NODRAIN study protocol: a non-interventional, prospective study for evaluating the effectiveness of intraoperative ventilation for the prediction of postoperative air leak in major pulmonary resections by conventional or robotic thoracoscopy

Introduction

Background

Prolonged air leakage (PAL), defined as an air leak persisting for ≥5 days postoperatively, is the most common complication after thoracic surgery, followed by pneumonia, respiratory failure, and bleeding (1,2). PAL is the main reason for longer hospital stays after lung surgery, and it is independently associated with an 18% to 27% increase in hospitalization costs (3-5), as well as higher post-discharge expenses up to 90 days after surgery (6). Previous literature by Muriana et al. (7) reports PAL (>5 days) rates of 7.4–10.8% after open surgery, 7.4–23.7% after conventional thoracoscopy, and 5.2–25.4% after robotic-assisted thoracoscopy. Postoperative air leaks of shorter duration (<5 days) also occur and represent an additional proportion of patients.

The high frequency of postoperative air leaks and their associated morbidity necessitate the placement of chest drains, devices that are painful for patients and source of postoperative complications (8).

In contrast, the rate of patients without postoperative air leaks, or with minimal air leaks resolving within the first postoperative hours, is not reported in the literature and remains unknown.

Although they are in the minority, these patients could safely avoid drainage during surgery, provided that they can be identified before drain placement and thoracic closure.

Rationale and knowledge gap

Traditionally, intraoperative detection of air leaks is performed by submerging the lung in saline and observing bubbles (9). However, with the advent of minimally invasive approaches for major lung resections, this technique has become impractical. In a closed chest setting, re-ventilating the lung may reduce camera visibility, making the method less effective.

Therefore, there is a need for a reliable method to detect and quantify air leaks intraoperatively after lung resections through a classic or robotic video-thoracoscopic approach. Such a method could eventually permit avoiding the use of drains for patients without air leaks and accelerate their postoperative recovery by reducing associated pain, while maintaining effective complication control.

A recent study demonstrated that the risk of postoperative PAL can be assessed exclusively through intraoperative ventilator measurements (10). In this study, Brunelli and colleagues found that an intraoperative air leak greater than 500 mL/min, measured directly from the ventilator, was significantly associated with prolonged postoperative air leak duration. Specifically, patients with >500 mL/min leakage had a mean postoperative duration of 10.1 days, compared with 1.5 days for those with <500 mL/min (P<0.001). While promising, these findings remain insufficient for broad clinical application, underscoring the need for larger, multicenter studies to confirm their validity and generalizability.

Objective

In this NODRAIN study, we aim to evaluate the effectiveness of intraoperative ventilation, commonly used in practice, for the prediction of postoperative air leakage during major lung resections by conventional or robotic thoracoscopy. We present this article in accordance with the SPIRIT reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2424/rc).

Methods

This study is registered at ClinicalTrials.gov (NCT07350265) on 20 January 2026. It is planned to last approximately 2 years, with 12 months allocated for patient enrollment. Each participant will be followed for up to 1 month (±4 days) after surgery.

Study design

It is a non-interventional, prospective, single-center, and single-cohort study.

At the end of the surgical procedure for lobectomy or segmentectomy resection, the air leaks recorded by the ventilator will be noted, first during one-lung ventilation on the non-operated lung, and then during two-lung ventilation. All patients will be drained with a single 24-French chest tube, connected to a digitalized autonomic drainage system (Thopaz system, Medela, Baar, Switzerland), under continuous suction, with a suction pressure set at −20 cmH₂O. Table 1 lists all data to be collected from the preoperative period through the 1-month follow-up.

The study will be conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study has been approved by the Institutional Review Board of the Scientific Committee of Ramsay Santé (IRB approval No. IRB00010835), and written informed consent will be obtained from all individual participants prior to inclusion in the study.

Setting and study population

This study will be set up in a center in France (Antony Private Hospital – Ramsay Santé). Patients for whom surgery is indicated will be recruited by the investigating physician after consultation with a thoracic surgeon.

During the preoperative consultation with the surgeon, in addition to verbal explanations, patients will receive written information outlining the objectives of the protocol. Patients will have a period of 30 days to oppose the collection of their personal data for the purposes of this research.

Eligible participants will include all adults aged 18 years or older undergoing pulmonary lobectomy or anatomical segmentectomy (via conventional or robotic thoracoscopy). Exclusion criteria will include thoracotomy, atypical resection, bi-lobectomy, or pneumonectomy; drainage with two chest tubes; absence of an autonomous drainage system; absence of extubation at the end of surgery; and early surgical revision for complications before drain removal.

