Cecilia Pompili

Peak Oxygen Consumption During Cardiopulmonary Exercise Test Improves Risk Stratification in Candidates to Major Lung Resection

BACKGROUND The objective of this investigation was to assess the association of peak oxygen consumption (Vo(2)) with postoperative outcome in a prospective cohort of patients undergoing major lung resection for the treatment of lung cancer. METHODS Preoperative symptom-limited cardiopulmonary exercise testing (CPET) performed using cycle ergometry was conducted in 204 consecutive patients who had undergone pulmonary lobectomy or pneumonectomy. Peak Vo(2) was tested for possible association with postoperative cardiopulmonary complications and mortality. Logistic regression analysis, validated by a bootstrap analysis, was used to adjust for the effect of other perioperative factors. The role of peak Vo(2) in stratifying the surgical risk was further assessed in different groups of patients subdivided according to their cardiorespiratory status. RESULTS Logistic regression showed that peak Vo(2) was an independent and reliable predictor of pulmonary complications (p = 0.04). All six deaths occurred in patients with a peak Vo(2) of < 20 mL/kg/min (four deaths in patients with a peak Vo(2) of < 12 mL/kg/min). The mortality rate in this high-risk group was 10-fold higher (4 of 30 patients; 13%) compared to those with higher peak Vo(2) (p = 0.006). Compared to patients with a peak Vo(2) of > 20 mL/kg/min, those with a peak Vo(2) of < 12 mL/kg/min had 5-fold, 8-fold, 5-fold, and 13-fold higher rates, respectively, of total cardiopulmonary complications pulmonary complications, cardiac complications, and mortality. CONCLUSIONS The present study supports a more liberal use of CPET before lung resection compared to the current guidelines since this test can help in stratifying the surgical risk and optimizing perioperative care.

Recalibration of the Revised Cardiac Risk Index in Lung Resection Candidates

BACKGROUND The revised cardiac risk index (RCRI) has been proposed as a tool for cardiac risk stratification before lung resection. However, the RCRI was originally developed from a generic surgical population including a small group of thoracic patients. The objective of this study was to recalibrate the RCRI in candidates for major lung resections to provide a more specific instrument for cardiac risk stratification. METHODS One thousand six hundred ninety-six patients who underwent lobectomy (1,426) or pneumonectomy (270) in two centers between the years of 2000 and 2008 were analyzed. Stepwise logistic regression and bootstrap analyses were used to recalibrate the six variables comprising the RCRI. The outcome variable was occurrence of major cardiac complications (cardiac arrest, complete heart block, acute myocardial infarction, pulmonary edema, or cardiac death during admission). Only those variables with a probability of less than 0.1 in more than 50% of bootstrap samples were retained in the final model and proportionally weighted according to their regression estimates. RESULTS The incidence of major cardiac morbidity was 3.3% (57 patients). Four of the six variables present in the RCRI were reliably associated with major cardiac complications: cerebrovascular disease (1.5 points), cardiac ischemia (1.5 points), renal disease (1 point), and pneumonectomy (1.5 points). Patients were grouped into four classes according to their recalibrated RCRI, predicting an incremental risk of cardiac morbidity (p < 0.0001). Compared with the traditional RCRI, the recalibrated score had a higher discrimination (c indexes, 0.72 versus 0.62; p = 0.004). CONCLUSIONS The recalibrated RCRI can be reliably used as a first-line screening instrument during cardiologic risk stratification for selecting those patients needing further cardiologic testing from those who can proceed with pulmonary evaluation without any further cardiac tests.

Multicenter international randomized comparison of objective and subjective outcomes between electronic and traditional chest drainage systems.

BACKGROUND The aim of this study was to assess the impact of digital versus traditional drainage devices on chest tube removal and patient satisfaction. METHODS A randomized trial of digital versus traditional devices after lobectomy/segmentectomy was conducted at 4 international centers (United Kingdom, Europe, Asia, United States). Patients were managed with overnight suction followed by gravity drainage. Chest tubes were removed when an air leak was not evident anymore and the drained fluid was less than 400 mL/d. RESULTS The groups (digital, 191 patients; traditional, 190 patients) were well matched for baseline and surgical characteristics. There were 325 lobectomies/bilobectomies and 56 segmentectomies, 308 of which were performed by video-assisted thoracic surgery (VATS). Patients randomized to digital systems had a significantly shorter air leak duration (1.0 versus 2.2 days; p=0.001), duration of chest tube placement (3.6 versus 4.7 days; p=0.0001), and postoperative length of stay (4.6 versus 5.6 days; p<0.0001). Subjective end points revealed a perceived improved ability to arise from bed (p=0.008), system convenience for patients and personnel (p=0.02), and the potential for being comfortable when discharged home with the device (p=0.06). A mean difference of 2.6 days from air leak cessation to tube removal was observed, which was similar in the 2 groups (p=0.7). Multivariable regression analysis showed that duration of chest tube placement after air leak cessation was directly associated with the amount of fluid drained during the first 48 hours (p=0.01) and the duration of air leak (p=0.008), independent of hospital location. CONCLUSIONS Patients managed with digital drainage systems experienced a shorter duration of chest tube placement, shorter hospital stays, and higher satisfaction scores compared with those managed with traditional devices. ( CLINICAL TRIAL REGISTRATION NUMBER NCT01747889.).

