Personalized Mechanical Ventilation for Sepsis

Overseen By Marcos F Vidal Melo, MD/PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Columbia University

Disqualifiers: Age < 18, Hemodynamic instability, Hypoxemia, BMI > 40, Pregnancy, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores two methods of using ventilators to assist people with sepsis, a serious infection affecting the body's organs, in breathing better. Researchers aim to determine which method benefits the lungs more by comparing traditional ventilator settings with a personalized approach using PEEP (positive end-expiratory pressure) therapy. Special lung images will illustrate how air moves and spreads in the lungs with each method. Individuals who have been on a ventilator for less than 5 days due to sepsis might be suitable candidates. As an unphased trial, this study provides a unique opportunity to contribute to innovative research that could enhance ventilator care for sepsis patients.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it focuses on patients with sepsis who are on mechanical ventilation, so it's best to discuss your medications with the trial team.

What prior data suggests that these ventilator settings are safe for patients with sepsis?

Research has shown that a personalized approach to setting PEEP (positive end-expiratory pressure) can be safe for patients. One study found that adjusting PEEP to fit individual needs reduced lung issues after surgery. Another study confirmed that this personalized method is safe for patients with ARDS (a type of lung failure) and causes few blood flow problems.

PEEP is a technique used to keep the lungs open and often treats various lung conditions. Studies have shown that customizing PEEP settings can reduce the risk of lung problems after surgery by almost half, suggesting that the treatment is well-tolerated and safe.

In summary, evidence indicates that personalized PEEP can be safely used in patients needing breathing support, such as those with sepsis. This approach seems to lower the risk of complications compared to standard methods. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores a personalized approach to mechanical ventilation for patients with sepsis, specifically through the use of PEEP, or positive end-expiratory pressure. Unlike the standard ARDSNet protocol, which applies a one-size-fits-all low-stretch PEEP, the individualized PEEP strategy tailors the pressure to each patient's unique needs. This personalized method could potentially improve lung function and patient outcomes by optimizing the ventilation process, making it a promising development in the management of sepsis-related respiratory issues.

What evidence suggests that this trial's ventilator settings could be effective for sepsis?

This trial will compare two approaches to mechanical ventilation for sepsis. Participants in Group 1 will receive the standard ARDSNet low-stretch PEEP (positive end-expiratory pressure) protocol, while Group 2 will receive an individualized PEEP strategy. Research has shown that adjusting ventilator settings to each person's needs might improve lung function for those with sepsis requiring ventilation. One study found that this personalized approach increased oxygen levels in the blood, indicating better lung function. It also reduced pressure inside the lungs, potentially preventing further lung damage. Although more research is needed, these findings suggest that customizing ventilator settings for each person could be beneficial. ^{6 7 8 9 10}

Who Is on the Research Team?

Charles W. Emala, MD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for adults with sepsis who've been on a ventilator for less than 5 days due to severe lung issues. They must have a SOFA score >=2, indicating organ dysfunction from infection. Excluded are those under 18, pregnant women, patients exposed to other research radiation recently or with unstable blood pressure/oxygen levels, and anyone with conditions that make CT scans risky.

Inclusion Criteria

I have sepsis with significant organ dysfunction.

I was put on a ventilator no more than 5 days ago.

Exclusion Criteria

I do not have any health conditions that could affect imaging tests.

I have had air leaks in my chest that needed a tube to fix.

You have problems with your heart or breathing that get worse when you have to pause your breathing for 20 seconds. This will be checked by asking you to pause your breathing before moving you.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive mechanical ventilation with either standard ARDSNet low-stretch PEEP or individualized PEEP strategy

Up to 5 days

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• PEEP (positive end-expiratory pressure) - maximum
• PEEP (positive end-expiratory pressure) - standard

Trial Overview The study compares two methods of setting positive end-expiratory pressure (PEEP) on ventilators for sepsis patients: one personalized based on individual breathing needs and another standard approach. It aims to determine which method better supports the lungs using CT scan imaging.

How Is the Trial Designed?

