponsor category [1]

University

Name [1]

The University of Western Australia

Address [1]

35 Stirling Highway
Crawley WA 6009

Country [1]

Australia

Secondary sponsor category [2]

Government body

Name [2]

NHMRC

Address [2]

National Health and Medical Research Council
GPO Box 1421
Canberra ACT 2601

Country [2]

Australia

Secondary sponsor category [3]

Government body

Name [3]

SHRAC

Address [3]

State Health Research Advisory Council (SHRAC)
C/o Research Development Unit
Department of Health
PO Box 8172
Perth Business Centre, WA 6849

Country [3]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Princess Margaret Hospital for Children Ethics Committee

Ethics committee address [1]

Robert Road
Subiaco, WA 6008

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

30/04/2012

Approval date [1]

21/06/2012

Ethics approval number [1]

2009/EP

Summary

Brief summary

Despite the development of anaesthesia management guidelines, perioperative respiratory
adverse events (PRAE) remain a major cause of morbidity and mortality during paediatric
anaesthesia, causing more than three quarters of critical incidents and nearly one third of
all perioperative cardiac arrests.
In a previous large cohort study in over 9000 children, we identified several risk factors
(current or recent upper respiratory tract infection, wheezing >3 times in the last 12
months, eczema, nocturnal dry cough, a family history of asthma, eczema, rhinitis or
passive smoking) which can help in every day clinical practice to identify the children at a
particularly high risk for PRAE. Additionally, we demonstrated in an audit of children with a
recent URTI, that inhaled salbutamol reduced the incidence of perioperative
bronchospasm (5% vs. 11%, p=0.027) and persistent coughing (5.5% vs. 11.5%,
p=0.0314) in the perioperative period. The role of pre-treatment with reliever medications
for other PRAE risk factors (such as asthma, present/past eczema) is unknown. We
therefore propose a double blinded randomised controlled trial of the use of inhaled
salbutamol in children with two or more known risk factors for PRAE on the incidence of
PRAE.
We will randomise 470 children (6-16 years) to receive either inhaled salbutamol or an
inhaled placebo prior to the administration of anaesthesia. We will also assess lung
function before and 15 minutes after the administration of salbutamol or placebo.
Furthermore, we will monitor and record all respiratory complications (laryngospasm,
bronchospasm, severe and persistent coughing, airway obstruction, oxygen desaturation
(<95%) and postoperative stridor).
We hypothesise that children receiving salbutamol will experience significantly less PRAE
when compared with children who did not receive salbutamol preoperatively.
This study may help to reduce the health costs associated with respiratory complications
(e.g. unplanned hospital admissions, prolonged hospital stay, additional treatment) and
may help us to avoid unexpected admissions to the intensive care unit. Additionally, our
findings may lead to a reduction in waiting list times and aid us in deciding the best time for
the child’s surgery. Finally, this study may increase the availability of preventative
strategies that may reduce the numbers of children who have their surgery cancelled due
to respiratory issues. Cancellation of surgery has an adverse economic impact for
hospitals, causes enormous emotional and financial burdens on the child and his/her
family who have made many arrangements to attend hospital. Reducing the number of
cancellations will ease the distress experienced by children and their parents when
surgery does not go ahead as planned, which will have add on effects for child/parent
satisfaction regarding their hospital experience.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Prof Britta Regli-von Ungern-Sternberg

Address

Department of Anaesthesia and Pain Management
Princess Margaret Hospital for Children
Roberts Road
Subiaco
WA 6008

Country

Australia

Phone

+61893408109

Fax

[email protected]

Contact person for public queries

Name

Prof Britta Regli-von Ungern-Sternberg

Address

Department of Anaesthesia and Pain Management
Princess Margaret Hospital for Children
Roberts Road
Subiaco, WA 6008

Country

Australia

Phone

+61893408109

Fax

[email protected]

Contact person for scientific queries

Name

Prof Britta Regli-von Ungern-Sternberg

Address

Department of Anaesthesia and Pain Management
Princess Margaret Hospital for Children
Roberts Road
Subiaco, WA 6008

Country

Australia

Phone

+61893408109

Fax

[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

Type	Is Peer Reviewed?	DOI	Citations or Other Details	Attachment
Study results article	Yes		Premedication with salbutamol prior to surgery doe... [More Details]	362604-(Uploaded-27-01-2023-09-49-39)-Journal results publication.pdf

Documents added automatically

Source	Title	Year of Publication	DOI
Embase	Premedication with salbutamol prior to surgery does not decrease the risk of perioperative respiratory adverse events in school-aged children.	2017	https://dx.doi.org/10.1093/bja/aex139

N.B. These documents automatically identified may not have been verified by the study sponsor.

Trial Review

Documents added manually

Documents added automatically