Comparison of Two Strategies of One-lung Ventilation in Patients Undergoing Carcinological Lung Resection Surgery.

Lung Diseases Clinical Trial

— I-PEEP-THO  

Official title:

Comparison of Two Strategies of One-lung Ventilation in Patients Undergoing Carcinological Lung Resection Surgery: "Open Lung" Approach With Individualized Level of Positive End-expiratory Pressure Titrated According to the Best Lung Compliance, Versus "Standard" Care: a Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05525312
• Other study ID #: RECHMPL19_0492
• Status: Recruiting
• Phase: N/A
• Start date: March 20, 2024
• Est. completion date: December 20, 2025

Study information

• Verified date: May 2023
• Source: University Hospital, Montpellier
• Contact: Hélène Dr DAVID
• Phone: 06.65.84.95.24
• Email: h-david[@]chu-montpellier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

During thoracic surgery, one-lung ventilation (OLV) is associated with hypoxemia, lung injury, and perioperative respiratory complications. The level of positive-end expiratory pressure (PEEP) to apply during OLV remains controversial. The open-lung approach consists in setting a level of PEEP corresponding to the best lung compliance, using an esophageal catheter to measure the transpulmonary pressure. This approach has been effective in laparoscopic surgeries or acute respiratory distress syndrome, but has never been evaluated in thoracic surgery.

Description:

Pulmonary resection surgery plays a key role in the treatment of localized lung cancer. During thoracic surgery, lung isolation is necessary. One-lung ventilation (OLV) is associated with frequent intraoperative respiratory complications, hypoxemia or lung injury related to mechanical ventilation. Intraoperative events increase the risk of postoperative complications resulting from either hypoxemia (atrial fibrillation, delirium, acute kidney injury) or lung injury (atelectasis, pulmonary edema, pneumonia, acute respiratory distress syndrome (ARDS)).

During OLV, a protective ventilation strategy is now recommended, including a low tidal volume (VT), using the lowest fraction of inspired oxygen (FiO2) due to the toxicity of high-oxygen concentration, and recruitment maneuvers (RM). But there is no consensus on the level of positive end-tidal pressure (PEEP) to apply. A low level of PEEP increases the risk of alveolar collapse, when a too high level leads to alveolar overdistension and increases lung dead space. The PEEP is usually arbitrary fixed to 5 cmH2O for every patient, which does not take into account the individual characteristics of the patient. Recent clinical trials in thoracic surgery showed that titration of PEEP according to the lowest airway driving pressure [end-inspiratory plateau pressure - total end-expiratory pressure], compared to a standard PEEP of 5 cmH2O, increased oxygenation and lung mechanics, and decreased significantly respiratory complications.

The transpulmonary pressure (PTP) is the instantaneous difference between alveolar pressure and pleural pressure. In order to optimize the alveolocapillary gas exchange, the level of PEEP should be titrated until achieving the best lung compliance (CL), defined by the ratio [(tidal volume) / (driving PTP = end-inspiratory PTP - end-expiratory PTP)]. As the tidal volume is set on the ventilator, the level of PEEP corresponding to the best CL is the one associated with the lowest driving PTP. The "open lung" strategy consists in setting the level of PEEP according to the best CL, which is an individualized approach, probably more physiologic than the standard care.

The esophageal pressure (PES) measured by an esophageal catheter is a validated estimation of the pleural pressure. Then, the PTP could be approximated by the difference [airway plateau pressure - PES]. The placement of an esophageal catheter is safe provided that the use respects contraindications (mainly esophageal disease or varices).

In ARDS, the open lung approach using an esophageal catheter was associated with a better clinical outcome than the standard non-individualized protocol. In laparoscopic surgery, the effects of PEEP on the PTP is also well described. In thoracic surgery, to date, monitoring PES and PTP is not part of the usual care. To our knowledge, only one study described the PTP changes during OLV. In this study, the best PEEP during OLV differed from one patient to another, which goes against the "one size fits all" theory. Thus, the PEEP should be titrated and individualized. Nevertheless, the airway driving pressure is only an approximation of the PTP, since it does not take into account the pleural pressure, which is a non-negligible extra-alveolar factor when talking about patients with lung or pleural diseases. Measuring the driving PTP using an esophageal catheter is certainly more accurate.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: December 20, 2025
• Est. primary completion date: September 20, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• To be over 18 years old,

• To be able to attend all scheduled visits and to comply with all trial procedures,

• To be scheduled for a lung cancer resection surgery (performed by either video-assisted thoracoscopy or thoracotomy).

