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

12 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to compare two different ways of helping patients with a condition called sepsis who need help breathing using a machine called a ventilator. The investigators want to study which way of setting the ventilator is better for the lungs. Here are the main questions the investigators want to answer: 1. How does the amount of air in the lungs and the way it moves differ between the two ways? 2. How does the way air spreads out in different parts of the lungs differ between the two ways? In this study, the investigators will take special pictures of the lungs using a machine called a CT scan. The pictures will show us how much the lungs stretch and how much air is in different parts of the lungs. The investigators will compare two different ways of using the ventilator: one personalized for each patient based on their breathing, and another way that is commonly used. By comparing these two ways, the investigators hope to learn which one is better for helping patients with sepsis who need the ventilator. This information can help doctors make better decisions about how to care for these patients and improve their breathing.

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 data supports the idea that Personalized Mechanical Ventilation for Sepsis is an effective treatment?

The available research shows that using Personalized Mechanical Ventilation, specifically with positive end-expiratory pressure (PEEP), can be effective in treating conditions like acute respiratory distress syndrome (ARDS). One study found that applying the optimal PEEP early led to better results in patients with ARDS. Although the research doesn't directly address sepsis, these findings suggest that PEEP can help improve breathing and oxygen levels in similar conditions, which might indicate its potential effectiveness for sepsis as well. ^{1 2 3 4 5}

What safety data exists for personalized mechanical ventilation using PEEP in sepsis treatment?

The safety data for PEEP in mechanical ventilation primarily comes from studies on acute respiratory distress syndrome (ARDS) and acute lung injury. Research indicates that PEEP is a critical component in managing these conditions, but its independent effect on mortality is not fully understood. Higher PEEP levels have been analyzed for their prognostic impact, and auto-PEEP has been identified as a potential risk factor for hemodynamic issues like shock and cardiac arrest. Weaning strategies and optimal PEEP settings are still under investigation, especially in severe cases requiring extracorporeal membrane oxygenation. ^{1 3 4 5 6}

Is PEEP a promising treatment for sepsis?

Yes, PEEP is a promising treatment for sepsis. It helps improve breathing by keeping the lungs open, which can enhance oxygen levels and lung function. Studies suggest that using PEEP in a personalized way can be beneficial for patients with sepsis-related lung issues. ^{1 5 7 8 9}

Research Team

Marcos F VIdal Melo, MD/PhD

Principal Investigator

Columbia University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. United States 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. [2022]

2. France pubmed.ncbi.nlm.nih.gov

[Optimal positive and expiratory pressure in adult respiratory distress syndrome (author's transl)]. [2020]

3. England pubmed.ncbi.nlm.nih.gov

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

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

Optimal positive-end expiratory pressure weaning in acute respiratory distress syndrome patients. [2023]

5. United States 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. [2020]

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

Hemodynamic consequences of auto-PEEP. [2022]

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

Positive end-expiratory pressure modulates local and systemic inflammatory responses in a sepsis-induced lung injury model. [2020]

8. United States 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. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Evaluating the effects of protective ventilation on organ-specific cytokine production in porcine experimental postoperative sepsis. [2018]