Ventilator Induced Lung InjuryNCT01502332
Intensive Alveolar Recruitment Protocol After Cardiac Surgery
A study testing Intensive Alveolar Recruitment and Moderate Alveolar Recruitment in people with Ventilator Induced Lung Injury and Cardiac Disease, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
The purpose of this study was to evaluate prospectively the impact of two protective mechanical ventilation strategies, both using low tidal volume ventilation (6 mL/kg/ibw) after cardiac surgery. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Ventilator Induced Lung Injury, Cardiac Disease, Acute Lung Injury
- What is being tested?
- Intensive Alveolar Recruitment and Moderate Alveolar Recruitment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 320 participants
- Where
- 1 siteBrazil
- Study dates
- Dec 2011to Mar 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Immediate postoperative period of myocardial revascularization and/or heart valve surgery (aortic and/or mitral)
- Age > 18 years and < 80 years
- No previous pulmonary disease
- Left ventricular ejection fraction > 35%
- Body mass index < 40 kg/m2
- Oxygen index (PaO2/FiO2) < 250
- Corrected volemic status (negative raising legs mean arterial pressure [MAP] variation < 10%)
- Written inform consent
Who cannot join
- MAP (mean arterial pressure) < 60 mmHg
- Noradrenaline > 2 micrograms/Kg/min
- Acute arrhythmias
- Blooding associated to hemodynamic instability
- Need of re-surgery and/or mechanical circulatory assistance
- Suspicion of neurological alteration
- Chest tube with persistent air leak
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Instituto do Coração (Incor) - University of São Paulo
São Paulo, São Paulo
About this study
Official title: Comparison of Two Protective Mechanical Ventilation Strategies After Cardiac Surgery: Aggressive Versus Moderate Alveolar Recruitment Strategies
The purpose of this study was to evaluate prospectively the impact of two protective mechanical ventilation strategies, both using low tidal volume ventilation (6 mL/kg/ibw) after cardiac surgery. The study selected patients presenting signals of deficient gas exchange (PaO2/FIO2 < 250 at a PEEP [positive end expiratory pressure] of 5 cmH2O) in the immediate post-operative period. An aggressive alveolar recruitment protocol applying opening pressures of 45 cmH2O, followed by ventilation with PEEP = 13 cmH2O, was compared to the standard alveolar recruitment protocol of the institution, where an opening pressure of 20 cmH2O in the airways is followed by ventilation with PEEP = 8 cmH2O. After a stabilizing period of four hours of controlled mechanical ventilation, the patients followed the routine weaning protocol and physiotherapy protocol of the institution.
Read the detailed description
The postoperative period of cardiac surgery is associated with the development of pulmonary complications. Functional residual capacity can be reduced up to 50% and pulmonary volumes may be decreased until three months after surgery.
Lung injury is the result of pulmonary inflammation (activated by cardiopulmonary bypass, the surgical procedure itself and ischemia-reperfusion injury), the adopted mechanical ventilation strategy and a consequence of previous cardiac and/or pulmonary dysfunction.
The use of protective mechanical ventilation strategies with low tidal volumes since the immediate postoperative period, or since the operating room, has been shown to attenuate and prevent lung injury in previous studies selecting with high-risk patients.
A more complex topic, however, has been the proof of the additional benefit of alveolar recruitment maneuvers during the brief period of mechanical ventilation after surgery. While the experimental evidence suggests that the use of an open lung approach could minimize the shearing forces in the lung parenchyma, enhancing the protection afforded by low tidal volume ventilation, innumerous concerns about the hemodynamic side effects, and the possibility of barotrauma have prevented the routine use of intensive alveolar recruitment protocols. Another matter of concern is the net efficacy of a recruitment maneuver applied in the post-operative period, instead of the intra-operative period.
Thus, this study compared the impact of two protective mechanical ventilation strategies, both using low-tidal volume ventilation (6 mL/kg/ibw) after cardiac surgery, in a selective population of patients presenting signals of deficient gas exchange (PaO2/FIO2 < 250 at a PEEP of 5 cmH2O) in the immediate post-operative period. In a previous study at this institution, this subgroup of patients was shown to be at higher risks of postoperative pulmonary complications.
