HYPERMIND - Hyperoxia Effects on Cerebral Hemodynamics
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Change in Mean Flow Index (Mx) During Normobaric Hyperoxia
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
盲法说明
Not applicable. This physiological study cannot be masked due to the nature of FiO₂ manipulation and continuous hemodynamic monitoring.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Normobaric Hyperoxic Stimulus (NBHO) (Other)
结局指标
主要结局
Change in Mean Flow Index (Mx) During Normobaric Hyperoxia
时间窗: Baseline (prior to hyperoxic exposure), during normobaric hyperoxia steps, assessed during the intervention period, and after returning to baseline (assessed up to 20 minutes)
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.
次要结局
- Change in Middle Cerebral Artery Cerebral Blood Flow 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 Autoregulation Index (ARI) 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(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))
研究者
Fabio Taccone
MD, PHD
Erasme University Hospital