Incidence and Risk Factors of Persistent Air Leak After Major Pulmonary Resection and Use of Chemical Pleurodesis

Transcription

1 Incidence and Risk Factors of Persistent Air Leak After Major Pulmonary Resection and Use of Chemical Pleurodesis Moishe Liberman, MD, Alona Muzikansky, Cameron D. Wright, MD, John C. Wain, MD, Dean M. Donahue, MD, James S. Allan, MD, Henning A. Gaissert, MD, Christopher R. Morse, MD, Douglas J. Mathisen, MD, and Michael Lanuti, MD Divisions of Thoracic Surgery and Biostatistics, Massachusetts General Hospital, Boston, Massachusetts Background. Persistent air leak (PAL; defined as air leak > 5 days) after major pulmonary resection is prevalent and associated with significant morbidity. This study examines an incompletely characterized treatment for the management of PAL, chemical pleurodesis. Methods. A retrospective case-control study examining all isolated lobectomies and bilobectomies by thoracotomy was performed. The PALs (1997 to 2006) and controls (2002 to 2006) were identified from a prospective database. Incidence, risk factors, management, and outcome were defined. Results. Over 9 years, 78 PALs were identified in 1,393 patients (5.6%). Controls consisted of 700 consecutive patients. Propensity score analysis matching case and controls showed no predictive risk factors for air leak using a logistic regression model. Univariate analysis demonstrated that female gender, smoking history, and forced vital capacity were predictive risk factors. Treatment of PAL consisted of observation (n 33, 42.3%), pleurodesis (n 41, 52.6%), Heimlich valve (n 3, 3.8%), and reoperation (n 1, 1.3%). Seventy-three patients (93.6%) required no further intervention. One patient required a muscle flap, one readmission for pneumothorax, and one empyema resulting in death. Sclerosis was successful in 40 of 41 patients (97.6%). Mean time to treatment was days, mean duration of air leak was , and mean duration of air leak postsclerotherapy was days. Postoperative pneumonia occurred with increased frequency in PAL patients (6 of 45 [13.3%] vs 34 of 700 [4.9%], p 0.014). PAL was associated with increased length of stay (14.2 vs 7.1 days, p < 0.001) and time with chest tube (11.5 vs 3.4 days, p < 0.001). Conclusions. Air leaks remain an important cause of morbidity. Pleurodesis is an effective option in management of PAL after major pulmonary resection. (Ann Thorac Surg 2010;89:891 8) 2010 by The Society of Thoracic Surgeons Prolonged air leak occurs in up to 26% of patients [1 6] after major pulmonary resection. These air leaks represent a significant source of morbidity and cost secondary to prolonged tube thoracostomy and hospital stay. Various techniques have been devised in order to decrease the incidence of prolonged air leak including: buttressing suture/staple lines [7 10], fissureless resections, visceral pleural sealants [11 13], pleural tents [14, 15], pneumoperitoneum [16], use of water seal as opposed to suction postoperatively [17 19), alternate suction-water seal [20], and phrenic nerve paresis-paralysis [21]. Unfortunately, despite these efforts, prolonged air leaks still occur. Traditionally, treatment for prolonged air leaks after major pulmonary resection included: watchful waiting and (or) Heimlich valve placement. These strategies Accepted for publication Dec 9, Presented at the Forty-fourth Annual Meeting of the Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28 30, Address correspondence to Dr Lanuti, 55 Fruit St, Blake 1570, Boston, MA 01748; mlanuti@partners.org. require prolonged tube thoracostomy and often discharge home with a chest tube in situ. Recently, sclerosis has been employed in order to create visceral-parietal pleurodesis in an attempt to curtail the air leak, allow early removal of the chest tube, and decrease length of stay. This study evaluates risk factors for persistent air leak after routine pulmonary resection and the feasibility and outcome of pleurodesis in the management of persistent air leak. Material and Methods This study consists of a retrospective case-control study examining all isolated lobectomies and bilobectomies performed by thoracotomy at a single institution. Exclusion criteria consisted of the following: all video-assisted pulmonary resections; wedge resections; segmentectomies; and pneumonectomies. All patients underwent resection and received all of their postoperative care at a single institution. Intraoperative and postoperative management of chest tubes were similar among eight thoracic 2010 by The Society of Thoracic Surgeons /10/$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 892 LIBERMAN ET AL Ann Thorac Surg PERSISTENT AIR LEAK AFTER LUNG RESECTION 2010;89:891 8 