Introduction
Alveolar air leak is one of the most common complications after pulmonary resection and accounts for approximately 20–30% of all postoperative morbidity [1–3]. It not only increases length of hospital stay but is also associated with pain, risk of postoperative empyema thoracis, and associated complications [4]. Standard protocols for intraoperatively controlling air leaks include meticulous dissection of the structures along the anatomical plane between the lobe and the segment, suture techniques, and stapling. Currently, many products such as fibrin glue and synthetic and polymeric sealant are available and have been reported to reduce parenchymal air leak after pulmonary resection [5, 6]. However, these sealants are expensive, especially in developing countries.
Aim
Therefore, this study analyzed whether fibrin sealant use can improve postoperative outcomes, including reducing length of hospital stay, after pulmonary resection.
Material and methods
This retrospective study was approved by a local ethical committee (242/64E) and included patients who underwent pulmonary resection in the cardiothoracic surgery unit between January 1, 2016, and July 30, 2021. During this period, 375 patients underwent elective pulmonary resection, and all data were extracted from institutional medical records. Patients requiring emergency surgery and those younger than 18 years old were excluded from this study. All eligible patients were categorized into one of two groups, viz., the fibrin sealant group (n = 107) or control group (n = 268).
Both intraoperative parameters and postoperative outcomes, including cost of hospital stay, were compared between the two groups. Demographic and surgical variables such as age, gender, smoking history, underlying disease, chronic obstructive pulmonary disease (COPD), approach type (open thoracotomy (OT) vs. video-assisted thoracic surgery (VATS)), operation types (wedge, segmentectomy, or lobectomy), laterality (right or left), and redo surgery, were evaluated. Primary outcomes were duration of chest tube, length of hospital stay, and cost of hospital stay.
Surgical protocol
All procedures were performed under general anesthesia by board-certified cardiovascular thoracic surgeons using the lung isolation technique. Sealant application and the use of either VATS or OT depended on surgeon preference.
A fibrin sealant called Tisseel (Baxter Healthcare, Immuno Co, Vienna, Austria), composed of human-derived fibrinogen and thrombin, was used throughout and was applied either on the raw surface of lung parenchyma or on the staple line at the resection site to prevent alveolar air leak. Patients in whom the fibrin sealant was used were included in the fibrin sealant group, whereas the others were included in the control group.
After surgery, a small chest tube (24-French or 28-French) was inserted to drain air and fluid, and it was routinely connected to a thoracic suction device that was set to a pressure of −10 mm Hg. The intercostal chest drain was removed when there was no air leakage and drainage was < 300 ml of pleural fluid per day.
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 was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Institutional Review Board of Vajira Hospital, Navamindradhiraj University, Bangkok, Thailand (COA number: 242/64E), and individual consent for this retrospective analysis was waived.
Statistical analysis
Categorical variables are presented as frequencies and percentages, and continuous variables are presented as median and interquartile range (Q1–Q3). Propensity score matching (1 : 1) was performed to minimize selection bias in both groups, and the variables included for propensity score matching were age, gender, diagnosis laterality, and operation type. Standardized mean difference between the groups was determined for all covariates.
The χ2 test was used to compare categorical variables and differences between the two groups for dichotomous data. Skewed data were analyzed using the Mann-Whitney U test. Multivariable regression analysis was performed to assess the association between the two groups and primary outcomes. A p-value of < 0.05 was considered statistically significant. All statistical analyses were performed using STATA v. 16.0 software (StataCorp, College Stata, TX, USA).
Results
Records showed that 375 patients underwent pulmonary resection between 2016 and 2021; of these, sealant was used in 107 patients (fibrin sealant group), whereas it was not used in the remaining 268 patients (control group). Before propensity matching, patients in the fibrin sealant group were older (64 vs. 59 years, p < 0.001) and underwent lobectomy (43.9% vs. 34.7%; p < 0.001), segmentectomy (12.2% vs. 3.4%; p < 0.001), and VATS (94.4% vs. 82.5%; p = 0.003). There were no differences in sex, smoking status, laterality, or diagnosis (Table I).
Table I
Patients’ demographic data between control group and fibrin sealant group before and after propensity score matching analysis
After surgery, duration of chest tube (3 vs. 4 days, p = 0.068) and hospital stay (3 vs. 4 days; p = 0.463) were shorter in the sealant group; however, the differences were not statistically significant. There was no difference in operative time, blood transfusion requirement, blood loss, or postoperative complications. Cost of hospitalization was significantly higher in the fibrin sealant group than in the control group (USD 3,010 vs. 4,391; p < 0.001). Peri- and post-operative outcomes compared between the control group and fibrin sealant group before and after propensity score matching analysis are shown in Table II.
Table II
Peri- and post-operative outcomes compares between control group and fibrin sealant group before and after propensity score matching analysis
After propensity score matching (Table II), length of hospital stay was shorter in the fibrin sealant group than in the control group; however, the difference was not statistically significant (4 vs. 5 days; p = 0.499). Further, there were no differences in duration of chest drain or postoperative outcomes, including persistent air leak (PAL), pneumonia, or re-operation. However, hospitalization costs in the fibrin sealant group were significantly higher (USD 4,360 vs. 3,614; p < 0.001)
Multivariate linear regression analysis (Table III) showed that male sex (95% CI: 1.979 (0.43–3.53); p = 0.013), history of COPD (95% CI: 4.176 (1.38–6.97); p = 0.004), and open approach (95% CI: 4.794 (2.09–7.50); p < 0.001) were associated with PAL.
Table III
Multivariate linear regression analysis for factors associated with persistent air leak
Discussion
Prolonged air leak (PAL), defined as air leak for > 5 days, is one of the most common complications encountered after pulmonary resection and is a major cause of longer hospital stay compared with other postoperative complications such as pneumonia, atrial fibrillation, or desaturation [7]. The reported incidence of intraoperative air leaks after pulmonary resection ranges between 48% and 70% [8]. Brunelli et al. reported that 15.6% of patients who underwent pulmonary resection had PAL that lasted > 7 days [9]. Although improvements in surgical techniques, such as avoiding dissection at fissure (fissure last technique), using a surgical stapler for parenchyma division, or buttressing the staple line using biological or synthetic materials, have helped in reducing PAL [10], several factors, including incomplete fissure, presence of emphysematous lung, and pleural adhesions, continue to cause PAL [5, 6, 8].
In 2022, Shintani et al. analyzed data from the national clinical database in Japan (N = 30,967) and concluded that male, older age, body mass index, and smoking are risk factors for PAL [11]. Pischik et al. analyzed data from 319 patients who underwent pulmonary resection in their institution, and they identified male gender, smoking history, chronic obstruction lung disease, and preoperative hypoproteinemia as the main risk factors for PAL; however, they found no differences between open or thoracoscopic approaches [12]. However, in our results, we observed that the open approach was associated with PAL. We believe that the reason why our data identifies the open approach as a risk factor is because the surgery is procedurally more difficult compared to the VATS approach.
The use of new products such as sealants, as adjuvant therapy, can help reduce alveolar leakage [6, 13–17]. Further, although most studies have demonstrated the safety of sealant use in surgical patients, a meta-analysis by McGuire and Yee used data from 2,357 patients to evaluate sealant use in pulmonary resection, and they reported that use of a polymeric sealant can significantly reduce postoperative alveolar air leak and length of hospital stay by 1 day [18]. In contrast, a randomized controlled trial by Wong et al., which compared fibrin glue and a control group, found no difference in duration of air leak and chest tube, or hospital stay [6]. Similarly, we also found no differences in duration of chest tube or hospital stay between the fibrin sealant and control groups.