A Scoring System to Predict the Risk of Prolonged Air Leak After Lobectomy

BACKGROUND Prolonged air leak (PAL) remains a frequent complication after lung resection. Perioperative preventative strategies have been tested, but their efficacy is often difficult to interpret due to heterogeneous inclusion criteria. The objective of this study was to develop and validate a practical score to stratify the risk of PAL after lobectomy. METHODS Six hundred fifty-eight consecutive patients were submitted to pulmonary lobectomy (2000 to 2008) in center A and were used to develop the risk-adjusted score predicting the incidence of PAL (> 5 days). Exclusion criteria were chest wall resection and postoperative assisted mechanical ventilation. No sealants, pleural tent, or buttressing material were used. To build the aggregate score numeric variables were categorized by receiver operating curve analysis. Variables were screened by univariate analysis and then used in stepwise logistic regression analysis (validated by bootstrap). The scoring system was developed by proportional weighing of the significant predictor estimates and was validated on patients operated on in a different center (center B). RESULTS The incidence of PAL in the derivation set was 13% (87 of 658 cases). Predictive variables and their scores were the following: age greater than 65 years (1 point); presence of pleural adhesions (1 point); forced expiratory volume in one second less than 80% (1.5 points); and body mass index less than 25.5 kg/m(2) (2 points). Patients were grouped into 4 risk classes according to their aggregate scores, which were significantly associated with incremental risk of PAL in the validation set of 233 patients. CONCLUSIONS The developed scoring system reliably predicts incremental risk of PAL after pulmonary lobectomy. Its use may help in identifying those high-risk patients in whom to adopt intraoperative prophylactic strategies; in developing inclusion criteria for future randomized clinical trials on new technologies aimed at reducing or preventing air leak; and for patient counseling.

Performance at Preoperative Stair-Climbing Test Is Associated With Prognosis After Pulmonary Resection in Stage I Non-Small Cell Lung Cancer

BACKGROUND This investigation evaluated whether the performance at a preoperative symptom-limited stair-climbing test was a prognostic factor in resected pathologic stage I non-small cell lung cancer (NSCLC). METHODS Observational analysis was performed on a prospective database that included 296 patients who underwent pulmonary lobectomy for pathologic stage T1 N0 or T2 N0 NSCLC (2000 to 2008). Patients who received induction chemotherapy were excluded. Survival was calculated by the Kaplan-Meyer method. The log-rank test was used to assess differences in survival between groups. The relationships between survival and baseline and clinical variables were determined by Cox multivariate analyses. RESULTS Median follow-up was 43 months. The best cutoff associated with prognosis was an 18-meter stair climb. Median (months) survival and 5-year survival of patients who climbed more than 18 meters were significantly longer than those who climbed less than 18 meters (97 vs 74; 77% vs 54%, p=0.001). Cox regression model (hazard ratio) showed that climbing more than 18 meters (0.5; p=0.003), diffusion capacity of the lung for carbon monoxide (0.98; p=0.02), and pT stage (1.8; p=0.02) were independent prognostic factors. Patients who climbed less than 18 meters had increased deaths from cancer (24% vs 15%, p=0.1) or other causes (19% vs 9%, p=0.02). CONCLUSIONS Preoperative cardiopulmonary fitness is a significant prognostic factor in patients after resection for early-stage NSCLC. Interventions aimed at improving exercise tolerance can be useful to improve long-term prognosis after NSCLC operations.

Does chronic obstructive pulmonary disease affect postoperative quality of life in patients undergoing lobectomy for lung cancer? A case-matched study

