Physiological Dead SpaceCODE-EtANCT06947486
Correlation of EtCO₂- and P(A-a)O₂-Based Dead Space Calculations in Mechanically Ventilated ICU Patients
An observational study of Physiological Dead Space and Ventilation-Perfusion Mismatch, run by Karadeniz Technical University at 1 site in Turkey (Türkiye).
Trial summary
This study aims to evaluate two different methods for calculating physiological dead space in adult patients undergoing invasive mechanical ventilation in the intensive care unit (ICU). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Physiological Dead Space, Ventilation-Perfusion Mismatch, Mechanical Ventilation
- How many people
- 41 participants
- Where
- 1 siteTurkey (Türkiye)
- Study dates
- 5 Jan 2025to 18 Apr 2025
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: The study population includes adult patients (aged 18 years and older) who are admitted to a tertiary academic intensive care unit and require invasive mechanical ventilation for respiratory failure. Eligible patients must be expected to remain intubated for at least 24 hours and undergo both volumetric capnography and arterial blood gas monitoring. Participants are enrolled prospectively and consecutively based on predefined inclusion and exclusion criteria. Patients with circulatory shock, severe metabolic or respiratory derangements, or technical limitations interfering with capnographic measurement are excluded. The study represents a critically ill cohort commonly encountered in ICU practice.
Who may be able to join
- Age ≥ 18 years
- Admission to the intensive care unit (ICU)
- Receiving invasive mechanical ventilation
- Expected ICU stay ≥ 24 hours
- Availability of both arterial blood gas and volumetric capnography measurements
- Central venous cathater for central venous blood analyses
- Informed consent obtained from legal representative
Who cannot join
- Refusal of participation by the patient or legal surrogate
- Hemoglobin < 7 g/dL
- PaCO₂ > 70 mmHg
- Lactate > 4 mmol/L
- Capillary refill time > 3 seconds
- Mean arterial pressure (MAP) < 65 mmHg
Show all 14Show fewer
- Mottling score ≥ 2
- PaCO₂ - PcCO₂ gradient > 8 mmHg
- pH < 7.20
- Body temperature > 38°C
- BMI > 40 kg/m²
- VCO₂ > 4 mL/kg/min
- Technical limitations preventing accurate capnographic monitoring
- Patients who are extubated, transferred, or deceased within the first 24 hours
Trial locations and contacts
1 site in 1 country.
Turkey (Türkiye)1 site
Karadeniz Technical University Faculty of Medicine, Department of Chest Diseases, Intensive Care Unit
Trabzon, 61080
About this study
Official title: COmparison of Physiological Dead Space Calculations Using EtCO₂ and P(A-a)O₂ in Mechanically Ventilated ICU Patients: A Prospective Observational Study
This study aims to evaluate two different methods for calculating physiological dead space in adult patients undergoing invasive mechanical ventilation in the intensive care unit (ICU). Physiological dead space refers to the portion of air that is ventilated but does not participate in gas exchange due to impaired perfusion or ventilation-perfusion mismatch.
Traditionally, dead space is calculated using the end-tidal carbon dioxide (EtCO₂) method, which estimates the difference between arterial and exhaled CO₂ values. However, this method may be influenced by circulatory failure or abnormal CO₂ distribution. An alternative method using the alveolar-arterial oxygen gradient [P(A-a)O₂] has been proposed, as it may provide a more stable measurement under critical conditions by relying on oxygenation efficiency rather than CO₂ elimination.
Read more
In this prospective observational study, patients receiving mechanical ventilation in a tertiary ICU will be monitored. Physiological dead space will be calculated using both the EtCO₂-based method and the P(A-a)O₂-based method. Various respiratory and clinical parameters, including arterial blood gases, ventilator settings, and severity scores, will be recorded. The correlation between the two methods will be assessed, and their relationship with ICU mortality will be analyzed.
The results of this study may help determine whether the P(A-a)O₂ method can be used as a reliable alternative for estimating dead space in ICU patients and whether it has prognostic value in predicting patient outcomes.
Read the detailed description
Physiological dead space (VD/VT) is a key parameter in evaluating the efficiency of gas exchange in mechanically ventilated patients. It represents the fraction of each breath that does not participate in effective alveolar ventilation due to perfusion defects, shunt physiology, or mismatched ventilation-perfusion (V/Q) ratios. An elevated dead space fraction has been associated with poor clinical outcomes, especially in patients with acute respiratory failure or circulatory impairment.
