BrainProtect-guided, Real-time Cerebral Autoregulation Monitoring and Protection of Brain During Cardiac Surgery With Cardiopulmonary Bypass Requiring Heart-lung Machine

Based on a review of the current literature and consultations regarding currently known clinical practice standards the "BrainProtect" study will be the first multicenter trial of cardiac surgery using a heart-lung machine with modulated blood flow by rectangular pulses and also with real-time cerebrovascular autoregulation monitoring. The feasibility and safety of this approach have been previously validated in two of our clinical studies.

Postoperative cognitive dysfunction (POCD and POD) with incidences up to 70% and 42% respectively after cardiac surgery with cardiopulmonary bypass (CPB) are common postoperative complications that affect the participant's quality of life and increase the risk of death. Our previous trials confirm that POCD and POD are associated with impaired cerebral autoregulation (CA) after increased or decreased mean ABP values above or below the upper or lower participant specific limits during cardiac bypass surgery. The upper and lower limits of CA are individual and variable.

In most scientific studies, cerebral autoregulation impairments are identified retrospectively. Currently available real-time monitoring methods for CA status identification are too slow and lack the sensitivity required for timely interventions to correct autoregulatory impairment. The identification of start and finish time moments of ischemic and hyperemic transient events after impairment of CA in individual participant's brain is the way to immediately stop such events to restore optimal brain perfusion.

In order to make perioperative transient hyperemic and ischemic events as short as possible we proposed a novel mode of HLM operation with blood flow modulation by continuous automatic blood flow change from value f1 to value f2 and back to generate rectangular continuous blood flow pulsation. Such modulated blood flow is transformed into rectangularly modulated arterial blood pressure (ABP) with stabilized amplitude of ABP(t) rectangular pulsation in the participant's body. Each front of rectangular ABP(t) is an input signal for testing of CA transient response. Shape of CA transient response is an indicator of CA status - CA rectangular transient response which passively follow rectangular pulsation of ABP(t) indicates impaired CA and Exponential CA transient response shows intact CA. Novel non-invasive participant's brain monitoring technology Archimedes 02 records transient responses of CA in real-time. Timely mean ABP management by perfusionists after identification of a start moment of CA impairment restores optimal participant's brain and other organs' perfusion within seconds to protect the brain from cognitive impairment and delirium.

The BrainProtect System is a non-invasive physiological monitoring medical device designed to continuously assess cerebral autoregulation and intracranial pressure pulse waveforms through closed eyelids using high-sensitivity pressure sensors. The device processes acquired signals using validated algorithms to derive indices of cerebral autoregulation and intracranial compliance, providing real-time feedback to clinicians during surgical procedures.

Impairment of cerebral autoregulation is common during cardiac surgery with cardiopulmonary bypass due to fluctuations in arterial blood pressure, temperature, anesthesia, and non-pulsatile or modified blood flow. Numerous clinical studies have demonstrated an association between cerebral autoregulation disturbances and adverse neurological outcomes following cardiac surgery. However, routine intraoperative monitoring of cerebral autoregulation is not part of standard clinical practice, primarily due to the lack of practical, non-invasive, and continuous monitoring solutions.

The current standard of care during cardiac surgery with cardiopulmonary bypass includes monitoring of systemic hemodynamic parameters such as arterial blood pressure, heart rate, oxygen saturation, and cerebral oxygenation using near-infrared spectroscopy (when available). Management of cerebral perfusion is typically based on population-based blood pressure targets and institutional protocols rather than individualized cerebral autoregulation limits.

Direct monitoring of cerebral autoregulation or intracranial pressure dynamics is not routinely performed in this participant population. As a result, periods of cerebral hypoperfusion or hyperperfusion may remain undetected during surgery, potentially contributing to postoperative neurological complications.

For participants in Group I the BrainProtect System monitoring will be used. The anesthesiologist and perfusionist will have real-time access to CA monitoring data and, immediately after CA impairment event is detected he will see an alarm sign on the screen of CA monitor. Perfusionist will follow instruction on the screen of CA monitor to increase mean ABP in the case of transient ischemic event or to decrease mean ABP in the case of hyperemic event to restore optimal participant's brain perfusion in seconds and to stop the brain injury. Alarm sign will automatically switch off when brain ischemic or hyperemic event will be stopped.

Before and after the appearance of an alarm sign on the monitor in Group I, the perfusionist will follow the existing guidelines for ABP management. Perfusionist will manage mean ABP according a usual practice in their site even in the case when an alarm will not switch off after an adequate change of mean ABP value. For participants in Group II a standard mode of constant HLM blood flow will be used and brain CA monitoring will not be used.