Procedure

The lobectomies or anatomical segmentectomies will be performed by two senior thoracic surgeons using a thoracoscopic approach (conventional or robotic) with CO₂ insufflation (closed chest). All thoracic procedures will be conducted under general anesthesia, with the use of single-lung ventilation through a double-lumen endotracheal tube. Ventilation will be performed using the Datex-Ohmeda Aisys™ CS2 anesthesia machine (GE Healthcare, Chicago, IL, USA). The patients will be placed in a classical posterolateral decubitus position. For the robotic approach, we will use a da Vinci Xi surgical system (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Depending on the surgeon and type of intervention, three or four robotic ports will be used and an accessory 12 mm port for the assistant, placed anteriorly at the 6^th or 7^th intercostal space. Robotic ports will be placed at 2–3 cm below the tip of the scapula for the camera port, one anterior port at the 4^th or 7^th intercostal space, and one or two posterior ports, in the 4^th and 7^th intercostal, respectively (Figure 1A,1B) (11). For the conventional thoracoscopic approach, only four video access ports will be necessary: a 12 mm camera port at 2–3 cm below the tip of the scapula, one anterior 12 mm port at the 6^th or 7^th intercostal space, and two 5 mm ports in the 5^th and 7^th intercostal respectively. The 5 mm ports will be placed posteriorly, in the interscapulo-vertebral space for the right approach and anterior, along the anterior axillary line for the left approach (Figure 2A-2C). Only airtight trocars will be used. The surgeon is positioned behind the patient for the right lung resections and in front of the patient for the left lung resections.

Figure 1 Patient positioning and trocar placement for right- and left-side classical thoracoscopic approaches (11). Patients are placed in the classical posterolateral decubitus position. The yellow stars indicate the patient’s back. (A) Right-side approach: the surgeon stands behind the patient. The scapula is outlined in black. (B) Left-side approach: the surgeon stands in front of the patient. For female patients, the breast contour is drawn to avoid trocar placement within the breast. The scapula is outlined in black.

Figure 2 Trocar placement for a three-arm robotic approach. (A) Example of a patient positioned in the classical right posterolateral decubitus position. (B) Trocar placement for either the right or left approach. (C) Final setup after docking of the robotic arms.

In both types of approach, robotic or conventional thoracoscopy, after entry in the pleural space, a medium flow CO₂ insufflation will be started, with a gas pressure set at 8 mmHg, and the lung resection procedure will be conducted similarly. Standard lobectomies will be performed using a fissure-based approach. For the anatomical segmentectomies, a preoperative surgical three-dimensional (3D) reconstruction of the patient’s lung anatomy will be done using the Fuji Synapse platform (3D-CT SYNAPSE VINCENT, Fuji Film, Tokyo, Japan). The extend of the resection will be then planned. Intraoperatively, the inter-segmentary plan will be determined using an intravenous administration of 25 mL of indocyanine and cut with Endo-GIA™ staplers (Medtronic, Minneapolis, MN, USA) in both types of approaches, robotic or conventional thoracoscopy.

At the end of the intervention, the specimen will be placed in an Endobag (Endo Catch™ Gold, Covidien, Dublin, Ireland) and extracted through the 12 mm assistant trocar, which will be slightly enlarged. The CO₂ insulation is stopped. A 24 French chest tube will be inserted through one port. The trocar orifices and the chest drain are left open during the ventilator-based air leak measurement protocol.

Quantification of air leaks on the ventilation device

Set the ventilator to volume-controlled mode:

• Airway pressure range: 5 to 20 cmH₂O;
• Respiratory rate: 10–16 breaths/min;
• Tidal volume: 6 mL/kg;
• Positive end-expiratory pressure (PEEP): 5 cmH₂O.

The procedure for quantifying air leaks during one-lung ventilation of the non-operated lung is carried out as follows:

• One-lung ventilation of the non-operated lung;
• Note the exhaled volume (i.e., the recovered volume) for each respiratory cycle over 12 consecutive cycles (approximately 1 minute).

This step allows identification of any minor leaks around the double-lumen or bronchial tube cuff. If leaks are detected, the bronchial and/or tracheal cuff(s) are reinflated to restore a proper seal.

