HYPER MIND - Hyperoxia Effects on Cerebral Hemodynamics

Patients will be studied under controlled mechanical ventilation with stable ventilatory, hemodynamic, and sedative settings. Continuous transcranial Doppler (TCD) monitoring will be performed using a 2-MHz probe insonating the middle cerebral artery through the temporal bone window. Cerebral blood flow velocity signals and arterial blood pressure waveforms will be recorded continuously for offline analysis.

The experimental protocol consists of stepwise increases in the fraction of inspired oxygen (FiO₂), according to baseline oxygen requirements. Patients with a baseline FiO₂ < 0.5 will undergo two consecutive hyperoxic steps (FiO₂ 0.5 followed by FiO₂ 1.0), whereas patients with a baseline FiO₂ ≥ 0.5 will undergo a single hyperoxic step (FiO₂ 1.0). Each hyperoxic step will include a stabilization period of approximately 5 minutes to allow attainment of a physiological steady state, followed by a 10-minute recording period dedicated to cerebral hemodynamic and autoregulation assessment. After completion of the hyperoxic exposure(s), FiO₂ will be returned to baseline values. In total, there will be 3 or 4 steps, depending on the baseline FiO₂.

Arterial blood gas samples will be obtained at baseline, at the end of each hyperoxic step, and after return to baseline oxygen settings to document changes in arterial oxygen and carbon dioxide tensions. Ventilation parameters, sedation, vasoactive drug infusion rates, and fluid therapy will be kept constant throughout the protocol whenever clinically feasible.

Cerebral hemodynamic assessment will include mean flow velocity, pulsatility index, and resistive index derived from TCD signals. Dynamic cerebral autoregulation will be evaluated using established indices (the mean flow index (Mxa), transfer function analysis (TFA) parameters, autoregulation index (ARI)), and metrics derived from spontaneous fluctuations in arterial blood pressure and cerebral blood flow velocity.

Analyses will primarily rely on paired statistical methods. Exploratory subgroup analyses according to baseline oxygen requirements, illness severity, or relevant comorbidities may be conducted.

Patient safety will be continuously monitored throughout the protocol, and the procedure will be immediately discontinued in case of any clinical instability, including hemodynamic deterioration, arrhythmias, or oxygenation abnormalities.

Inclusion criteria

• Adult patients aged ≥18 years
• Admitted to the intensive care unit (ICU)
• Intubated and mechanically ventilated for ≤72 hours
• Receiving volume-controlled mechanical ventilation
• Arterial partial pressure of carbon dioxide (PaCO₂) between 35 and 45 mmHg
• Invasive arterial blood pressure monitoring in place
• Adequate transcranial Doppler (TCD) acoustic window
• Clinically judged to be suitable for a brief normobaric hyperoxic stimulus
• Expected to receive one or two hyperoxic steps based on baseline FiO₂ requirements: a) Baseline FiO₂ < 0.5: two-step hyperoxic stimulus (FiO₂ 0.5 followed by FiO₂ 1.0); b) Baseline FiO₂ ≥ 0.5: one-step hyperoxic stimulus (FiO₂ 1.0)

Exclusion criteria

• Age <18 years
• Pregnancy
• Extracorporeal membrane oxygenation (ECMO)
• Continuous renal replacement therapy (CRRT)
• Contraindications to hyperoxia, as judged by the treating physician
• Severe hemodynamic instability requiring changes in vasopressor dose during the recording period
• Inability to obtain a reliable transcranial Doppler signal through the temporal acoustic windows
• Any clinical condition deemed by the treating physician to pose unacceptable risk during hyperoxic exposure