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Ann Thorac Surg 2002;73:420-426
© 2002 The Society of Thoracic Surgeons

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Original article: general thoracic

Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation

^a Department of Thoracic and Cardiovascular Surgery and Medical Informatics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA

* Address reprint requests to Dr Vaporciyan, Department of Thoracic and Cardiovascular Surgery, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 445, Houston, TX 77030, USA
e-mail: avaporci{at}mdanderson.org

Presented at the Forty-seventh Annual Meeting of the Southern Thoracic Surgical Association, Marco Island, FL, Nov 9–11, 2000.

	Abstract

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Background. The prevention of major pulmonary events (MPEs) after pneumonectomy may minimize postoperative mortality rates. The purpose of this study was to identify preoperative and perioperative factors associated with the development of MPEs after pneumonectomy to help predict which patients are at increased risk for MPEs.

Methods. We retrospectively reviewed the medical records of all patients (n = 261) who underwent pneumonectomies between January 1990 and May 1999. We analyzed preoperative and perioperative risk factors, the primary end point of an MPE and the secondary end points of mortality (in-hospital or 30 days postprocedure), length of stay, and hospital charges. A postoperative MPE included only pneumonia or acute respiratory distress syndrome as defined by the Centers for Disease Control and the American and European Consensus Conference’s established criteria. Simple atelectasis that did not progress to pneumonia or a documented aspiration was not included.

Results. Four patients died within 12 hours of operation; the records of the remaining 257 patients were analyzed. An MPE occurred in 33 (12.8%) of 257 patients; 16 (6.2%) of 257 patients died. A multivariate analysis performed on relevant variables showed that only the timing of smoking cessation (1 month or sooner before operation) was a significant predictor of an MPE. Age, side of pneumonectomy, and the use of preoperative chemotherapy or combined chemotherapy and radiation therapy were not significant predictors of an MPE. An MPE significantly increased the mortality rate 2.1% versus 39.3%, p < 0.001).

Conclusions. Mortality after pneumonectomy increased significantly with the development of an MPE. Patients who continue to smoke within 1 month of operation are at an increased risk for developing an MPE. Interventions to minimize MPEs may minimize the mortality rate after pneumonectomy.

	Introduction

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Despite the availability of anatomical lobar resections and other lung sparing techniques, pneumonectomies are still performed in 10% to 30% of curative resections for cancer [1]. Because of improved surgical technique and perioperative care the outcome after pulmonary resection has greatly improved throughout the last four decades [2]. In the last decade, however, the mortality rates associated with pneumonectomy still ranged from 4.8% to 10.9% [3–7], whereas major morbidity occurred in 15% to 36% [5, 7–10]. Most of these morbidities are pulmonary in origin and appear to be responsible for a substantial portion of the mortality [11, 12].

Recent multimodality trials have required a pneumonectomy in 36% to 52% of all resections [13–15]. The desired survival benefits of aggressive multimodality therapy would be eroded by an associated increase in the operative morbidity and mortality rates from the more frequent use of pneumonectomies. Every effort must be made to limit both the incidence and severity of complications after pneumonectomy. Although the overall predictors of morbidity and mortality after pneumonectomy have been examined [4–8, 10], these tend to be generalized predictors and are not associated with specific complications. Evaluation of the incidence of a specific type of complication will allow an accurate determination of factors associated with its development.

Because pulmonary complications are responsible for a significant portion of the mortality after pneumonectomy [11], we focused our efforts on factors associated with their occurrence. We hypothesized that preoperative and perioperative factors can be identified that predict patients at increased risk to develop a major pulmonary event (MPE). To test this hypothesis we performed a retrospective review of patients who received a pneumonectomy during a recent 10-year period, and analyzed these patients for factors that predicted the occurrence of MPE.

	Material and methods

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We retrospectively reviewed the medical records of all patients who underwent a pneumonectomy at our institution from January 1, 1990, to May 1, 1999. Data were collected on a number of preoperative and perioperative factors, as well as on the occurrence of the primary end point MPEs, and secondary end points: mortality, length of stay, and hospital charges. Patients who died within 12 hours of operation from a cardiac or hemorrhagic complication were excluded from the study. Hence, the death of patients included in the study could be related to an MPE. Mortality was defined as in-hospital death or death within 30 days after pneumonectomy. Hospital-cost data were not available; however, data on hospital charges were available from September 1, 1994, onward.

A major pulmonary event was defined as either pneumonia or acute respiratory distress syndrome (ARDS). The diagnostic criteria for each of these were strictly defined using the Centers for Disease Control and the American and European Consensus Conference’s established definitions [16, 17] (Table 1). We limited MPE to these two diagnoses because they have similar traits that suggest a shared etiology. Both pneumonia and ARDS are forms of acute lung injury. Their clinical progression can be similar and clinical differentiation between the two conditions is difficult. Many patients who develop either pneumonia or ARDS after pneumonectomy develop the other during their hospital course. Other forms of pulmonary morbidity were not included as MPE because their etiologies were believed to differ significantly from those of pneumonia and ARDS. For example, simple atelectasis and aspiration are associated with mechanical factors whereas empyema and bronchopleural fistulas are either a later sequela of pneumonia or related to technical factors.

The ² test for categorical variables and the Student’s t test for continuous variables were used to test for significant differences between those who developed MPE and those who did not. A multivariate logistic regression analysis [18] was performed to simultaneously evaluate the effects of risk factors. The model was constructed using factors identified as significant in the univariate analysis along with historically implicated factors. All statistical analyses were performed using SPSS software (SPSS Inc, Chicago, IL). Statistical significance was defined as p less than 0.05.

	Results

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Between January 1, 1990, and May 1, 1999, 261 patients underwent a pneumonectomy at our institution. During the same time more than 2,700 pulmonary resections were performed at our institution, and thus, our 261 patients represented 9.7% of all pulmonary resections. We excluded 4 patients because they died either during operation or within 12 hours of operation from cardiac complications. The remaining 257 patients were included in the study. Data on hospital charges were available only since September 1, 1994, and thus accumulated on only 106 patients. The demographics, tumor characteristics, smoking histories, and types of pneumonectomy performed are presented in Table 2. Thirty-three patients (12.8%) had MPEs, and 16 patients (6.2%) died.

	Comment

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Previous reports have identified a wide variety of factors associated with overall morbidity and mortality after pneumonectomy [7]. However, specific factors related to the development of pneumonia and ARDS are less prevalent in the literature.

In our study the timing of smoking cessation was the most consistent predictor of the development of MPEs. Studies analyzing the timing of smoking cessation in patients who have undergone pneumonectomy are rare. A recent study showed no increase in the overall morbidity or mortality rates among patients who were smokers within 2 months of their pneumonectomy [7]. In contrast, of patients who underwent elective cardiac operation those who smoked within 2 months of their operation were four times more likely than nonsmokers to develop pulmonary complications [19]. In our study, smoking within 1 month of pneumonectomy was strongly associated with the development of pneumonia and ARDS. It is logical to conclude that the association between smoking and MPEs is not an all-or-nothing phenomenon, but that the degree of increased risk of MPE is inversely related to the duration of smoking abstinence before operation.

The association between increased intraoperative transfusions and the development of MPE was difficult to interpret. Others have reported a similar association [7, 20]. Because we collected our data retrospectively, we could not accurately identify the indications for the intraoperative transfusions. Most likely, the need for substantially increased intraoperative transfusion volume is a marker of a complex procedure and difficult dissection associated with increased intraoperative blood loss [21, 22]. The influence of an intraoperative transfusion volume on the incidence of MPEs was difficult to demonstrate. Tantalizing evidence from a number of prospective randomized trials involving patients who had undergone cardiac or colorectal operation has suggested that autologous transfusions are associated with an increase in postoperative infectious complications [23–25]. Because our study was retrospective with a limited population, we could not conclude that a small intraoperative transfusion volume contributes to the development of postoperative MPE.

Increasing age, right-sided pneumonectomy, and increasing fluid balance have been implicated as factors that contribute to the development of postoperative complications and overall mortality [7, 20]. However, their significance has not been demonstrated consistently between studies. We were unable to identify any association between these factors and MPEs in our study. Kutlu and associates [11] reported a similar lack of correlation between these factors and both the incidence of acute lung injury (a mild form of ARDS) and ARDS after 198 pneumonectomies.

The association between preoperative chemotherapy and the development of postoperative complications is hotly debated [20, 26, 27]. Forty-four (19.7%) of the patients included in our study received neoadjuvant chemotherapy or chemoradiotherapy; the incidence of MPEs in these patients was not increased. Although our study was retrospective, our findings were consistent with those in some studies designed to specifically address this question [20, 27].

The 7.7% overall mortality rate in our study was consistent with the mortality rates after pneumonectomy in other published reports [3–7]. As in other studies, the development of MPEs in our study was associated with a significantly increased mortality rate [7, 11]. Our data also confirmed that MPEs are associated with increases in the length of hospital stay and hospital costs.

