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

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.