Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616000320459
Ethics application status
Approved
Date submitted
1/03/2016
Date registered
10/03/2016
Date last updated
21/01/2020
Date data sharing statement initially provided
12/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Cerebral oxygenation and carbon dioxide in patients undergoing surgery
Scientific title
Evaluation of cerebral oxygenation in response to changes in arterial carbon dioxide in patients undergoing major surgery
Secondary ID [1] 288665 0
Nil Known
Universal Trial Number (UTN)
U1111-1180-2285
Trial acronym
Not applicable
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cerebral blood flow 297854 0
Postoperative confusion 297855 0
Condition category
Condition code
Surgery 298028 298028 0 0
Other surgery
Anaesthesiology 298029 298029 0 0
Anaesthetics
Neurological 298030 298030 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patient with age greater than 18 years undergoing major surgery of at least 2 hours duration with be treated with controlled ventilation maintaining an arterial CO2 level (PaCO2) between 45 to 55 mmHg. The duration of mild hypercapnia will be from induction of anaesthesia to end of the surgical procedure i.e. skin closure. Controlled ventilation will be managed by the anaesthetist responsible for the conduct of the case. The target CO2 will be achieved by adjusting the minute ventilation on the ventilator by changing the respiratory rate, tidal volume, or adjusting both of these variables. These will be adjusted by the treating clinical anaesthetist by following a standardised algorithm:- first the respiratory rate will be adjusted by 2 breaths/min. The blood gas will then be repeated 5-minutes later. Second, if the CO2 is still not within target rage, the tidal volume will be adjusted by 20%. These steps will be repeated until the target CO2 is achieved. Once the target CO2 has been achieved, adherence to the intervention i.e. maintaining an arterial CO2 level between 45 to 55 mmHg, will be verified by the clinical anaesthetist checking the PaCO2 on arterial blood gases at hourly intervals. Blood gases will be performed on a blood gas analyser located in the theatre complex
Intervention code [1] 294082 0
Treatment: Other
Comparator / control treatment
Patient with age greater than 18 years undergoing major surgery of at least 2 hours duration with be treated with controlled ventilation maintaining an arterial CO2 level (PaCO2) between 35 to 40 mmHg. The duration of mild hypercapnia will be from induction of anaesthesia to end of the surgical procedure i.e. skin closure. Controlled ventilation will be managed by the anaesthetist responsible for the conduct of the case. The target CO2 will be achieved by adjusting the minute ventilation on the ventilator by changing the respiratory rate, tidal volume, or adjusting both of these variables. These will be adjusted by the treating clinical anaesthetist by following a standardised algorithm:- first the respiratory rate will be adjusted by 2 breaths/min. The blood gas will then be repeated 5-minutes later. Second, if the CO2 is still not within target rage, the tidal volume will be adjusted by 20%. These steps will be repeated until the target CO2 is achieved. Once the target CO2 has been achieved, adherence to the intervention i.e. maintaining an arterial CO2 level between 35 to 40 mmHg, will be verified by the clinical anaesthetist checking the PaCO2 on arterial blood gases at hourly intervals. Blood gases will be performed on a blood gas analyser located in the theatre complex.
Control group
Active

Outcomes
Primary outcome [1] 297548 0
Cerebral oxygenation measured with non-invasive cerebral oximetry using the Masimo O3 (TradeMark) regional oximetry component of the Root (TradeMark) Patient Monitor platform (O3 (TradeMark) Masimo, Irvine, CA). This regional oximetry device uses NIRS and reflectance oximetry to monitor rSO2 in the brain, capturing both absolute and trend rSO2 data.
Timepoint [1] 297548 0
Measured continuously commencing prior to induction of anaesthesia until completion of surgery.
Secondary outcome [1] 321368 0
Intraoperative end-tidal CO2. Measurement will be done on an ABL Blood Gas Analyzer with a fully automated micromode.
Timepoint [1] 321368 0
Baseline prior to anaesthesia and at completion of surgery.
Secondary outcome [2] 321369 0
Intraoperative plasma pH. Measurement will be done on an ABL Blood Gas Analyzer with a fully automated micromode.
Timepoint [2] 321369 0
Baseline prior to anaesthesia and at completion of surgery.
Secondary outcome [3] 321370 0
Intraoperative plasma bicarbonate. Measurement will be done on an ABL Blood Gas Analyzer with a fully automated micromode.
Timepoint [3] 321370 0
Baseline prior to anaesthesia and at completion of surgery.
Secondary outcome [4] 321371 0
Intraoperative base excess. Measurement will be done on an ABL Blood Gas Analyzer with a fully automated micromode.
Timepoint [4] 321371 0
Baseline prior to anaesthesia and at completion of surgery.
Secondary outcome [5] 321372 0
Intraoperative plasma potassium. Measurement will be done on an ABL Blood Gas Analyzer with a fully automated micromode.
Timepoint [5] 321372 0
Baseline prior to anaesthesia and at completion of surgery.
Secondary outcome [6] 321376 0
Postoperative delirium. Measurement will be done using the "Confusion Assessment Method" (CAM).
Timepoint [6] 321376 0
Postoperative Day 1
Secondary outcome [7] 378986 0
Length of hospital stay
Timepoint [7] 378986 0
Measured in days from completion of surgery to hospital discharge . This will be assessed from hospital’s electronic medical records system.