The most commonly used method for estimating dead space in the intensive care setting is based on the Enghoff modification of the Bohr equation:
VD/VT = (PaCO₂ - EtCO₂) / PaCO₂
This approach utilizes the arterial carbon dioxide pressure (PaCO₂) and end-tidal carbon dioxide pressure (EtCO₂) to estimate the proportion of ventilation that does not contribute to CO₂ elimination. However, it assumes a relatively homogenous V/Q distribution and may lose accuracy in the presence of increased shunt, circulatory shock, or CO₂ transport abnormalities.
To improve on these limitations, the present study also incorporates the alveolar-arterial oxygen gradient [P(A-a)O₂] as an alternative method for estimating physiological dead space. The gradient is calculated as:
P(A-a)O₂ = PAO₂ - PaO₂, where PAO₂ = FiO₂ × (Patm - PH₂O) - (PaCO₂ / R)
The dead space ratio can then be estimated by a similar structure:
VD/VT = (PAO₂ - PaO₂) / PAO₂
The P(A-a)O₂-based method may offer more robust estimations under critically ill conditions, particularly in cases with oxygenation defects or hemodynamic compromise, as it is less affected by variations in CO₂ distribution or metabolism.
In addition to Enghoff and oxygen-based approaches, this study also evaluates the Kuwabara modification, which adjusts for venous admixture and attempts to more accurately reflect the effective alveolar ventilation in the presence of shunt physiology. Kuwabara and Duncalf introduced a correction to the dead space formula to account for anatomical and functional shunts, reducing potential overestimation caused by disproportionate alveolar ventilation:
Corrected VD/VT = [(PaCO₂ - EtCO₂) / PaCO₂] × α
Where α represents a correction factor that adjusts for venous admixture and other circulatory influences.
This prospective observational study will include adult patients undergoing invasive mechanical ventilation in a tertiary ICU. Participants will be evaluated at multiple time points using volumetric capnography, arterial and venous blood gases, and ventilator-derived parameters. Physiological dead space will be calculated in parallel using:
Enghoff's method
P(A-a)O₂-based oxygenation gradients
Kuwabara correction for venous admixture
Daily clinical scores (SOFA, APACHE II), ventilator mechanics (PEEP, tidal volume, FiO₂, plateau pressure, driving pressure), and gas exchange variables (PaCO₂, PaO₂/FiO₂, VCO₂, VO₂) will also be recorded.
The study aims to assess:
The correlation between the EtCO₂- and P(A-a)O₂-based dead space methods
The influence of shunt and hemodynamic variables on dead space estimation
The prognostic relevance of each method in relation to ICU mortality
This study seeks to contribute to the optimization of dead space measurement in the ICU by evaluating alternative, potentially more reliable physiologic methods. It also aims to inform future clinical practice by identifying the most accurate and clinically useful dead space assessment tools in the context of severe critical illness.
- Conditions
- Physiological Dead Space, Ventilation-Perfusion Mismatch, Mechanical Ventilation, Enghoff Correction
- Keywords
- Physiological Dead Space, EtCO₂, P(A-a)O₂ Gradient, Mechanical Ventilation, Volumetric Capnography, Ventilation-Perfusion Mismatch, Enghoff Modification, Kuwabara Equation, Intensive Care Unit
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Mechanically Ventilated ICU Patients | Adult patients (≥18 years old) admitted to a tertiary ICU and receiving invasive mechanical ventilation for at least 24 hours. Participants are prospectively monitored with capnographic and arterial blood gas measurements, and physiological dead space is calculated using both EtCO₂- and P(A-a)O₂-based methods. Patients are followed until ICU discharge or death. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Correlation between EtCO₂- and P(A-a)O₂-based dead space calculations
Description: Pearson or Spearman correlation coefficient calculated between dead space values obtained from EtCO₂ (Enghoff modification) and P(A-a)O₂-based gradient methods in mechanically ventilated ICU patients.
Measured: Within the first 72 hours of ICU admission
Secondary outcomes (3)
Association of each dead space method with ICU mortality
Evaluation of whether EtCO₂- and P(A-a)O₂-derived dead space values are independently associated with ICU mortality.
Measured: From ICU admission until ICU discharge or death
Agreement between EtCO₂- and P(A-a)O₂-based dead space estimates
Bland-Altman and bias analysis to evaluate agreement between the two measurement methods.
Measured: Within first 3 days of ICU stay
Relationship between dead space values and gas exchange/ perfusion variables
Correlation between VD/VT and parameters such as PaO₂/FiO₂, lactate, MAP, and mottling score.
