Low Tidal Volume Ventilation for Cardiac Surgery

Overseen By Esra Kutlu, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: The Cleveland Clinic

Disqualifiers: Emergency surgeries, Lung transplants, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: During surgery

5502 Participants Needed

Trial Summary

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Low Tidal Volume Ventilation for Cardiac Surgery?

Research shows that using low tidal volume ventilation, which involves giving smaller breaths to patients on a ventilator, can reduce lung complications and improve outcomes in patients with lung injuries. This approach is also being explored for patients without lung injuries, including those undergoing cardiac surgery, to potentially reduce lung-related complications. ^{1 2 3 4 5}

Is low tidal volume ventilation generally safe for humans?

Low tidal volume ventilation is considered safe and is standard care for patients with acute respiratory distress syndrome (ARDS). It has been shown to reduce complications and improve outcomes in patients without lung injury, although it may present some clinical challenges. ^{1 4 5 6 7}

How is low tidal volume ventilation unique for cardiac surgery patients?

Low tidal volume ventilation is unique for cardiac surgery patients because it uses smaller breaths to protect the lungs, even in those without lung injury, and can reduce complications after surgery. This approach is different from traditional methods that use larger breaths, and it includes careful control of oxygen levels and pressure to improve outcomes. ^{1 3 5 6 8}

What is the purpose of this trial?

This is a multi-institutional study (CCF, UPMC, OSU) evaluating different ventilation strategies during cardiopulmonary bypass on mortality and postoperative pulmonary complications, with sub-study investigating 8-iso-prostaglandin F2a and sRAGE levels.

Research Team

Marta Kelava, MD

Principal Investigator

The Cleveland Clinic

Eligibility Criteria

Adults over 18 years old needing elective cardiac surgery with cardiopulmonary bypass can join. It's not for those requiring one-lung ventilation, emergency surgeries, lung or heart transplants, or mechanical circulatory support device implantation.

Inclusion Criteria

I am scheduled for heart surgery that will use a heart-lung machine.

I am older than 18 years.

Exclusion Criteria

I have not had a lung transplant surgery.

I have had a heart or lung transplant.

I have not had a heart transplant or a device implanted to help my heart pump.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo cardiopulmonary bypass with different ventilation strategies to evaluate effects on mortality and pulmonary complications

During surgery

1 visit (in-person)

Follow-up

Participants are monitored for postoperative complications and mortality within 30 days of surgery

30 days

Sub-study

Sub-study investigates 8-iso-prostaglandin F2a and sRAGE levels during CPB

During surgery

Treatment Details

Interventions

• Apnea During CPB
• Continuous low-tidal volume ventilation with using FiO2 of 0.21
• Continuous low tidal volume ventilation with using FiO2 of 1.0

Trial Overview The FOCUS Trial is comparing two ways of helping patients breathe during heart surgery with a heart-lung machine: either using normal oxygen levels or high oxygen levels. Researchers will see which method is better for survival and lung health after surgery.

Participant Groups

Group I: Apnea Active Control 1 Intervention

The investigator will investigate the effect of apnea during on PPCs and mortality compared to hyperoxic low-tidal volume ventilation (with FiO2 of 1.0) or hyperoxia avoidance (FiO2 of 0.21) during CPB, and during the sub-study..

Group II: Continuous low-tidal volume ventilation with using FiO2 of 0.21 Active Control 1 Intervention

The investigator will investigate the effect of continuous low tidal volume ventilation with hyperoxia avoidance (using FiO2 of 0.21) on PPCs and 30-day mortality compared to low-tidal volume ventilation (with FiO2 of 0.21) or apnea during CPB, and during the sub-study.

Group III: Continuous low tidal volume ventilation with using FiO2 of 1.0 Active Control 1 Intervention

The investigator will investigate the effect of low tidal volume lung ventilation with hyperoxia avoidance (FiO2 of 0.21) on PPCs and mortality compared to hyperoxic low-tidal volume ventilation (with FiO2 of 1.0) or apnea during CPB, and during the sub-study.

Continuous low-tidal volume ventilation with using FiO2 of 0.21 is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Low Tidal Volume Ventilation for:

• Cardiac surgery
• Prevention of postoperative pulmonary complications

Approved in European Union as Low Tidal Volume Ventilation for:

• Cardiac surgery
• Prevention of postoperative pulmonary complications
• Acute respiratory distress syndrome

Approved in Canada as Low Tidal Volume Ventilation for:

• Cardiac surgery
• Prevention of postoperative pulmonary complications

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Society of Cardiovascular Anesthesiologists

Collaborator

Trials

3

Recruited

5,600+

University of Pittsburgh Medical Center

Collaborator

Trials

78

Recruited

77,600+

Ohio State University

Collaborator

Trials

891

Recruited

2,659,000+

Findings from Research

Low tidal volume ventilation is effective in reducing morbidity and mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), but it is often underutilized due to clinical challenges.

