- Email: [email protected]
Estimating the Risk of Prolonged Air Leak after Pulmonary Resection Using a Simple Scoring System
Estimating the Risk of Prolonged Air Leak after Pulmonary Resection Using a Simple Scoring System Lawrence Lee, MD, Stephen C Hanley, PhD, Catherine Robineau, RN, Christian Sirois, MD, FRCSC, David S Mulder, MD, FACS, Lorenzo E Ferri, MD, PhD, FACS The high rate of prolonged air leak (PAL) after pulmonary resection has prompted interest in surgical adjuncts designed to prevent this complication. However, these adjuncts are costly and might not be beneficial if used routinely. Identification of patients at highest risk might allow for more effective use of these adjuncts. Therefore, we sought to develop a simple scoring system to predict PAL. STUDY DESIGN: A derivation set of 580 patients was identified from a prospectively entered database of consecutive pulmonary resections at a single institution from 2002 to 2007. Patient and operative characteristics were compared using Student’s t-test and chi-square tests. Significant variables on univariate analysis were entered into a stepwise logistic regression to establish a simple predictive model to estimate the risk of PAL. This scoring system was then validated in a consecutive set of 381 patients operated at the same institution from 2007 to 2009. RESULTS: The rate of PAL was 14% in the derivation set and 18% in the validation set. Poor pulmonary function (forced expiratory volume in 1 second and carbon monoxide diffusing capacity, percent predicted) and pleural adhesions were significantly associated with PAL in the derivation set. A weighted scoring system was devised using pleural adhesions (⫹2 points), forced expiratory volume in 1 second (⫹1 per 10% below 100%), and carbon monoxide diffusing capacity (⫹1 per 20% below 100%). Total number of points estimated the probability of PAL. Hosmer-Lemeshow goodness-of-fit test confirmed validity (p ⬎ 0.2) of this scoring system in the validation set. CONCLUSIONS: We have devised and validated a simple scoring system to predict the probability of PAL after pulmonary resection. (J Am Coll Surg 2011;212:1027–1032. © 2011 by the American College of Surgeons) BACKGROUND:
Prolonged air leak (PAL) is a common complication after pulmonary resection, with a reported incidence of up to 26% after surgery for lung cancer.1 PAL represents a major clinical problem because it is associated with considerable economic costs and increased rates of other postoperative complications, length of hospitalization, and mortality.2,3 Intraoperative pneumostasis, postoperative maintenance of lung expansion, and pleural apposition remain imperative in preventing this complication.4 Surgical adjuncts including biologic sealants, autologous blood pleurodesis, and staple-line buttressing have been developed in an effort Disclosure Information: Nothing to disclose. Received December 18, 2010; Revised March 4, 2011; Accepted March 7, 2011. From the Department of Surgery, Division of Thoracic Surgery, McGill University Health Center, Montreal, QC, Canada. Correspondence address: Lorenzo E Ferri, MD, PhD, FACS, Department of Surgery, McGill University, Montreal General Hospital, L9-112, 1650 Cedar Ave, Montreal, Quebec H3G 1A4, Canada. email: [email protected]
© 2011 by the American College of Surgeons Published by Elsevier Inc.
to decrease postoperative air leak. However, routine use of these adjuncts are of unproven use, and are often very costly. A Cochrane meta-analysis investigating the effectiveness of biologic and synthetic sealants or glues could not demonstrate a substantial reduction in the incidence of PAL or duration of hospitalization.5 Pleural-based adjuncts, such as pleural tenting or autologous blood patch pleurodesis, have been described, but they are technically difficult and associated with their own set of complications. The true effectiveness of these adjuncts might be hidden by the fact that these trials did not specifically target patients at high risk for PAL. Multiple risk factors for PAL have been described previously, but predicting the patients in whom PAL will develop remains an inexact science. Identifying high-risk patients can lead to more targeted and effective use of these expensive surgical sealants and other adjuncts. Therefore, the aim of this study was to identify risk factors for PAL and to derive a simple scoring system to predict the risk of PAL.