surgeons. Most surgeons placed one or two 28Fr chest tubes after lobectomy. Both water seal and suction (20 cm H 2 O) were used postoperatively depending on surgeon preference. Persistent air leaks were defined as those patients with ongoing air leak after the fifth postoperative day, as well as patients undergoing an intervention for a large volume air leak prior to day six. This study was approved by the Institutional Review Board (IRB) at the Massachusetts General Hospital and individual consent was waived. The persistent air leak cohort consisted of consecutive patients with prolonged air leak (as defined above) between January 1, 1997 and December 31, The control group consisted of consecutive patients undergoing pulmonary resection between January 1, 2002 and December 31, Both groups were identified from a prospective thoracic surgery database at the Massachusetts General Hospital, Boston, MA. Data were obtained from the medical record, including office charts, anesthesia records, and in-hospital charts. Demographics of the sample as well as all results are based on the 778 patients with complete preoperative and postoperative data available (78 patients with prolonged air leak and 700 controls). In order to perform pleurodesis for the treatment of prolonged air leaks after pulmonary resection, a pleural sclerosing agent was sterilely instilled through the indwelling chest tube, and then the Pleur-evac (Teleflex Medical, Research Triangle Park, NC) flexible tubing was raised above the patient s bed for 1 to 2 hours. The sclerosant was administered in a sterile manner into the chest tube to avoid empyema. Patients chest tubes were first evaluated on water seal to ensure the absence of any significant lung collapse prior to attempting bedside pleurodesis. The chest tube was not clamped. The patient was instructed to turn from side to side every 15 minutes to facilitate uniform intrapleural application of the agent. After 1 to 2 hours, the pleurovac tubing is placed back on the floor and low level suction (10 to 20 cm H 2 O) is applied for 48 hours to potentiate apposition of visceral and parietal pleura. Multiple sclerosing agents were used independently throughout the study period including talc, bleomycin, doxycycline, and minocycline. More commonly, 5 grams of sterile talc was used as the sclerosant of choice in most patients. Success of pleurodesis was measured by resolution of air leak and removal of chest drain before discharge from the hospital. Sterile preparation of talc (Humco, Texarkana, TX) during the study period was performed in our pharmacy. The preparation comes in uniform particle size and is batched in 5 gram aliquots and subsequently sterilized. The talc preparation is diluted in 50 cc of normal saline producing a talc slurry which is sterilely delivered through a 60 cc syringe. The incidence of prolonged air leak was calculated based on the number of major pulmonary resections performed over the entire study period (1997 to 2006). Risk factors for prolonged air leak were compared between groups. The 2, the Fisher exact, and the Student t tests were used to compare outcome between groups. Because the control group and test group did not completely overlap in time, propensity score analysis was performed to better match cases with controls. A multivariable logistic regression model was constructed to evaluate predictors of postoperative air leak, using only the subset of variables that came out significant on a univariate analysis. Results Over 9 years, 78 PALs were identified in 1,393 patients. The incidence of prolonged air leak after major pulmonary resection was therefore 5.6%. Results are based on 778 patients with complete preoperative and postoperative datasets (78 persistent air leak patients and 700 controls). Patient age ranged from 22 to 89 years with a median age of Table 1 describes the sample demographics for the overall (n 778) and the prolonged air leak (n 78) cohorts, respectively. Table 2 compares Table 1. Demographics: Overall Study and Test Population Overall Study Population (n 778) Prolonged Air Leak Cohort (n 78) Variables Mean SD Median (Range) Mean SD Median (Range) Age (22 89) (23 89) Preoperative FEV 1.0 (L) ( ) ( ) Percent predicted preoperative FEV 1.0 (L) (20 162) (29 123) Smoking pack-years (1 200) (12 200) Days with chest tube (0 57) (6 27) Postoperative day of intervention for N/A N/A (4 24) prolonged air leak Days with air leak after intervention N/A N/A (0 9) Length of stay (days) (2 373) (6 104) Frequency (%): Sex: Female 431 (55.4%) 34 (43.6%) Steroid use 11 (1.5%) 2 (4.4%) Smoking history 605 (81.2%) 42 (93.3%) FEV 1.0 forced expiratory volume in the first second of expiration; N/A not applicable.