Measured: Daily for up to 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2025
- Study start5 Jan 2025
- Primary completion10 Apr 2025
- Study completion18 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Physiological Dead SpaceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Karadeniz Technical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, A. Oguzhan KUCUK, Karadeniz Technical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06947486
- Sponsor's protocol ID
- 2025/3
- Acronym
- CODE-EtA
- Status last verified
- Apr 2025
- First submitted
- 20 Apr 2025
- Last updated
- 27 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared due to ethical and confidentiality considerations, and because no public data-sharing plan has been established for this study.
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- COmparison of Physiological Dead Space Calculations Using EtCO₂ and P(A-a)O₂ in Mechanically Ventilated ICU Patients: A Prospective Observational Study
- ClinicalTrials.gov ID
- NCT06947486
- Acronym / sponsor ID
- CODE-EtA / 2025/3
- Conditions
- Physiological Dead Space, Ventilation-Perfusion Mismatch, Mechanical Ventilation, Enghoff Correction
- Keywords
- Physiological Dead Space, EtCO₂, P(A-a)O₂ Gradient, Mechanical Ventilation, Volumetric Capnography, Ventilation-Perfusion Mismatch, Enghoff Modification, Kuwabara Equation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Karadeniz Technical UniversityUniversity, hospital or other
- Study start
- 5 Jan 2025 (actual)
- Primary completion
- 10 Apr 2025 (actual)
- Study completion
- 18 Apr 2025 (actual)
- First posted
- 27 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to evaluate two different methods for calculating physiological dead space in adult patients undergoing invasive mechanical ventilation in the intensive care unit (ICU). Physiological dead space refers to the portion of air that is ventilated but does not participate in gas exchange due to impaired perfusion or ventilation-perfusion mismatch.
Traditionally, dead space is calculated using the end-tidal carbon dioxide (EtCO₂) method, which estimates the difference between arterial and exhaled CO₂ values. However, this method may be influenced by circulatory failure or abnormal CO₂ distribution. An alternative method using the alveolar-arterial oxygen gradient [P(A-a)O₂] has been proposed, as it may provide a more stable measurement under critical conditions by relying on oxygenation efficiency rather than CO₂ elimination.
In this prospective observational study, patients receiving mechanical ventilation in a tertiary ICU will be monitored. Physiological dead space will be calculated using both the EtCO₂-based method and the P(A-a)O₂-based method. Various respiratory and clinical parameters, including arterial blood gases, ventilator settings, and severity scores, will be recorded. The correlation between the two methods will be assessed, and their relationship with ICU mortality will be analyzed.
The results of this study may help determine whether the P(A-a)O₂ method can be used as a reliable alternative for estimating dead space in ICU patients and whether it has prognostic value in predicting patient outcomes.
Detailed description
Physiological dead space (VD/VT) is a key parameter in evaluating the efficiency of gas exchange in mechanically ventilated patients. It represents the fraction of each breath that does not participate in effective alveolar ventilation due to perfusion defects, shunt physiology, or mismatched ventilation-perfusion (V/Q) ratios. An elevated dead space fraction has been associated with poor clinical outcomes, especially in patients with acute respiratory failure or circulatory impairment.
The most commonly used method for estimating dead space in the intensive care setting is based on the Enghoff modification of the Bohr equation:
VD/VT = (PaCO₂ - EtCO₂) / PaCO₂
This approach utilizes the arterial carbon dioxide pressure (PaCO₂) and end-tidal carbon dioxide pressure (EtCO₂) to estimate the proportion of ventilation that does not contribute to CO₂ elimination. However, it assumes a relatively homogenous V/Q distribution and may lose accuracy in the presence of increased shunt, circulatory shock, or CO₂ transport abnormalities.
To improve on these limitations, the present study also incorporates the alveolar-arterial oxygen gradient [P(A-a)O₂] as an alternative method for estimating physiological dead space. The gradient is calculated as:
P(A-a)O₂ = PAO₂ - PaO₂, where PAO₂ = FiO₂ × (Patm - PH₂O) - (PaCO₂ / R)
The dead space ratio can then be estimated by a similar structure:
VD/VT = (PAO₂ - PaO₂) / PAO₂
The P(A-a)O₂-based method may offer more robust estimations under critically ill conditions, particularly in cases with oxygenation defects or hemodynamic compromise, as it is less affected by variations in CO₂ distribution or metabolism.