The procedure for quantifying air leaks during two-lung ventilation is carried out as follows:

• Perform bronchial suctioning.
• Two-lung ventilation with standardized recruitment maneuver performed by the ventilator. This automatic maneuver consists of stepwise continuous inspiratory pressures of 15, 20, and 25 cmH₂O, with PEEP levels of 5, 8, and 10 cmH₂O over a total duration of 120 seconds. The maneuver may be repeated, if necessary, based on the surgeon’s visual assessment of lung expansion.
• Note the exhaled volume (i.e., the recovered volume) for each respiratory cycle over 12 consecutive cycles (approximately 1 minute); these measurements are then used to calculate the mean air leak volume (mL/min) on the operated lung.

Finally, remaining wounds will be closed in the standard techniques, and the chest tube will be connected to a digitalized autonomic drainage system (Thopaz system, Medela). The suction pressure will be set at −20 cmH₂O with continuous suction. A confirmed postoperative air leak is defined as an air leak ≥10 mL/min measured by the Thopaz device. The system allows quantitative measurement of air leaks: 0–1,000 mL/min displayed in 10 mL increments, >1,000 mL/min in 100 mL increments, with a measurement tolerance of ±20%. The display rounds values <5 to 0 mL/min and values between 5 and 15 to 10 mL/min.

All devices used for measuring air leaks (both the anesthesia ventilator and the digital drainage system) are standard clinical equipment, maintained and calibrated by the hospital’s biomedical engineering team according to routine protocols and the manufacturers’ recommendations. Leak-check procedures of the digital drainage device are performed before each use, as per the manufacturer’s instructions.

Outcomes measures

The primary outcome will be the correlation between intraoperative air leak volume, measured by the ventilator (mL/min), and postoperative air leak volume measured by the digitalized autonomic drainage system on the patient’s postoperative drain, after extubation [reported as daily mean flow (mL/min)], throughout the whole hospital stay.

The secondary outcomes will be: (I) the air leak flow evolution during time; (II) duration of postoperative air leak and drainage; (III) duration of post-operative hospitalization; (IV) post-operative complications related to air leak will be documented during the whole hospital stay; and (V) postoperative incidence of re-drainage.

Data quality assurance

Before trial initiation, research staff will receive training in study objectives and processes, data collection, entry, and outcome assessment. Clinical data will be entered into a secure, web-based ENNOV Clinical electronic case report form (eCRF) (hosted by Euraxi Pharma), with each user assigned a unique login and password, and each patient a unique identification number to ensure confidentiality. Periodic monitoring visits will verify protocol compliance and validate data against source documents. Site investigators will report safety outcomes in accordance with national regulations.

Statistical methods

Sample size

As no prior data are available for this new study, the sample size calculation follows the recommendations of Ludbrook [2010] and Bablok and Passing [1985] (12,13) in their assumptions regarding slope, coefficient of variation, and range ratio of the parameter studied. Considering a primary risk of 5% and a uniform distribution of results, at least 50 subjects are needed to obtain reliable confidence intervals and ensure statistical robustness. Considering the center’s recruitment capacity, 100 patients will be enrolled, which will also help to ensure the inter-individual variability of observations to be integrated in the results.

No pre-adjustment for individual airway pressures will be applied. The ventilator will be set in a volume-control mode, and measurements over multiple respiratory cycles, together with inclusion of a representative patient population, will allow inter-patient variability in lung mechanics to be naturally incorporated into the analysis.

Statistical analysis

Main analysis

Correlation between intraoperative ventilation and postoperative drainage device leakage measurements will be assessed using Passing-Bablok regression, with slope (B) and intercept (A) reported alongside their 95% confidence intervals. To complement this analysis, a Bland-Altman plot will illustrate agreement between methods, and the Pearson correlation coefficient will quantify the linear relationship between intraoperative and postoperative measurements.

Secondary analyses

Cohen’s kappa coefficient will be calculated to assess agreement between the two air leak detection techniques. Diagnostic performance will be evaluated using a confusion matrix, with calculation of sensitivity, specificity, positive predictive value, and negative predictive value, each reported with 95% confidence intervals. Postoperative drainage measurements will serve as the reference standard for comparison with intraoperative ventilation data. Duration of air leak and drainage, length of hospitalization, incidence of postoperative complications, and incidence of re-drainage will be summarized as mean ± standard deviation, median with quartiles, and frequency with percentage. Means and proportions for all secondary endpoints will be presented with their 95% confidence intervals, and graphical representations of data collected at each follow-up visit will also be provided.

Exploratory analysis

A receiver operating characteristic (ROC) curve will be generated from intraoperative ventilation measurements to identify the threshold air leakage rate, recorded by the ventilator, below which no air leak (defined as an absolute air flow of 0 mL/min sustained for at least 12 hours as indicated by the Thopaz device) will occur during spontaneous breathing after patient extubation.

