Intrathoracic oxygen detects alveolar air leak following video-assisted thoracoscopic lung resection

Ethical statement

This single-centre prospective study was presented in accordance with the STROBE Reporting Checklist and registered in the UMIN Registry (UMIN000016006, 19/12/2014). It was conducted in accordance with principles of the Declaration of Helsinki (revised 2013), and was approved by the Ethics Committee of the Joetsu General Hospital (J-77). All patients provided written informed consent prior to study participation.

Inclusion and exclusion criteria

This study included all patients who underwent elective lung resections at Joetsu General Hospital (Joetsu, Niigata) between November 2013 and May 2015. The exclusion criteria were: local anaesthesia, American Society of Anaesthesiologists Physical Status 4, interstitial pneumonia, thoracotomy, sternotomy, bronchial stump air leak, any thoracic surgery except lung resection, and missing data.

Preoperative tests

All patients underwent chest X-ray, computed tomography, blood tests, urine tests, electrocardiograms, and pulmonary function tests. Cerebral magnetic resonance imaging and positron emission tomography were performed in patients with lung cancer. Patients aged 80 years or more underwent preoperative echocardiography and exercise stress testing.

Anaesthesia

Anaesthesia was managed using a combination of general anaesthesia and thoracic epidural anaesthesia. Following placement of the epidural catheter in the awake patient, general anaesthesia was initiated with a bolus administration of propofol (1.0–2.0 mg/kg) and fentanyl (50–100 µg), followed by a continuous infusion of remifentanil (0.25–0.5 µg/kg/min). After a bolus of rocuronium (0.6–1.0 mg/kg) to achieve muscle relaxation, the airway was secured using a double-lumen endotracheal tube (35–37 Fr. Blue line endobronchial tube for left lung, PORTEX, Smiths Medical, USA) for single-lung ventilation. After positioning the patient laterally, bronchoscopy confirmed the endobronchial tube position: the affected side tube was clamped, and auscultation confirmed the position. Single-lung ventilation was maintained at E_TCO₂ 35–45 mmHg and a maximum airway pressure of 18 cmH₂O using pressure control mode. Positive end-expiratory pressure was not applied. General anaesthesia was maintained with desflurane (Des), remifentanil, and rocuronium. Des was adjusted between 40 and 60 using the bispectral index (BIS Brain Monitoring System, COVIDIEN, USA).

Surgical procedure

Partial lung resection was performed using three-port VATS, with an additional 5-mm port for lobectomy and segmentectomy. The ports utilized an AESCULAP Flexibile trocar (B-Braun, Germany). A thoracoscope with a 30-degree, 5- or 10-mm camera was used. All surgeries were performed by the same surgeon.

Intraoperative air leak test

The W-test and G-test were performed according to the procedure described below (Fig. 1).

1. G-control

For the measurement of intrathoracic gas concentrations, the inhaled gases were fixed (oxygen (O₂) 5 L/min, Des 5.0%, FiO₂ equivalent to 95%) and airway pressure maintained at 15 cmH₂O for at least 5 min before measurement. Thoracoscopic ports were placed, the thoracic cavity was observed, and the affected lung was confirmed to be sufficiently collapsed and unventilated. Intrathoracic gas components were measured before lung parenchyma operation. The sampling tube of the multi-gas channel of the anaesthesia gas monitor (Lifescope, NIHON KOHDEN, Japan) was removed from the anaesthesia machine. An extension tube (50 cm, Suffed, TERUMO, Japan) of a 12 Fr. suction catheter (NIPRO, Japan) and a tracheal suction kit (MD-33050, Sumitomo Bakelite, Japan) for water trapping were connected to the sampling tube. A 12 Fr. suction catheter was inserted into the thoracic cavity from one port, and intrathoracic gases were continuously collected and measured (Fig. 2A). Baseline levels of Des. (%), O₂ (%), and carbon dioxide (CO₂) (mmHg) were recorded 1 min after starting intrathoracic gas sampling (Fig. 2B). During gas collection, the surgeon manually blocked other ports to prevent air inflow into the thoracic cavity.

2. W-test

Warm distilled water (1 L) was administered to the thoracic cavity after specimen removal. After re-inflating the operated lung (peak pressure 15 cmH₂O), the location of any fistula was identified. Bronchial stump air leaks were excluded in this study. Alveolar air leaks were rated as follows: 0, none; 1, mild, characterized by non-coalescent single bubbles; 2, moderate, characterized by intermittent coalescent single bubbles; and 3, severe air leak with coalescent bubbles or multiple air leaks. Rating was based on surgeon-anaesthesiologist agreement. After the W-test, a G-test was performed without fistula repair.

