Analysis of pulmonary complications and predicted postoperative pulmonary function in oncologic lung resections

Introduction

Respiratory complications following thoracic surgery represent a significant contributor to morbidity and mortality, accounting for up to 80% of all lung resection related deaths (1). To date, many studies have identified strategies aimed at reducing postoperative pulmonary complications (PPCs), including preoperative exercise training, lung-protective ventilation strategies, and standardized perioperative fast-track protocols (2-4). Yet, PPCs remain the most common type of adverse events (AEs) following thoracic surgery (5).

PPCs are defined as a postoperative respiratory abnormality that produces identifiable disease or dysfunction that is clinically significant and adversely affects the patient’s clinical course. Further categories of PPCs include atelectasis, respiratory infection (e.g., bronchitis and pneumonia), respiratory failure (e.g., need for postoperative mechanical ventilation for >48 hours), and exacerbation of pre-existing lung diseases including chronic obstructive pulmonary disease (COPD) (e.g., worsening of respiratory symptoms requiring treatment with corticosteroids and/or antibiotics) (6). Previously identified predictors of PPCs include advanced age, current or prior smoking history, preoperative chemotherapy, existing respiratory disease, and active cancer (7-9). Intraoperative factors also include the type and length of operation, the anesthetic administered, type of incision, use of vasoactive drugs, use of supraglottic devices, as well as ventilation parameters.

Several predictive indices have been developed to identify patients at an increased risk of pulmonary complications in the clinical setting. For example, the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) score estimates the risk of in-hospital PPCs using readily available clinical information (e.g., preoperative oxygen saturation and anemia) (10). This tool, however, is limited by the inclusion of minor abnormalities such as small radiographic effusions and wheezing which may overestimate the true morbidity rate. In addition, the Arozullah index is used to predict the likelihood of respiratory failure based on clinical factors, functional status, and laboratory results, but can be time-consuming and cumbersome for regular use in clinical practice (11).

Assessment of baseline respiratory status by way of pulmonary function testing (PFT) is recommended by major society guidelines for patients requiring lung resection (12). Certain preoperative PFT parameters, such as poor forced expiratory volume in the first second (FEV1) and diffusing capacity of the lung for carbon monoxide (DLCO), have been associated with pulmonary complications and morbidity (13,14). However, reliable models for prediction of postoperative AEs or identification of patients who would benefit from targeted preoperative interventions are lacking. The use of predicted postoperative (ppo) FEV1, a simple value readily obtainable in the preoperative setting, has been thought to be inversely related to PPCs following lung resection (15). In the context of new paradigm shifts in oncologic thoracic surgery such as the exponential adoption of minimally invasive surgery as well as enhanced perioperative pathways, there remains a paucity of clinical data on the prognostic value of ppo FEV1 on respiratory complications (16). The aim of this study was to identify the incidence and severity of PPCs in patients undergoing oncologic lung resection, and determine if impaired ppo FEV1 is associated with increased risk of PPCs after pulmonary resections. We present this article in accordance with the STROBE reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-600/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). This study was approved by the institutional ethics board of The Ottawa Hospital Research Institute (OHSN-REB 20190210-01H) and individual consent for this retrospective analysis was waived. A retrospective analysis of prospectively collected AE data of patients undergoing pulmonary resection for lung malignancy at The Ottawa Hospital was performed. Any patient over 18 years of age who underwent an elective open or thoracoscopic oncologic lung resection between January 1, 2008 and December 31, 2018 were included. Patients who did not have preoperative PFTs or those who underwent multiple lung resections were excluded from the study given that PFT values could not be delineated to a specific surgery.

Data were collected from the Thoracic Surgery Quality monitoring, Information management, and Clinical documentation (TSQIC) system which prospectively records all thoracic surgical cases within the institution to track complications, surgical volume and quality, and clinical documentation. Data included patient age and sex, type of incision (minimally invasive, open, converted) and pulmonary resection (sublobar resection, lobectomy, pneumonectomy) performed, ppo FEV1, and complications including PPCs. Complications were defined based on the Ottawa Thoracic Morbidity & Mortality (TM&M) system, which represents a standardized classification system for identifying the presence and severity of thoracic surgical complications. PPCs included atelectasis, acute respiratory distress syndrome (ARDS), pneumonia, and need for ventilation support for more than 48 hours in the postoperative period (17). Severity of PPCs were classified as minor (grade I–II complications requiring no treatment, or pharmacological or minor intervention only) or major (grade III–V complications requiring major intervention, causing organ dysfunction, or leading to death) as per the Clavien-Dindo system. Occurrence of PPCs was evaluated and compared at different ppo FEV1 cut-off values: 40%, 50%, and 60%. The following equation was used to calculate ppo FEV1: ppo FEV1 = preoperative FEV1 × [1 − (number of segments resected/19 total segments)]. The outcome variable evaluated was the presence of at least one PPC defined by the development of atelectasis, pneumonia, or any respiratory complications requiring antibiotics, bronchoscopy, high flow oxygen, and/or intubation.