Discussion

Despite continuous advancements in minimally invasive surgical techniques and the overall improvement in surgical expertise, air leaks remain a significant postoperative morbidity. With the growing proficiency and confidence in video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopy, surgeons are increasingly extended indications, a factor that may contribute to air leak incidence. Traditionally, patients with a predicted postoperative forced expiratory volume in 1 second (FEV₁)% or diffusion capacity of the lungs for carbon monoxide (DLCO)% below 40% were considered high risk for lobectomy; however, with minimally invasive approaches, these patients are now more often accepted for surgery, with complication rates reported at <12.8% for VATS compared with 21.9% for open thoracotomy (14). In addition, complex cases such as centrally located large lesions, N2-positive lymph nodes, and recurrent pulmonary metastasectomy are increasingly managed via a thoracoscopic approach (conventional or robotic) (15). These higher-risk scenarios inherently increase the likelihood of postoperative complications, including PAL, and highlight the need for predictive strategies that can be applied intraoperatively.

The NODRAIN study is designed to assess the correlation between intraoperative air leak, measured using ventilator data, and postoperative air leak, quantified via chest drainage, in patients undergoing either conventional or robotic-assisted thoracoscopy. Known risk factors for air leaks include male sex, reduced lung function, low body mass index, high American Society of Anesthesiologists (ASA) score, pulmonary comorbidities, upper lobe resection, bi-lobectomy, right-sided tumor, and use of robotic surgery (16). The NODRAIN study excludes bi-lobectomy cases, and multivariate statistical analysis will be used to adjust for potential confounders such as comorbidities and baseline lung function. The presence of pleural adhesions and the intraoperative use of surgical sealants or stapler reinforcements are not exclusion criteria and will not be recorded, since they do not affect the objective of the study, which is to assess the correlation between intraoperative air leaks measured by the ventilator and postoperative air leaks measured by the digital drainage device, regardless of their magnitude.

A multicenter analysis of 12,382 patients (17) reported PAL rates of 9%, with significant inter-hospital variation (2.6% to 19.3%), illustrating the influence of institutional factors and perioperative practices. The single-center design of the NODRAIN study offers the advantage of standardized surgical workflows and measurement protocols, potentially reducing variability and improving the precision of the correlation assessment.

Many studies have attempted to evaluate the feasibility of a non-drainage strategy after major lung resections (18,19). These studies typically involve placing a drain at the end of the surgical procedure and connecting it to a drainage system for monitoring air leaks. The drain is then removed either on the operating table or immediately in the recovery room, provided no air leak is observed. However, we have not found any protocol that aims to identify patients who do not require a drain without initially placing one and using a suction device, which is then discarded if no air leaks are detected. Moreover, we believe that the assessment of air leaks in an intubated patient may be biased by the positive pressures of mechanical ventilation, which may result in retaining drains in patients who ultimately would not have air leaks once transitioned to spontaneous breathing. Furthermore, the assessment of air leaks in the recovery room may be skewed by hypoventilation, which is often present in the immediate postoperative period. Consequently, this could lead to the removal of a drain in a patient who ultimately required one.

If our study confirms a strong relationship between intraoperative and postoperative air leak, it may be possible to establish a threshold value below which chest drainage could be avoided, thereby reducing postoperative pain, shortening hospital stay, and lowering costs, while maintaining patient safety. Such a finding would provide a practical, intraoperative decision-making tool to guide postoperative drain management.

In summary, the NODRAIN protocol proposes a structured approach in order to determine which patients should not be drained at the end of a major lung resection (lobectomy or anatomical segmentectomy).

The results of our study will serve as preliminary evidence to support risk stratification strategies and inform the design of future multicenter validation studies.

Acknowledgments

The authors wish to thank to Ms. Seyedeh Tayebeh Naseri, PhD and Mr. Nicolas Bonneville from Euraxi Pharma for medical writing support, and Ms. Delphine Etienne (Euraxi Pharma) for her help on study methodology design.

Footnote

Reporting Checklist: The authors have completed the SPIRIT reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2424/rc

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2424/prf

Funding: This work is supported by Le GCS pour l’Enseignement et la Recherche Ramsay Santé, which provides research assistance to the institution involved in this trial (No. COS-RGDS-2024-06-015-P-GRIGOROIU-M).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2424/coif). All authors report that this study has received funding from GCS Ramsay Santé and medical writing and study methodology design help from Euraxi Pharma. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study will be conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study has been approved by the Institutional Review Board of the Scientific Committee of Ramsay Santé (IRB approval No. IRB00010835), and written informed consent will be obtained from all individual participants prior to inclusion in the study.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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