Exclusion Criteria:

• Non-carcinologic indication of lung resection (e.g. Lung volume reduction for bullous emphysema reduction, lung abscess),

• Bilateral pulmonary resection surgery or history of lung resection surgery,

• Lung resection under sternotomy

• Contraindication to esophageal catheter (history of esophageal varices, hepatic cirrhosis child = b, esophageal or gastric surgery, thoracic radiotherapy, latex allergy),

• ASA (American Society of Anesthesiologists) score = 4,

• Chronic obstructive pulmonary disease GOLD III or IV (Forced Expiratory Volume, FEV<50%),

• Uncontrolled asthma (FEV <50%),

• Intracardiac shunt,

• Hemoglobinopathy making the SpO2 values invalid,

• Heart failure NYHA III or IV,

• Documented pulmonary hypertension (Mean Pulmonary Arterial Pressure at rest, mPAP>20 mmHg),

• To be under legal protection,

• Unable to read or write,

• Lack of informed consent, or unable to give consent,

• Refusal to participate in the study,

• Pregnancy in progress or planned during the study period, pregnant or nursing women,

• Not being affiliated to a French social security system or being a beneficiary of such a system.

Related Conditions & MeSH terms

• Lung Diseases

Intervention

Procedure:
• "Open-lung" protective ventilation strategy
In the "open-lung" group, the positive end-tidal pressure (PEEP) is titrated to match the best lung compliance. During a "PEEP decrement trial", PEEP is decreased from 20 cmH2O to 4 cmH2O by steps of 2 cmH2O/minute, and the driving the transpulmonary pressure (PTP) is calculated at each level of PEEP. In the "open-lung" group, the targeted PEEP corresponds to the lowest driving PTP during the "PEEP decrement trial", meaning the best lung compliance. Thereafter, the PEEP is set at this level and maintained until extubation.
• "Standard" protective ventilation strategy
In the "standard" group, the positive end-tidal pressure (PEEP) is arbitrarily set at 5 cmH2O, since this is the currently recommended level of PEEP, commonly used in control groups of previous clinical trials.

Locations

Country	Name	City	State
France	Département d'Anesthésie et Réanimation Cardiothoracique - CHU Arnaud de Villeneuve	Montpellier

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Montpellier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of intraoperative hypoxemia	A SpO2<92% while the FiO2 is progressively decreased to 50% according to a standardized algorithm.	During the Open-Lung Ventilation (OLV) period
Secondary	Hypoxemia events	The number of hypoxemia events, depth, and duration of hypoxemia.	During the OLV period
Secondary	The ventilatory parameters	Plateau pressure (mbar)	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	The ventilatory parameters	Driving PTP (cmH2O)	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	The ventilatory parameters	Airway driving pressure (cmH2O)	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	The ventilatory parameters	Lung compliance (ml/cmH2O)	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	Blood gas analysis	PaO2/FiO2 ratio (mmHg)	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	Blood gas analysis	PaCO2 (mmHg)	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	Blood gas analysis	pH	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	Blood gas analysis	HCO3- (mmol/L)	T1: baseline, two-lung ventilation, before OLV ; T2: 45 minutes after OLV ; T3: at the end of OLV, before re-expansion and ventilation of the operated lung ; T4: at the end of surgery, before extubation
Secondary	Intraoperative events related to hypoxemia	Additional recruitment maneuvers (cmH2O)	During the OLV period
Secondary	Intraoperative events related to hypoxemia	Additional bronchoscopy	During the OLV period
Secondary	Intraoperative events related to hypoxemia	Application of a selective PEEP to the operated lung using an auxiliary valve	During the OLV period
Secondary	Intraoperative events related to hypoxemia	Re-expansion and ventilation of the operated lung performed for hypoxemia	During the OLV period
Secondary	Intraoperative events not only due to hypoxemia	Atrial fibrillation (bpm), hypotension defined by systolic arterial pressure < 90 mmHg, needs for vasopressor,	During the OLV period
Secondary	Postoperative respiratory complications until postoperative day 28	Acute respiratory distress syndrome (ARDS) (diagnosed according to the Berlin definition), atelectasis or pleural effusion (documented on a postoperative chest radiograph), pneumonia (postoperative fever combined with an evocating chest radiograph, requiring antibiotics, with or without microbiologic confirmation), need for prolonged oxygen therapy (> 48 hours), need for high-flow nasal oxygen therapy, needs for postoperative invasive or noninvasive mechanical ventilation	Day 28
Secondary	Non-respiratory postoperative complications until postoperative day-28 (POD28)	Cardiovascular events such as myocardial infarction (troponin > threshold, combined with EKG modification or chest pain) or new-onset of atrial fibrillation (if the cardiac rhythm was sinus before surgery), acute kidney injury (defined by an AKIN stage = 1), stroke (with CT scan or MRI confirmation) or transient ischemic attack, delirium (acutely disturbed state of mind)	Day 28
Secondary	The hospital stay	The in-hospital length of stay and hospital free-days at POD28, the hospital re-admission, ICU admission, and mortality at POD28 and POD90.	Day 28 and Day 90