Statistical analysis

Descriptive statistics were used to describe the patient and surgical characteristics of the study population. Chi-squared or Fisher’s exact test was used to compare independent variables based on the sample size. A multivariable logistic regression analysis was performed to predict PPCs based on a ppo FEV1 cut-off value, controlling for patients’ age, sex, type of incision, and type of procedure. P values <0.05 were considered significant.

Results

Of 2,544 patients who underwent oncologic lung resections, 229 patients were excluded due to missing preoperative PFTs. Following an additional 366 patients who were excluded due to multiple subsequent lung resections, a total of 1,949 patients formed the study group (Table 1). The mean age of participants was 65.8 years, consisting of 1,062 (54.5%) females. Video-assisted thoracoscopic surgery (VATS) was performed in 1,256 (64.4%) patients, while 572 (29.3%) had open procedures and 121 (6.2%) required conversion to open for safety or anatomical factors. Lobectomy was the most common procedure performed (n=1,179; 60.5%), followed by wedge resections (n=536; 27.5%) and segmentectomies (n=108; 5.5%). Of the 1,403 complications reported, 231 (16.5%) were PPCs while pleural complications (n=542; 38.6%) were the most common type of AEs by anatomic classification.

PPCs occurred in 106 (5.4%) patients, characterized by grade I, II, III, IV, and V AEs in 3 (0.2%), 59 (3.0%), 16 (0.8%), 23 (1.2%), and 5 (0.3%) patients, respectively. Of patients with ppo FEV1 ≥50%, 73 (4.4%) had PPCs compared to 33 (11.6%) with ppo FEV1 <50% (P<0.001). Minor (grade I–II) PPCs occurred in 42 (2.5%) patients in the ppo FEV1 ≥50% group vs. 20 (7.0%) patients in the ppo FEV1 <50% group (P<0.001). Major (grade III–V) PPCs occurred in 31 (1.9%) patients in the ppo FEV1 ≥50% group vs. 13 (4.6%) patients in the ppo FEV1 <50% group (P=0.005). The incidence of PPCs were also analyzed for ppo FEV1 cut-off values of 40% and 60% (Table 2). As ppo FEV1 decreased, the incidence of any PPCs increased (Figure 1). The cut-off value associated with all complications including any, major, and minor complications was ppo FEV1 of 50%. A sub-analysis was performed excluding wedge resections and pneumonectomies to further evaluate procedures with relatively more similar perioperative risks (segmentectomy, lobectomy, extended lobectomy). The cut-off value of ppo FEV1 <50% was associated with a higher occurrence of all (P=0.04) and minor (P=0.007) PPCs compared to ppo FEV1 ≥50% whereas 60% and 40% were not associated with any significant differences.

Figure 1 Incidence of any PPCs based on ppo FEV1 (%). Error bars represent the 95% confidence interval. The n value represents the total number of patients with and without PPCs for each ppo FEV1 group. ppo FEV1, predicted postoperative forced expiratory volume in the first second; PPC, postoperative pulmonary complication.

The incidence of PPCs using a cut-off ppo FEV1 of 50% was further analyzed based on surgical characteristics (Table 3). PPCs occurred more frequently in the ppo FEV1 <50% group in both VATS (P=0.03) and open approaches (P=0.003). Moreover, a ppo FEV1 <50% was associated with a higher occurrence of PPCs in wedge resections (P=0.01) and lobectomies (P=0.043).

Predictors of any PPCs were analyzed using a multivariable logistic regression including a cut-off ppo FEV1 of 50% (Table 4). Occurrence of PPCs was associated with a ppo FEV1 of <50% (P=0.03). Need for conversion also predicted occurrence of PPCs (P<0.001) while wedge resections decreased the risk of developing PPCs (P=0.008).

Discussion

In this study, the occurrence of PPCs was found to be inversely proportional to ppo FEV1, with a cut-off value of <50% being associated with all PPCs including minor and major complications. These results suggest that ppo FEV1 may be effectively used to guide operative planning, identify patients at risk of PPCs who may benefit from strategies aimed at reducing respiratory complications, and improve informed consent and shared decision making with high-risk patients.