3. G-test

After aspirating distilled water, both lungs were continuously re-pressurized at 15 cmH₂O. Intrathoracic gas concentrations were measured then as in the G-control after 1 min of pressurization. We assumed a G-test positive if their G-test values were higher than the G-control value at least two gases. If the initial G-test was positive but the W-test was negative, only the W-test was repeated for the second test to minimize potential lung damage from further inflation.

Air leak repair

For mild leaks, the fistula was covered with a polyglycolic acid sheet (Neoveil, Gunze, Japan) and fibrin glue⁶. For severe leaks, the fistula was sutured with 4 − 0 Prolene (Ethicon, USA) and covered with a polyglycolic acid sheet and fibrin glue.

Chest tube management

A 20 Fr. chest tube was used with a Thopaz (Medela, Switzerland) and controlled at − 10 cmH₂0. The tube was removed when drainage was < 200 mL/day, and air leak was < 10 mL/min for over 12 h.

Variables and assessments

The primary endpoint was the association between intraoperative alveolar air leakage assessed by the W-test and intrathoracic gas concentrations evaluated by the G-test.

Patient and surgical characteristics, as well as follow-up parameters, were recorded from the preoperative period to 3 months after surgery. This included age, sex, past medical history, smoking history, body mass index, estimated glomerular filtration rate, spirometry-measured respiratory function, diagnosis, diseased side, emphysema, procedure type (partial resection, segmentectomy, lobectomy), intraoperative bleeding, W-test, G-test, operative time, chest tube duration, and complications (including prolonged air leak ≥ 5 days). Complications were defined as any deviation from the expected postoperative course and graded according to the Clavien–Dindo classification¹³. Diagnoses of interstitial lung diseases were confirmed based on a combination of clinical and radiological findings following the 2011 guidelines of the American Thoracic Society¹⁴.

Data management and statistical analysis

This prospective study investigated data collected from the Joetsu General Hospital. Surgical procedures, anaesthesia management, and data measurements were performed by the surgeon and four anaesthesiologists.

The sample size was calculated based on previous studies and our experience with the frequency of prolonged air leak^5,6,15,16. We expected to include 25% of patients with intraoperative alveolar air leaks in this study. Considering a statistical power of 80% and significance level of 5% (one-arm), the sample size was estimated to be 95. Expecting a dropout rate of 20%, we aimed to recruit 114 patients.

Continuous variables are presented as means with interquartile ranges (IQRs) for normally and non-normally distributed data, respectively. Categorical variables are presented as numbers (percentages). Air leaks that occurred after returning to the ward were not included in the analysis. The relationship between the number of bubbles in the W-test and the intrathoracic gas concentration in the G-test was evaluated using the correlation coefficient.

The prognostic value of the intraoperative air leak test was evaluated using its sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy to predict the outcome in the dataset. These analyses were performed based on the results of the first and second W-test and each intrathoracic gas measurement of the G-test. In this analysis, the G-test was considered positive only when all three gas types were elevated. Air leaks were defined as present if the W-test yielded a positive result or if air leaks were observed immediately after wound closure before the patient left the operating room. Air leaks that occurred after the patient returned to the ward were not included from this analysis. Based on these results, we calculated the sensitivity, specificity, PPV, and NPV of each test.

All statistical analyses were performed using JMP version 16.0 (SAS Institute Inc., Cary, NC, USA).

Of 114 patients initially considered, 88 were enrolled due to 26 dropouts (Fig. 3; Table 1). In the G-control, no increases in Des or O₂ were observed. The median CO₂ concentration was 1.0 mmHg [IQR: 1–2 mmHg], which was higher than the atmospheric pressure.

Intrathoracic O₂ as a primary indicator for air leak detection

The W-test was positive in 32 of 88 cases (36.3%), with air bubbles of 1.5 degree [IQR: 1.0–3.0 degree]. Among these 32 patients, the G-test revealed elevated concentrations of all three gases in 31 cases (96.9%). After air leas site repair, all four cases that remained positive on the 2nd W-test again showed elevated levels of all gases in the 2nd G-test. Additionally, two patients with negative 2nd W-test also showed all gases elevated in the 2nd G-test, indicating immediate postoperative air leaks despite the W-test result.

Notably, the single patient with a positive W-test and intermittent, small air bubbles only showed elevated CO₂ (5 mmHg). Aside from this specific patient, all other negative W-test cases exhibited either no elevated gas concentration, elevated CO₂ only, or elevated CO₂ and Des. No isolated Des, O₂, O₂/CO₂, or O₂/Des increases were observed, emphasizing the robust association of intrathoracic O₂ with the presence of air leak (Table 2).

