Low Tidal Volume VentilationNCT01927237
Pulmonary Vascular Effects of Respiratory Rate & Carbon Dioxide
A study testing HLR and EHR in people with Low Tidal Volume Ventilation and Acute Respiratory Distress Syndrome, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
The purpose of this protocol is to perform serial physiological measurements and blood testing on mechanically ventilated patients comparing conditions of eucapnia and hypercapnia in the same patient. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Low Tidal Volume Ventilation, Acute Respiratory Distress Syndrome
- What is being tested?
- HLR and EHR
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Aug 2014
- Phase
- Interventional
- 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 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years old.
- Able to consent pre-operatively prior to scheduled cardiac surgery.
- Intubation on mechanical ventilation post-operatively.
- Presence of a pulmonary artery catheter and/or central venous catheter as part of usual care post-operatively.
- Presence of a radial, brachial, or femoral arterial catheter as part of usual care post-operatively.
Who cannot join
- Significant intra-operative or immediate post-operative complications, such as uncontrolled bleeding or persistent hemodynamic instability.
- Intra-cardiac or intrapulmonary shunt.
- Persistent post-operative moderate or severe hypoxemia, defined as PaO2/FiO2 < 200 mmHg.
- Moderate or severe lung disease, including moderate or severe chronic obstructive pulmonary disease (COPD) or asthma.
- Recently treated for bleeding varices, stricture, or hematemesis, esophageal trauma, recent esophageal surgery, or other contraindication to transesophageal echocardiography.
- Severe coagulopathy (platelet count < 10,000 or international normalized ratio [INR] > 4).
Show all 16Show fewer
- History of lung, heart, or liver transplant.
- Elevated intracranial pressure or conditions where hypercapnia-induced elevations in intracranial pressure should be avoided, including:
- Intracranial hemorrhage
- Cerebral contusion
- Cerebral edema
- Mass effect (midline shift on head CT)
- Flat EEG for > 2 hours
- Evidence of active air leak from the lung, such as broncho-pleural fistula or ongoing air leak from an existing chest tube.
- Treating physician refusal.
- Inability to obtain informed consent directly from the subject prior to surgery.
Trial locations and contacts
1 site in 1 country.
United States1 site
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02122
About this study
Official title: The Pulmonary Vascular Consequences of Divergent Strategies for Low Tidal Volume Ventilation: Hypercapnia or High Respiratory Rate?
The purpose of this protocol is to perform serial physiological measurements and blood testing on mechanically ventilated patients comparing conditions of eucapnia and hypercapnia in the same patient. We will be testing two hypotheses: (1) while administering inspired carbon dioxide (CO2), eucapnia achieved by high respiratory rate (EHR) significantly decreases pulmonary artery pressures compared to hypercapnia with a lower respiratory rate (HLR), and (2) that EHR decreases myocardial strain compared to HLR.
Read the detailed description
The purpose of this protocol is to perform serial physiological measurements and blood testing on mechanically ventilated patients comparing conditions of eucapnia (maintaining alveolar ventilation to target carbon dioxide partial pressure (pCO2) 35-40 mm Hg) and hypercapnia (providing inspired CO2 to target pCO2 55-60 mm Hg) in the same patient. This prospective clinical study will enroll consenting adult patients scheduled for elective cardiac surgery and who require postoperative mechanical ventilation, pulmonary artery (Swan-Ganz) catheter monitoring, and arterial catheterization as part of routine standard care during the immediate postoperative period. The study will perform measurements using available ventilator monitors, ventilator in-line pneumotachograph and capnograph, measurements from the indwelling pulmonary artery catheter, transesophageal echocardiography, and other measurements available as part of routine care. The entire experimental protocol will be performed in one day over 2-4 hours, and the protocol will not interfere with routine postoperative care, nor prolong the need for mechanical ventilation, pulmonary artery catheterization, arterial catheterization, or intensive care unit length of stay.