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METHODS A derivation set was identified from a prospectively entered database of patients who underwent pulmonary resection between August 2002 and March 2007 at a single university teaching hospital. Patients with potential confounding operative and postoperative factors were excluded (pneumonectomy, immediate postoperative mechanical ventilation, trauma, blebectomy, major chest wall or diaphragmatic resections, and trans-sternal resection). Patients were also excluded if surgical sealants or other buttressing materials were used. Real-time documentation of all postoperative outcomes, including air leak, was performed by a nurse clinician rounding daily with the ward service and entered in the database. PAL was defined as an air leak lasting longer than 7 days. Variables were compared between patients with PAL and those without. Variables considered were patient sex and age, open thoracotomy versus video-assisted thoracoscopic surgery, anatomic versus wedge resection, presence of pleural adhesions at the time of operation, surgeon, and pulmonary function testing. Results are presented as mean ⫾ SEM. Statistical significance between means was determined using two-tailed Student’s t-test for continuous variables, and chi-square analysis for categorical variables. Differences were considered significant at p ⬍ 0.05. Given that patients having undergone wedge resections were at limited risk of PAL as compared with those having undergone anatomic resection, additional analyses were restricted to the subset of patients having undergone anatomic resection. Stepwise logistic regression analysis was performed to establish a simple predictive model to estimate the risk of PAL. Coefficients were then rounded to provide a simple weighted scoring system to allow a rapid estimation of risk of PAL. This scoring system was then validated in a set of patients who underwent pulmonary resection between April 2007 and June 2009 at the same university teaching hospital identified here. Patients were assigned into bins using the developed scoring system and observed and expected frequencies were compared by Hosmer-Lemeshow goodness-of-fit test. RESULTS From August 2002 to March 2007, five hundred and eighty patients underwent pulmonary resection for suspected or confirmed malignancy and fit the inclusion criteria described here. Patient and operative variables are presented in Table 1. Overall incidence of PAL was 14.1%. Of note, the vast majority of resections were performed by open thoracotomy and two-thirds of re-
J Am Coll Surg
Table 1. Derivation and Validation Set Variables (All Patients)
Variable
Sex, male (%) Age (y), mean ⫾ SD Open thoracotomy (%) Anatomic resection (%) Presence of pleural adhesions (%) FEV1 (% predicted), mean ⫾ SD DLCO (% predicted), mean ⫾ SD PAL (%)
Derivation set (n ⴝ 580)
Validation set (n ⴝ 381)
51 63 ⫾ 1 88 68 25 85 ⫾ 1 82 ⫾ 1 14
45 68 ⫾ 1 76 67 18 86 ⫾ 1 77 ⫾ 1 18
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second; PAL, prolonged air leak.
sections were anatomic (lobectomy or segmentectomy), with the remainder being wedge resections (Table 1). To identify factors that predict the risk of PAL, we performed univariate analysis of these variables. Of the variables considered, procedures performed by open thoracotomy (98% PAL⫹ versus 87% PAL⫺; p ⫽ 0.082), anatomic resection (89% versus 64%; p ⬍ 0.001), the presence of pleural adhesions (34% versus 23%; p ⫽ 0.031), forced expiratory volume in 1 second (FEV1; 74 versus 87% predicted; p ⬍ 0.001) and carbon monoxide diffusing capacity (DLCO; 71 versus 84% predicted; p ⬍ 0.001) were associated with an increased risk of PAL. Of these variables, the risk of PAL appeared to correlate most with anatomic resection (wedge: 4.8% versus lobectomy/segmentectomy: 18.6%, p ⬍ 0.001). Given the limited risk of PAL in patients undergoing wedge resection and the fact that more than two-thirds of patients underwent anatomic resection, we elected to restrict additional analysis to the subset of patients having undergone anatomic resection. Patient and operative variables for the subset of patients having undergone anatomic resection are presented in Table 2. The incidence of PAL in this group was 18.6%. Univariate analysis of this group indicated that the presence of pleural adhesions and impaired pulmonary function continued to be associated with increased risk of PAL (Table 2), and open thoracotomy was no longer significantly correlated. This stands to reason, as most wedge resections were performed by video-assisted thoracoscopic surgery and most anatomic resections were performed by open thoracotomy, as evidenced by the significant association between these two variables (p ⬍ 0.001). To establish a model to predict the risk of PAL, we performed stepwise logistic regression using the variables identified in Table 2. To account for the increased risk of PAL associated with impaired pulmonary func-
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Table 2. Derivation Set Variables Associated with Prolonged Air Leak (Anatomic Resection) Air leak Variable
Overall
<7 Days
>7 Days
p Value
Sex, male (%) Age (y), mean ⫾ SD Open thoracotomy (%) Presence of pleural adhesions (%) FEV1 (% predicted), mean ⫾ SD DLCO (% predicted), mean ⫾ SD
50 64 ⫾ 1 98 27 84 ⫾ 1 82 ⫾ 1
48 63 ⫾ 1 97 24 87 ⫾ 1 84 ⫾ 1
59 66 ⫾ 1 99 37 74 ⫾ 3 71 ⫾ 3
0.092 0.053 0.558 0.029 ⬍0.001 ⬍0.001
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second.
tion, pulmonary function testing values were entered into the model as 100 ⫺ FEV1, and 100 ⫺ DLCO. The coefficients from the logistic regression model (Table 3) were then rounded to provide a simple weighted scoring system to allow a rapid estimation of risk of PAL (Table 4). In this model, baseline risk for a patient undergoing anatomic resection with normal pulmonary function tests and no pleural adhesions is 8.2%. A patient with pleural adhesions and poor pulmonary function is most at risk for PAL developing, with the presence of pleural adhesions having the same prognostic value as a 20% decrease in FEV1, or a 40% decrease in DLCO. For example, a patient with mild chronic obstructive pulmonary disease (predicted FEV1 ⫽ 70% and DLCO ⫽ 80%) undergoing a pulmonary lobectomy with the presence of intrapleural adhesions has an estimated probability of PAL of 28.5%. To validate this model, the scoring system was applied to a set of 381 consecutive patients who underwent pulmonary resection between April 2007 and June 2009 at the same university teaching hospital identified above (Table 1). Scores were calculated for each patient, and observed and expected frequencies were compared between weighted groups of patients by Hosmer-Lemeshow goodness-of-fit test (Table 5). Although the scores appeared less accurate at predicting low risk of PAL, the model was found to be well-calibrated (p ⬎ 0.2).