BACKGROUND The objective of this investigation was to assess the quality of life (QoL) before and after pulmonary lobectomy in patients with chronic obstructive pulmonary disease (COPD) and to compare these values with a case-matched population of patients with normal respiratory function. METHODS This is an observational analysis performed on a prospective dataset of 220 consecutive patients submitted to pulmonary lobectomy for lung cancer (2006-2008). Patients submitted to extended procedures (chest wall resection and superior sulcus) were excluded from the analysis. Pre- and postoperative (3 months) QoL were assessed in all patients through the administration of the Short Form 36v2 (SF36v2) health survey, a generic QoL instrument assessing eight health physical and mental concepts. Propensity score was used to match COPD patients (according to the NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria: forced expiratory volume in 1s/forced expiratory vital capacity (FEV1/FVC) ratio <0.7 and FEV1 <80%) with counterparts without COPD. QoL scales were compared between the two matched groups by means of the Mann-Whitney test. RESULTS Propensity score yielded 50 well-matched pairs of patients with and without COPD. Compared with non-COPD patients, those with COPD had a threefold higher rate of cardiopulmonary morbidity (14 cases vs 5 cases, 28% vs 10%, p=0.04), lower reduction in FEV1 (6% vs 13%, p=0.0002), but lower residual postoperative FEV1 values (62% vs 74%, p<0.0001). Postoperative carbon monoxide lung diffusion capacity (DLCO) (69% vs 65%, p=0.1) and VO(2 max) (15.3 ml kg(-1)min(-1) vs 14.3 ml kg(-1)min(-1)p=0.4) values were similar between the groups. Although most of the preoperative and postoperative QoL domains in both groups were reduced compared with normal population (<50), we were not able to find differences between the groups in any of the preoperative and postoperative physical and mental QoL scales. CONCLUSIONS The evidence of an acceptable QoL in COPD patients may help both patients and physicians in the surgical decision-making process in the face of high rates of complications.

Minute Ventilation-to-Carbon Dioxide Output ( V ˙e/ V ˙co2) Slope Is the Strongest Predictor of Respiratory Complications and Death After Pulmonary Resection

BACKGROUND This study assessed whether the minute ventilation-to-carbon dioxide output (VE/VCO2) slope, a measure of ventilatory efficiency routinely measured during cardiopulmonary exercise testing (CPET), is an independent predictor of respiratory complications after major lung resections. METHODS Prospective observational analysis was performed on 225 consecutive candidates after lobectomy (197 patients) or pneumonectomy (28 patients) from 2008 to 2010. Inoperability criteria were peak oxygen consumption (VO2) of less than 10 mL/kg/min in association with predicted postoperative forced expiratory volume in 1 second of less than 30% and diffusion capacity of the lung for carbon monoxide of less than 30%. All patients performed a symptom-limited CPET on cycle ergometer. Respiratory complications (30 days or in-hospital) were prospectively recorded: pneumonia, atelectasis requiring bronchoscopy, respiratory failure on mechanical ventilation exceeding 48 hours, adult respiratory distress syndrome, pulmonary edema, and pulmonary embolism. Univariable and multivariable regression analyses were used to identify independent predictors of respiratory complications. RESULTS Cardiopulmonary morbidity and mortality rates were 23% (51 patients) and 2.2% (5 patients). The 25 patients with respiratory complications had a significantly higher VE/VCO2 slope than those without complications (34.8 vs 30.9, p=0.001). Peak VO2 was not associated with respiratory complications. Logistic regression and bootstrap analyses showed that, after adjusting for other baseline and perioperative variables, the strongest predictor of respiratory complications was VE/VCO2 slope (regression coefficient, 0.09; bootstrap frequency, 89%; p=0.004). Patients with a VE/VCO2 slope exceeding 35 had a higher incidence of respiratory complications (22% vs 7.6%, p=0.004) and mortality (7.2% vs. 0.6%, p=0.01). CONCLUSIONS VE/VCO2 slope is a better predictor of respiratory complications than peak VO2. This inexpensive and operator-independent variable should be considered in the clinical practice to refine operability selection criteria.

Digital measurements of air leak flow and intrapleural pressures in the immediate postoperative period predict risk of prolonged air leak after pulmonary lobectomy

BACKGROUND The objective of this prospective observational study was to evaluate the association between the airflow and intrapleural pressures digitally recorded during the immediate postoperative period after lobectomy and their ability to predict the risk of subsequent prolonged air leak (PAL). METHODS A total of 145 consecutive patients underwent pulmonary lobectomy in two centers. All patients were managed with the chest tube placed on suction (-20 cm H(2)O) until the morning of the first postoperative day. Measurement of airflow and maximum and minimum intrapleural pressures were recorded during the 6th postoperative hour using a digital chest drainage device. Logistic regression analysis validated by bootstrap was used to test independent association of variables with PAL (air leak>72 h). RESULTS The mean air leak flow at the 6th postoperative hour was 86 ml min(-1) (0-1100 ml min(-1)). The mean maximum and minimum pleural pressures at the 6th postoperative hour were -11.4 cm H(2)O and -21.9 cm H(2)O, respectively. Logistic regression and bootstrap showed that the mean air leak flow (p=0.007) and the mean differential pleural pressure (ΔP: maximum-minimum intrapleural pressure) (p=0.02) at the 6th postoperative hour were reliably associated with PAL, independent of the effect of age, forced expiratory volume 1 (FEV1), chronic obstructive pulmonary disease (COPD) status, diffusing capacity of the lung for carbon monoxide (DLCO), side, and site of lobectomy. According to best cutoffs derived by receiver operating characteristic (ROC) analysis the following combinations showed incremental risk of PAL: ΔP<10+Flow<50: 4% (3/73); ΔP>10+Flow<50: 15% (5/33); ΔP<10+Flow>50: 36% (5/14); ΔP>10+Flow>50: 52% (13/25). CONCLUSIONS The levels of both air leak flow and pleural pressure measured at the 6th postoperative hour are associated to a different extent with the duration of air leak. Interpretation of the data measured at an early time point by digital chest drainage systems allows estimation of the risk of subsequent PAL. In this way, digital devices may help to plan postoperative management to allow both safe and more accurate implementation of fast-tracking strategies.

