Brat, Kristián

Introduction Studies have revealed circadian rhythms affect many organ systems and time of injury can impact healing, lung function, and inflammation. We hypothesized operative time may impact post-operative risk. Accordingly, the aim of this study was to compare post-operative complications in patients whose surgery started and finished before 12pm (Group 1); after 12pm (Group 2); and started before 12pm and finished after 12pm (Group 3). Methods Patients from two previous prospective studies were included in this post-hoc analysis. Inclusion criteria were indication for lung resection surgery (confirmed or highly suspicious tumor), age ≥18 and ability to undergo cardiopulmonary exercise testing (CPET). Exclusion criterion was inability to perform surgery (either low predicted postoperative oxygen consumption or inoperability). All patients underwent pre-operative CPET and spirometry. Post-operative pulmonary (PPC) and cardiovascular complications (PCC) were prospectively assessed from the hospital stay up to 30 days. Results Data from 497 patients were analyzed. On comparison of groups, there were differences in BMI (highest in Group 3), surgery duration (lowest in Group 1) and frequency of lobectomies (lowest in Group 1). Incidence of PPC was lowest in Group 1 (n=17; 9%) compared to n=17 (21%) in Group 2 and n=37 (17%) in Group 3 (p=0.01). Incidence of PCC was lowest in Group 1 n=25 (13%) compared to n=19 (23%) in Group 2 and n=46 (21%) in Group 3 (p=0.05). Multivariate logistic regression adjusted for confounders (BMI, surgery duration and lobectomy) showed time of surgery after 12pm was independently associated with PPC with OR = 2.17 (95% CI 1.07-4.41); p=0.03. Conclusion Time of surgery may impact the incidence of PPC in lung resection surgery patients with highest risk in patients undergoing the surgery after 12pm.

Rationale Despite significant advances in patient care and outcomes, criteria for cardiopulmonary exercise testing (CPET) in risk stratification guidelines for lung resection have not been updated in over a decade. We hypothesised that CPET no longer holds additional predictive value for postoperative complications. Methods In this secondary analysis, we included lung resection candidates from two prospective, multicentre studies eligible for CPET and assessed with preoperative pulmonary function tests (PFTs) and arterial blood gas analysis. Postoperative pulmonary (PPCs) and cardiovascular complications (PCCs) were documented during hospitalisation. We trained five types of machine learning models applying nested cross-validation to predict complications and compared predictive performance based on four metrics, including area under the receiver operating characteristic curve (AUC-ROC). Results A total of 497 patients were included. PPCs developed in 71 (14%) patients. Adding CPET parameters to PFTs and baseline clinical data did not improve the ability of models to predict PPCs in unselected patients (AUC-ROC=0.72–0.78; p=0.47), nor in those meeting American College of Chest Physicians (ACCPs) (n=236; AUC-ROC=0.64–0.78; p=0.70) or European Respiratory Society/European Society of Thoracic Surgery (ERS/ESTS) criteria (n=168; AUC-ROC=0.59–0.76; p=0.92). PCCs developed in 90 (18%) patients. CPET parameters likewise did not improve model performance for the prediction of PCCs in unselected patients (AUC-ROC=0.65–0.73; p=0.96), nor in the ACCP (AUC-ROC=0.61–0.73; p=0.82) or ERS/ESTS subgroups (AUC-ROC=0.62–0.69; p=0.87). Conclusions In contemporary surgical practice, CPET did not improve the predictive performance of machine learning models for PPCs or PCCs in patients with an indication based on established guidelines or in those without. The role of CPET in preoperative risk stratification for lung resection should be re-evaluated. Trial registration number NCT03498352 , NCT04826575 .

Abstract Poor ventilatory efficiency, defined as the increase in minute ventilation relative to carbon dioxide production during exercise (VE/VCO2 slope), may be associated with dynamic hyperinflation and thereby promote the development of prolonged air leak (PAL) after lung resection. Consecutive lung lobectomy candidates (n = 96) were recruited for this prospective two-centre study. All subjects underwent pulmonary function tests and cardiopulmonary exercise testing prior to surgery. PAL was defined as the presence of air leaks from the chest tube on the 5th postoperative day and developed in 28 (29%) subjects. Subjects with PAL were not different in terms of age, sex, American Society of Anesthesiologists class, type of surgery (thoracotomy/video-assisted thoracoscopic surgery) and site of surgery (right/left lung; upper/lower lobes). Subjects with PAL had more frequent pleural adhesions (50% vs 21%; P = 0.006) and steeper VE/VCO2 slope (35 ± 7 vs 30 ± 5; P = 0.001). Stepwise logistic regression showed that only the presence of pleural adhesions [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.4–10.9; P = 0.008] and VE/VCO2 slope (OR 1.1, 95% CI 1.0–1.2; P = 0.003) were independently associated with PAL (AUC 0.74, 95% CI 0.62–0.86). We conclude that a high VE/VCO2 slope during exercise may be helpful in identifying patients at greater risk for the development of PAL after lung lobectomy. Clinical trial registration number: ClinicalTrials.gov identifier: NCT03498352.