3 Ann Thorac Surg LIBERMAN ET AL 2010;89:891 8 PERSISTENT AIR LEAK AFTER LUNG RESECTION 893 Table 2. Operative Procedure, Laterality, TNM Classification, and Stage Variables Overall (n 778) Control (n 700) Air Leak (n 78) Procedure: Right upper lobectomy 280 (36.0%) 242 (34.6%) 38 (48.7%) Right middle lobectomy 71 (9.1%) 69 (9.9%) 2 (2.6%) Right lower lobectomy 129 (16.6%) 117 (16.7%) 12 (15.4%) Bilobectomy 29 (3.7%) 24 (3.4%) 5 (6.4%) Left upper lobectomy 152 (19.5%) 139 (19.9%) 13 (16.7%) Left lower lobectomy 113 (14.5%) 109 (15.6%) 4 (5.1%) Other 4 (0.5%) 0 4 (0.5%) Laterality: Right-sided resection 509 (65.4%) 452 (64.6%) 57 (73.1%) Left-sided resection 269 (34.6%) 248 (35.4%) 21 (26.9%) NSCLC stage: IA 277 (43.6%) 249 (43.8%) 28 (42.4%) IB 168 (26.5%) 150 (26.4%) 18 (27.3%) IIA 35 (5.5%) 34 (6.0%) 1 (1.5%) IIB 69 (10.9%) 64 (11.2%) 5 (7.6%) IIIA 67 (10.6%) 57 (10.0%) 10 (15.2%) IIIB 12 (1.9%) 9 (1.6%) 3 (4.5%) IV 7 (1.1%) 6 (1.1%) 1 (1.5%) NSCLC non-small cell lung carcinoma; TNM tumor, nodes, metastasis. the operative procedure, laterality, and pathologic stage for all cohorts. Risk factors for prolonged air leak are shown in Table 3. On univariate analysis, female sex (p 0.031), a history of smoking (p 0.030), decreased preoperative forced expiratory volume (FEV 1.0 )(p 0.022), and decreased preoperative percent predicted FEV 1.0 (p 0.001) were associated with increased likelihood of postoperative prolonged air leak. Matched case-controls after propensity scoring showed no predictive variables for prolonged air leak using a logistic regression model with parameters that were significant on univariate analysis. The surgeon was not found to be an independent predictor of air leak on univariate logistic regression analysis. Treatment of prolonged air leaks consisted of observation in 33 (42.3%), pleurodesis in 41 (52.6%), discharge home with a Heimlich valve in 3 patients (3.8%), and reoperation in 1 patient (wedge resection) (1.3%) (Fig 1). Long-term outcome in the prolonged air leak cohort included: no further intervention in 73 patients (93.6%), muscle flap in one patient (1.3%), readmission for pneumothorax and placement of a chest tube in one patient (1.3%) (this patient was sclerosed successfully on readmission with bleomycin and then talc), Heimlich valve placement in one patient (1.3%), hydropneumothorax not requiring treatment in one patient (1.3%), and empyema resulting in death in one patient (1.3%). In the prolonged air leak cohort (n 78), the mean time to treatment was days, mean duration of air leak was , the mean duration of air leak postsclerotherapy was days, the mean number of days with a chest tube in place was days, and the mean length of stay was For the pleurodesis group (n 41), the mean time to treatment was days, mean duration of air leak was , the mean duration of air leak postsclerotherapy was days, the mean number of days with a chest tube in place was days, and the mean length of stay was There were no immediate adverse events related to pleurodesis. Table 3. Univariate Analysis: Prolonged Air Leak Risk Factors Risk Factor Air Leak Present Air Leak Absent p Value Female sex (n, %) 34/78 (43.6%) 397/700 (56.7%) Age (mean, SD) Right-sided (n, %) 57/78 (73.1%) 452/700 (64.6%) Steroids (n, %) 2/45 (4.4%) 9/700 (1.3%) Smoking history (n, %) 42/45 (93.3%) 563/700 (80.4%) Pack/years (mean, SD) FEV 1.0 (mean, SD) % predicted FEV 1.0 (mean, SD) FEV 1.0 forced expiratory volume in the first second of expiration.

4 894 LIBERMAN ET AL Ann Thorac Surg PERSISTENT AIR LEAK AFTER LUNG RESECTION 2010;89:891 8 failure to thrive two months later and had a chest tube placed for a purulent pleural effusion growing Staph aureus. The patient was taken to the operating room for decortication. Postoperatively, he required escalating inotropic support for worsening sepsis and died 9 days later. Fig 1. Treatment of prolonged air leak. Sclerosis for the treatment of prolonged air leak was successful in 40 of 41 patients (97.6%). Five patients (12.2%) required repeat sclerosis, which was successful in four patients (80%). Sclerosing agents used in pleurodesis included the following: talc (n 30, 73.2%); bleomycin (n 1, 2.4%); doxycycline (n 7, 17.1%); minocycline (n 1, 2.4%); a combination of bleomycin and talc (n 1, 2.4%); and a combination of doxycycline and talc (n 1, 2.4%). Postoperative pneumonia occurred with increasing frequency in patients with prolonged air leak (6 of 45 [13.3%]; pneumonia data only available for 45 patients) compared with patients without air leak (34 of 700 [4.9%]), p Pneumonia was defined as documentation of a new pulmonary infiltrate with associated leucocytosis and (or) fever that prompted antibiotic use. Prolonged air leak was associated with increased length of stay (14.2 vs 7.1, p 0.001) and increased chest tube duration (11.5 vs 3.4, p 0.001). The one patient who failed pleurodesis had a right upper lobectomy after neoadjuvant chemoradiotherapy and underwent talc pleurodesis (2.5 grams, two attempts) on postoperative days 6 and 7. He had a persistent right apical space on suction and required pectoralis muscle flap on postoperative day 8 for persistent air leak. His air leak stopped 7 days later and the chest tube was