|
|
||||||||
a Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts
b Division of Biostatistics, Massachusetts General Hospital, Boston, Massachusetts
Accepted for publication December 9, 2009.
* Address correspondence to Dr Lanuti, 55 Fruit St, Blake 1570, Boston, MA 01748 (Email: mlanuti{at}partners.org).
Presented at the Forty-fourth Annual Meeting of the Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 28–30, 2008.
| Abstract |
|---|
|
|
|---|
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 8.4 ± 3.6 days, mean duration of air leak was 10.7 ± 4.5, and mean duration of air leak postsclerotherapy was 2.8 ± 2.2 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.
| Introduction |
|---|
|
|
|---|
Traditionally, treatment for prolonged air leaks after major pulmonary resection included: watchful waiting and (or) Heimlich valve placement. These strategies 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 |
|---|
|
|
|---|
The persistent air leak cohort consisted of consecutive patients with prolonged air leak (as defined above) between January 1, 1997 and December 31, 2006. The control group consisted of consecutive patients undergoing pulmonary resection between January 1, 2002 and December 31, 2006. 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 H2O) 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 |
|---|
|
|
|---|
|
|
|
|
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 = 0.014. 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 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.
| Comment |
|---|
|
|
|---|
Historic risk factors for prolonged air leak include the following: steroid use [26]; chronic obstructive pulmonary disease; decreased FEV1.0 (8,33); decreased percent predicted FEV1.0; decreased FEV1.0/ 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 FEV1.0 and low percent predicted FEV1.0), 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 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 7.9 ± 2.7 days, mean duration of air leak was 11.4 ± 4.5 days, and the mean duration of air leak postsclerotherapy was 2.8 ± 2.2 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].
|
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 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.
| Discussion |
|---|
|
|
|---|
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 FEV1 [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.
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 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 e-mail and tell him that we can do it without him.
| Acknowledgments |
|---|
|
|
|---|
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
C.-Y. Li, S.-W. Kuo, and J.-M. Lee Life-Threatening Complications Related to Minocycline Pleurodesis Ann. Thorac. Surg., September 1, 2011; 92(3): 1122 - 1124. [Abstract] [Full Text] [PDF] |
||||
![]() |
A. Bille, P. Borasio, M. Gisabella, L. Errico, P. Lausi, E. Lisi, M. C. Barattoni, and F. Ardissone Air leaks following pulmonary resection for malignancy: risk factors, qualitative and quantitative analysis Interact CardioVasc Thorac Surg, June 1, 2011; 13(1): 11 - 15. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. De Leyn, M.-R. Muller, J. W. A. Oosterhuis, T. Schmid, C. K. C. Choong, W. Weder, and Y. Sokolow Prospective European multicenter randomized trial of PleuraSeal for control of air leaks after elective pulmonary resection J. Thorac. Cardiovasc. Surg., April 1, 2011; 141(4): 881 - 887. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |