Are reductions in oxygen to the brain associated with behavioral changes in children undergoing anesthesia?

ISRCTN	ISRCTN11799594
DOI	https://doi.org/10.1186/ISRCTN11799594
Secondary identifying numbers	NIRSKIDS 1.1

Submission date: 25/08/2021
Registration date: 26/08/2021
Last edited: 02/10/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Surgery

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
Behavioural changes in small children, after general anesthesia, are not uncommon but the causes have not been well elucidated. A previous study from Spain has found an association between such changes and surprisingly small changes in the brain regional oxygen saturation during general anesthesia. If the latter results can be confirmed, it could have major implications on management of children under anesthesia. However, brain oxygen saturation can not always be measured, and reductions are often the result of reduced blood flow and oxygen delivery. Therefore, we aim to investigate the association between brain regional oxygen saturation, and as secondary aim episodes of low blood pressure or peripheral saturation and behavioral changes. We will also check the blood levels of a set of proteins that can be markers of damage to the brain and other tissue.

Who can participate?
All children between 2 and 6 years of age can participate, if their parents are available to fill in the structured questionnaire (PHBQ) one week after the procedure.

What does the study involve?
1. Measurement of brain regional oxygen saturation with a NIRS probe - a light sensor that is taped to the forehead when the child is in the operating room.
2. Blood samples are taken when the child is under anesthesia.
3. Recording of behavioral changes according to the PHBQ form, performed by the parents at 1 and 30 days after the procedure

What are the possible benefits and risks of participating?
There are no direct benefits from participating.
NIRS is non-invasive and without any known side-effects.
The total volume of blood that is taken is around 5 mL which is without risk.

Where is the study run from?
The pediatric anesthesia section at Uppsala University Hospital, Uppsala, Sweden

When is the study starting and how long is it expected to run for?
March 2021 to November 2022

Who is funding the study?
Department of Anaesthesia and Intensive Care and the Gillbergska Foundation, Uppsala, Sweden.

Who is the main contact?
Associate Professor Peter Frykholm, peter.frykholm@surgsci.uu.se

Contact information

Dr Peter Frykholm
Scientific

Dept of Anesthesia and Intensive Care
Uppsala University Hospital
Uppsala
75185
Sweden

ORCID ID	0000-0001-6402-136X
Phone	+46 6171240
Email	peter.frykholm@surgsci.uu.se

