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Ann Thorac Surg 2007;84:417-422
© 2007 The Society of Thoracic Surgeons
a Service of Thoracic Surgery, Salamanca University Hospital, Salamanca, Spain
b Unit of Thoracic Surgery, "Umberto I°" Regional Hospital, Ancona
c Division of Thoracic Surgery, National Cancer Institute, Naples, Italy
Accepted for publication March 5, 2007.
* Address correspondence to Dr Varela, Thoracic Surgery, Salamanca University Hospital, Salamanca, 37007, Spain (Email: gvs{at}usal.es).
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Abstract |
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 Top Abstract IntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Methods: One hundred eighty-five patients undergoing nonextensive lobectomy were included. Selection criteria and perioperative management were homogeneous; all procedures were performed by muscle-sparing or video-assisted thoracoscopic surgical approach. Multivariate regression analysis was performed to identify whether COPD index (calculated by adding the percent preoperative forced expiratory volume in 1 second to the preoperative ratio of forced expiratory volume in 1 second to forced vital capacity, both values taken in decimal form) had an independent and reliable association with the decrease in forced expiratory volume in 1 second observed on the first postoperative day corrected for the effect of other preoperative and operative factors. The regression analysis was then validated by bootstrap analysis.
Results: Thirty-day mortality of the series was 1.1% (2 patients) and cardio-respiratory morbidity 20% (37 patients). Patients with lower preoperative pulmonary volumes had lower postoperative decrease of the pulmonary function (Pearson correlation coefficient, 0.28; p < 0.001). At linear regression, COPD index (p = 0.008), modality of analgesia (p < 0.0001), pain score (p = 0.01), the percentage of functioning parenchyma removed during operation (p = 0.006), and the presence of coronary artery disease (p = 0.03) had independent and reliable influence on the dependent variable (p < 0.001 and 0.003, respectively).
Conclusions: Preoperative COPD degree (measured as COPD index) has a direct independent correlation with the decrease in postoperative forced expiratory volume in 1 second the day after surgery.
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Introduction |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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In most cited reports, lung function was measured 1 to 15 months after surgery and was compared with predicted postoperative volumes (predicted postoperative forced expiratory volume in 1 second [ppo-FEV1]). Although these findings are relevant and affect outcomes such as quality of life and COPD-related long-term survival, there is scanty information with regard to the influence of COPD on pulmonary function in the early postoperative period [12]. In previous reports we have shown that the postoperative FEV1 measured on the first postoperative day was 30% lower than ppoFEV1 [13] and that this value was much more predictive of cardiorespiratory morbidity than the traditional ppoFEV1 [14]. For this reason, we think that an effort to understand the mechanisms underlying the early changes of FEV1 in the immediate postoperative period is warranted to refine risk stratification. In particular, the relationship between the degree of COPD and the FEV1 measured on the first day after lobectomy has not been investigated. Thus, we expanded the series used in previous papers and focused our analysis on lobectomy patients only with the aim of verifying whether airflow limitation may limit the decrease of FEV1 during the immediate postoperative period similarly to what has been proven to occur at later postoperative periods.
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Patients and Methods |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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Data were prospectively collected in electronic data sets after patients gave their informed consent to use their data. The study was approved by the local institutional review boards of individual centers.
Patients undergoing concomitant chest wall or diaphragm resection, or needing prolonged postoperative assisted mechanical ventilation, were excluded from the analysis. Exclusion criteria for major lung resection at both centers were homogeneous and included ppoFEV1% and predicted postoperative diffusing capacity for carbon monoxide below 30% of the normal values in association with insufficient cardiorespiratory reserve (height reached on stair-climbing test lower than 12 m or maximal oxygen consumption lower than 10 mL · kg–1 · min–1). All patients were operated on by qualified thoracic surgeons using an anterolateral muscle-sparing (146 patients) or video-assisted small axillary thoracotomy (39 patients). One or two chest tubes were left in the pleural space and kept until no air leak was detected or daily output was less than 200 mL.
Postoperative management was standardized in all cases: intensive physiotherapy was instituted by dedicated staff starting the morning after surgery, and analgesia was achieved by epidural bupivacaine and opiates plus oral dexketoprofen (unit B) or continuous infusion of a combination of tramadol and ketorolac (unit A). Daily visual analog pain score (VAS) was measured on a 0 to 100 scale, and analgesia was modified to keep the patient under the level of 30 to 40 during the first 48 to 72 hours after the operation.