Peak Oxygen Consumption Measured during the Stair-Climbing Test in Lung Resection Candidates

Background: The stair-climbing test is commonly used in the preoperative evaluation of lung resection candidates, but it is difficult to standardize and provides little physiologic information on the performance. Objective: To verify the association between the altitude and the VO2peak measured during the stair-climbing test. Methods: 109 consecutive candidates for lung resection performed a symptom-limited stair-climbing test with direct breath-by-breath measurement of VO2peak by a portable gas analyzer. Stepwise logistic regression and bootstrap analyses were used to verify the association of several perioperative variables with a VO2peak <15 ml/kg/min. Subsequently, multiple regression analysis was also performed to develop an equation to estimate VO2peak from stair-climbing parameters and other patient-related variables. Results: 56% of patients climbing <14 m had a VO2peak <15 ml/kg/min, whereas 98% of those climbing >22 m had a VO2peak >15 ml/kg/min. The altitude reached at stair-climbing test resulted in the only significant predictor of a VO2peak <15 ml/kg/min after logistic regression analysis. Multiple regression analysis yielded an equation to estimate VO2peak factoring altitude (p < 0.0001), speed of ascent (p = 0.005) and body mass index (p = 0.0008). Conclusions: There was an association between altitude and VO2peak measured during the stair-climbing test. Most of the patients climbing more than 22 m are able to generate high values of VO2peak and can proceed to surgery without any additional tests. All others need to be referred for a formal cardiopulmonary exercise test. In addition, we were able to generate an equation to estimate VO2peak, which could assist in streamlining the preoperative workup and could be used across different settings to standardize this test.

Preoperative quality of life predicts survival following pulmonary resection in stage I non-small-cell lung cancer

OBJECTIVES The objective of this study was to assess the prognostic role of preoperative quality of life (QoL) in patients operated on for early-stage non-small-cell lung cancer (NSCLC). METHODS This is an observational analysis of 131 consecutive patients (2003-08) submitted to pulmonary lobectomy and systematic nodal dissection for pathological pT1N0 or pT2N0 stages NSCLC with a complete follow-up (median 40 months). QoL was measured by the Short Form 36v2, a multidimensional survey assessing eight domains and two composite scales (physical component score [PCS] and mental component score [MCS]). Survival was calculated by the Kaplan-Meier method. The log-rank test was used to assess differences between groups. The relationships between survival and QoL composite scales were determined by Cox proportional hazards regression analysis adjusting for the effect of several baseline and clinical variables. PCS and MCS were categorized according to their values greater or lower than 50 percentiles (general population norms). RESULTS Fifty-three (40%) patients had PCS <50 and 71 (54%) had MCS <50. Results from physical functioning (P = 0.03) and general health (P = 0.03) scales were directly associated with survival. Multivariable regression showed that significant factors associated with overall survival were age >70 (hazard ratio [HR] 2.4, 95% confidence interval [95% CI] 1.2-4.8, P = 0.01) and PCS <50 (HR 2.3, 95% CI 1.4-4.4, P = 0.01). MCS, pT stage, histology, forced expiratory volume in 1 s, DLCO were not associated with prognosis. Patients with PCS >50 lived longer than those with PCS <50 (5-year overall survival 79 vs 49%, P = 0.01), in both pT1 (5-year overall survival 80 vs 49%) and pT2 stages (5-year overall survival 78 vs 48%). Cancer-specific 5-year survival was better in patients with a preoperative PCS >50 compared with those with PCS <50 (89 vs 73%, P = 0.05). Deaths due to cancer recurrence were similar in patients with PCS <50 and >50 (55 vs 53%, P = 0.9). CONCLUSIONS The physical component of QoL was associated with overall and cancer-specific survivals in patients operated on for early-stage NSCLC. Supportive interventions aimed at improving the perception of physical well-being should be tested to verify whether they can improve long-term prognosis after lung cancer surgery.