Group I: Group 2: Individualized PEEP (positive end expiratory pressure) Strategy Experimental Treatment 1 Intervention

Participants will receive individualized PEEP (positive end-expiratory pressure).

Group II: Group 1: ARDSNet Active Control 1 Intervention

Participants will receive standard ARDSNet low-stretch PEEP (positive end-expiratory pressure) protocol.

Who Is Running the Clinical Trial?

Columbia University

Lead Sponsor

Trials

1,529

Recruited

2,832,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

In a study using septic male Sprague-Dawley rats, applying positive end-expiratory pressure (PEEP) above the inflection point during mechanical ventilation with low tidal volume significantly reduced lung damage and mortality rates (25% vs. 0%).

Conversely, using high tidal volume with PEEP increased lung damage and mortality (19% vs. 50%), indicating that the effectiveness of PEEP is highly dependent on the tidal volume used during ventilation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positive end-expiratory pressure modulates local and systemic inflammatory responses in a sepsis-induced lung injury model. Herrera, MT., Toledo, C., Valladares, F., et al.[2020]

In a study involving 30 pigs, protective ventilation with lower tidal volume (VT) during surgery was found to significantly reduce TNF-alpha levels in the hepatic vein during endotoxemia, indicating a potential benefit in managing inflammation in the liver.

The study showed that initiating protective ventilation before endotoxemia did not affect organ-specific cytokine levels, suggesting that the timing of protective ventilation may not be critical, but its use during endotoxemia can help lower the overall inflammatory response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis. Sperber, J., Lipcsey, M., Larsson, A., et al.[2018]

Auto-positive end-expiratory pressure (PEEP) is a significant issue in critically ill patients that can lead to serious complications like shock and cardiac arrest.

Effective treatment involves relieving airflow obstruction and adjusting ventilation settings, with sedation and fluid management as important supportive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemodynamic consequences of auto-PEEP. Berlin, D.[2022]

A review of PEEP weaning strategies in ARDS management suggests that a physiologic approach, particularly for patients with elevated BMI, may improve respiratory outcomes compared to standard protocols.

Optimizing PEEP during spontaneous breathing trials could enhance alveolar recruitment, indicating that personalized weaning strategies may be more effective than the current one-size-fits-all model used in many ICUs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal positive-end expiratory pressure weaning in acute respiratory distress syndrome patients. McNamara, L., Baedorf Kassis, E.[2023]

A systematic review of 6 trials involving 2,484 patients suggests that using higher levels of positive end expiratory pressure (PEEP) may lead to a trend towards improved mortality in patients with acute lung injury, with a 4% reduction in absolute risk of death.

There was no significant increase in baro-trauma associated with high PEEP, indicating that the potential benefits of this strategy in reducing mortality outweigh the risks, making it a preferred option for ventilating patients with severe acute respiratory distress syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does a higher positive end expiratory pressure decrease mortality in acute respiratory distress syndrome? A systematic review and meta-analysis. Phoenix, SI., Paravastu, S., Columb, M., et al.[2022]

In a study of 30 patients undergoing thoracic surgery, individualized positive end-expiratory pressure (PEEP) significantly improved oxygenation and lung mechanics during one-lung ventilation compared to a standardized PEEP of 5 cm·H2O.

The study group maintained higher arterial oxygenation levels (306 mm·Hg) and showed significant improvements in static compliance after adjusting PEEP, while the control group experienced decreased oxygenation, highlighting the efficacy of individualized PEEP in enhancing respiratory function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Setting individualized positive end-expiratory pressure level with a positive end-expiratory pressure decrement trial after a recruitment maneuver improves oxygenation and lung mechanics during one-lung ventilation. Ferrando, C., Mugarra, A., Gutierrez, A., et al.[2022]

A new optimal positive end expiratory pressure (PEEP) was defined for treating adult respiratory distress syndrome (ARDS), aiming for a PaO2 of at least 400 mmHg and an intrapulmonary shunt of 15% or less, while maintaining constant cardiac output.

