Efficacy of High-Flow Humidified Oxygen (HFHO) in Apneic Oxygenation for Apnea Testing: A Comparison With Continuous Positive Airway Pressure (CPAP)

Official title

Efficacy of High-Flow Humidified Oxygen in Apneic Oxygenation During Apnea Testing Compared With Continuous Positive Airway Pressure: A Randomized Multicenter Crossover Trial

Overview

Brain death (BD) is characterized by a severe brain injury resulting in irreversible loss of all brain and brainstem functions, while other organs may remain viable. The diagnosis of BD is based on the presence of coma, absence of brainstem reflexes, and absence of spontaneous breathing confirmed by an apnea test. In France, the apnea test is mandatory prior to organ procurement. The apnea test aims to demonstrate that hypercapnia, a strong ventilatory stimulus, does not induce any respiratory movements. In current practice, the apnea test is performed by disconnecting the patient from mechanical ventilation for 8-10 minutes while administering oxygen. Oxygenation strategies during apnea vary across French centers. Although the use of continuous positive airway pressure (CPAP) is recommended, a substantial proportion of tests are still performed without positive end-expiratory pressure (PEEP) effect, using either an open T-piece or an intratracheal oxygen catheter. These methods are associated with a higher risk of complications, such as hypoxemia, and potential adverse effects on organ function, which is particularly relevant in the context of organ donation. Humidified high-flow oxygen (HHFO), delivered via a specialized device connected to the endotracheal tube, provides high flow rates (up to 60 L/min), allows precise adjustment of the fraction of inspired oxygen (FiO₂ up to 1.0), and generates a minimal PEEP effect. HHFO is routinely used in intensive care units. While its feasibility during apnea testing has been reported, its efficacy during BD diagnosis has not been well evaluated. Preliminary observations in intensive care patients with clinical brain death suggest that HHFO can be safely used during the apnea test, allowing achievement of hypercapnia and confirmation of absence of spontaneous respiration while maintaining better oxygenation compared with conventional oxygen delivery via an open T-piece. This study aims to evaluate the efficacy of HHFO for apneic oxygenation during the apnea test, in comparison with the recommended method using CPAP.

Detailed description

The study strategy is based on performing two consecutive apnea tests in patients with clinical brain death, conducted in a randomized order. Only patients in whom the first apnea test confirms the absence of spontaneous breathing will proceed to the second apnea test. Consistency of clinical brain death at the end of the first apnea test are defined by the absence of any respiratory movement and the presence of either an arterial partial pressure of carbon dioxide (PaCO₂) ≥ 60 mmHg or an increase in PaCO₂ \> 20 mmHg compared with the PaCO₂ measured at the end of the preoxygenation period.

Each of the two apnea tests will be preceded by a standardized 15-minute preoxygenation period using assisted controlled ventilation with a tidal volume of 6mL/kg of predicted body weight.

The two consecutive apnea tests will be performed in randomized order under CPAP and under HHFO with standardized parameters.

As per routine clinical practice, an arterial blood gas sample will be obtained before disconnection from the ventilator at the end of the preoxygenation period to confirm normocapnia, defined as 35 mmHg ≤ PaCO₂ ≤ 45 mmHg. A second arterial blood gas sample will be obtained at the end of the apnea test, prior to reconnection to the ventilator, to measure PaCO₂ and arterial partial pressure of oxygen (PaO₂).

Specifically for the purposes of the study, during each apnea test, the investigator will perform arterial blood gas sampling every 2 minutes to measure PaO₂, PaCO₂, and pH. At the same time points, arterial blood pressure, heart rate, pulse oximetry, and catecholamine infusion doses will be recorded.

In addition to these measurements required to meet the study objectives, demographic and clinical data will be collected primarily from the medical records to characterize the study population.

Interventions

• Other Apnea test under HHFO followed by an apnea test under CPAP.
  For each 10-minute apnea test, regardless of the oxygenation device used, arterial blood gas will be analysed and heart rate, arterial pressure, and pulse oximetry will be recorded in 2-minute intervals.
• Other Apnea test under CPAP followed by an apnea test under HHFO.
  For each 10-minute apnea test, regardless of the oxygenation device used, arterial blood gas will be analysed and heart rate, arterial pressure, and pulse oximetry will be recorded in 2-minute intervals.

Primary outcome measures

• Change in PaO₂ (mmHg) between the beginning and the end of an apnea test under HHFO and CPAP [Time frame: From ventilator disconnection to 10th minute of the apnea test]

Secondary outcome measures (9)

• Evolution of arterial blood PaO2 parameters during the apnea test under HHFO and the apnea test with CPAP [Time frame: At 2-minute intervals from ventilator disconnection to the 10th minute of each apnea test]
• Evolution of arterial blood PaCO2 parameters during the apnea test under HHFO and the apnea test with CPAP [Time frame: At 2-minute intervals from ventilator disconnection to the 10th minute of each apnea test]
• Evolution of arterial blood pH parameters during the apnea test under HHFO and the apnea test with CPAP [Time frame: At 2-minute intervals from ventilator disconnection to the 10th minute of each apnea test]
• Evolution of arterial blood pressure during the apnea test under HHFO and the apnea test with CPAP [Time frame: At 2-minute intervals from ventilator disconnection to the 10th minute of each apnea test]
• Evolution of heart rate during the apnea test under HHFO and the apnea test with CPAP [Time frame: At 2-minute intervals from ventilator disconnection to the 10th minute of each apnea test]
• Evolution of pulse oximetry during the apnea test under HHFO and the apnea test with CPAP [Time frame: At 2-minute intervals from ventilator disconnection to the 10th minute of each apnea test]
• Time required to reach the hypercapnia thresholds necessary to confirm brain death during an apnea test under HHFO and with CPAP [Time frame: From ventilator disconnection until the hypercapnia threshold is reached]
• Occurrence of apnea test interruptions during HHFO and CPAP. [Time frame: From ventilator disconnection until apnea test termination due to intolerance]
• Nurse-rated numeric scale evaluations of Humidified High Flow Oxygen and Continuous Positive Airway Pressure use for each enrolled patient [Time frame: Within 1 hour after each apnea test.]

Eligibility criteria

Inclusion criteria

• Adult intensive care unit patients
• fulfilling all criteria for clinical brain death, for whom confirmation of the absence of spontaneous breathing requires performance of an apnea test
• And for whom consent to participate in the study was sought from a trusted person or a family member

Exclusion criteria

• History of chronic obstructive pulmonary disease (COPD) classified as GOLD stage III or IV.
• Current extracorporeal life support, including veno-arterial (VA) or veno-venous (VV) extracorporeal membrane oxygenation (ECMO).
• PaO₂/FiO₂ ratio ≤ 150 on the most recent arterial blood gas analysis, obtained within 24 hours prior to the screening visit.
• Presence of at least one clear or absolute contraindication to the procurement of at least one organ.
• Presence of a high cervical spinal cord injury.
• Patient in the prone position and/or with a contraindication to placement in the supine position at 30°.
• Minor patient.
• Protected adult under legal guardianship or curatorship.
• Individual under judicial protection (safeguard of justice).
• Individuals deprived of liberty.
• Individual not covered by a social security or health insurance system.
• Pregnant or breastfeeding woman.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Open label

Primary purpose

Other

Study locations

France · 4 centers

• Chu Angers — Angers
• Chu de Nantes — Nantes
• Chu Orleans — Orléans
• Chru de Tours — Tours

Identifiers

NCT: NCT07640009 · CHUO-2025-05

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