The FEV1 was measured in every patient at hospital admission and daily until discharge or up to postoperative day 6, under maximal bronchodilator therapy according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations. The FEV1 recordings were performed three times—after measuring VAS—by means of a calibrated portable spirometer (SpiroPro E. Jaeger GmbH, Wurzburg, Germany), with the patient seated or standing up, and the best value selected. The FEV1 was expressed as a percentage of predicted for age, sex, and height, according to the European Community for Steel and Coal prediction equations [15]. The ppoFEV1 was calculated by taking into account the number of the functioning segments removed during operation and estimated by means of bronchoscopy or computed tomographic scan [16].
Analyzed Variables
The percent postoperative FEV1 decrease (
FEV1) was used as dependent variable and calculated as follows: (preoperative FEV1 – first postoperative day FEV1)/preoperative FEV1 x 100.
For the purpose of this study the following factors were tested for a possible association with the postoperative FEV1 decrease: elderly status (age >70 years), body mass index, presence of coronary artery disease, COPD index [5] (calculated by adding the preoperative FEV1% to the preoperative ratio of FEV1 to forced vital capacity, both values taken in decimal form), surgical approach (muscle-sparing thoracotomy versus VATS), site of resection (upper resections versus lower resections), side of resection (right versus left), percentage of functioning parenchyma removed during operation (estimated by computed tomographic scan, bronchoscopy, or lung perfusion scan), and pain control (VAS scale on the first postoperative day). For the purpose of the present analysis, the following operations were defined as upper resections: right upper lobectomy, right upper bilobectomy, middle lobectomy, and left upper lobectomy. The following operations were defined as lower resections: right lower lobectomy, right lower bilobectomy, and left lower lobectomy.
Postoperative cardiopulmonary complications and mortality were considered as those occurring within 30 days from operation or during a longer period if the patient was still in the hospital. For the sake of comparison with other authors [17] and according to the European Thoracic Database [18], the following cardiopulmonary complications were included: respiratory failure requiring mechanical ventilation for more than 48 hours; pneumonia; atelectasis requiring bronchoscopy; pulmonary edema; pulmonary embolism; myocardial infarction; hemodynamically unstable arrhythmia requiring medical treatment; cardiac failure; stroke; and acute renal insufficiency.
Data were prospectively entered in each center and then sent to a centralized data set where they were checked for accuracy and inconsistency by a data manager. All variables entered in this study were complete.
Statistical Analysis
Normality of continuous variables under analysis was tested by means of the Shapiro-Wilk normality test. A scatter plot of COPD index and FEV1 was examined to determine whether a linear model was reasonable, and the linear association of both variables was measured by Pearson correlation coefficient (with two-tailed significance test).
A multivariate stepwise regression model was constructed to assess whether the COPD index had an independent effect on the decrease of FEV1 measured the first postoperative day after correcting for the effect of a number of preoperative and operative cofactors. A probability value of less than 0.05 was selected for retention of variables in the final model. To avoid multicollinearity, only one variable in a set of variables with a correlation coefficient greater than 0.5 was selected (by bootstrap procedure) and used in the regression model. The stability of the final model was then assessed by the bootstrap analysis. The multivariate procedure was then validated by bootstrap bagging with 1,000 samples. In the bootstrap procedure, repeated samples of the same number of observations as the original database (185) were selected with replacement from the original set observations. For each sample, stepwise multivariate regression was performed. The stability of the final stepwise model can be assessed by identifying the variables that enter most frequently in the repeated bootstrap models and comparing those variables with the variables in the final stepwise model. If the final stepwise model variables occur in a majority (>50%) of the bootstrap models, the original final stepwise regression model can be judged to be stable [19–21].
Data were analyzed using the Stata 8.2 software (Stata Corp, College Station, TX).
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Results |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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FEV1 decreased from 46.2% observed on the first postoperative day to 33.3% observed on the fifth postoperative day.
A statistically significant linear correlation was found (Fig 1) between COPD index and FEV1 (Pearson correlation coefficient, 0.28; p < 0.001), indicating that patients with lower preoperative pulmonary volumes had lower postoperative decrease of the pulmonary function. The distribution of COPD index in the population under analysis is shown in Figure 2. Fifty percent of patients had a COPD index less than 1.58. In these patients, the percent reduction in FEV1 observed on the first postoperative day was 16% lower compared with the one observed in those with a higher COPD index (42% versus 50%; p = 0.0001).
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FEV1 between the two centers performing operations (unit A, 50.6 versus unit B, 38.4; p < 0.0001). When used as an independent variable in the multivariate regression, however, this factor lost its significance. As the only factor that differed between the units was the modality of analgesia, it is reasonable to conclude that the difference observed between the centers was mainly related to a different analgesic treatment, favoring epidural versus systemic administration. |
Comment |
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TopAbstractIntroductionPatients and MethodsResultsCommentAcknowledgmentsReferences |
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As the value of FEV1 on the immediate postoperative phase may have a role in predicting major cardiopulmonary complications [14], its determination in relationship to other characteristics of the patients may have important clinical implications in risk stratification. In particular, the influence of obstructive pulmonary disease on the early postoperative changes of expiratory volume has rarely been investigated. Recently, Brunelli and colleagues [22] found that at discharge (median, 10 days after operation), the FEV1 value of patients with COPD was 13% higher than those without COPD.