During the short period of controlled mechanical ventilation after the patient arrival from the operating theater, an aggressive alveolar recruitment protocol applying opening pressures of 45 cmH2O, followed by ventilation with PEEP = 13 cmH2O, was compared to the standard alveolar recruitment protocol of the institution, where an opening pressure of 20 cmH2O in the airways is followed by ventilation with PEEP = 8 cmH2O. After an stabilizing period of four hours of controlled mechanical ventilation, the patients followed the routine weaning protocol and physiotherapy protocol of the institution.
Our hypothesis was that the aggressive alveolar recruitment strategy might help in the reversal of collapse created during the surgery and short term mechanical ventilation during anesthesia and patient transportation. Previous studies have shown that this effect may extend to the post-extubation period, impairing lung function for a few days.
Thus, we tested if the effect of an aggressive alveolar recruitment protocol was translated in a better lung compliance, better gas exchange, and fewer pulmonary complications in the post-operative periods (this latter was our primary outcome). Analysis of the length of stay was also scrutinized, consisting in our secondary outcome. All hemodynamic complications was reported, since we also anticipated that events of hemodynamic impairment might be more frequent in the aggressive recruitment arm, eventually obscuring the expected benefits .
- Being tested
- Intensive Alveolar Recruitment, Moderate Alveolar Recruitment
- Keywords
- Mechanical ventilation, Open lung approach, Blood gases, Cardiac surgery, Pulmonary complications
- Medical subject headings
- Ventilator-Induced Lung Injury, Heart Diseases, Acute Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intensive Alveolar RecruitmentOther
Recruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with tidal volume (VT) = 6 mL/kg/pbw.
Moderate Alveolar RecruitmentOther
Recruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw.
| Study group | Role | What they receive |
|---|---|---|
| Intensive Alveolar Recruitment | Experimental | Recruitment with opening pressures of 45 cmH2O in the airways. Receives: Other: Intensive Alveolar Recruitment |
| Moderate Alveolar Recruitment | Active comparator | Recruitment with opening pressures of 20 cmH2O in the airways. Receives: Other: Moderate Alveolar Recruitment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Severity of Pulmonary Complications in the Post-operative Period
Score of pulmonary complications adapted from previous publications, with 5 degrees, where the higher one means death before hospital discharge, degree (4) means the need of mechanical ventilation for more than 48 hours after surgery or after reintubation, degree (3) means pneumonia or intense noninvasive ventilation need, degree (2) means hypoxemia and abnormal lung findings, degree 1 means simple atelectasis and degree (0) means no complication.
The comparison used this ordinal variable, representing the highest score achieved during the post-operative period. The comparison between arms was made through the Mann-Whitney U test.
Data shown are percentage of participants with pulmonary complications grade ≥ 3.
Measured: Participants were followed for the duration of hospital stay.
Secondary outcomes (4)
Length of ICU Stay
Days since surgery until ICU discharge, analyzed through Kaplan-Meyer curves (log-Rank test), where the time to event is the time of discharge from the ICU. The censoring was performed at 28 days. Patients dying before leaving the ICU were censored as not discharged from ICU at day 28.
Measured: From the day of surgery up to ICU discharge, maximum censoring at day 28 after surgery
Length of Hospital Stay
Days since surgery until Hospital discharge, analyzed through Kaplan-Meyer curves (log-Rank test), where the time to event is the time of discharge from the Hospital. The censoring was performed at 28 days. Patients dying before leaving the Hospital were censored as not discharged from Hospital at day 28.
Measured: From the day of surgery up to Hospital discharge, maximum censoring at day 28 after surgery
Incidence of Barotrauma
Confirmed by X-ray. Test with logistic regression
Measured: Five days after surgery
Hospital Mortality
Deaths occurred during hospital stay, tested with logistic regression.
Measured: From the day of surgery up to Hospital discharge or death, with no maximum censoring.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Dec 2011 (estimated)
- Study startDec 2011
- Primary completionFeb 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ventilator Induced Lung InjuryStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 320 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- InCor Heart Institute
- Responsible party
- Principal investigator, Alcino Costa Leme, University of Sao Paulo
- Investigators
- Marcelo BP Amato, PhD, Study director, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01502332
- Sponsor's protocol ID
- InCor-OLA
- Status last verified
- Oct 2016
- First submitted
- 21 Dec 2011
- Last updated
- 23 Nov 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Costa Leme A, Hajjar LA, Volpe MS, Fukushima JT, De Santis Santiago RR, Osawa EA, Pinheiro de Almeida J, Gerent AM, Franco RA, Zanetti Feltrim MI, Nozawa E, de Moraes Coimbra VR, de Moraes Ianotti R, Hashizume CS, Kalil Filho R, Auler JO Jr, Jatene FB, Gomes Galas FR, Amato MB. Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial. JAMA. 2017 Apr 11;317(14):1422-1432. doi: 10.1001/jama.2017.2297.
