HYPER MIND - Hyperoxia Effects on Cerebral Hemodynamics (HYPER-MIND)

HYPERMIND - Hyperoxia Effects on Cerebral Hemodynamics

This study aims to better understand how short periods of exposure to high oxygen levels affect blood flow in the brain of patients who are intubated and mechanically ventilated in the Intensive Care Unit (ICU). Many ICU patients receive more oxygen than strictly necessary, and high blood oxygen levels (hyperoxemia) are very common. However, the immediate effects of short hyperoxic exposures on cerebral circulation and autoregulation remain poorly understood.

In this study, patients who already require mechanical ventilation for medical reasons will undergo a brief and controlled increase in the oxygen delivered through the ventilator (FiO₂). During this time, we will continuously monitor blood flow in one of the main brain arteries using a non-invasive ultrasound technique called transcranial Doppler (TCD). The goal is to evaluate how cerebral blood flow, pulsatility, and autoregulatory capacity change during and after a short hyperoxic stimulus.

No additional invasive procedures are required beyond standard ICU monitoring, except for the temporary adjustment of the ventilator's oxygen settings and arterial blood gas sampling, which are part of usual care in critically ill patients. Participation does not provide direct clinical benefit but may help improve future oxygen management in ICU patients. The study involves minimal risk, as short hyperoxic exposures are already common in routine care and will be interrupted immediately in case of any adverse event.

Study Overview

• Status: Recruiting
• Conditions: Critical Illness; Mechanical Ventilation; Cerebral Autoregulation; Cerebrovascular Circulation; Hyperoxemia
• Intervention / Treatment: Other: Normobaric Hyperoxic Stimulus (NBHO)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Michele Salvagno, MD; Phone Number: +32471386614; Email: michele.salvagno@ulb.be

Study Locations

• Belgium
  • Brussels, Belgium
    • Recruiting
    • Erasme Hospital - ULB
    • Contact: Michele Salvagno, MD; Phone Number: +32471386614; Email: michele.salvagno1@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental: Hyperoxic Stimulus; Participants receive one or two brief normobaric hyperoxic (NBHO) stimuli during mechanical ventilation. The inspired fraction of oxygen (FiO₂) is transiently increased to 0.5 or 1.0 depending on baseline FiO₂ requirements. Cerebral blood flow and autoregulation are continuously monitored using transcranial Doppler ultrasound.

Other: Normobaric Hyperoxic Stimulus (NBHO); The intervention consists of a short, controlled increase in the inspired oxygen fraction (FiO₂) delivered by the mechanical ventilator. Depending on baseline FiO₂, patients will receive: Depending on baseline FiO₂, patients will receive: Two-step NBHO (baseline FiO₂ < 0.5): FiO₂ raised to 0.5 and then to 1.0 One-step NBHO (baseline FiO₂ ≥ 0.5): FiO₂ raised to 1.0 Each step includes 5 minutes to reach steady state followed by a 10-minute recording period. Cerebral blood flow velocity and autoregulation are continuously assessed using transcranial Doppler ultrasound.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Mean Flow Index (Mx) During Normobaric Hyperoxia	Dynamic cerebral autoregulation will be assessed using the mean flow index (Mx), calculated as the moving Pearson correlation coefficient between mean arterial pressure (MAP) and mean middle cerebral artery (MCA) blood flow velocity measured by transcranial Doppler ultrasonography. The outcome will be reported as the absolute change in Mx from baseline, calculated as the average Mx value during normobaric hyperoxia minus the baseline average.	Baseline (prior to hyperoxic exposure), during normobaric hyperoxia steps, assessed during the intervention period, and after returning to baseline (assessed up to 20 minutes)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Middle Cerebral Artery Cerebral Blood Flow During Normobaric Hyperoxia	Cerebral hemodynamics will be assessed by transcranial Doppler ultrasonography of the middle cerebral artery (MCA). The cerebral blood flow velocity (cm/s) will be evaluated and analyzed as a change from baseline during normobaric hyperoxia. It will be expressed as the absolute change from baseline, calculated as the average value during the last 5 minutes of normobaric hyperoxia minus the baseline average.	Baseline (prior to hyperoxic exposure), during normobaric hyperoxia, assessed during the intervention period (up to 30 minutes per study session), and after returning to baseline (assessed up to 20 minutes)
Change in Autoregulation Index (ARI) During Normobaric Hyperoxia	Cerebral autoregulation will also be evaluated using the Autoregulation Index (ARI) derived from transfer function-based step response analysis, expressed on a scale from 0 to 9. The outcome will be expressed as the absolute change from baseline during normobaric hyperoxia.	Baseline (prior to hyperoxic exposure), during normobaric hyperoxia, assessed during the intervention period (up to 30 minutes per study session), and after returning to baseline (assessed up to 20 minutes)
Change in Transfer Function Analysis Parameters During Normobaric Hyperoxia	Transfer function analysis (TFA) between mean arterial pressure and middle cerebral artery blood flow velocity will be performed. Gain (cm/s/mmHg) will be analyzed in the low-frequency band (0.07-0.20 Hz). It will be expressed as absolute change from baseline during normobaric hyperoxia.	Baseline (prior to hyperoxic exposure), during normobaric hyperoxia, assessed during the intervention period (up to 30 minutes per study session), and after returning to baseline (assessed up to 20 minutes)
Change in Transfer Function Analysis Parameters During Normobaric Hyperoxia	Description: Transfer function analysis (TFA) between mean arterial pressure and middle cerebral artery blood flow velocity will be performed. Phase (radians) will be analyzed in the low-frequency band (0.07-0.20 Hz). It will be expressed as absolute change from baseline during normobaric hyperoxia.	Baseline (prior to hyperoxic exposure), during normobaric hyperoxia, assessed during the intervention period (up to 30 minutes per study session), and after returning to baseline (assessed up to 20 minutes)

Collaborators and Investigators

• Sponsor: Erasme University Hospital
• Investigators: Principal Investigator: Fabio Silvio Taccone, MD, PhD, Hôpital Erasme - Université Libre de Bruxelles (ULB)

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: December 11, 2025
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 29, 2026

Study Record Updates

• Last Update Posted (Actual): January 29, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: intensive care unit; Critical Illness; oxygen; cerebral autoregulation; hyperoxia; tcd; hyperoxemia; brain hemodynamics
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Genetic Diseases, Inborn; Eye Diseases; Eye Diseases, Hereditary; Signs and Symptoms, Respiratory; Genetic Diseases, X-Linked; Uveal Diseases; Choroid Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Critical Illness; Hyperoxia; Choroideremia
• Other Study ID Numbers: SRB2023205

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) will not be shared because the data are collected within Hôpital Erasme - ULB and contain coded clinical information that cannot be transferred outside the institution according to local ethical and data protection policies. Only aggregated, non-identifiable results will be shared through scientific publications or presentations.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No