removed. One patient in the pleurodesis cohort developed an empyema after sclerosis. He underwent right lower lobectomy and had a persistent air leak treated with 5 grams of talc on postoperative day 8. His air leak ceased four days later where he was discharged home after chest tube removal with a stable right apical and basilar loculated hydropneumothorax. He was readmitted with Comment Prolonged air leaks are a significant cause of morbidity, increased hospital stay, cost, and even death [1, 2, 22 24] after pulmonary surgery. Prolonged air leaks have been described to occur in up to 26% of patients after pulmonary resection [1 6]. Air leaks of greater than 7 days have been associated with an empyema rate of 8.2% compared with 0% in patients without prolonged air leaks [25]. The definition of prolonged air leak has been described to be an air leak that persists for more than 4 to 10 days after surgery. Five days was employed in our analysis as a consequence of the March 2009 harvest from the Society of Thoracic Surgeons database representing 97 institutions where the median length of stay after lobectomy (n 18,352) was 5 days. Thus, a prolonged air leak is differentiated from a routine postoperative air leak as one which prolongs the length of hospital stay more than 5 days. Historic risk factors for prolonged air leak include the following: steroid use [26]; chronic obstructive pulmonary disease; decreased FEV 1.0 (8,33); decreased percent predicted FEV 1.0 ; decreased FEV 1.0 / forced vital capacity (2); decreased carbon monoxide lung diffusion capacity; anatomic lobe resected (1); adhesions [26]; and surgeon (1). We demonstrated that females, patients with a smoking history, and decreased preoperative pulmonary function (low FEV 1.0 and low percent predicted FEV 1.0 ), have an increased incidence of air leak. Although steroids did not achieve statistical significance as a risk factor in this analysis, prolonged air leak was threefold higher in the test group compared with the control group. Right upper lobectomy was associated with the highest incidence of air leak among all lobectomy categories (49%). This is not surprising because the right upper lobe anatomically abuts two fissures where the minor fissure is nearly complete in approximately 50% of cases. Strategies used to decrease the risk of postoperative air leak include fissureless dissection, buttressing staple lines [7 10], use of surgical sealants [11 13], pleural tents for upper lobe resections [14, 15], minimization or elimination of postoperative suction [17 19], alternate suction-water seal [20], use of pneumoperitoneum [16], phrenic nerve paresis-paralysis [21], and minimization of airway pressures while on the ventilator. Despite these maneuvers, prolonged air leaks still occur and are a source of patient inconvenience, morbidity, increased cost, and frustration to both patient and surgeons. Management of prolonged air leaks consists of watchful waiting, Heimlich valve placement [27, 28], provocative chest tube clamping with removal several hours later in the absence of pneumothorax or subcutaneous emphysema [29], reoperation, and pleurodesis. Chemical pleurodesis in the context of persistent air leak after

5 Ann Thorac Surg LIBERMAN ET AL 2010;89:891 8 PERSISTENT AIR LEAK AFTER LUNG RESECTION 895 major pulmonary resection has not been well described in the literature. We report on 40 successful scleroses in 41 patients with prolonged air leak. In this group of patients, the mean time to treatment was days, mean duration of air leak was days, and the mean duration of air leak postsclerotherapy was days. There were no immediate adverse events related to the sclerosing agent seen in the pleurodesis group. One patient developed empyema two months after pleurodesis and subsequently died. Sclerosants are known to incite a vigorous inflammatory response in the pleura providing substrate for symphysis and obliteration of the pleural space and cessation of air leak. Sclerosants that can be used include talc, doxycycline, minocycline, bleomycin, tetracycline, silver nitrate, quinacrine, and iodopovidone [30 32]. These are typically instilled through the indwelling chest tube. We favor the use of talc as the primary sclerotic agent. Our treatment algorithm for the treatment of prolonged air leak in the context of pulmonary resection is outlined in Figure 2. Video-assisted thoracic surgery or thoracotomy can also be implemented to mechanically abrade the pleura and/or instill sclerosant as an adjunct to considering a muscle flap [33]. Sclerotherapy using an autologous blood patch has been recently described and appears to be effective [34 36]. Talc is composed of pulverized, natural, foliated, hydrated magnesium silicate. Calcium, aluminum, and iron are always present in variable amounts. There are more than threefold differences in the median particle size of various talc preparations (across different companies) used for pleurodesis, and there are also marked variabilities in the contaminants present in various talc preparations. Asbestos free talc is now the standard of care. Talc pleurodesis has been shown to be safe and has not been associated with increased mortality in patients with malignant pleural