PubMed 28322416
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Two Protective Mechanical Ventilation Strategies After Cardiac Surgery: Aggressive Versus Moderate Alveolar Recruitment Strategies
- ClinicalTrials.gov ID
- NCT01502332
- Acronym / sponsor ID
- InCor-OLA
- Keywords
- Mechanical ventilation, Open lung approach, Blood gases, Cardiac surgery, Pulmonary complications
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 320 participants (actual)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- InCor Heart Institute
- Study start
- Dec 2011
- Primary completion
- Feb 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 30 Dec 2011 (estimated)
- Results
- Posted 23 Nov 2016
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 study was to evaluate prospectively the impact of two protective mechanical ventilation strategies, both using low tidal volume ventilation (6 mL/kg/ibw) after cardiac surgery. The study selected patients presenting signals of deficient gas exchange (PaO2/FIO2 < 250 at a PEEP [positive end expiratory pressure] of 5 cmH2O) in the immediate post-operative period. An aggressive alveolar recruitment protocol applying opening pressures of 45 cmH2O, followed by ventilation with PEEP = 13 cmH2O, was compared to the standard alveolar recruitment protocol of the institution, where an opening pressure of 20 cmH2O in the airways is followed by ventilation with PEEP = 8 cmH2O. After a stabilizing period of four hours of controlled mechanical ventilation, the patients followed the routine weaning protocol and physiotherapy protocol of the institution.
Detailed description
The postoperative period of cardiac surgery is associated with the development of pulmonary complications. Functional residual capacity can be reduced up to 50% and pulmonary volumes may be decreased until three months after surgery.
Lung injury is the result of pulmonary inflammation (activated by cardiopulmonary bypass, the surgical procedure itself and ischemia-reperfusion injury), the adopted mechanical ventilation strategy and a consequence of previous cardiac and/or pulmonary dysfunction.
The use of protective mechanical ventilation strategies with low tidal volumes since the immediate postoperative period, or since the operating room, has been shown to attenuate and prevent lung injury in previous studies selecting with high-risk patients.
A more complex topic, however, has been the proof of the additional benefit of alveolar recruitment maneuvers during the brief period of mechanical ventilation after surgery. While the experimental evidence suggests that the use of an open lung approach could minimize the shearing forces in the lung parenchyma, enhancing the protection afforded by low tidal volume ventilation, innumerous concerns about the hemodynamic side effects, and the possibility of barotrauma have prevented the routine use of intensive alveolar recruitment protocols. Another matter of concern is the net efficacy of a recruitment maneuver applied in the post-operative period, instead of the intra-operative period.
Thus, this study compared the impact of two protective mechanical ventilation strategies, both using low-tidal volume ventilation (6 mL/kg/ibw) after cardiac surgery, in a selective population of patients presenting signals of deficient gas exchange (PaO2/FIO2 < 250 at a PEEP of 5 cmH2O) in the immediate post-operative period. In a previous study at this institution, this subgroup of patients was shown to be at higher risks of postoperative pulmonary complications.
During the short period of controlled mechanical ventilation after the patient arrival from the operating theater, an aggressive alveolar recruitment protocol applying opening pressures of 45 cmH2O, followed by ventilation with PEEP = 13 cmH2O, was compared to the standard alveolar recruitment protocol of the institution, where an opening pressure of 20 cmH2O in the airways is followed by ventilation with PEEP = 8 cmH2O. After an stabilizing period of four hours of controlled mechanical ventilation, the patients followed the routine weaning protocol and physiotherapy protocol of the institution.
Our hypothesis was that the aggressive alveolar recruitment strategy might help in the reversal of collapse created during the surgery and short term mechanical ventilation during anesthesia and patient transportation. Previous studies have shown that this effect may extend to the post-extubation period, impairing lung function for a few days.