We found that both ppo FEV1 <50% and procedures converted to open surgery were independently associated with the occurrence of PPCs. Compared to an open approach, VATS results in reduced postoperative pain and better preservation of chest wall mechanics which allows for improved pulmonary function and fewer respiratory complications (18,19). On evaluation of PPCs based on surgical characteristics, there was a higher occurrence of PPCs in patients with ppo FEV1 <50% for both VATS and open procedures. In a study of 585 and 220 patients who underwent open and VATS lobectomies, respectively, Zhang et al. also demonstrated that the predictive ability of ppo FEV1 was retained for both minimally invasive and open approaches (20). In robotic-assisted thoracoscopic surgery, a cut-off value of ppo FEV1 ≤50% was also shown to be predictive of increased pulmonary complications by Cao et al. in their study of 1,088 robotic-assisted lobectomies (21). With advancements in minimally invasive techniques, patients with compromised pulmonary function are increasingly able to undergo surgery with acceptable morbidity and mortality (22-24). In this context, our findings demonstrate that ppo FEV1 remains a useful predictor of pulmonary complications in modern day thoracic surgery practice.

Several attempts have been made to incorporate ppo FEV1 in risk prediction models. While validating the Clinical Prediction Rule for Pulmonary Complications, which consists of previous chemotherapy and ppo DLCO, Yepes-Temiño et al. developed a score that better predicted PPCs using age, smoking status, and ppo FEV1 (25). In another study, Yang et al. found ppo FEV1 to be associated with prolonged intensive care unit stay (26), while the European Society Objective Score (ESOS.01) was developed to predict in-hospital mortality following lung tumor resection using age and ppo FEV1 only (27). Despite the wide variability in individual pre-existing lung function and physiologic deficits from different approaches to resection and perioperative therapy in thoracic surgery patients, these findings along with our study suggest that ppo FEV1 remains a convenient and integral part of risk prediction in an otherwise complex surgical population.

The ppo FEV1 cut-off value has been debated in the literature. Nakahara et al. found that ppo FEV1 <30% was associated with a mortality rate as high as 60%, whereas other studies have predicted greater perioperative complication rates with ppo FEV1 <40% (28,29). Since then, the cut-off value of 40% has remained a useful reference point for preoperative evaluation of patients at increased risk. However, for reasons such as the aging surgical population, some have advocated for increasing this threshold as high as up to 60% (12,30). In this study, a cut-off value of 50% was able to identify those with significantly higher incidence of any, major and minor PPCs, and this remained significant for any and minor PPCs even on exclusion of wedge resections and pneumonectomies. Thus, a cut-off value of 50% may represent a useful threshold with which to offer additional therapy to prevent PPCs, although prospective studies must be performed to confirm this finding. Given that most studies investigating pulmonary function and operative morbidity have traditionally involved patients undergoing thoracotomy (31), the current study adds a significant number of patients who underwent thoracoscopic surgery to the literature, allowing for re-evaluation of the role of ppo FEV1 and an appropriate cut-off value. Nonetheless, a progressive increase in PPCs with worsening ppo FEV1 is seen, and we suggest that discussions around informed consent include ppo FEV1 in conjunction with other patient-specific data to best determine maximal acceptable risk.

This study explored a risk stratification approach involving an easily obtainable preoperative factor, making it clinically practical and suitable for all patients undergoing lung resection. The sample size and mix of surgical approach in this cohort further adds to the current literature. Limitations of the study include its retrospective nature as well as the potential for selection bias as this cohort of patients was ultimately considered fit for surgery following a preoperative assessment. Furthermore, ppo lung function ideally accounts for other factors such as functional pulmonary heterogeneity, but these were not available for investigation in the study. Lastly, PPCs have inconsistently been defined and measured throughout the literature, somewhat limiting external validity. However, this study used the Ottawa TM&M classification system which represents a standardized approach to identify the presence and severity of AEs following lung resection and has been adopted by surgical groups internationally (17,32).

Conclusions

In the setting of increasingly minimally invasive approaches in thoracic surgery, we demonstrated a practical strategy to identify the subgroup of patients at high risk of PPCs. These patients may benefit from preoperative optimization with prehabilitation, smoking cessation, and inspiratory muscle training, as well as consideration for targeted postoperative management with high flow heated humidity nasal cannula oxygen to support patient’s ability to expectorate. These interventions require further investigation to validate their utility in this patient population. Although further external validation of ppo FEV1 is also required prior to establishing its utility in other centres, this study highlights the value of routine assessment of ppo pulmonary function to help identify increased risk of PPCs following oncologic pulmonary resection.

Acknowledgments

We would like to acknowledge all the thoracic residents who participate in daily and weekly collection of morbidity and mortality data, as well as all the research staff involved, including Anna Fazekas, Molly Gingrich, Edita Delic, Kirby Bucciero, Dora Kosevic, and our software and data manager, Caitlin Anstee.

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-600/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-600/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-600/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-600/coif). The authors have no 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 was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional ethics board of The Ottawa Hospital Research Institute (OHSN-REB 20190210-01H) and individual consent for this retrospective analysis was waived.

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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