Ventilation with low tidal volumes has been shown definitively to improve mortality from acute respiratory distress syndrome (ARDS)1 and may provide benefit even in patients without ARDS.2 During low tidal volume ventilation, practice varies on whether to allow some degree of alveolar hypoventilation with incidental hypercapnic acidosis (termed "permissive hypercapnia"),3 or to increase respiratory rate to maintain alveolar ventilation and target eucapnia, often requiring respiratory rates > 30/min.4 The physiological consequences of these divergent strategies remain to be fully elucidated. We propose the following study to distinguish the effects of a eucapnic high respiratory rate (EHR) strategy from a hypercapnic low respiratory rate (HLR) strategy on pulmonary hemodynamics during low tidal volume ventilation.
Specific Aim: To test the hypothesis that, while administering inspired CO2, eucapnia achieved by high respiratory rate (EHR) significantly decreases pulmonary artery pressures compared to hypercapnia with a lower respiratory rate (HLR).
Specific Aim: To test the hypothesis that EHR decreases myocardial strain compared to HLR.
- Being tested
- HLR, EHR
- Keywords
- pulmonary artery pressure, ARDS, alveolar hypoventilation, hypercapnic acidosis, permissive hypercapnia, myocardial strain
- Medical subject headings
- Respiratory Distress Syndrome, Hypoventilation, Acidosis, Respiratory
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HLROther
Also called hypercapnia with low respiratory rate
EHROther
Also called eucapnia with high respiratory rate
| Study group | Role | What they receive |
|---|---|---|
| HLR-first | Experimental | Patients in this arm will have the "hypercapnia with low respiratory rate" (HLR) strategy first. Once hypercapnia is achieved via inspired carbon dioxide, no additional changes will be made to the ventilator. Once steady-state is achieved, physiological measurements will be taken. The patient will be returned to baseline settings for a 15-minute "rest period" before starting the EHR strategy per the cross-over design. Receives: Other: HLR; Other: EHR |
| EHR-first | Experimental | Patients in this arm will have the "eucapnia with high respiratory rate" (EHR) strategy first. Once hypercapnia is achieved via inspired carbon dioxide, respiratory rate will be increased until PetCO2 returns to baseline or up to 35 breaths per minute, as limited by the National Heart Lung and Blood Institute (NHLBI) ARDS Network protocol. fraction of inspired oxygen inspired oxygen fraction and set tidal volume will be maintained. Once steady-state is achieved, physiological measurements will be taken. The patient will be returned to baseline settings for a 15-minute "rest period" before starting the HLR strategy per the cross-over design. Receives: Other: HLR; Other: EHR |
What is being measured
The primary outcome is the main question the study is designed to answer.
mean pulmonary artery pressure (mPAP)
Pulmonary artery pressure will be measured directly by transducing the pulmonary artery catheter, and will include systolic (PASP) and diastolic (PADP) Ppa. The mean pulmonary artery pressure (mPAP) will be calculated according to the formula: mPAP = 1/3 PASP + 2/3 PADP
Measured: 4 hours
Secondary outcomes (1)
Right ventricular systolic function
Right ventricular systolic function will be assessed using strain echocardiography or peak tricuspid annular systolic velocity.
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2013 (estimated)
- Study startSep 2013
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Low Tidal Volume VentilationStudies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Talmor, Beth Israel Deaconess Medical Center
- Investigators
- Daniel Talmor, MD MPH, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01927237
- Sponsor's protocol ID
- 2013P000222
- Status last verified
- Aug 2014
- First submitted
- 20 Aug 2013
- Last updated
- 27 Feb 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Malhotra A. Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med. 2007 Sep 13;357(11):1113-20. doi: 10.1056/NEJMct074213.
PubMed 17855672Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Esposito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012 Oct 24;308(16):1651-9. doi: 10.1001/jama.2012.13730.