effusions [37]. Despite reports demonstrating a 5% to 33% incidence of an allergic or systemic inflammatory response to talc [38, 39], the incidence of acute lung injury after talc administration was an infrequent event in our study population. Our results provide additional evidence that talc has no significant adverse affects in patients with prolonged air leak after major pulmonary resection. The major contender in the treatment of prolonged air leak after pulmonary resection is patient discharge with a Heimlich valve or a mini-chest tube collection system with a one-way valve in place. Advantages to the Heimlich valve strategy include its ease of placement, immediate patient discharge from hospital, and lack of foreign substance instillation into the pleural cavity with its inherent risks. The disadvantages to the Heimlich strategy compared with pleurodesis include the inconvenience of discharging patients with a chest tube in place (often requiring home care services and supplies for site care), chest tube-related discomfort and pain, risk of pleural infection secondary to indwelling chest tube, and the inconvenience of bringing patients back to the hospital for frequent visits and X-rays until the leak seals. Removal of chest tubes at 2 to 3 weeks despite the presence of persistent air leak after pulmonary resection has been recently proposed by a single institution as an option with few complications [40]. We acknowledge limitations in our study design. The retrospective nature of data acquisition introduces several biases into our analysis. Treatment strategy in patients in the prolonged air leak cohort was surgeon dependent and often based on volume of air leak. This is the probable explanation for the fewer number of days with an air leak and chest tube days for patients in the observation, compared with the pleurodesis group. If the surgeon employed the use of a sclerosing agent, chest Fig 2. Persistent air leak treatment algorithm.

6 896 LIBERMAN ET AL Ann Thorac Surg PERSISTENT AIR LEAK AFTER LUNG RESECTION 2010;89:891 8 tubes would remain in place for a time period of 48 hours prior to removal, thus adding 2 days to patients who may have been close to sealing under observation. The control group does not cover the entire study period from which cases were accrued, requiring the implementation of propensity score analysis to better match cases with controls. Additionally, the small sample size of prolonged air leak due to modern techniques of air leak prevention weakens the statistical analysis. Strengths of this study include its large control sample size and uniformity of patient treatment as a consequence of a single institution s consecutive experience. This study demonstrates that talc pleurodesis is a simple, effective, and a rapid method of treating prolonged air leak after pulmonary resection. We recommend a trial of sclerosis for carefully selected patients with a nonresolving air leak after postoperative day 5. Talc sclerosis is not advisable in patients with previous pneumonectomy or suspicion of systemic infection or pneumonia for fear of empyema. If an air leak is very large, bronchoscopy should be performed to rule out bronchial stump dehiscence or bronchopleural fistula prior to attempts at pleurodesis. In patients in whom pleurodesis fails, a pectoralis major flap based on the thoraco-acromial artery is a good option in order to fill an apical space and hasten the air leak. Fibrin sealants should be avoided in the setting of persistent air leak because bacteria can be sequestered and thus potentiate development of empyema. Effective sclerosis allows patients with prolonged air leak to leave the hospital early without the need for an indwelling tube with its inherent inconvenience, care requirements, and risk. Financial support for this study was provided by the Division of Thoracic Surgery at the Massachusetts General Hospital. We would like to acknowledge our data manager and research coordinator, Sheila Cann and Diane Davies, respectively, for their diligence and dedication toward compiling and maintaining the Thoracic Surgery Database. References 1. Okereke I, Murthy SC, Alster JM, Blackstone EH, Rice TW. Characterization and importance of air leak after lobectomy. Ann Thorac Surg 2005;79: Abolhoda A, Liu D, Brooks A, Burt M. Prolonged air leak following radical upper lobectomy: an analysis of incidence and possible risk factors. Chest 113; Stolz AJ, Schützner J, Lischke R, Simonek J, Pafko P. Predictors of prolonged air leak following pulmonary resection. Eur J Cardiothorac Surg 2005;27: Rice TW, Kirby TJ. Prolonged air leak. Chest Surg Clin North Am 1992;2: Deslauriers J, Ginsberg RJ, Dubois P, Beaulieu M, Goldberg M, Piraux M. Current operative morbidity associated with elective surgical resection for lung cancer. Can J Surg 1989; 32: Brunelli A, Monteverde M, Borri A, Salati M, Marasco RD, Fianchini A. Predictors of prolonged air leak after pulmonary lobectomy. Ann Thorac Surg 2004;77: Miller JI Jr, Landreneau RJ, Wright CE, Santucci TS, Sammons BH. A comparative study of buttressed versus nonbuttressed staple line in pulmonary resections. Ann Thorac Surg 2001;71: 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: Venuta