Table 3. Logistic Regression of Variables Predicting Prolonged Air Leak (Anatomic Resection) Variable
Constant Presence of pleural adhesions 100 ⫺ FEV1 (% predicted) 100 ⫺ DLCO (% predicted)
 coefficient
p Value
2.420 ⫺0.483 ⫺0.026 ⫺0.013
⬍0.001 0.140 0.003 0.091
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second.
DISCUSSION PAL after pulmonary resection is a common complication, occurring in up to 26% of cases.1 It has been reported to increase complications, length of hospitalization, and hospital costs.2,3 Prevention of this common yet highly morbid complication begins with meticulous surgical technique to avoid tears in the lung parenchyma and the closure of macroscopic air leaks.6 Lack of an intraoperative air leak does not reliably indicate the absence of postoperative air leak.7 Considerable efforts have been made to develop surgical adjuncts to prevent PAL. Several surgical techniques have been described, including pleural tenting, pneumoperitoneum, mechanical pleurodesis, and staple line buttressing, but all of these procedures have their own limitations or are prohibitively expensive to be used routinely.8-10 New biologic and synthetic sealants have becoming increasingly popular as a method to prevent Table 4. Scoring System to Estimate the Risk of Prolonged Air Leak Anatomic resection
Wedge resection Presence of pleural adhesions FEV1 (% predicted) DLCO (% predicted) Risk (%) 8.2 10.2 12.8 15.8 19.5 23.7 28.5 33.8 39.7 45.8 52.0 58.2
Score
Risk ⫽ 4.8% ⫹2 ⫹1 per 10% below 100% ⫹1 per 20% below 100% 0 1 2 3 4 5 6 7 8 9 10 11
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second.
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Table 5. Hosmer-Lemeshow Goodness-of-FitTest in Validation Set Score
<1
2ⴚ3
4
5
6ⴚ7
>8
Expected risk (%) Observed risk (%)
9.0 16.7
14.5 17.5
19.5 16.0
23.7 31.8
31.6 22.2
44.4 46.2
postoperative air leaks, but results have been equivocal. Single-center trials have reported reductions in chest tube duration and incidence of PAL, but a decreased length of hospitalization has not been consistently demonstrated.11-13 A Cochrane meta-analysis also reported that PAL was reduced only in two of the seven trials that reported outcomes on PAL, and length of stay was considerably reduced in only 3 of 14 trials.5 Based on these results, authors of the Cochrane review could not recommend systematic use of surgical sealants. However, these adjuncts can be effective if used only in patients who are at high-risk of PAL. Therefore, we have derived a simple scoring system to predict the probability of PAL, and then validated it in a consecutive series of 381 patients. The incidence of PAL in the derivation and validation sets was 14% and 18%, respectively. PAL was strongly associated with anatomic resection, poor pulmonary function, and presence of pleural adhesions on unvariate analysis. Because of the limited incidence of PAL in nonanatomical resections in our derivation set (4.8%), we decided to restrict analysis to anatomic resections only. Even after excluding nonanatomical resections, poor pulmonary function and pleural adhesions remained significantly associated with PAL. Pleural adhesions, FEV1 (each 10% below 100% predicted) and DLCO (each 10% below 100% predicted) were assigned a score based on the  coefficient using stepwise logistic regression. The aggregate score then estimated the probability of PAL (Table 4). This scoring system was then validated in a consecutive set of 381 patients treated at the same institution (Table 5). Age approached statistical significance on univariate analysis in the original derivation set of patients, as well as the subset of patients who underwent anatomic resection (Table 2), but was not included in the final model. Given that FEV1 and DLCO values were expressed relative to predicted values corrected for age, sex, height, and weight, it was inherent that the effect of age would be included indirectly in the final model. To this end, re-analysis including age did not improve the accuracy of the model. In addition, Pearson correlation analysis demonstrated age to be correlated with FEV1 (r ⫽ ⫺0.100, p ⫽ 0.077) and DLCO (r ⫽ ⫺0.215, p ⬍ 0.001). Several studies have previously described the association of poor preoperative pulmonary function with increased
pulmonary complications and particularly PAL. Patients with pulmonary function tests consistent with chronic obstructive pulmonary diesase are at especially high risk for PAL. Abolhoda and colleagues found an FEV1/FVC ratio ⬍50% to be associated with a higher incidence of PAL in their series of 100 consecutive right upper lobectomies.1 Similarly, Stolz and colleagues identified COPD (defined as a preoperative predicted FEV1 ⬍70% and FEV1/FVC ⬍70%) as predictive for PAL.14 Studies by Cerfolio, Brunelli and their colleagues have similarly demonstrated decreased FEV1 to be associated with PAL.15,16 These abnormal spirometric values represent changes in lung mechanics of COPD, namely increased airway resistance, decreased pulmonary compliance, and emphysematous parenchyma, which result in incomplete apposition of the raw pulmonary surfaces essential in closing alveolar air leaks.17 The diffusing capacity of the lung has been shown in several studies to be a strong predictor of complications after pulmonary resection.18-20 Unlike flow and volumetric studies, which measure airflow limitation and lung volumes, DLCO assesses gas exchange at the alveolar level. Even in patients without COPD, DLCO can be abnormal and has been reported by to be associated with increased postoperative morbidity.21 Upper lobectomies, bi-lobectomies, and pleural adhesions have also been associated with PAL previously.15,16,22 This might be due, in part, to the large residual space after lobectomy, preventing complete parieto-visceral pleural apposition and tears in the lung parenchyma caused by blunt or sharp dissection of pleural adhesions. Other risk factors include age, sex, and factors impairing wound healing.9,16,23,24 There have been several attempts at creating a scoring system to predict PAL. Brunelli and colleagues first reported a prediction model for prolonged air leak.15 This first model incorporated predicted postoperative FEV1 and the presence or absence of upper lobectomy and pleural adhesions. However, the regression equation was difficult to calculate and predicted postoperative FEV1 is not routinely available in all centers. The authors then developed a second scoring system using a derivation set of 658 patients and validated with 233 patients from different center. This model used an aggregate score similar to the present study, including age older than 65 years, body mass index ⬍25.5, FEV1 ⬍80% of predicted, and the presence or absence of pleural adhesions. Although similar at first glance, several important differences can be noted. In our model, pulmonary function is ranked according to severity of impairment. It stands to reason that a 60-year-old with FEV1 70% predicted and a 60-year-old with FEV1 40% predicted
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would not have the same degree of air leak. In the model by Brunelli and colleagues, these 2 patients would both be assigned the same score, but the patient with the lower FEV1 would be appropriately given a higher risk of PAL in the present study. There are also concerns about the generalizability of the scoring system by Brunelli and colleagues, given that different body habitus of Italians and North Americans. Additionally, a low body mass index can be a confounder because pulmonary function testing is not only adjusted for age and sex, but usually also height and weight as well. In this case, body mass index could have been representative of altered chest wall and pulmonary mechanics instead of malnutrition. Limitations of the present study include the retrospective single-center study design and lack of standardized protocol for air leak assessment and chest tube removal. Chest tube management was dictated by surgeon preference; however, the majority of patients were kept on suction postoperatively until the absence of air leak on forced expiration. The chest tube was then removed if the no substantial pneumothorax was seen on chest x-ray performed 4 hours after suction was discontinued. Suction was reapplied if a pneumothorax was seen. Air leak was assessed clinically. The scoring system was also internally validated, so the selection biases present in the derivation set might have been present in the validation set as well. Despite these limitations, this study remains valuable as we have derived a scoring system to predict PAL that is easy to use. Patients identified by this scoring system to have a low or high probability of PAL can be managed accordingly. Patients at high risk can receive additional surgical adjuncts, and these interventions can be avoided in patients who are unlikely to benefit.
CONCLUSIONS PAL remains a common and morbid complication after pulmonary resection. Surgical adjuncts have been developed to prevent PAL, but are of limited use and often prohibitively expensive. On multivariate analysis, poor pulmonary function and pleural adhesions were strongly associated with PAL. We have devised a simple, easy-touse scoring system using these varibales to estimate the probability of PAL after pulmonary resection. Identification of patients at high risk for PAL can lead to more selective and effective use of surgical adjuncts. Author Contributions Study conception and design: Lee, Sirois, Mulder, Ferri Acquisition of data: Lee, Hanley, Robineau Analysis and interpretation of data: Lee, Hanley, Ferri
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Drafting of manuscript: Lee, Hanley, Ferri Critical revision: Robineau, Sirois, Mulder, Ferri
REFERENCES 1. Abolhoda A, Liu D, Brooks A, Burt M. Prolonged air leak following radical upper lobectomy: an analysis of incidence and possible risk factors. Chest 1998;113:1507–1510. 2. Varela G, Jimenez MF, Novoa N, Aranda JL. Estimating hospital costs attributable to prolonged air leak in pulmonary lobectomy. Eur J Cardiothorac Surg 2005;27:329–333. 3. Okereke I, Murthy SC, Alster JM, et al. Characterization and importance of air leak after lobectomy. Ann Thorac Surg 2005; 79:1167–1173. 4. Toloza EM, Harpole DH Jr. Intraoperative techniques to prevent air leaks. Chest Surg Clin N Am 2002;12:489–505. 5. Belda-Sanchis J, Serra-Mitjans M, Iglesias Sentis M, Rami R. Surgical sealant for preventing air leaks after pulmonary resections in patients with lung cancer. Cochrane Database Syst Rev 2010;(1):CD003051. 6. Hazelrigg SR, Nunchuck SK, LoCicero J 3rd. Video Assisted thoracic surgery study group data. Ann Thorac Surg 1993;56: 1039–1043. 7. Wain JC, Kaiser LR, Johnstone DW, Y, et al. Trial of a novel synthetic sealant in preventing air leaks after lung resection. Ann Thorac Surg 2001;71:1623–1628. 8. Brunelli A, Al Refai M, Monteverde M, et al. Pleural tent after upper lobectomy: a randomized study of efficacy and duration of effect. Ann Thorac Surg 2002;74:1958–1962. 9. Hazelrigg SR, Boley TM, Naunheim KS, et al. Effect of bovine pericardial strips on air leak after stapled pulmonary resection. Ann Thorac Surg 1997;63:1573–1575. 10. DeCamp MM, Blackstone EH, Naunheim KS, et al. Patient and surgical factors influencing air leak after lung volume reduction surgery: lessons learned from the National Emphysema Treatment Trial. Ann Thorac Surg 2006;82:197–206. 11. Belboul A, Dernevik L, Aljassim O, et al. The effect of autologous fibrin sealant (Vivostat) on morbidity after pulmonary lobectomy: a prospective randomised, blinded study. Eur J Cardiothorac Surg 2004;26:1187–1191. 12. Gagarine A, Urschel JD, Miller JD, et al. Effect of fibrin glue on air leak and length of hospital stay after pulmonary lobectomy. J Cardiovasc Surg (Torino) 2003;44:771–773. 13. Fabian T, Federico JA, Ponn RB. Fibrin glue in pulmonary resection: a prospective, randomized, blinded study. Ann Thorac Surg 2003;75:1587–1592. 14. Stolz AJ, Schutzner J, Lischke R, et al. Predictors of prolonged air leak following pulmonary lobectomy. Eur J Cardiothorac Surg 2005;27:334–336. 15. Brunelli A, Monteverde M, Borri A, et al. Predictors of prolonged air leak after pulmonary lobectomy. Ann Thorac Surg 2004;77:1205–1210; discussion 1210. 16. Cerfolio RJ, Bass CS, Pask AH, Katholi CR. Predictors and treatment of persistent air leaks. Ann Thorac Surg 2002;73:1727–1730. 17. Loran DB, Woodside KJ, Cerfolio RJ, Zwischenberger JB. Predictors of alveolar air leaks. Chest Surg Clin N Am 2002;12:477–488. 18. Cerfolio RJ, Bryant AS. Different diffusing capacity of the lung for carbon monoxide as predictors of respiratory morbidity. Ann Thorac Surg 2009;88:405–410. 19. Brunelli A, Refai MA, Salati M, et al. Carbon monoxide lung diffusion capacity improves risk stratification in patients
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without airflow limitation: evidence for systematic measurement before lung resection. Eur J Cardiothorac Surg 2006;29:567–570. 20. Ferguson MK, Little L, Rizzo L, et al. Diffusing capacity predicts morbidity and mortality after pulmonary resection. J Thorac Cardiovasc Surg 1988;96:894–900. 21. Ferguson MK, Vigneswaran WT. Diffusing capacity predicts morbidity after lung resection in patients without obstructive lung disease. Ann Thorac Surg 2008;85:1158–1164.
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22. Cerfolio RJ, Bass C, Katholi CR. Prospective randomized trial compares suction versus water seal for air leaks. Ann Thorac Surg 2001;71:1613–1617. 23. Rice TW, Okereke IC, Blackstone EH. Persistent air-leak following pulmonary resection. Chest Surg Clin N Am 2002;12: 529–539. 24. Cerfolio RJ, Tummala RP, Holman WL, et al. A prospective algorithm for the management of air leaks after pulmonary resection. Ann Thorac Surg 1998;66:1726–1731.
Prolonged air leak (PAL) is a common complication after pulmonary resection, with a reported incidence of up to 26% after surgery for lung cancer.1 PAL represents a major clinical problem because it is associated with considerable economic costs and increased rates of other postoperative complications, length of hospitalization, and mortality.2,3 Intraoperative pneumostasis, postoperative maintenance of lung expansion, and pleural apposition remain imperative in preventing this complication.4 Surgical adjuncts including biologic sealants, autologous blood pleurodesis, and staple-line buttressing have been developed in an effort Disclosure Information: Nothing to disclose. Received December 18, 2010; Revised March 4, 2011; Accepted March 7, 2011. From the Department of Surgery, Division of Thoracic Surgery, McGill University Health Center, Montreal, QC, Canada. Correspondence address: Lorenzo E Ferri, MD, PhD, FACS, Department of Surgery, McGill University, Montreal General Hospital, L9-112, 1650 Cedar Ave, Montreal, Quebec H3G 1A4, Canada. email: [email protected]
© 2011 by the American College of Surgeons Published by Elsevier Inc.
to decrease postoperative air leak. However, routine use of these adjuncts are of unproven use, and are often very costly. A Cochrane meta-analysis investigating the effectiveness of biologic and synthetic sealants or glues could not demonstrate a substantial reduction in the incidence of PAL or duration of hospitalization.5 Pleural-based adjuncts, such as pleural tenting or autologous blood patch pleurodesis, have been described, but they are technically difficult and associated with their own set of complications. The true effectiveness of these adjuncts might be hidden by the fact that these trials did not specifically target patients at high risk for PAL. Multiple risk factors for PAL have been described previously, but predicting the patients in whom PAL will develop remains an inexact science. Identifying high-risk patients can lead to more targeted and effective use of these expensive surgical sealants and other adjuncts. Therefore, the aim of this study was to identify risk factors for PAL and to derive a simple scoring system to predict the risk of PAL.
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METHODS A derivation set was identified from a prospectively entered database of patients who underwent pulmonary resection between August 2002 and March 2007 at a single university teaching hospital. Patients with potential confounding operative and postoperative factors were excluded (pneumonectomy, immediate postoperative mechanical ventilation, trauma, blebectomy, major chest wall or diaphragmatic resections, and trans-sternal resection). Patients were also excluded if surgical sealants or other buttressing materials were used. Real-time documentation of all postoperative outcomes, including air leak, was performed by a nurse clinician rounding daily with the ward service and entered in the database. PAL was defined as an air leak lasting longer than 7 days. Variables were compared between patients with PAL and those without. Variables considered were patient sex and age, open thoracotomy versus video-assisted thoracoscopic surgery, anatomic versus wedge resection, presence of pleural adhesions at the time of operation, surgeon, and pulmonary function testing. Results are presented as mean ⫾ SEM. Statistical significance between means was determined using two-tailed Student’s t-test for continuous variables, and chi-square analysis for categorical variables. Differences were considered significant at p ⬍ 0.05. Given that patients having undergone wedge resections were at limited risk of PAL as compared with those having undergone anatomic resection, additional analyses were restricted to the subset of patients having undergone anatomic resection. Stepwise logistic regression analysis was performed to establish a simple predictive model to estimate the risk of PAL. Coefficients were then rounded to provide a simple weighted scoring system to allow a rapid estimation of risk of PAL. This scoring system was then validated in a set of patients who underwent pulmonary resection between April 2007 and June 2009 at the same university teaching hospital identified here. Patients were assigned into bins using the developed scoring system and observed and expected frequencies were compared by Hosmer-Lemeshow goodness-of-fit test. RESULTS From August 2002 to March 2007, five hundred and eighty patients underwent pulmonary resection for suspected or confirmed malignancy and fit the inclusion criteria described here. Patient and operative variables are presented in Table 1. Overall incidence of PAL was 14.1%. Of note, the vast majority of resections were performed by open thoracotomy and two-thirds of re-
J Am Coll Surg
Table 1. Derivation and Validation Set Variables (All Patients)
Variable
Sex, male (%) Age (y), mean ⫾ SD Open thoracotomy (%) Anatomic resection (%) Presence of pleural adhesions (%) FEV1 (% predicted), mean ⫾ SD DLCO (% predicted), mean ⫾ SD PAL (%)
Derivation set (n ⴝ 580)
Validation set (n ⴝ 381)
51 63 ⫾ 1 88 68 25 85 ⫾ 1 82 ⫾ 1 14
45 68 ⫾ 1 76 67 18 86 ⫾ 1 77 ⫾ 1 18
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second; PAL, prolonged air leak.
sections were anatomic (lobectomy or segmentectomy), with the remainder being wedge resections (Table 1). To identify factors that predict the risk of PAL, we performed univariate analysis of these variables. Of the variables considered, procedures performed by open thoracotomy (98% PAL⫹ versus 87% PAL⫺; p ⫽ 0.082), anatomic resection (89% versus 64%; p ⬍ 0.001), the presence of pleural adhesions (34% versus 23%; p ⫽ 0.031), forced expiratory volume in 1 second (FEV1; 74 versus 87% predicted; p ⬍ 0.001) and carbon monoxide diffusing capacity (DLCO; 71 versus 84% predicted; p ⬍ 0.001) were associated with an increased risk of PAL. Of these variables, the risk of PAL appeared to correlate most with anatomic resection (wedge: 4.8% versus lobectomy/segmentectomy: 18.6%, p ⬍ 0.001). Given the limited risk of PAL in patients undergoing wedge resection and the fact that more than two-thirds of patients underwent anatomic resection, we elected to restrict additional analysis to the subset of patients having undergone anatomic resection. Patient and operative variables for the subset of patients having undergone anatomic resection are presented in Table 2. The incidence of PAL in this group was 18.6%. Univariate analysis of this group indicated that the presence of pleural adhesions and impaired pulmonary function continued to be associated with increased risk of PAL (Table 2), and open thoracotomy was no longer significantly correlated. This stands to reason, as most wedge resections were performed by video-assisted thoracoscopic surgery and most anatomic resections were performed by open thoracotomy, as evidenced by the significant association between these two variables (p ⬍ 0.001). To establish a model to predict the risk of PAL, we performed stepwise logistic regression using the variables identified in Table 2. To account for the increased risk of PAL associated with impaired pulmonary func-
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Table 2. Derivation Set Variables Associated with Prolonged Air Leak (Anatomic Resection) Air leak Variable
Overall
<7 Days
>7 Days
p Value
Sex, male (%) Age (y), mean ⫾ SD Open thoracotomy (%) Presence of pleural adhesions (%) FEV1 (% predicted), mean ⫾ SD DLCO (% predicted), mean ⫾ SD
50 64 ⫾ 1 98 27 84 ⫾ 1 82 ⫾ 1
48 63 ⫾ 1 97 24 87 ⫾ 1 84 ⫾ 1
59 66 ⫾ 1 99 37 74 ⫾ 3 71 ⫾ 3
0.092 0.053 0.558 0.029 ⬍0.001 ⬍0.001
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second.
tion, pulmonary function testing values were entered into the model as 100 ⫺ FEV1, and 100 ⫺ DLCO. The coefficients from the logistic regression model (Table 3) were then rounded to provide a simple weighted scoring system to allow a rapid estimation of risk of PAL (Table 4). In this model, baseline risk for a patient undergoing anatomic resection with normal pulmonary function tests and no pleural adhesions is 8.2%. A patient with pleural adhesions and poor pulmonary function is most at risk for PAL developing, with the presence of pleural adhesions having the same prognostic value as a 20% decrease in FEV1, or a 40% decrease in DLCO. For example, a patient with mild chronic obstructive pulmonary disease (predicted FEV1 ⫽ 70% and DLCO ⫽ 80%) undergoing a pulmonary lobectomy with the presence of intrapleural adhesions has an estimated probability of PAL of 28.5%. To validate this model, the scoring system was applied to a set of 381 consecutive patients who underwent pulmonary resection between April 2007 and June 2009 at the same university teaching hospital identified above (Table 1). Scores were calculated for each patient, and observed and expected frequencies were compared between weighted groups of patients by Hosmer-Lemeshow goodness-of-fit test (Table 5). Although the scores appeared less accurate at predicting low risk of PAL, the model was found to be well-calibrated (p ⬎ 0.2).
Table 3. Logistic Regression of Variables Predicting Prolonged Air Leak (Anatomic Resection) Variable
Constant Presence of pleural adhesions 100 ⫺ FEV1 (% predicted) 100 ⫺ DLCO (% predicted)
 coefficient
p Value
2.420 ⫺0.483 ⫺0.026 ⫺0.013
⬍0.001 0.140 0.003 0.091
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second.
DISCUSSION PAL after pulmonary resection is a common complication, occurring in up to 26% of cases.1 It has been reported to increase complications, length of hospitalization, and hospital costs.2,3 Prevention of this common yet highly morbid complication begins with meticulous surgical technique to avoid tears in the lung parenchyma and the closure of macroscopic air leaks.6 Lack of an intraoperative air leak does not reliably indicate the absence of postoperative air leak.7 Considerable efforts have been made to develop surgical adjuncts to prevent PAL. Several surgical techniques have been described, including pleural tenting, pneumoperitoneum, mechanical pleurodesis, and staple line buttressing, but all of these procedures have their own limitations or are prohibitively expensive to be used routinely.8-10 New biologic and synthetic sealants have becoming increasingly popular as a method to prevent Table 4. Scoring System to Estimate the Risk of Prolonged Air Leak Anatomic resection
Wedge resection Presence of pleural adhesions FEV1 (% predicted) DLCO (% predicted) Risk (%) 8.2 10.2 12.8 15.8 19.5 23.7 28.5 33.8 39.7 45.8 52.0 58.2
Score
Risk ⫽ 4.8% ⫹2 ⫹1 per 10% below 100% ⫹1 per 20% below 100% 0 1 2 3 4 5 6 7 8 9 10 11
DLCO, carbon monoxide diffusing capacity; FEV1, forced expiratory volume in 1 second.
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Table 5. Hosmer-Lemeshow Goodness-of-FitTest in Validation Set Score
<1
2ⴚ3
4
5
6ⴚ7
>8
Expected risk (%) Observed risk (%)
9.0 16.7
14.5 17.5
19.5 16.0
23.7 31.8
31.6 22.2
44.4 46.2
postoperative air leaks, but results have been equivocal. Single-center trials have reported reductions in chest tube duration and incidence of PAL, but a decreased length of hospitalization has not been consistently demonstrated.11-13 A Cochrane meta-analysis also reported that PAL was reduced only in two of the seven trials that reported outcomes on PAL, and length of stay was considerably reduced in only 3 of 14 trials.5 Based on these results, authors of the Cochrane review could not recommend systematic use of surgical sealants. However, these adjuncts can be effective if used only in patients who are at high-risk of PAL. Therefore, we have derived a simple scoring system to predict the probability of PAL, and then validated it in a consecutive series of 381 patients. The incidence of PAL in the derivation and validation sets was 14% and 18%, respectively. PAL was strongly associated with anatomic resection, poor pulmonary function, and presence of pleural adhesions on unvariate analysis. Because of the limited incidence of PAL in nonanatomical resections in our derivation set (4.8%), we decided to restrict analysis to anatomic resections only. Even after excluding nonanatomical resections, poor pulmonary function and pleural adhesions remained significantly associated with PAL. Pleural adhesions, FEV1 (each 10% below 100% predicted) and DLCO (each 10% below 100% predicted) were assigned a score based on the  coefficient using stepwise logistic regression. The aggregate score then estimated the probability of PAL (Table 4). This scoring system was then validated in a consecutive set of 381 patients treated at the same institution (Table 5). Age approached statistical significance on univariate analysis in the original derivation set of patients, as well as the subset of patients who underwent anatomic resection (Table 2), but was not included in the final model. Given that FEV1 and DLCO values were expressed relative to predicted values corrected for age, sex, height, and weight, it was inherent that the effect of age would be included indirectly in the final model. To this end, re-analysis including age did not improve the accuracy of the model. In addition, Pearson correlation analysis demonstrated age to be correlated with FEV1 (r ⫽ ⫺0.100, p ⫽ 0.077) and DLCO (r ⫽ ⫺0.215, p ⬍ 0.001). Several studies have previously described the association of poor preoperative pulmonary function with increased