In conclusion, our analysis of patients who underwent pneumonectomy because of malignant disease identified smoking within 1 month of operation as a significant predictor of postoperative pneumonia or ARDS. In addition, intraoperative blood loss contributed to postoperative pneumonia or ARDS. Aggressive attention to smoking cessation, initiated at the first patient contact, must be used to maximize the smoke-free duration before resection.

	Discussion

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DR CAROLYN E. REED (Charleston, SC): I enjoyed your paper very much. I have a couple of questions for you. I think we all fear pulmonary complications in pneumonectomy patients. The number of events you reported was low. Do you think that perhaps this has something to do with your statistics?

The next question: other people have shown that in patients undergoing neoadjuvant therapy, particularly radiation therapy, there is an association with problems postoperatively, particularly after pneumonectomy. I wondered how many of your patients underwent radiation therapy. Again, perhaps you had too few to show an association.

And the final question is, because you showed a fairly dramatic association with the use of blood intraoperatively, do you consider now using leukocyte-poor transfusions?

Thank you.

DR VAPORCIYAN: The low number of events was actually a significant factor in designing the multivariate analysis and in doing the univariate analysis. We could not embark on a search of all of the factors that might affect the incidence of pulmonary events because of the small numbers of patients, and I am sure that had an impact on some of the other things that have been suggested in other studies.

One thing that is different about this study, though, is we did not look at overall mortality or overall complications, and some of the factors that have been cited may have to do more with cardiac complications or cardiac-induced death rather than a pulmonary-induced morbidity. When we looked at the radiation, yes, not many patients received considerable amounts of radiotherapy preoperatively. In fact, that is why we looked at that variable as an all-or-none variable or in subgroup analysis as it showed in that slide. I think the total number that received considerable radiation was only about 60 patients.

As far as leukocyte-poor blood, yes, that is a consideration and actually has been shown in some prospective randomized studies, primarily in orthopedic literature, to actually reduce the number of infectious complications after, say, joint replacement. In addition, things such as initiating Procrit or some form of erythropoietin therapy, if the patient is undergoing neoadjuvant therapy, might also be beneficial.

DR FREDERICK L. GROVER (Denver, CO): I enjoyed your presentation very much. In terms of blood transfusion effecting outcomes, how did you control for the transfusions being a marker of more advanced disease, or a more difficult operation instead?

DR VAPORCIYAN: That was difficult to control. One thing we did was remove patients who died from hemorrhagic complications. The other areas we looked at it as a continuous variable to determine if even a small amount of blood transfusion did impact, which it did. The number I showed, the odds ratio of 1.13, was when transfusions were being looked at as a continuous variable. So each unit of blood did impart a statistically significant increase in the risk of complications developing.

And then there is supporting literature. As I said, there was a nice study that looked at autologous blood versus allogeneic blood transfusions; it was well designed. The patients all gave autologous blood but then were randomized to receive either their own blood or an allogeneic bank blood, and the patients who received bank blood did have in fact an increased risk of infectious complications after joint replacement. So there is confirmatory evidence from other regions of medicine to confirm these findings.

DR JOHN R. ROBERTS (Nashville, TN): I enjoyed your paper very much. I have two quick questions. One, you talked about respiratory failure. Did you separate respiratory failure into pneumonia and aspiration? I would think that failing to smoke might increase one’s chance of pneumonia but might not affect one’s aspiration risk.

And then second, I think most of us want our patients to stop smoking 3 to 4 weeks before operations but are not able to get them to do so. What do you do with them?

DR VAPORCIYAN: The aspiration was actually a third group that we were going to include. Unfortunately, using the strict criteria that we established, we could find only 1 patient who had a true documented evidence of aspiration after the operation. That just was not enough, so we just lumped them together with pneumonia.

As far as getting them to stop smoking yes, of course, it is difficult. We work with our social workers, and all our patients who have difficulty stopping are sent to a smoking cessation class. The other area, though, is in patients who are going to receive neoadjuvant therapy, if they are undecided about whether they should take neoadjuvant therapy but they happen to smoke when they come to your clinic, it may be one piece of evidence to support undergoing neoadjuvant therapy to get them further away from their smoking prior to taking them to the operating room.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Ara A. Vaporciyan Jack A. Roth W. Roy Smythe Stephen G. Swisher Garrett L. Walsh Jonathan C. Nesbitt Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vaporciyan, A. A. Articles by Putnam, J. B. Search for Related Content PubMed PubMed Citation Articles by Vaporciyan, A. A. Articles by Putnam, J. B., Jr Related Collections Lung - other