F, Rendina EA, Giacomo TD, et al. Technique to reduce air leaks after pulmonary lobectomy. Eur J Cardiothorac Surg 1998;13: Cooper JD. Technique to reduce air leaks after resection of emphysematous lung. Ann Thorac Surg 1994;57: Macchiarini P, Wain J, Almy S, Dartavelle P. Experimental and clinical evaluation of a new synthetic, absorbable sealant to reduce air leaks in thoracic operations. J Thorac Cardiovasc Surg 1999;117: Wain JC, Kaiser LR, Johnstone DW, et al. Trial of a novel synthetic sealant in preventing air leaks after lung resection. Ann Thorac Surg 2001;71: D Andrilli AD, Andreetti C, Ibrahim M, et al. A prospective randomized study to assess the efficacy of a surgical sealant to treat air leaks in lung surgery. Eur J Cardiothorac Surg 2009;35: Okur E, Kir A, Halezeroglu S, Alpay AL, Atasalihi A. Pleural tenting following upper lobectomies or bilobectomies of the lung to prevent residual air space and prolonged air leak. Eur J Cardiothorac Surg 2001;20: Brunelli A, Refai MA, Monteverde M, et al. Pleural tent after upper lobectomy: a randomized study of efficacy and duration of effect. Ann Thorac Surg 2002;74: De Giacomo T, Rendina EA, Venuta F, et al. Pneumoperitoneum for the management of pleural air space problems associated with major pulmonary resections. Ann Thorac Surg 2001;72: Cerfolio RJ, Bass C, Katholi CR. Prospective randomized trial compares suction versus water seal for air leaks. Ann Thorac Surg 2001;71: Brunelli A, Monteverde M, Borri A, et al. Comparison of water seal and suction after pulmonary lobectomy: a prospective, randomized trial. Ann Thorac Surg 2004;77: Marshall MB, Deeb ME, Bleier JIS, et al. Suction vs water seal after pulmonary resection. A randomized prospective study. Chest 2002;121: Brunelli A, Sabbatini A, Xiume F, Refai MA, Salati M, Marasco R. Alternate suction reduces prolonged air leak after pulomonary lobectomy: A randomized comparison versus water seal. Ann Thorac Surg 2005;80: Clavero JM, Cheyre JE, Solovera ME, Aparicio RP. Transient diaphragmatic paralysis by continuous para-phrenic infusion of bupivacaine: a novel technique for the management of residual spaces. Ann Thorac Surg 2007;83: Varela G, Jiménez MF, Novoa N, Aranda JL. Estimating hospital costs attributable to prolonged air leak in pulmonary lobectomy. Eur J Cardiothorac Surg 2005;27: 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: Irshad K, Feldman LS, Chu VF, Dorval JF, Baslaim G, Morin JE. Causes of increased length of hospitalization on a general thoracic surgery service: a prospective observational study. Can J Surg 2002;45: Brunelli A, Xiume F, Refai MA, et al. Air leaks after lobectomy increase risk of empyema but not cardiopulmonary complications: a case-matched analysis. Chest 2006;130: Cerfolio RJ. Chest tube management after pulmonary resection. Chest Surg Clin North Am 2002;12: Cerfolio RJ, Sale Bass C, Harrison Pask A, Katholi CR. Predictors and treatment of persistent air leaks. Ann Thorac Surg 2002;73: McKenna RJ, Fischel RJ, Brenner M, Gelb AF. Use of the Heimlich valve to shorten hospital stay after lung reduction surgery for emphysema. Ann Thorac Surg 1996;61:

7 Ann Thorac Surg LIBERMAN ET AL 2010;89:891 8 PERSISTENT AIR LEAK AFTER LUNG RESECTION Kirschner PA. Provocative clamping and removal of chest tubes despite persistent air leak. Ann Thorac Surg 1992;53: Macoviak JA, Stephenson LW, Ochs R, Edmunds LH Jr. Tetracycline pleurodesis during active pulmonary-pleural air leak for prevention of recurrent pneumothorax. Chest 1982;81: Weatherhead M, Antunes G. Chemotherapeutic management of malignant pleural effusion. Expert Opin Pharmacother 2004;5: Dikensoy O, Light RW. Alternative widely available, inexpensive agents for pleurodesis. Curr Opin Pulm Med 2005; 11: Suter M, Bettschart V, Vandoni RE, Cuttat J-F. Thoracoscopic pleurodesis for prolonged (or intractable) air leak after lung resection. Eur J Cardiothorac Surg 1997;12: Shackcloth MJ, Poullis M, Jackson M, Soorae A, Page RD. Intrapleural instillation of autologous blood in the treatment of prolonged air leak after lobectomy: a prospective DISCUSSION DR ALESSANDRO BRUNELLI (Ancona, Italy): Congratulations for this study, a very interesting and large series. Did you try to consider propensity score matching analysis to balance the two groups, those with PAL [persistent air leak] and those without PAL? Because you are clearly comparing apples to oranges when dealing with complications. We recently published a paper in Chest showing that patients with prolonged air leak do not have a higher incidence of cardiopulmonary complication and that study was propensity score matched. For example, in your PAL group, patients were more frequently male, smokers with a higher pack per years level, and with a lower FEV 1 [forced expiratory volume in the first second of expiration], and these factors may all have an influence in the higher occurrence of pneumonia that you found. My second question is, have you considered other important intraoperative factors such as the presence of pleural adhesions or the site of resection, because you showed that the upper lobectomies have more frequent incidence of prolonged air leak, that may be factored in the regression analysis Thank you. Excellent