There is emerging evidence suggesting that protective ventilation may also benefit patients without lung injury, highlighting the need for further exploration and strategies to encourage its use in broader clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome: A Paradigm Shift in Mechanical Ventilation. Lipes, J., Bojmehrani, A., Lellouche, F.[2021]

In a study of 2,484 patients with acute respiratory failure, it was found that 78% were already receiving low tidal volumes (≤8 ml/kg), indicating a common practice that aligns with the principles of low-tidal volume ventilation (LTVV).

Models estimated a potential mortality benefit of 0-2% from LTVV compared to usual care, but the proposed large-scale trial to further investigate this was deemed infeasible due to the need for over 106,000 patients to achieve sufficient statistical power.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prospective Assessment of the Feasibility of a Trial of Low-Tidal Volume Ventilation for Patients with Acute Respiratory Failure. Lanspa, MJ., Gong, MN., Schoenfeld, DA., et al.[2022]

In a study of 4,694 nonemergent cardiac surgeries, using a bundled lung-protective ventilation strategy significantly reduced the odds of pulmonary complications, with an adjusted odds ratio of 0.56, indicating a strong protective effect.

Among the components of the ventilation strategy, maintaining a modified driving pressure below 16 cm H2O was particularly effective in reducing complications, while lower tidal volumes and positive end-expiratory pressure did not show independent benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative Mechanical Ventilation and Postoperative Pulmonary Complications after Cardiac Surgery. Mathis, MR., Duggal, NM., Likosky, DS., et al.[2020]

In a study of 2,184 ICU patients without acute respiratory distress syndrome, using low tidal volumes (≤ 7 mL/kg) during mechanical ventilation was linked to a lower incidence of pulmonary complications, such as acute respiratory distress syndrome and pneumonia, compared to higher tidal volumes.

Patients who developed pulmonary complications had significantly fewer ICU-free and hospital-free days and higher mortality rates, highlighting the importance of low tidal volume ventilation in improving outcomes for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis. Neto, AS., Simonis, FD., Barbas, CS., et al.[2022]

In a study of 51 mechanically ventilated patients in a cardiac intensive care unit, high tidal volumes (above the median of 9.3 ml/kg) were linked to a significantly increased risk of mortality, with an odds ratio of 9.0, indicating a strong association between high tidal volume and death.

The overall mortality rate in the cohort was 29.4%, suggesting that careful management of tidal volumes is crucial in this patient population to potentially reduce morbidity and mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanical ventilation with high tidal volume and associated mortality in the cardiac intensive care unit. Shorofsky, M., Jayaraman, D., Lellouche, F., et al.[2014]

In a study of 9864 patients undergoing surgery, women were found to receive higher tidal volumes (VT) during ventilation compared to men, with a median VT of 8.6 ml/kg for women versus 7.6 ml/kg for men, indicating a significant difference in ventilation practices based on sex.

Women were twice as likely not to receive low tidal volume ventilation (LTVV) compared to men (68.8% vs. 36.0%), with height and actual body weight accounting for most of this difference, suggesting that these factors should be considered in ventilation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study. Nijbroek, SG., Hol, L., Swart, P., et al.[2023]

In a study of 249 surgical patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS), only 54 (22%) adhered to low tidal volume (LTV) ventilation during surgery, indicating low compliance with this potentially beneficial strategy.

Despite the use of preoperative LTV ventilation being linked to intraoperative adherence, there were no significant differences in respiratory or clinical outcomes, such as oxygenation or hospital length of stay, between patients who received intraoperative LTV and those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraoperative adherence to a low tidal volume ventilation strategy in critically ill patients with preexisting acute lung injury. Chaiwat, O., Vavilala, MS., Philip, S., et al.[2011]

Prophylactic protective ventilation strategies, including low tidal volumes and higher positive end-expiratory pressure (PEEP), can significantly improve respiratory and overall outcomes in patients undergoing cardiac surgery, even if they do not have acute respiratory distress syndrome (ARDS).

Effective implementation of these ventilatory strategies requires a comprehensive approach that starts from the induction of anesthesia and continues throughout the postoperative period, ensuring optimal management of ventilation during and after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perioperative ventilatory strategies in cardiac surgery. Lellouche, F., Delorme, M., Bussières, J., et al.[2023]

References

1. Egypt pubmed.ncbi.nlm.nih.gov

Low Tidal Volume Ventilation in Patients without Acute Respiratory Distress Syndrome: A Paradigm Shift in Mechanical Ventilation. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Prospective Assessment of the Feasibility of a Trial of Low-Tidal Volume Ventilation for Patients with Acute Respiratory Failure. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Intraoperative Mechanical Ventilation and Postoperative Pulmonary Complications after Cardiac Surgery. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Lung-Protective Ventilation With Low Tidal Volumes and the Occurrence of Pulmonary Complications in Patients Without Acute Respiratory Distress Syndrome: A Systematic Review and Individual Patient Data Analysis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Mechanical ventilation with high tidal volume and associated mortality in the cardiac intensive care unit. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Sex difference and intra-operative tidal volume: Insights from the LAS VEGAS study. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Intraoperative adherence to a low tidal volume ventilation strategy in critically ill patients with preexisting acute lung injury. [2011]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Perioperative ventilatory strategies in cardiac surgery. [2023]