Correlation and test performance

Intrathoracic gas concentrations positively correlated with the degree of air bubbles on the W-test (Des r = 0.84, O₂ r = 0.80, and CO₂ r = 0.77) (Fig. 4).

The total W-test demonstrated a sensitivity of 78.2%, a specificity of 100%, a PPV of 100%, and a NPV of 87.9%. The G-test demonstrated a sensitivity of 97.8%, a specificity of 100%, a PPV of 100%, and a NPV of 98.6% (Table 3).

Prolonged air leak cases

Two patients with air leaks ≥ 5 days required pleurodesis. In one patient (right upper lobectomy, emphysema), the W-test remained positive after initial repair, necessitating a second repair. The other patient (right upper lobectomy and middle lobe partial resection) had a negative initial W-test, but the 2nd W-test was positive due to ≥ 2 elevated gases on the G-test.

This study demonstrated that positive W-tests correlated with higher intrathoracic gas levels (CO₂, O₂, Des) during air leaks. All leaks showed elevation of all three gases in the G-test. Especially, 10 patients with negative W-test but with elevated all gases, all of whom showed air leaks after skin closure. Among the gaseous components, elevated intrathoracic O₂ concentration suggested air leaks. Our findings supported the experience of volatile anaesthetics odor for air leak detection. The G-test may be as effective or superior to the W-test. It would be particularly valuable in cases with W-test limitations (severe emphysema, severe intrathoracic adhesions, or interthoracic communication). In short, rising intrathoracic O₂ would suggest air leaks, even with negative W-test.

The intrathoracic O₂ detection could work even with total intravenous anaesthesia, avoiding volatile anaesthetics. Since propofol widely has individual variations in blood concentration, anaesthetic depth needs to be monitored; however, this is easier to control with Des. Des offers straightforward administration via general anaesthesia machines and does not require an additional machine, so we routinely use Des in our hospital. There are global calls to phase out the use of Des due to its greenhouse effect. Consequently, Des is expected to be discontinued in the future. Moreover, Des detection is not essential for G-test, as O₂ concentrations alone can adequately supplement the results.

Pre-resection intrathoracic gas (G-control) was expected to match atmospheric concentrations, only increasing only during air leaks. However, median intrathoracic CO₂ in the G-control showed 1.0 mmHg, exceeding atmosphere levels (below 0.5 mmHg, undetectable by the gas analyser). Additionally, 43 cases with negative W-test had elevated CO₂, and 2 had elevated CO₂ and Des. This suggested CO₂ diffusion from the pleural tissue into the thoracic cavity. Diffusion capacity of gas through a biological membrane within a unit time is expressed by the equation: Diffusing capacity = (SA x ΔP x Sol)/{h x (MW) ^1/2 }, (SA, surface area of the membrane exposed to gas; ΔP, the partial pressure gradient of the gas between tissue and chest cavity; Sol, the gas’s membrane solubility; h, the membrane thickness; MW, the gas’s molecular weight)¹⁷.

Pleural diffusion is over 10 times less efficient than gas exchange in the alveolar membrane¹⁸. G-control detected intrathoracic CO₂ in most cases. However, Des and O₂ absence in G-control likely related to their differing partial pressure, solubility, and molecular weight compared to CO₂. Assuming similar membrane solubility to water¹⁹, the solubility of each gas in water per unit volume is 0.275 for Des, 0.024 for O₂, and 0.57 for CO₂ at human body temperature^19,20. Therefore, the amount of diffused CO₂ is approximately 20 times and 4 times higher than O₂ and Des.

O₂ detection was also affected by the small difference in partial pressure between tissue oxygen and atmospheric oxygen. Partial pressure of arterial oxygen (PaO₂) is approximately 100–250 mmHg even with fraction of inspiratory oxygen (FiO₂) 1.0, decreasing further during transport to peripheral tissues^21,22,23. Therefore, the partial pressure of O₂ in the peripheral lung tissue is lower than that of PaO₂, with a small difference (approximately 160 mmHg in room air). This could also relate to the fact that the affected lung almost collapses and shunt formation in the G-control group. Because the O₂ display of the gas analyser used in this study is rounded off to the first decimal place, detecting ≥ 22% intrathoracic O₂ via diffusion is theoretically improbable^24,25.