paper. DR LIBERMAN: Thank you. I will start backwards. In terms of right upper lobectomy, this did not bear out in univariate or multivariate analysis, fortunately or unfortunately. Fortunately, being that the incidence of prolonged air leak was so low that even though it appeared that prolonged air leaks were associated with a higher incidence of air leak, it did not reach statistical significance on either univariate or multivariate analysis, and that s why it was dropped off. Unfortunately, in terms of not being able to reach statistical significance due to low numbers. In terms of propensity matching, I think that is a great idea. It is something we did not do. We have a very low number of patients that we are looking at in the sclerosis group and in the prolonged air leak group, comparing it to a very large number of control patients. Propensity matching would be something that would be good to consider. However, the major topic of this paper was to look at sclerosis as opposed to the incidence of risk factors. Thank you. DR CLIFF K. CHOONG (Cambridge, United Kingdom): Congratulations to you and your co-authors on the very nice study and presentation. randomized controlled trial. Ann Thorac Surg 2006;82: Droghetti A, Schiavini A, Muriana P, et al. Autologous blood patch in persistent air leak after pulmonary resection. J Thorac Cardiovasc Surg 2006;132: Lang-Lazdunski L, Coonar AS. A prospective study of autologous blood patch pleurodesis for persistent air leak after pulmonary resection. Eur J Cardiothorac Surg 2004;26: Shaw P, Agarwal R. Pleurodesis for malignant pleural effusions. Cochrane Database Syst Rev 2004;1:CD Brant A, Eaton T. Serious complications with talc slurry pleurodesis. Respirology 2001;6: Kuzniar TJ, Blum MG, Kasibowska-Kuzniar K, Mutlu GM. Predictors of acute lung injury and severe hypoxemia in patients undergoing operative talc pleurodesis. Ann Thorac Surg 2006;82: Cerfolio RJ, Minnich DJ, Bryant AS. The removal of chest tubes despite an airleak or pneumothorax. Ann Thorac Surg 2009;87: The incidence of air leakage of 5.6% is very good. My first question is what intraoperative and postoperative measures does your group take to minimize air leakage? Is there a standard protocol that the group follows? The second question is regarding some of your patients who were treated by observation alone. How do you decide which patients would undergo observation alone versus pleurodesis versus Heimlich valve treatment? Thirdly, based on your results, pleurodesis appears to work well. Have you considered treating postoperative air leakage earlier using pleurodesis? And lastly, have you considered using an endobronchial one-way valve such as the Emphyasys or Spiration valves for those patients with very difficult persistent air leakage? Thank you. DR LIBERMAN: Thank you very much. In terms of intraoperative maneuvers that are used at Mass General to prevent persistent air leaks, it is very surgeon dependent. There are eight different thoracic surgeons performing a high volume of pulmonary resection. In general, there are certain surgeons who use a lot of visceral pleural sealants and buttressing of suture lines when they appear to be in weak areas of lung; especially confluence of staple lines. And pleural tents are used especially for upper lobectomies in patients when there is a belief in the OR to be a space problem. So I think all of those things, as well as trying not to operate in the fissure or as little as possible in the fissure, will prevent air leaks or persistent air leaks. In terms of the observation versus pleurodesis, that is surgeon preference. This study is retrospective. The protocol that I showed you was not put forth at the beginning of the study. We are looking backwards and therefore the allocation of observation versus pleurodesis was surgeon and situation dependent. So, obviously, patients who had air leaks that were resolving or were very small were not considered for sclerosis, and that is why the chest tube time and the air leak time in the observation group is so much shorter than in the sclerosis group. If someone on day five had an air leak that was almost completely resolved most surgeons would not talc that patient, and that s why you see a difference there. In terms of earlier sclerosis, I think that there is a trend to do that. Again, this study is retrospective, and those five days are

8 898 LIBERMAN ET AL Ann Thorac Surg PERSISTENT AIR LEAK AFTER LUNG RESECTION 2010;89:891 8 just a suggestion, not based on the data but on what we use clinically. And there are times when sclerosis is used earlier, such as in patients with a very large air leak or an air leak that does not appear to be slowing down. In terms of one-way valve, there are times that we use one-way valves and send patients home with a Heimlich or a mini-pleur-evac or Atrium. However, we find that patients have a lot of discomfort from that and it is inconvenient for the patient. Many patients also are referred from far away, and therefore, for them to go home with their chest tube in place, because they are often not from the local surroundings, is more inconvenient. DR CHOONG: What I meant in terms of one-way valve was the intrabronchial one-way