Physiological Effects of Different Preoxygenation Strategies

Official title

Physiological Effects of Different Preoxygenation Strategies in Adults and Children: A Comparative Study of NRM and BVM With and Without PEEP

Overview

The goal of this clinical trial is to evaluate the performance and physiological effects of different preoxygenation devices in healthy adult and pediatric volunteers (children aged 5-12 years). The study aims to determine how these devices influence oxygen delivery, airway pressure, and cardiopulmonary physiology during preoxygenation. The main questions it aims to answer are: * What fraction of inspired oxygen (FiO₂) is delivered by non-rebreather masks (NRM) compared to bag-valve masks (BVM) with and without positive end-expiratory pressure (PEEP)? * How do these devices differ in terms of generated PEEP, inspiratory effort, and their effects on lung ventilation and cardiac function? Researchers will compare NRM, BVM without PEEP, and BVM with PEEP (each with or without supplemental oxygen via nasal cannula) to evaluate differences in oxygenation and physiological effects. Participants will: * Complete multiple 3-minute preoxygenation sessions using each device in randomized order * Breathe spontaneously through each device, with or without additional oxygen via nasal cannula * Undergo non-invasive monitoring of oxygen concentration (FiO₂), respiratory parameters, airway pressures, and ultrasound assessment of the lungs, diaphragm, and heart * Perform a brief breath-holding maneuver to assess airway pressure generation

Detailed description

Hypoxemia is a frequent and potentially life-threatening complication during advanced airway management, associated with adverse outcomes such as hypoxic brain injury, cardiovascular collapse, and death. Effective preoxygenation is essential to increase oxygen reserves and prolong safe apnea time during intubation. Although several devices are routinely used for preoxygenation, including non-rebreather masks (NRM) and bag-valve masks (BVM) with or without positive end-expiratory pressure (PEEP), important uncertainties remain regarding their actual performance and physiological effects.

Current evidence suggests that techniques providing PEEP may improve oxygenation by increasing functional residual capacity, enhancing ventilation of dependent lung regions, and reducing ventilation-perfusion mismatch. However, the relative contribution of FiO₂ delivery versus PEEP, as well as the physiological effects on respiratory mechanics and cardiovascular function, are not fully understood. In addition, it remains unclear whether BVM devices without a dedicated PEEP valve can generate measurable PEEP, and whether patients can generate sufficient inspiratory effort to effectively operate BVM valves without assisted ventilation. Data in pediatric populations are particularly limited.

This randomized crossover study is designed to systematically evaluate the performance of commonly used preoxygenation devices under controlled conditions in healthy adult and pediatric volunteers. By comparing NRM, BVM without PEEP, and BVM with PEEP-with and without supplemental oxygen via nasal cannula-the study aims to characterize differences in oxygen delivery, airway pressure generation, inspiratory effort, and their physiological impact.

The study will focus on key physiological domains, including oxygenation (FiO₂), respiratory mechanics (tidal volume, airway pressures, and diaphragm activity), lung aeration (with particular attention to dependent lung regions), and cardiovascular responses (including right ventricular dimensions and function). Measurements will be obtained using non-invasive monitoring techniques, including gas analysis and ultrasound.

The crossover design allows within-subject comparisons across all study conditions, minimizing inter-individual variability and enabling precise assessment of device-related effects. The findings of this study are expected to improve understanding of the mechanisms and physiological consequences of preoxygenation strategies, with potential implications for optimizing airway management practices in both adult and pediatric populations.