Des diffusion is one-quarter that of CO₂, and Des was undetectable in G-control^19,20. Increased pleural surface area likely could explain the two W-test negative cases with elevated G-test CO2 and Des. This is supported by the elevated CO₂ (median 1.0 mmHg [IQR: 1–2]) in G-control, suggesting a larger inflated lung pleural surface area. Inhaled Des was reported to diffuse through the pleura, peritoneum, and skin over time; therefore, the time effect may also be relevant^26,27.

G-test under 15 cmH₂O pressure effectively correlated air bubbles (W-test) with intrathoracic gas, but the relationship between the degree of pressurization and air leak detection was not examined in this study. While the current G-test cannot pinpoint the leak site, its key role is not missing air leaks^3,28. Addressing intraoperative air leaks significantly impacts postoperative outcomes. This research aimed to overcome the limitations of the W-test using the G-test. While the G-test currently cannot identify the exact fistula, the location can be estimated from the resected stump. Therefore, determining whether to use sealants based on the G-test could avoid unnecessary medical resources. In cases of secondary pneumothorax, not only sealants but intrathoracic pleurodesis may also be a viable option²⁹. Postoperative persistent air leaks are influenced by risk factors such as COPD, upper lobectomy, and male sex; hence, they may still occur despite intraoperative intervention¹.

The W-test classification system is subjective. There is no established method for the quantitative evaluation or a unified classification system for the W-test³⁰, highlighting the significance of our research in providing a quantitatively assessment of air leaks using the G-test. Future intraoperative air leak management (sealants, suturing, observation) may become clearer based on G-test. Additionally, coloured and visible anaesthetic gases may be developed to identify the fistula.

Limitations

This study has several limitations. It was a single-centre study with a limited number of cases and anaesthesia management. However, the reproducibility would be high due to the standardized procedures and evaluations. Pressurization was maintained at 15 cmH₂O, but results might differ with 20 cmH₂O. However, the correlation between air leaks and intrathoracic gas concentrations would be unchangeable. Repeating W-test and G-test could potentially cause secondary lung damage. If the first W-test yielded a negative result and the G-test was positive, a second G-test was not conducted. Additionally, this study’s hypotheses were¹: all gas concentrations increase in positive patients with a positive W-test, and² if gas concentrations increase in patients with a negative W-test, it indicates an overlooked air leak. The methodology was based on these hypotheses.

This study did not fully examine the relationship between the G-test and postoperative prolonged air leak, and included postoperative Thopaz data. Future studies should include detailed postoperative Thopaz data to confirm the correlation with the postoperative course. This study used O₂, CO₂, and Des. Considering the greenhouse effect, reducing Des use is necessary, and our findings suggest that it can be replaced with O₂ alone. Future studies will explore this with intravenous anaesthesia.

The W-test and G-test were performed in the lateral decubitus position. Further studies should investigate different positions as air leaks may stop spontaneously due to positional or ventilation changes. G-test’s higher sensitivity may the possibility of overestimation and unnecessary repair.

Finally, due to some dropouts, the intended sample size was not met. However, since there is no previous research in this area, this study incorporates elements of a pilot study. Therefore, prospective, multicenter clinical trials with larger cohorts would be required in the future.

W-test :

water submersion test

VATS :

video-assisted thoracoscopic surgery

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Authors and Affiliations

1. Division of Anaesthesia, Joetsu General Hospital, Niigata, Japan

   Takehisa Asahi, Kappei Matsumoto & Susumu Kato

2. Division of Thoracic Surgery, Joetsu General Hospital, Niigata, Japan

   Takahiro Homma

3. Division of Thoracic Surgery, Kurobe City Hospital, Toyama, Japan

   Takahiro Homma

4. Department of Thoracic Surgery, St. Marianna University School of Medicine, 2-16-1, Sugao, Kanagawa, Kawasaki, 216-8511, Japan

   Takahiro Homma & Hisashi Saji

Contributions

(I) Conception and design: Takahiro Homma, Takehisa Asahi(II) Administrative support: Takahiro Homma, Takehisa Asahi, Hisashi Saji(III) Provision of study materials or patients: Takahiro Homma, Takehisa Asahi, Kappei Matsumoto, Susumu Kato(IV) Collection and assembly of data: Takahiro Homma, Takehisa Asahi, Kappei Matsumoto, Susumu Kato(V) Data analysis and interpretation: Takahiro Homma, Takehisa Asahi, Hisashi Saji(VI) Manuscript writing: All authors(VII) Final approval of manuscript: All authors.

Corresponding author

Correspondence to Takahiro Homma.

Competing interests

The authors declare no competing interests.

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