In addition to Enghoff and oxygen-based approaches, this study also evaluates the Kuwabara modification, which adjusts for venous admixture and attempts to more accurately reflect the effective alveolar ventilation in the presence of shunt physiology. Kuwabara and Duncalf introduced a correction to the dead space formula to account for anatomical and functional shunts, reducing potential overestimation caused by disproportionate alveolar ventilation:
Corrected VD/VT = [(PaCO₂ - EtCO₂) / PaCO₂] × α
Where α represents a correction factor that adjusts for venous admixture and other circulatory influences.
This prospective observational study will include adult patients undergoing invasive mechanical ventilation in a tertiary ICU. Participants will be evaluated at multiple time points using volumetric capnography, arterial and venous blood gases, and ventilator-derived parameters. Physiological dead space will be calculated in parallel using:
Enghoff's method
P(A-a)O₂-based oxygenation gradients
Kuwabara correction for venous admixture
Daily clinical scores (SOFA, APACHE II), ventilator mechanics (PEEP, tidal volume, FiO₂, plateau pressure, driving pressure), and gas exchange variables (PaCO₂, PaO₂/FiO₂, VCO₂, VO₂) will also be recorded.
The study aims to assess:
The correlation between the EtCO₂- and P(A-a)O₂-based dead space methods
The influence of shunt and hemodynamic variables on dead space estimation
The prognostic relevance of each method in relation to ICU mortality
This study seeks to contribute to the optimization of dead space measurement in the ICU by evaluating alternative, potentially more reliable physiologic methods. It also aims to inform future clinical practice by identifying the most accurate and clinically useful dead space assessment tools in the context of severe critical illness.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Mechanically Ventilated ICU Patients | – | –Adult patients (≥18 years old) admitted to a tertiary ICU and receiving invasive mechanical ventilation for at least 24 hours. Participants are prospectively monitored with capnographic and arterial blood gas measurements, and physiological dead space is calculated using both EtCO₂- and P(A-a)O₂-based methods. Patients are followed until ICU discharge or death. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- The study population includes adult patients (aged 18 years and older) who are admitted to a tertiary academic intensive care unit and require invasive mechanical ventilation for respiratory failure. Eligible patients must be expected to remain intubated for at least 24 hours and undergo both volumetric capnography and arterial blood gas monitoring. Participants are enrolled prospectively and consecutively based on predefined inclusion and exclusion criteria. Patients with circulatory shock, severe metabolic or respiratory derangements, or technical limitations interfering with capnographic measurement are excluded. The study represents a critically ill cohort commonly encountered in ICU practice.
Key inclusion criteria (7 listed)
- Age ≥ 18 years
- Admission to the intensive care unit (ICU)
- Receiving invasive mechanical ventilation
- Expected ICU stay ≥ 24 hours
- Availability of both arterial blood gas and volumetric capnography measurements
Key exclusion criteria (14 listed)
- Refusal of participation by the patient or legal surrogate
- Hemoglobin < 7 g/dL
- PaCO₂ > 70 mmHg
- Lactate > 4 mmol/L
- Capillary refill time > 3 seconds
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Correlation between EtCO₂- and P(A-a)O₂-based dead space calculations
Time frame: Within the first 72 hours of ICU admission
Description: Pearson or Spearman correlation coefficient calculated between dead space values obtained from EtCO₂ (Enghoff modification) and P(A-a)O₂-based gradient methods in mechanically ventilated ICU patients.
3 secondary outcomes
Association of each dead space method with ICU mortality
Time frame: From ICU admission until ICU discharge or death
Agreement between EtCO₂- and P(A-a)O₂-based dead space estimates
Time frame: Within first 3 days of ICU stay
Relationship between dead space values and gas exchange/ perfusion variables
Time frame: Daily for up to 72 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2025.
- Individual participant dataSharing planned: No. Individual participant data will not be shared due to ethical and confidentiality considerations, and because no public data-sharing plan has been established for this study.
Related trials for Physiological Dead Space
Recruiting
Incremental Dead Space Versus Capping Trial Before Tracheostomy Decannulation
Tracheostomy, Prolonged Mechanical Ventilation
RecruitingObservational study
Physiological Studies in the Prone Position in Patients With ARDS
Acute Respiratory Distress Syndrome, Mechanical Ventilation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Physiological Dead Space and Ventilation-Perfusion Mismatch, run by Karadeniz Technical University at 1 site in Turkey (Türkiye).
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Turkey (Türkiye). Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Correlation between EtCO₂- and P(A-a)O₂-based dead space calculations (time frame: Within the first 72 hours of ICU admission). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2025.