Thus, we tested if the effect of an aggressive alveolar recruitment protocol was translated in a better lung compliance, better gas exchange, and fewer pulmonary complications in the post-operative periods (this latter was our primary outcome). Analysis of the length of stay was also scrutinized, consisting in our secondary outcome. All hemodynamic complications was reported, since we also anticipated that events of hemodynamic impairment might be more frequent in the aggressive recruitment arm, eventually obscuring the expected benefits .
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intensive Alveolar Recruitment | Experimental | Other: Intensive Alveolar RecruitmentRecruitment with opening pressures of 45 cmH2O in the airways. |
| Moderate Alveolar Recruitment | Active comparator | Other: Moderate Alveolar RecruitmentRecruitment with opening pressures of 20 cmH2O in the airways. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Immediate postoperative period of myocardial revascularization and/or heart valve surgery (aortic and/or mitral)
- Age > 18 years and < 80 years
- No previous pulmonary disease
- Left ventricular ejection fraction > 35%
- Body mass index < 40 kg/m2
Key exclusion criteria (7 listed)
- MAP (mean arterial pressure) < 60 mmHg
- Noradrenaline > 2 micrograms/Kg/min
- Acute arrhythmias
- Blooding associated to hemodynamic instability
- Need of re-surgery and/or mechanical circulatory assistance
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 |
|---|---|---|
| Intensive Alveolar RecruitmentRecruitment with opening pressures of 45 cmH2O in the airways, followed by ventilation with PEEP = 13 cmH2O, during 4 hours of protective mechanical ventilation with tidal volume (VT) = 6 mL/kg/pbw. | Other | Intensive Alveolar Recruitment |
| Moderate Alveolar RecruitmentRecruitment with opening pressures of 20 cmH2O in the airways, followed by ventilation with PEEP = 8 cmH2O, during 4 hours of protective mechanical ventilation with VT = 6 mL/kg/pbw. | Other | Moderate Alveolar Recruitment |
Primary outcome
Severity of Pulmonary Complications in the Post-operative Period
Time frame: Participants were followed for the duration of hospital stay.
Score of pulmonary complications adapted from previous publications, with 5 degrees, where the higher one means death before hospital discharge, degree (4) means the need of mechanical ventilation for more than 48 hours after surgery or after reintubation, degree (3) means pneumonia or intense noninvasive ventilation need, degree (2) means hypoxemia and abnormal lung findings, degree 1 means simple atelectasis and degree (0) means no complication. The comparison used this ordinal variable, representing the highest score achieved during the post-operative period. The comparison between arms was made through the Mann-Whitney U test. Data shown are percentage of participants with pulmonary complications grade ≥ 3.
4 secondary outcomes
Length of ICU Stay
Time frame: From the day of surgery up to ICU discharge, maximum censoring at day 28 after surgery
Length of Hospital Stay
Time frame: From the day of surgery up to Hospital discharge, maximum censoring at day 28 after surgery
Incidence of Barotrauma
Time frame: Five days after surgery
Hospital Mortality
Time frame: From the day of surgery up to Hospital discharge or death, with no maximum censoring.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 28322416Costa Leme A, Hajjar LA, Volpe MS, Fukushima JT, De Santis Santiago RR, Osawa EA, Pinheiro de Almeida J, Gerent AM, Franco RA, Zanetti Feltrim MI, Nozawa E, de Moraes Coimbra VR, de Moraes Ianotti R, Hashizume CS, Kalil Filho R, Auler JO Jr, Jatene FB, Gomes Galas FR, Amato MB. Effect of Intensive vs Moderate Alveolar Recruitment Strategies Added to Lung-Protective Ventilation on Postoperative Pulmonary Complications: A Randomized Clinical Trial. JAMA. 2017 Apr 11;317(14):1422-1432. doi: 10.1001/jama.2017.2297.
- 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.
Marcelo BP Amato, PhD study director
University of Sao Paulo
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intensive Alveolar Recruitment and Moderate Alveolar Recruitment in people with Ventilator Induced Lung Injury and Cardiac Disease, run by University of Sao Paulo at 1 site in Brazil.
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 8 inclusion and 7 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 23 Nov 2016. 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 Brazil. 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?
Yes. Results are posted in the registry (first posted 23 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Severity of Pulmonary Complications in the Post-operative Period (time frame: Participants were followed for the duration of hospital stay.). 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 NCT01502332, which also lists 1 linked publication.
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 23 Nov 2016; AzTrials last refreshed its copy on 1 Nov 2026.