valve like the Spiration or Emphasis valves? DR LIBERMAN: We have not used that in terms of treating persistent air leaks. DR MALCOLM M. DECAMP (Boston, MA): One of the strengths of your data is you had 70 patients with prolonged air leak and you have 7,000 others. So I think you likely could propensity match them given the type of patients that are referred to you. If you do the propensity matching, I think it will be a very valuable addition to the literature to guide us on the type of patients that we should consider earlier intervention. I would also suggest that you add the surgeon to the mix as a variable for your analysis. We did a similar analysis at the Cleveland Clinic and found that one of our colleagues was very much into sclerosis and some of us weren t. We discovered that the sclerotherapy was more treating the surgeon than the patient. I noticed that on average it was a couple of days between the sclerosant and the time the chest tube was removed. How did you decide to go to a second sclerosing procedure versus observing them for a couple of days? And in that sense, can you or is there an interest in formalizing your protocol so that there is unanimity amongst the eight surgeons now about how to approach this complication systematically? DR LIBERMAN: Thank you. We did look at the data in terms of surgeons having more air leaks versus other surgeons having less air leaks, and there was no difference. We also compared sclerosis between treating surgeons; however, all surgeons are using pleurodesis occasionally, and obviously, because the incidence is so low, none of them are using it very often and therefore no differences were observed. In terms of how to decide when you should talc or sclerose a patient, I think that s very much based on surgeon preference, at least in this retrospective study. However, air leaks that are resolving or appear to be resolving, those are the patients that obviously you would not consider retalcing or repleurodesing. In patients with air leaks that are continuing or continue to be at the same level and are not improving, those are the patients that usually get resclerosed. DR SCOTT J. SWANSON (New York, NY): I enjoyed that as well. Two things. It struck me that the average length of stay of the chest tube in the non-pal group was 3.4, but they stayed another 3 or 4 days in the hospital. I m just curious what that was about. Second question, was there any difference minimally invasive versus open? And thirdly, what percentage of patients were getting this intraop sealant or buttressing? Did that play into this at all? DR LIBERMAN: Thank you. In terms of patients staying in the hospital, it s hard for me to stay. Obviously this is a retrospective study. There is no fast-tracking algorithm being used. However, because some of the patients come from very far, they often stay a little longer than they would in some hospitals that see a lot of local patients. Could you please repeat the second question? DR SWANSON: The second was minimally invasive versus open. DR LIBERMAN: We excluded all minimally invasive procedures from this analysis to clean it up. DR SWANSON: And the third was the buttressing or sealant, what percentage is that? DR LIBERMAN: I don t have data on that. It s hard to know from the database. DR GIUSEPPE CARDILLO (Rome, Italy): I have three questions. Do you never bronchoscope the patient? I mean, if you see failure of sclerosis and you do a second time sclerosis, do you never perform a bronchoscope to rule out even if there is any evidence of fistula? Second question, talc slurry is a painful procedure as we know. What do you do for pain control? Third question, have you never reoperated a patient after talc slurry? DR LIBERMAN: Thank you for the questions. In terms of bronchoscopy, patients who have large air leak after major pulmonary resection are obviously bronchoscoped, as you said, in order to rule out broncho-pleural fistula which would obviously not be treated in our institution with talc. In terms of pain, patients receive prophylactic, parenteral narcotics around the time of their talc slurry, and some patients have lidocaine mixed in with the talc slurry; however, that is not uniform in all cases. We rarely have problems with significant pain during or after the procedure. DR CARDILLO: The reoperation. I mean, have you reoperated any patient after failure of sclerosis. DR LIBERMAN: It is rare, but there were two patients in the series who were reoperated on. One had a muscle flap placed, and the sclerosis actually made it a lot easier. This was because the rest of the lung was stuck to the chest wall, except for the persistent upper lobe space which had been there. So all that needed to be done was to drop a pectoralis muscle flap into that apical space, and that solved the problem. The other patient was the patient who died. He wasn t reoperated for his air leak. He was reoperated for an empyema two months after the talc pleurodesis. DR DANIEL L. MILLER (Atlanta, GA): Thank you. And I want to congratulate the audience on an excellent discussion. It s nice to talk about air leaks with doctors without Dr. Cerfolio here. I think you all should send him an and tell him that we can do it without him.