Physiological Effects of Different Preoxygenation Strategies (PREOXY II)

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

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

Study Overview

• Status: Recruiting
• Conditions: Preoxygenation
• Intervention / Treatment: Device: Nasal cannula (NC); Device: Non-rebreather mask (NRM); Device: Non-rebreather mask (NRM) plus Nasal cannula (NC); Device: Bag-valve mask (BVM) without PEEP; Device: Bag-valve mask (BVM) without PEEP + nasal cannula (NC); Device: Bag-valve mask (BVM) with PEEP; Device: Bag-valve mask (BVM) with PEEP + nasal cannula (NC)

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Giulia Roveri, MD; Phone Number: +390471055115; Email: giulia.roveri@eurac.edu
• Study Contact Backup: Name: Simon Rauch, MD, PhD; Phone Number: +390471055544; Email: simon.rauch@eurac.edu

Study Locations

• Italy
  • BZ
    • Bolzano, BZ, Italy, 39100
      • Recruiting
      • Eurac research, Institute of mountain emergency medicine
      • Contact: Giulia Roveri, MD; Phone Number: +390471055115; Email: giulia.roveri@eurac.edu
      • Contact: Simon Rauch, MD, PhD; Phone Number: +390471055544; Email: simon.rauch@eurac.edu
      • Sub-Investigator: Ruth Martintoni
      • Principal Investigator: Simon Rauch, MD, PhD
      • Principal Investigator: Giulia Roveri, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nasal Cannula (NC); Preoxygenation over 3 minutes with a nasal cannula (NC) with supplemental oxygen delivered at 15 L/min, during spontaneous breathing.	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.
Experimental: Non-rebreather facemask (NRM); Preoxygenation over 3 minutes with a Non-rebreather facemask (NRM) with supplemental oxygen delivered at 15 L/min, 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.
Experimental: Non-rebreather facemask (NRM) plus Nasal Cannula (NC); Preoxygenation for 3 minutes using a non-rebreather mask (NRM) combined with a nasal cannula delivering supplemental oxygen at 15 L/min for each device, during spontaneous breathing.	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.
Experimental: Bag valve mask (BVM); Preoxygenation for 3 minutes using a bag-valve-mask (BVM) with supplemental oxygen delivered at 15 L/min, during spontaneous breathing.	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.
Experimental: Bag valve mask (BVM) plus Nasal cannula (NC); Preoxygenation for 3 minutes using a bag -valve-mask (BVM) combined with a nasal cannula delivering supplemental oxygen at 15 L/min for each device, during 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.
Experimental: Bag valve mask (BVM) plus PEEP; Preoxygenation for 3 minutes using a bag-valve mask (BVM) with positive end-expiratory pressure (PEEP) set at 10 cmH₂O and supplemental oxygen delivered at 15 L/min, during 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.
Experimental: Bag valve mask (BVM) plus PEEP plus Nasal Cannula (NC); Preoxygenation for 3 minutes using a bag-valve mask (BVM) with positive end-expiratory pressure (PEEP) set at 10 cmH₂O, combined with a nasal cannula delivering supplemental oxygen at 15 L/min for each device, 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in fraction of inspired oxygen (FiO₂) between preoxygenation devices	Fraction of inspired oxygen (FiO₂) delivered during preoxygenation will be continuously measured at the airway opening using a gas analyzer. FiO₂ values will be recorded breath-by-breath during each 3-minute preoxygenation session under all study conditions. The primary outcome is the difference in mean FiO₂ achieved between the different preoxygenation devices (non-rebreather mask, bag-valve mask without PEEP, and bag-valve mask with PEEP), with and without supplemental oxygen via nasal cannula.	During each 3-minute preoxygenation session

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Positive end-expiratory pressure (PEEP) generated during preoxygenation	Airway pressures will be continuously measured to quantify the presence and magnitude of PEEP generated during preoxygenation with bag-valve mask (BVM) with and without a dedicated PEEP valve, with and without nasal cannula oxygen supplementation.	During each 3-minute preoxygenation session
Inspiratory effort required to open the BVM valve	The negative pressure required to open the BVM valve will be measured using airway pressure monitoring, and diaphragm ultrasound parameters (thickening fraction and excursion) will be used as surrogate markers of inspiratory effort.	During each 3-minute preoxygenation session
Ventilation of dependent lung regions	Lung ultrasound will be used to assess regional ventilation of dependent lung areas, with findings quantified using a validated scoring system to compare the effects of preoxygenation with and without PEEP.	During each 3-minute preoxygenation session
Correlation between FiO₂ and tidal volume	The relationship between fraction of inspired oxygen (FiO₂) and tidal volume during preoxygenation will be assessed using continuous, breath-by-breath measurements.	During each 3-minute preoxygenation session
Cardiac output	Changes in cardiac output (l/min/m²) will be assessed using echocardiography before and after preoxygenation to evaluate the hemodynamic effects of different devices and PEEP.	Baseline and at the end of each 3-minute preoxygenation session
Changes in right ventricular dimensions	Changes in right ventricular dimensions (mm) will be assessed using echocardiography before and after preoxygenation to evaluate the hemodynamic effects of different devices and PEEP.	Baseline and at the end of each 3-minute preoxygenation session
Right ventricular strain	Changes in right ventricular strain (%) will be assessed using echocardiography before and after preoxygenation to evaluate the hemodynamic effects of different devices and PEEP.	Baseline and at the end of each 3-minute preoxygenation session

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Airway pressure during breath-holding maneuver	Airway pressure generated during a brief voluntary breath-holding maneuver will be measured when oxygen is delivered via nasal cannula under a bag-valve mask (with or without PEEP), to assess potential continuous positive airway pressure generation.	Immediately following the preoxygenation session with bag-valve mask (with or without PEEP)

Collaborators and Investigators

• Sponsor: Institute of Mountain Emergency Medicine
• Investigators: Principal Investigator: Simon Rauch, Eurac research, Institute of mountain emergency medicine

Publications and helpful links

General 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): May 23, 2026
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 26, 2026
• First Submitted That Met QC Criteria: April 26, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 8, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Preoxygenation; Respiratory physiology; Bag-valve mask (BVM); Non-rebreather mask (NRM); Positive end-expiratory pressure (PEEP); Fraction of inspired oxygen (FiO₂)
• Additional Relevant MeSH Terms: Equipment and Supplies; Catheters; Cannula
• Other Study ID Numbers: PREOXY II

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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