Interventions

• Device Nasal cannula (NC)
  Preoxygenation performed using a nasal cannula delivering supplemental oxygen at a flow rate of 15 L/min, without the use of an additional mask or ventilation device, during spontaneous breathing.
• Device Non-rebreather mask (NRM)
  Preoxygenation performed using a non-rebreather mask with reservoir, delivering oxygen at a flow rate of 15 L/min. The mask is fitted to ensure an optimal seal, and participants breathe spontaneously without assisted ventilation.
• Device Non-rebreather mask (NRM) plus Nasal cannula (NC)
  Preoxygenation performed using a non-rebreather mask with reservoir, delivering oxygen at a flow rate of 15 L/min, combined with a nasal cannula delivering supplemental oxygen at 15 L/min. The mask is fitted to ensure an optimal seal, and participants breathe spontaneously without assisted ventilation.
• Device Bag-valve mask (BVM) without PEEP
  Preoxygenation performed using a bag-valve mask without a PEEP valve, delivering oxygen at a flow rate of 15 L/min. The mask is held with a two-handed technique to ensure an airtight seal, without providing assisted ventilation, allowing spontaneous breathing.
• Device Bag-valve mask (BVM) without PEEP + nasal cannula (NC)
  Preoxygenation performed using a bag-valve mask without a PEEP valve, delivering oxygen at a flow rate of 15 L/min, combined with a nasal cannula delivering supplemental oxygen at 15 L/min. The mask is held with a two-handed technique to ensure an airtight seal, without providing assisted ventilation, allowing spontaneous breathing.
• Device Bag-valve mask (BVM) with PEEP
  Preoxygenation performed using a bag-valve mask equipped with a PEEP valve set at 10 cmH₂O, delivering oxygen at a flow rate of 15 L/min. The mask is held with a two-handed technique to ensure an airtight seal, without assisted ventilation, during spontaneous breathing.
• Device Bag-valve mask (BVM) with PEEP + nasal cannula (NC)
  Preoxygenation performed using a bag-valve mask equipped with a PEEP valve set at 10 cmH₂O, delivering oxygen at a flow rate of 15 L/min, combined with a nasal cannula delivering supplemental oxygen at 15 L/min. The mask is held with a two-handed technique to ensure an airtight seal, without assisted ventilation, during spontaneous breathing.

Primary outcome measures

• Difference in fraction of inspired oxygen (FiO₂) between preoxygenation devices [Time frame: During each 3-minute preoxygenation session]

Secondary outcome measures (7)

• Positive end-expiratory pressure (PEEP) generated during preoxygenation [Time frame: During each 3-minute preoxygenation session]
• Inspiratory effort required to open the BVM valve [Time frame: During each 3-minute preoxygenation session]
• Cardiac output [Time frame: Baseline and at the end of each 3-minute preoxygenation session]
• Changes in right ventricular dimensions [Time frame: Baseline and at the end of each 3-minute preoxygenation session]
• Right ventricular strain [Time frame: Baseline and at the end of each 3-minute preoxygenation session]
• Ventilation of dependent lung regions [Time frame: During each 3-minute preoxygenation session]
• Correlation between FiO₂ and tidal volume [Time frame: During each 3-minute preoxygenation session]

Eligibility criteria

Inclusion criteria

• Adults with an American Society of Anesthesiologists (ASA) physical status score ≤ 2
• Children aged 5 to 12 years with an ASA physical status score ≤ 2
• Ability (or legal guardian ability) to provide written informed consent

Exclusion criteria

• Children aged < 5 years or 13 to 18 years
• ASA physical status score > 2
• Body mass index (BMI) ≥ 30 kg/m²
• Known airway pathology or anatomical abnormality that could affect mask fit, ventilation, or oxygenation
• Presence of an active airway infection at the time of the study
• Pregnancy
• Refusal or inability to provide informed consent

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

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Prevention

Study locations

Italy · 1 center

• Eurac research, Institute of mountain emergency medicine — Bolzano

Publications

• Roveri G, Camporesi A, Hofer A, Kahlen S, Breidt F, Rauch S. Preoxygenation With and Without Positive End-Expiratory Pressure in Lung-Healthy Volunteers: A Randomized Clinical Trial. JAMA Netw Open. 2025 May 1;8(5):e2511569. doi: 10.1001/jamanetworkopen.2025.11569. PMID 40392551
• Rauch S, Pietsch U, Roveri G. Preoxygenation in prehospital critical care: a survey of HEMS practices in eight European countries. Emerg Med J. 2026 Jan 16:emermed-2025-215335. doi: 10.1136/emermed-2025-215335. Online ahead of print. No abstract available. PMID 41545175

Identifiers

NCT: NCT07564050 · PREOXY II

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