PubMed 23093163Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54. doi: 10.1056/NEJM199802053380602.
PubMed 9449727Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. doi: 10.1056/NEJMoa050333.
PubMed 16236739Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
PubMed 10793162
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Pulmonary Vascular Consequences of Divergent Strategies for Low Tidal Volume Ventilation: Hypercapnia or High Respiratory Rate?
- ClinicalTrials.gov ID
- NCT01927237
- Acronym / sponsor ID
- 2013P000222
- Keywords
- pulmonary artery pressure, ARDS, alveolar hypoventilation, hypercapnic acidosis, permissive hypercapnia, myocardial strain
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 22 Aug 2013 (estimated)
- 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.
The purpose of this protocol is to perform serial physiological measurements and blood testing on mechanically ventilated patients comparing conditions of eucapnia and hypercapnia in the same patient. We will be testing two hypotheses: (1) while administering inspired carbon dioxide (CO2), eucapnia achieved by high respiratory rate (EHR) significantly decreases pulmonary artery pressures compared to hypercapnia with a lower respiratory rate (HLR), and (2) that EHR decreases myocardial strain compared to HLR.
Detailed description
The purpose of this protocol is to perform serial physiological measurements and blood testing on mechanically ventilated patients comparing conditions of eucapnia (maintaining alveolar ventilation to target carbon dioxide partial pressure (pCO2) 35-40 mm Hg) and hypercapnia (providing inspired CO2 to target pCO2 55-60 mm Hg) in the same patient. This prospective clinical study will enroll consenting adult patients scheduled for elective cardiac surgery and who require postoperative mechanical ventilation, pulmonary artery (Swan-Ganz) catheter monitoring, and arterial catheterization as part of routine standard care during the immediate postoperative period. The study will perform measurements using available ventilator monitors, ventilator in-line pneumotachograph and capnograph, measurements from the indwelling pulmonary artery catheter, transesophageal echocardiography, and other measurements available as part of routine care. The entire experimental protocol will be performed in one day over 2-4 hours, and the protocol will not interfere with routine postoperative care, nor prolong the need for mechanical ventilation, pulmonary artery catheterization, arterial catheterization, or intensive care unit length of stay.
Ventilation with low tidal volumes has been shown definitively to improve mortality from acute respiratory distress syndrome (ARDS)1 and may provide benefit even in patients without ARDS.2 During low tidal volume ventilation, practice varies on whether to allow some degree of alveolar hypoventilation with incidental hypercapnic acidosis (termed "permissive hypercapnia"),3 or to increase respiratory rate to maintain alveolar ventilation and target eucapnia, often requiring respiratory rates > 30/min.4 The physiological consequences of these divergent strategies remain to be fully elucidated. We propose the following study to distinguish the effects of a eucapnic high respiratory rate (EHR) strategy from a hypercapnic low respiratory rate (HLR) strategy on pulmonary hemodynamics during low tidal volume ventilation.
Specific Aim: To test the hypothesis that, while administering inspired CO2, eucapnia achieved by high respiratory rate (EHR) significantly decreases pulmonary artery pressures compared to hypercapnia with a lower respiratory rate (HLR).
Specific Aim: To test the hypothesis that EHR decreases myocardial strain compared to HLR.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HLR-first | Experimental | Other: HLR, Other: EHRPatients in this arm will have the "hypercapnia with low respiratory rate" (HLR) strategy first. Once hypercapnia is achieved via inspired carbon dioxide, no additional changes will be made to the ventilator. Once steady-state is achieved, physiological measurements will be taken. The patient will be returned to baseline settings for a 15-minute "rest period" before starting the EHR strategy per the cross-over design. |
| EHR-first | Experimental | Other: HLR, Other: EHRPatients in this arm will have the "eucapnia with high respiratory rate" (EHR) strategy first. Once hypercapnia is achieved via inspired carbon dioxide, respiratory rate will be increased until PetCO2 returns to baseline or up to 35 breaths per minute, as limited by the National Heart Lung and Blood Institute (NHLBI) ARDS Network protocol. fraction of inspired oxygen inspired oxygen fraction and set tidal volume will be maintained. Once steady-state is achieved, physiological measurements will be taken. The patient will be returned to baseline settings for a 15-minute "rest period" before starting the HLR strategy per the cross-over design. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years old.
