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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different methods of assisting breathing during heart surgery to determine which is safer and reduces lung problems post-operation. It compares three methods: continuous low tidal volume ventilation with normal oxygen levels (FiO2 of 0.21), continuous low tidal volume ventilation with high oxygen levels (FiO2 of 1.0), and apnea during cardiopulmonary bypass without extra oxygen. Patients undergoing planned heart surgeries that require a heart-lung machine may be suitable candidates. The trial aims to improve post-surgery recovery by identifying the optimal breathing method. As an unphased trial, it allows patients to contribute to significant research that could enhance surgical recovery for future patients.

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 prior data suggests that these ventilation strategies are safe for cardiac surgery patients?

Research shows that low tidal volume ventilation is generally safe for patients. This method is already a standard treatment for people with acute respiratory distress syndrome (ARDS). Studies have found that using low tidal volume during surgeries can protect the lungs and may lower the risk of lung problems afterward.

This trial examines two versions of low tidal volume ventilation: one with normal oxygen levels (FiO2 0.21) and one with pure oxygen (FiO2 1.0). FiO2 refers to the amount of oxygen in the air given to patients. Previous studies support the safety of using low tidal volume with either oxygen level, suggesting it does not increase the risk of complications. In fact, it might help keep the lungs healthier during surgery. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores unique ventilation approaches during cardiac surgery that could significantly impact patient outcomes. Unlike standard practices that often use higher tidal volumes or fixed oxygen levels, this trial examines continuous low tidal volume ventilation with varying oxygen concentrations (FiO2 of 0.21 and 1.0). The goal is to understand how these methods affect postoperative pulmonary complications (PPCs) and mortality rates. By investigating the effects of hyperoxia avoidance and apnea, the trial aims to refine ventilation strategies, potentially leading to safer procedures and better recovery for patients undergoing cardiac surgery.

What evidence suggests that this trial's ventilation strategies could be effective for reducing mortality and postoperative pulmonary complications?

This trial will compare different ventilation strategies during cardiac surgery. Research has shown that low tidal volume ventilation can reduce complications and improve outcomes for heart surgery patients. This method uses smaller breaths to protect the lungs, lowering the risk of lung injuries. In this trial, one arm will use continuous low tidal volume ventilation with an oxygen level (FiO2) of 0.21. Studies have found this reduces lung damage and improves survival rates. Another arm will use low tidal volume ventilation with an oxygen level (FiO2) of 1.0, which has effectively reduced complications after surgery, especially for those with existing lung issues. Both approaches aim to protect the lungs during surgery, leading to better recovery and fewer problems afterward. ^{3 6 7 8 9}

Who Is on the Research Team?

Marta Kelava, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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 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]

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]

Citations

1. withpower.com withpower.com/trial/phase-hyperoxia-6-2021-59ef7

Low Tidal Volume Ventilation for Cardiac Surgery It has been shown to reduce complications and improve outcomes in patients without lung injury, although it may present some clinical challenges. Show more.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4381817/

Lung protective ventilation in Cardiac Surgery - PMC Multicenter, randomized, controlled trials and meta-analyses have demonstrated that, during abdominal surgery, protective ventilation, based on low tidal ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10068651/

Perioperative ventilatory strategies in cardiac surgery - PMC The major components of ventilatory management include assist-controlled mechanical ventilation with low tidal volumes (6–8 mL kg −1 of predicted body weight)

4. researchgate.net researchgate.net/publication/232648380_Association_Between_Use_of_Lung-Protective_Ventilation_With_Lower_Tidal_Volumes_and_Clinical_Outcomes_Among_Patients_Without_Acute_Respiratory_Distress_Syndrome_A_Meta-analysis

Association Between Use of Lung-Protective Ventilation ... We evaluated the impact of tidal volumes on cardiac surgery outcomes. We examined prospectively recorded data from 3,434 consecutive adult ...

5. ahrq.gov ahrq.gov/hai/tools/mvp/modules/technical/ltvv-lit-review.html

Low Tidal Volume (Lung Protective) Ventilation Literature ... Evaluated the impact of low, traditional, and high tidal volumes on cardiac surgery outcomes. They enrolled 3,434 consecutive adult patients. Three groups ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04978636

Low Tidal Volume Ventilation With Hyperoxia Avoidance ... The investigators will evaluate the effect of low tidal volume with varying FiO2 fractions during cardiopulmonary bypass on postoperative mortality and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12130150/

Maintaining ventilation with very low tidal volume and ... Maintaining ventilation with very low tidal volume and positive-end expiratory pressure versus no ventilation during cardiopulmonary bypass for cardiac surgery ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02090205

Mechanical Ventilation During Cardiac Surgery | ... Small randomized clinical and animals trials suggest that ventilation during cardio-pulmonary bypass (CPB) could be protective on the lungs. This evidence is ...

9. ahajournals.org ahajournals.org/doi/pdf/10.1161/JAHA.124.035011

Low Frequency Ventilation During Cardiopulmonary ... In this trial we assessed the feasibility, safety, and efficacy of low frequency ventilation (LFV) during CPB in patients undergoing valvular surgery. METHODS ...