Eligibility
Key inclusion criteria
Adult patients (age > 18 years) undergoing major surgery (greater than 2 hours duration) that require the routine use of an arterial line for continuous blood pressure monitoring and intermittent positive pressure ventilation via an endotracheal tube as part of standard anaesthesia care.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. All patients aged less than 18 years
2. Patients undergoing cardiac surgery
3. Intracranial procedures
4. Glasgow Coma Score < 15
5. Thoracic surgery requiring for one lung isolation
6. Moderate pulmonary hypertension (MPA greater than or equal to 40 mmHg)
7. American Society of Anaesthesiologists (ASA) physical status V

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
All adult patients undergoing major surgery who require controlled ventilation and invasive monitoring using an arterial line will be evaluated preoperatively at the anaesthesia pre-admissions clinic at least 1-2 weeks prior to surgery. Patients will be identified for study entry by the investigators, an anaesthetist or research co-ordinator acting on behalf of the principle investigators by surveillance of patients in the pre-admissions clinic. Informed written consent in the form of a Participant Information and Consent Form (PICF) will then be obtained.

Once informed consent has been obtained, randomisation will be by means of sealed opaque envelopes with permuted blocks of variable size. Each envelope will contain a study arm allocation with the partial pressure of CO2 allocated i.e. normocapnia (PaCO2 35-40mmHg) or Mild hypercapnia (PaCO2 45-55mmHg)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Permuted block randomisation will be used using computer generated software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Normal cerebral saturations (rSO2) prior to the induction of general anaesthesia, range from 60% to 80%. Sample size calculations for this study are based on normal rSO2 values for awake patients. Sample size calculations used inferences for means and comparing two independent samples. We consider a 15% change in absolute rSO2 values from baseline to be clinically important. Therefore, assuming a mean rSO2 of 65% in the normocapnic group (mu1), and an 15% increase in rSO2 values to 75% in the mild hypercapnic group (mu2) and sigma/common standard deviation of 9.5%, with an a-value of (type I error rate) of 0.05, and a desired power of 90%, 19 participants will be required in each group. To allow for any breaches in protocol, we will randomise 20 subjects in each group. A total of 40 participants will be included.

Statistical analysis will be performed using computerized software (SPSS for Windows version 12.0). For data that is non-normally distributed a Mann-Whitney test will be used and normally distributed data will be compared using the Student T test. Ordinal and nominal data will be compared using Chi square analysis. A p<0.05 will be considered significant. Correlation coefficients will be used to measure how strong the relationship is between changes in PaCO2 and cerebral oximetry. Repeated measures ANOVA will be used to examine changes in mean CO2 and cerebral oximetry over the duration of surgery. Where appropriate, a mixed linear regression model will be used to adjust for variables such as age, gender and duration of surgery.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/03/2016
Actual
14/03/2016
Date of last participant enrolment
Anticipated
31/07/2016
Actual
31/03/2017
Date of last data collection
Anticipated
Actual
14/04/2017
Sample size
Target
40
Accrual to date
Final
40
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 5394 0
Austin Health - Austin Hospital - Heidelberg

Funding & Sponsors
Funding source category [1] 293026 0
Hospital
Name [1] 293026 0
Department Anaesthesia, Austin Hospital
Country [1] 293026 0
Australia
Primary sponsor type
Hospital
Name
Deparments of Anaesthesia, Austin Hospital
Address
Studley Road, Heidelberg, Victoria, 3084, Australia
Country
Australia
Secondary sponsor category [1] 291801 0
None
Name [1] 291801 0
Address [1] 291801 0
Country [1] 291801 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294536 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 294536 0
Ethics committee country [1] 294536 0
Australia
Date submitted for ethics approval [1] 294536 0
25/11/2015
Approval date [1] 294536 0
06/01/2016
Ethics approval number [1] 294536 0
HREC/15/Austin/488

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 791 791 0 0
/AnzctrAttachments/370245-HREC Approval Letter For Study.pdf

Contacts
Principal investigator
Name 64038 0
A/Prof Laurence Weinberg
Address 64038 0
Department of Anaesthesia, Austin Hospital, 145 Studley Rd, Heidelberg, VIC, 3084
Country 64038 0
Australia
Phone 64038 0
+61394965000
Fax 64038 0
+61394596421
Email 64038 0
[email protected]
Contact person for public queries
Name 64039 0
Laurence Weinberg
Address 64039 0
Department of Anaesthesia, Austin Hospital, 145 Studley Rd, Heidelberg, VIC, 3084
Country 64039 0
Australia
Phone 64039 0
+61394965000
Fax 64039 0
+61394596421
Email 64039 0
[email protected]
Contact person for scientific queries
Name 64040 0
Laurence Weinberg
Address 64040 0
Department of Anaesthesia, Austin Hospital, 145 Studley Rd, Heidelberg, VIC, 3084
Country 64040 0
Australia
Phone 64040 0
+61394965000
Fax 64040 0
+61394596421
Email 64040 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
SourceTitleYear of PublicationDOI
EmbaseRandomised controlled trial to investigate the relationship between mild hypercapnia and cerebral oxygen saturation in patients undergoing major surgery.2020https://dx.doi.org/10.1136/bmjopen-2019-029159
N.B. These documents automatically identified may not have been verified by the study sponsor.