pulmonary complications and particularly PAL. Patients with pulmonary function tests consistent with chronic obstructive pulmonary diesase are at especially high risk for PAL. Abolhoda and colleagues found an FEV1/FVC ratio ⬍50% to be associated with a higher incidence of PAL in their series of 100 consecutive right upper lobectomies.1 Similarly, Stolz and colleagues identified COPD (defined as a preoperative predicted FEV1 ⬍70% and FEV1/FVC ⬍70%) as predictive for PAL.14 Studies by Cerfolio, Brunelli and their colleagues have similarly demonstrated decreased FEV1 to be associated with PAL.15,16 These abnormal spirometric values represent changes in lung mechanics of COPD, namely increased airway resistance, decreased pulmonary compliance, and emphysematous parenchyma, which result in incomplete apposition of the raw pulmonary surfaces essential in closing alveolar air leaks.17 The diffusing capacity of the lung has been shown in several studies to be a strong predictor of complications after pulmonary resection.18-20 Unlike flow and volumetric studies, which measure airflow limitation and lung volumes, DLCO assesses gas exchange at the alveolar level. Even in patients without COPD, DLCO can be abnormal and has been reported by to be associated with increased postoperative morbidity.21 Upper lobectomies, bi-lobectomies, and pleural adhesions have also been associated with PAL previously.15,16,22 This might be due, in part, to the large residual space after lobectomy, preventing complete parieto-visceral pleural apposition and tears in the lung parenchyma caused by blunt or sharp dissection of pleural adhesions. Other risk factors include age, sex, and factors impairing wound healing.9,16,23,24 There have been several attempts at creating a scoring system to predict PAL. Brunelli and colleagues first reported a prediction model for prolonged air leak.15 This first model incorporated predicted postoperative FEV1 and the presence or absence of upper lobectomy and pleural adhesions. However, the regression equation was difficult to calculate and predicted postoperative FEV1 is not routinely available in all centers. The authors then developed a second scoring system using a derivation set of 658 patients and validated with 233 patients from different center. This model used an aggregate score similar to the present study, including age older than 65 years, body mass index ⬍25.5, FEV1 ⬍80% of predicted, and the presence or absence of pleural adhesions. Although similar at first glance, several important differences can be noted. In our model, pulmonary function is ranked according to severity of impairment. It stands to reason that a 60-year-old with FEV1 70% predicted and a 60-year-old with FEV1 40% predicted
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would not have the same degree of air leak. In the model by Brunelli and colleagues, these 2 patients would both be assigned the same score, but the patient with the lower FEV1 would be appropriately given a higher risk of PAL in the present study. There are also concerns about the generalizability of the scoring system by Brunelli and colleagues, given that different body habitus of Italians and North Americans. Additionally, a low body mass index can be a confounder because pulmonary function testing is not only adjusted for age and sex, but usually also height and weight as well. In this case, body mass index could have been representative of altered chest wall and pulmonary mechanics instead of malnutrition. Limitations of the present study include the retrospective single-center study design and lack of standardized protocol for air leak assessment and chest tube removal. Chest tube management was dictated by surgeon preference; however, the majority of patients were kept on suction postoperatively until the absence of air leak on forced expiration. The chest tube was then removed if the no substantial pneumothorax was seen on chest x-ray performed 4 hours after suction was discontinued. Suction was reapplied if a pneumothorax was seen. Air leak was assessed clinically. The scoring system was also internally validated, so the selection biases present in the derivation set might have been present in the validation set as well. Despite these limitations, this study remains valuable as we have derived a scoring system to predict PAL that is easy to use. Patients identified by this scoring system to have a low or high probability of PAL can be managed accordingly. Patients at high risk can receive additional surgical adjuncts, and these interventions can be avoided in patients who are unlikely to benefit.
CONCLUSIONS PAL remains a common and morbid complication after pulmonary resection. Surgical adjuncts have been developed to prevent PAL, but are of limited use and often prohibitively expensive. On multivariate analysis, poor pulmonary function and pleural adhesions were strongly associated with PAL. We have devised a simple, easy-touse scoring system using these varibales to estimate the probability of PAL after pulmonary resection. Identification of patients at high risk for PAL can lead to more selective and effective use of surgical adjuncts. Author Contributions Study conception and design: Lee, Sirois, Mulder, Ferri Acquisition of data: Lee, Hanley, Robineau Analysis and interpretation of data: Lee, Hanley, Ferri
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Drafting of manuscript: Lee, Hanley, Ferri Critical revision: Robineau, Sirois, Mulder, Ferri
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