In a study of 14 ARDS cases, applying this optimal PEEP earlier led to more effective treatment outcomes, suggesting timely intervention is crucial for improving patient results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Optimal positive and expiratory pressure in adult respiratory distress syndrome (author's transl)]. Labrousse, J., Tenaillon, A., Coussa, ML., et al.[2020]

In a study involving 15 patients with severe ARDS on extracorporeal membrane oxygenation, the optimal positive end-expiratory pressure (PEEP) varied widely, highlighting the need for personalized ventilation settings.

Electrical impedance tomography (EIT) proved to be a useful noninvasive tool for real-time monitoring of PEEP effects, helping to identify the best compromise PEEP that minimizes lung collapse while avoiding overdistention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bedside Contribution of Electrical Impedance Tomography to Setting Positive End-Expiratory Pressure for Extracorporeal Membrane Oxygenation-treated Patients with Severe Acute Respiratory Distress Syndrome. Franchineau, G., Bréchot, N., Lebreton, G., et al.[2020]

A systematic review of 11 randomized control trials found no significant difference in hospital, 28-day, or ICU mortality rates between patients with acute respiratory distress syndrome (ARDS) treated with higher versus lower levels of positive end-expiratory pressure (PEEP).

The results indicate that using higher PEEP does not lead to better clinical outcomes in ARDS patients, suggesting that both higher and lower PEEP strategies can be considered safe and effective without a clear advantage for one over the other.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential Prognostic Analysis of Higher and Lower PEEP in ARDS Patients: Systematic Review and Meta-Analysis. Liang, M., Chen, X.[2023]

Citations

1. trialsjournal.biomedcentral.com trialsjournal.biomedcentral.com/articles/10.1186/s13063-023-07883-z

Effects of individualized positive end-expiratory pressure on ... It has been demonstrated that individualized positive end-expiratory pressure (iPEEP) can effectively improve intraoperative oxygenation, ...

2. clinicalview.gehealthcare.com clinicalview.gehealthcare.com/article/importance-individualized-perioperative-peep

Importance of individualized perioperative PEEP Importance of individualized perioperative PEEP ; 1. Improve pulmonary function postoperatively · Lower intraoperative driving pressure; Better oxygenation ; 2.

3. nature.com nature.com/articles/s41392-025-02127-9

Advances in acute respiratory distress syndrome CFH could be detected in the plasma of 80% of patients with sepsis, which was associated with mortality in patients with ARDS. This data has ...

4. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/181426

Positive End-Expiratory Pressure Setting in Adults With ... A strategy for setting PEEP aimed at increasing alveolar recruitment while limiting hyperinflation did not significantly reduce mortality.

5. annalsofintensivecare.springeropen.com annalsofintensivecare.springeropen.com/articles/10.1186/s13613-019-0484-0

Positive end-expiratory pressure titration with electrical ... In the present study, EIT-guided PEEP titration was prospectively performed in severe ARDS patients. It significantly improved PaO2/FiO2, APACHE ...

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK441904/

Positive End-Expiratory Pressure - StatPearls - NCBI Bookshelf PEEP is essential in managing acute respiratory distress syndrome, cardiogenic pulmonary edema, and perioperative or postoperative atelectasis.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8284741/

Individualized positive end-expiratory pressure (PEEP) ... The rate of postoperative pulmonary complications was reduced in the individualized PEEP group with a risk ratio of 0.52 (95% CI:0.37–0.73; P = ...

8. jeccm.amegroups.org jeccm.amegroups.org/article/view/9012/html

Evaluating the safety of setting positive end-expiratory ... Our study showed that PEEP guided by transpulmonary end-expiratory pressure is safe for hemodynamic status for ARDS patients and has minimal complications.

9. withpower.com withpower.com/trial/phase-toxemia-4-2023-098a0

Personalized Mechanical Ventilation for Sepsis A systematic review of 11 randomized control trials found no significant difference in hospital, 28-day, or ICU mortality rates between patients with acute ...

10. journals.lww.com journals.lww.com/md-journal/fulltext/2021/07160/individualized_positive_end_expiratory_pressure.42.aspx

Individualized positive end-expiratory pressure (PEEP ... Individualized PEEP setting during one-lung ventilation in patients undergoing thoracic surgery was associated with fewer postoperative pulmonary complications.