The minimal deterioration or even the improvement of FEV1 in these patients after lobectomy has been explained with an improvement in elastic recoil and airway conductance by the relief of hyperinflation [5, 6], which apparently takes place early in the postoperative course [12, 22]. However, in addition to the removal of lung tissue, other factors play an important role in the first 2 weeks after operation, such as impairment in chest wall compliance, diaphragm dysfunction, accumulated bronchial secretion, bronchial hyperreactivity, microatelectasis, increased lung water, and reduced surfactant activity [23]. Therefore, the aim of this study was to assess whether the degree of obstructive disease, as assessed by the COPD index, had an influence on the decrease of FEV1 even on the first postoperative day.
The COPD index was recently proposed in the literature as a variable indicating the purity of COPD and was calculated by adding the FEV1 (percent of predicted, in decimal form) and the FEV1 to forced vital capacity ratio [5]. This variable has already been inversely associated with postoperative long-term changes in FEV1 [5, 8]. In patients with a lower COPD index, corresponding to a higher degree of obstructive disease, the lung resection may improve the airway conductance by relieving hyperinflation and ameliorate respiratory mechanics, similarly to what happens in typical lung volume reduction candidates [5].
In this study we showed that there was a correlation between COPD index and early postoperative FEV1 decrease even after adjusting for the effect of other preoperative and operative factors by multiple regression analysis. This association in fact was independent of postoperative pain, type of analgesia, presence of coronary artery disease, and amount of functioning lung tissue removed at operation, and it was not influenced by the side and site of resection and the type of surgical approach.
Immediate postoperative pulmonary function depends on several factors [24, 25] and is directly related to postoperative pain [26]. To control potential bias, we have considered the quality of analgesia in the regression model. We have tried in this way to minimize the limitation secondary to different analgesia methods that were not controlled in our series. Our results confirm the relevance of analgesia on postoperative pulmonary function, but despite the effect of pain, we have demonstrated that patients with lower preoperative COPD index have lower decrease of postoperative FEV1.
Our study confirmed that beyond the quality of the analgesia (VAS score), the modality of analgesia had an even greater influence on the postoperative FEV1 This may be related to the fact that continuous epidural infusion of small doses of local anesthetics with opiates provides better control of dynamic pain without undue sedation and attenuates the neuroendocrine stress response by blocking the nociceptive inputs and sympathetic outflow [27, 28].
A formal radiologic visual assessment to grade the severity of the emphysema in the resected parenchyma and to correlate it with COPD index or postoperative FEV1 changes was not performed in this study. However, the analysis was corrected for the amount of functioning tissue removed during operation, which does not include the lung tumor mass, areas of atelectasis, pneumonia, or emphysematous destruction. Predictably, this variable was directly associated with a greater loss of FEV1 after operation, confirming previous findings [12].
We have not observed differences in postoperative pulmonary function depending on the site of lobectomy, as reported by Sekine and coworkers [9] and Kushibe and associates [29]. According to the latter study, upper lobectomy might have a lung volume reduction effect in COPD patients that is evidenced 6 months to 1 year after the operation. On the contrary, Sekine and colleagues [9] showed that lower lobectomy was a factor associated with minimal FEV1 loss 1 month after surgery. In our case, the lack of influence of the site of resection on FEV1 changes could be related to the early measurement of postoperative pulmonary volumes. In fact, other factors that are relevant in the immediate postoperative phase may have offset the influence of the site of resection on the postoperative function.
Surgical approach was not standardized in our series and it was surgeon’s choice. Nevertheless, only two types of incisions were performed: video-assisted axillary minithoracotomy and muscle-sparing anterolateral thoracotomy. There is evidence in the literature that both approaches have similar effects on postoperative pulmonary function, although VATS approach produces less pain in the immediate days after resection [30–32]. For this reason, the type of surgical approach was used as an independent variable in the multivariate regression to control its effect on postoperative FEV1 changes.
In conclusion, we have shown that in patients with airflow limitation the FEV1 measured as early as the first postoperative day after lobectomy was better preserved compared with patients with higher preoperative values of COPD index. Although many factors concur in the immediate postoperative phase to attenuate its effect, we found that a precocious lung volume reduction effect may nevertheless take place. This finding warrants, in our view, future risk stratification analyses taking into account early expiratory volume measurements that can contribute to clarify the role of preoperative FEV1 as a major risk factor [33] in the face of reported good results after lobectomy in advanced COPD cases [34].
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Acknowledgments |
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