- Able to consent pre-operatively prior to scheduled cardiac surgery.
- Intubation on mechanical ventilation post-operatively.
- Presence of a pulmonary artery catheter and/or central venous catheter as part of usual care post-operatively.
- Presence of a radial, brachial, or femoral arterial catheter as part of usual care post-operatively.
Key exclusion criteria (16 listed)
- Significant intra-operative or immediate post-operative complications, such as uncontrolled bleeding or persistent hemodynamic instability.
- Intra-cardiac or intrapulmonary shunt.
- Persistent post-operative moderate or severe hypoxemia, defined as PaO2/FiO2 < 200 mmHg.
- Moderate or severe lung disease, including moderate or severe chronic obstructive pulmonary disease (COPD) or asthma.
- Recently treated for bleeding varices, stricture, or hematemesis, esophageal trauma, recent esophageal surgery, or other contraindication to transesophageal echocardiography.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HLRAlso: hypercapnia with low respiratory rate | Other | EHR-first, HLR-first |
| EHRAlso: eucapnia with high respiratory rate | Other | EHR-first, HLR-first |
Primary outcome
mean pulmonary artery pressure (mPAP)
Time frame: 4 hours
Pulmonary artery pressure will be measured directly by transducing the pulmonary artery catheter, and will include systolic (PASP) and diastolic (PADP) Ppa. The mean pulmonary artery pressure (mPAP) will be calculated according to the formula: mPAP = 1/3 PASP + 2/3 PADP
1 secondary outcome
Right ventricular systolic function
Time frame: 4 hours
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2017.
- Background: PubMed 17855672Malhotra A. Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med. 2007 Sep 13;357(11):1113-20. doi: 10.1056/NEJMct074213.
- Background: PubMed 23093163Serpa Neto A, Cardoso SO, Manetta JA, Pereira VG, Esposito DC, Pasqualucci Mde O, Damasceno MC, Schultz MJ. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA. 2012 Oct 24;308(16):1651-9. doi: 10.1001/jama.2012.13730.
- Background: PubMed 9449727Amato MB, Barbas CS, Medeiros DM, Magaldi RB, Schettino GP, Lorenzi-Filho G, Kairalla RA, Deheinzelin D, Munoz C, Oliveira R, Takagaki TY, Carvalho CR. Effect of a protective-ventilation strategy on mortality in the acute respiratory distress syndrome. N Engl J Med. 1998 Feb 5;338(6):347-54. doi: 10.1056/NEJM199802053380602.
- Background: PubMed 16236739Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med. 2005 Oct 20;353(16):1685-93. doi: 10.1056/NEJMoa050333.
- Background: PubMed 10793162Acute Respiratory Distress Syndrome Network; Brower RG, Matthay MA, Morris A, Schoenfeld D, Thompson BT, Wheeler A. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J Med. 2000 May 4;342(18):1301-8. doi: 10.1056/NEJM200005043421801.
- Individual participant dataSharing planned: No
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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.
Daniel Talmor, MD MPH principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HLR and EHR in people with Low Tidal Volume Ventilation and Acute Respiratory Distress Syndrome, run by Beth Israel Deaconess Medical Center at 1 site in United States.
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 5 inclusion and 16 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: withdrawn, as of the sponsor's last update on 27 Feb 2017. 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 United States. 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 was withdrawn before enrolling participants, so there are no results.
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?
mean pulmonary artery pressure (mPAP) (time frame: 4 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01927237, which also lists 5 linked publications.
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 Feb 2017.