Study information

Study design	Prospective observational cohort
Primary study design	Observational
Secondary study design	Longitudinal study
Study setting(s)	Hospital
Study type	Diagnostic
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet.
Scientific title	Are reductions in cerebral oxygenation associated with postoperative behavioral changes in children undergoing anesthesia?
Study acronym	NIRSKIDS
Study objectives	Reduction in crSO2 of more than 5% from baseline is associated with increased behavioral changes 7 days after general anesthesia
Ethics approval(s)	Approved 15/07/2021, Swedish Ethical Review Authority (Etikprövningsmyndigheten, Box 2110, 750 02, Uppsala, Sweden; +46 10-475 08 00; registrator@etikprovning.se), ref: 2021-02927
Health condition(s) or problem(s) studied	Children 2 - 6 years of age undergoing general anesthesia
Intervention	Cerebral oxygenation saturation (crSO2) is continuously measured in the operating room starting before anesthesia induction and ending at the end of the procedure when anesthesia has been stopped. The children´s parents are asked to fill in a questionnaire on behavioral changes in their child after 1 and 4 weeks postoperatively. The association between crSO2 changes and behavioral changes are analyzed. Blood samples for analysing markers of cell damage are obtained at the beginning and end of the anesthesia.
Intervention type	Procedure/Surgery
Primary outcome measure	1. Behavioral changes according to the Post Hospitalization Behavioral Questionnaire (PHBQ) are measured at 7 days after the general anaesthesia 2. crSO2 during the general anaesthesia measured using Near Infrared Spectroscopy (Invos, www.medtronic.com) using an age-appropriate sensor on the forehead
Secondary outcome measures	Current secondary outcome measures as of 18/10/2021: 1. Behavioral changes according to the PHBQ measured at 30 days after the general anesthesia. Similarly, the OR of persistent changes is calculated for crSO2 more or less than 5%. 2. Episodes of hypotension and/or desaturation during anesthesia and PHBQ changes measured using patient records 3. Perioperative behavioural changes: a score of more than 2 of the Pediatric Anesthesia Behavior score at induction and/or a score of more than 14 of the Pediatric Anesthesia Emergence Delirium score in the post-anesthesia care unit. 4. The association between changes in PHBQ and the following biomarkers are investigated at a single time point: 4.1. Neurofilament light chain (NfL) and Glial fibrillary acidic protein (GFAp) measured using Single molecule array (Simoa) technology (Quanterix, Billerica, MA) 4.2. Ubiquitin C-terminal hydrolase L1 (UCHL1), NGAL, KIM-1, NAG measured using commercial immunoflourescence assay panels _____ Previous secondary outcome measures: 1. Behavioral changes according to the PHBQ measured at 30 days after the general anesthesia. Similarly, the OR of persistent changes is calculated for crSO2 more or less than 5%. 2. Episodes of hypotension and/or desaturation during anesthesia and PHBQ changes measured using patient records 3. The association between changes in PHBQ and the following biomarkers are investigated at a single time point: 3.1. Neurofilament light chain (NfL) and Glial fibrillary acidic protein (GFAp) measured using Single molecule array (Simoa) technology (Quanterix, Billerica, MA) 3.2. Ubiquitin C-terminal hydrolase L1 (UCHL1), NGAL, KIM-1, NAG measured using commercial immunoflourescence assay panels
Overall study start date	01/03/2021
Completion date	30/11/2022

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	2 Years
Upper age limit	6 Years
Sex	Both
Target number of participants	180
Total final enrolment	180
Key inclusion criteria	Children 2 - 6 years of age scheduled for general anesthesia of at least 30 minutes duration
Key exclusion criteria	1. Age <2 years 2. Age >6 years 3. Children with significant neurodevelopmental delay 4. General anesthesia <30 minutes 5. Access to the forehead for the NIRS probe unavailable (e.g. neurosurgery)
Date of first enrolment	15/09/2021
Date of final enrolment	30/06/2022

Locations

Countries of recruitment

Sweden

Study participating centre

Uppsala University Hospital

Department of Anaesthesia and intensive care
Uppsala
75185
Sweden

Sponsor information

Uppsala Regional Council
Hospital/treatment centre

Box 602
Uppsala
751 25
Sweden

Phone	+46 186110000
Email	region.uppsala@regionuppsala.se
Website	http://www.fou.nu/is/rfr/www.regionuppsala.se

Funders

Funder type

Government

Region Uppsala
Government organisation / Local government

Location: Sweden

Gillbergska stiftelsen
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): Gillbergska Foundation
Location: Sweden

Results and Publications

Intention to publish date	15/11/2023
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Data sharing statement to be made available at a later date
Publication and dissemination plan	The results will be published in a peer-reviewed medical journal.
IPD sharing plan	The current data sharing plans for this study are unknown and will be available at a later date

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol file	Swedish		26/08/2021	No	No

Additional files

40328_Protocol_Swedish.pdf: Swedish

Editorial Notes

02/10/2023: The following changes were made to the trial record:
1. The total final enrolment was added.
2. The intention to publish date was changed from 15/04/2023 to 15/11/2023.
08/12/2022: The following changes were made to the trial record:
1. The overall end date was changed from 01/07/2022 to 30/11/2022.
2. The intention to publish date was changed from 01/11/2022 to 15/04/2023.
3. The plain English summary was updated to reflect these changes.
18/10/2021: The secondary outcome measures were changed.
26/08/2021: Trial's existence confirmed by Swedish Ethical Review Authority (Etikprövningsmyndigheten)