The Effect of FiO2 on PaO2/FiO2 Ratio

The Effect of Inspiratory Oxygen Fraction on the Ratio of Partial Arterial Oxygen Pressure and Inspiratory Oxygen Fraction (PaO2/FiO2 Ratio) in Mechanically Ventilated Patients With and Without Mild to Moderate ARDS

The PaO2/FiO2 ratio is frequently used to determine the severity of lung injury in mechanically ventilated patients. However, several mathematical models have shown that PaO2/FiO2 ratio depends on FiO2. The relationship is complex and depends on numerous physiological variables, including shunt fraction, and arterio-venous oxygen difference. The nonlinear relation between PaO2/FiO2 and FiO2 underlines the limitations describing the intensity of hypoxemia using PaO2/FiO2 and is thus of major importance for the clinician. Surprisingly, this relationship has only been assessed mathematically. Obviously, the accuracy of the mathematical relationship depends on the input variables used.

The current study is designed to assess the PaO2/FiO2 vs FiO2 relation in mechanically ventilated patients without ARDS (n =10) and with mild or moderate ARDS (n =10). In order to explain the dependency of the PaO2/FiO2 on FiO2, shunt fraction and alveolar - arterial oxygen difference ((A-a)DO2) will be determined in these patients.

Study Overview

• Status: Unknown
• Conditions: PaO2/FiO2 Ratio
• Intervention / Treatment: Drug: Modulation of FiO2

Detailed Description

Rationale:

The PaO2/FiO2 ratio is frequently used to determine the severity of lung injury in mechanically ventilated patients. However, several mathematical models have shown that PaO2/FiO2 ratio depends on FiO2. The relationship is complex and depends on numerous physiological variables, including shunt fraction, and arterio-venous oxygen difference. The nonlinear relation between PaO2/FiO2 and FiO2 underlines the limitations describing the intensity of hypoxemia using PaO2/FiO2 and is thus of major importance for the clinician. Surprisingly, this relationship has only been assessed mathematically. Obviously, the accuracy of the mathematical relationship depends on the input variables used.

The current study is designed to assess the PaO2/FiO2 vs FiO2 relation in mechanically ventilated patients without ARDS (n =10) and with mild or moderate ARDS (n =10). In order to explain the dependency of the PaO2/FiO2 on FiO2, shunt fraction and alveolar - arterial oxygen difference ((A-a)DO2) will be determined in these patients.

Objective:

To study the relation between PaO2/FiO2-ratio and FiO2

Study design:

An unblinded, prospective, interventional study

Study population:

Mechanically ventilated patients > 18 years, admitted to the Intensive Care Unit of VU-Medical Center post cardiac surgery without ARDS (n = 10) and with mild to moderate ARDS (n = 10).

Intervention:

Two interventions will be performed:

1. Modulation of FiO2: FiO2 will be reduced to 21% or until peripheral oxygen saturation of 92%, whatever occurs first. Subsequently FiO2 will be increased up to 100%.
2. Withdrawal of blood: Blood will be withdrawn from the indwelling arterial line and pulmonary artery catheter. No catheters will be inserted for the study. The maximum number of time points is 7. At each time point 1.5 ml of blood will be withdrawn from both the arterial and pulmonary artery catheter for blood gas analysis. At the start and the end of the study period 2 additional blood samples of 5 ml each will be drawn. Accordingly, the maximum amount of blood obtained will be less than 50 ml.

Main study parameters/endpoints:

At each level of FiO2 the following parameters will be assessed:

• Arterial blood gas analysis, including SaO2
• Central Venous oxygen saturation and content
• Hemoglobin
• Body temperature
• End tidal CO2
• VO2 and VCO2
• Ventilatory parameters (tidal volume, respiratory rate, Ppeak Paw)
• Hemodynamics (Bloodpressure and Heart Rate)

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • VU University Medical Center
    • Contact: Angelique Spoelstra - de Man, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

All mechanically ventilated patients, admitted to the Intensive Care Unit of VU-Medical Center post cardiac surgery without ARDS and with mild to moderate ARDS. In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• Mechanically ventilated patients
• Stable hemodynamics
• Stable haemoglobin level
• Stable body temperature
• Stable level of sedation
• Pulmonary-Artery and Artery catheter

Exclusion Criteria:

• Incomplete revascularization after CABG
• Cardiac ischemia
• Neurotrauma

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Without ARDS; Patients admitted to the ICU after cardiac surgery with a PaO2/FiO2 ratio > 300. Modulation of FiO2: FiO2 will be reduced to 21% or until peripheral oxygen saturation of 92%, whatever occurs first. Subsequently FiO2 will be increased up to 100%.	Drug: Modulation of FiO2; Modulation of FiO2: FiO2 will be reduced to 21% or until peripheral oxygen saturation of 92%, whatever occurs first. Subsequently FiO2 will be increased up to 100%.
Experimental: With mild to moderate ARDS; Patients admitted to the ICU after cardiac surgery with a PaO2/FiO2 ratio > 100 and < 300. Modulation of FiO2: FiO2 will be reduced to 21% or until peripheral oxygen saturation of 92%, whatever occurs first. Subsequently FiO2 will be increased up to 100%.	Drug: Modulation of FiO2; Modulation of FiO2: FiO2 will be reduced to 21% or until peripheral oxygen saturation of 92%, whatever occurs first. Subsequently FiO2 will be increased up to 100%.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The effect of FiO2 on the PaO2/FiO2-ratio	To study the effect of FiO2 on the PaO2/FiO2-ratio in mechanically ventilated patients post cardiac surgery without ARDS and with mild to moderate ARDS	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shunt fraction, arteriovenous oxygen difference and alveolar - arterial oxygen difference	Shunt fraction, arteriovenous oxygen difference and alveolar - arterial oxygen difference will be determined to explain the relationship between FiO2 and the PaO2/FiO2-ratio	2 hours

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Investigators: Principal Investigator: Angelique Spoelstra - de Man, MD, PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2017
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): August 1, 2020

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): April 26, 2019
• Last Update Submitted That Met QC Criteria: April 25, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: PaO2/FiO2 ratio, hyperoxia, mechanical ventilation, ARDS
• Other Study ID Numbers: NL61945.029.17

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