ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12623001198617

Ethics application status

Approved

Date submitted

9/10/2023

Date registered

20/11/2023

Date last updated

20/11/2023

Date data sharing statement initially provided

20/11/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Evaluation of wavelet semblance analysis for determining the lower limit of cerebral autoregulation in a non-cardiac surgery population

Scientific title

Evaluation of wavelet semblance analysis for determining the lower limit of cerebral autoregulation in a non-cardiac surgery population

Secondary ID [1]

Nil known

Universal Trial Number (UTN)

U1111-1263-9335

Trial acronym

WAVELET

Linked study record

Health condition

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

Intraoperative hypotension

Condition category

Condition code

Anaesthesiology

Anaesthetics

Cardiovascular

Diseases of the vasculature and circulation including the lymphatic system

Neurological

Studies of the normal brain and nervous system

Intervention/exposure

Study type

Observational

Patient registry

False

Target follow-up duration

Target follow-up type

Description of intervention(s) / exposure

Robust research has established a clear association between perioperative complications and intraoperative hypotension (IOH) with even minor degrees of hypotension, below a mean arterial blood pressure (MAP) of 65 mmHg, associated with significant morbidity and mortality.

Using the brain as the index organ and raw data generated from intraoperative monitoring with near-infrared spectroscopy (NIRS) combined with invasive blood pressure, this study aims to evaluate wavelet semblance analysis in a surgical population. In doing so, aim to also determine the previously undefined lower limit of cerebral autoregulation (LLA) of patients under general anaesthetic in the non-cardiac surgery setting.

As an observational study, this study will not alter clinical care. All patients will be managed with general anaesthesia performed by, or under the supervision of, a consultant anaesthetist. Qualified medical or nursing personnel will complete a detailed, standardised data collection form to ensure patient eligibility, identify other potential confounders, document basic demographic and medical data, and assign formal surgical and anaesthetic risk scores.

Qualified clinical staff will also deliver neuropsychiatric/cognitive assessments pre operatively including the Repeatable Battery for the Assessment of Neuropsychological status (RBANS) and the Institute of cognitive neurology (INECO) Frontal screening assessments. Concurrent mood state assessments will be performed using the Depression, Anxiety and Stress Scale (DASS-21). Individual changes from baseline will be assessed on day 3 post-operatively for evidence of cognitive impairment. Cognitive decline will be defined as a deterioration of greater than a 20% reduction from baseline in at least two cognitive components assessed.

Routine clinical parameters will be captured iintraoperatively ncluding basic respiratory (pulse oximetry saturation, inspired and end- tidal oxygen, carbon dioxide, and anaesthetic agent), and cardiac (electrocardiogram, heart rate) measures. These will be downloaded using data capture software. Information regarding management (e.g. drug administration, procedural details including type/duration of surgery and any anaesthetic issues) will also be recorded. An arterial line will be placed by the treating anaesthetist for routine invasive blood pressure monitoring and blood sampling.

Additional study specific data will be recorded intraoperatively through routine clinical methods including:
- Arterial blood gas measurements performed every 30 minutes to assess acid/base status and arterial partial pressures of oxygen and carbon dioxide, both of which can affect cerebrovascular reactivity.
- NIRS monitoring, which is often used routinely during many types of surgery in The Prince Charles Hospital (TPCH and
- Electroencephalography will be performed (as recommended for routine clinical practice) with a Bispectral Index (BIS) sensor over the forehead, which also will be placed pre-induction.
- Prior to induction, an appropriately sized ClearSight Cuff (or AIQ Cuff) (Edwards Lifesciences, CA, USA) will also be placed on the patient’s non-operative second, third, or fourth digit at the middle phalanx. The ClearSight Heart Reference Sensor will be zeroed and placed at the patient’s phlebostatic axis. This cuff will be connected to an Edwards Haemodynamic monitoring platform (EV1000 or HemoSphere), and all Cardiac Output parameters will be transferred to a research-specific laptop.

Blood samples will be collected at baseline (day 0) and at 6, 24 and 48 hoursdaily for 3 days post-op. Sample collection will follow standard phlebotomy procedures and be performed by either the treating anaesthetist or a trained phlebotomist. At all timepoints, two EDTA tubes (3 mL, lavender-top) and one serum separator tube or SST (5 mL, gold-top) will be drawn for study samples. Tubes will be filled by vacuum and gently inverted 6 - 8 times to ensure adequate mixing. All samples will be immediately transferred to the Queensland Pathology laboratories at TPCH and PAH for processing. Processing will include testing for creatinine, troponin I and BNP. One of the EDTA tubes will be centrifuged (for 15 min at 4 degrees Celcius, 3000 x g) and stored at -80 degree Celcius until study completion, when it will be processed for biomarkers for neurological injury.

Intervention code [1]

Not applicable

Comparator / control treatment

No control group, observational

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Autoregulation analysis will be undertaken by comparing rSO2 and arterial blood pressure, using both wavelet semblance analysis and the COx index (Pearson correlation of 5 minute epochs rSO2 vs MAP). The primary outcome measures will be the proportion of patients where the LLA inflexion point can be determined (i.e. with a detectable LLA) reported as a percentage of the total cases. A 50% success is predicted to be the limit of feasibility and it the typical value achieved in the literature

Timepoint [1]

Following enrollment and data collection for the final patient in the study

Secondary outcome [1]

Data from near-infrared spectroscopy (NIRS) and invasive blood pressure monitor will determine the magnitude of intraoperative hypotension calculated as time MAP< LLA (time x mmHg)

Timepoint [1]

Continuously measured during surgery, with signal processing taking place once data captured post surgery.

Secondary outcome [2]

Occurrence of any perioperative complications assessed from patient surgical records

Timepoint [2]