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Eur J Cardiothorac Surg 2006;30:644-648
© 2006 Elsevier Science NL

Predicted versus observed FEV1 in the immediate postoperative period after pulmonary lobectomy

^a Service of Thoracic Surgery. Salamanca University Hospital, 37007 Salamanca, Spain
^b Unit of Thoracic Surgery, "Umberto I°" Regional Hospital, Ancona, Italy
^c Division of Thoracic Surgery, National Cancer Institute, Naples, Italy

Received 9 February 2006; received in revised form 27 June 2006; accepted 3 July 2006.

^_* Corresponding author. Tel.: +34 923 291 383; fax: +34 923 291 383. (Email: gvs{at}usal.es).

	Abstract

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
Objective: Scanty information can be found regarding ppoFEV1% correlation with true FEV1% in the immediate days after surgery, when most cardio-respiratory complications are developed. This prospective multicentric investigation aims to describe the evolution of FEV1 in a series of uneventful lobectomy cases before hospital discharge, and to identify factors associated with the variation of postoperative residual FEV1, with the ratio between the actual and the predicted postoperative FEV1 measured during the first 6 postoperative days. Methods: One hundred and sixty-one patients submitted to lobectomy were prospectively enrolled in the study. Patients with chest wall resections and postoperative complications were excluded. Data from a total of 125 patients were thus used for the analysis. The following clinical variables were recorded: age, preoperative FEV1, ppoFEV1, presence of chronic obstructive pulmonary disease (COPD), surgical approach (VATS or muscle-sparing thoracotomy), side (right or left) and site (upper or lower) of resection, type of analgesia (epidural or intravenous), and daily visual analogue pain score (VAS). FEV1 was measured in every patient at hospital admission and daily until discharge or up to postoperative day 6. Random effects time-series cross-sectional regression analyses were performed to identify factors associated with variation of postoperative residual function (100 – (preoperative FEV1 – postoperative FEV1/preoperative FEV1 x 100)), and of FEV1 ratio ((actual postoperative FEV1 x 100)/ppoFEV1). For these analyses, the dependent variables (postoperative residual function and FEV1 ratio) and the pain score were analysed as panel longitudinal data. The regression analyses were subsequently validated by bootstrap procedure. Results: FEV1% was lower at first postoperative day and increased gradually up to day 6 but mean values never reached ppoFEV1%. Pain scores decreased from day 1 to day 6. Preoperative FEV1 (p < 0.0001) and postoperative pain score (p < 0.0001) resulted independently and reliably inversely associated with postoperative residual FEV1 (model R ², 0.16). Preoperative FEV1 (p = 0.001), postoperative pain score (p < 0.0001), and epidural analgesia (p = 0.04) resulted independently and reliably associated with postoperative FEV1 ratio (model R ², 0.13). Conclusion: Current methods of prediction of postoperative FEV1 greatly underestimated the real functional loss in the immediate postoperative period. Therefore, for the purpose of a more accurate risk stratification we need to correct the traditional prediction of postoperative FEV1.

Key Words: Thoracic surgical procedures • Lung volume measurements • Postoperative care • Postoperative pain

	1. Introduction

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
Estimation of postoperative FEV1% (ppoFEV1%) is a frequently used criterion to define functional operability in patients undergoing lung resection [1] since low ppoFEV1% value correlates with the occurrence of postoperative morbidity and mortality as a single predictor [2] or in combination with other variables [3].

It has been demonstrated that simple calculation of ppoFEV1% based on resected pulmonary segments is as accurate as calculation using perfusion scanning [4] and correlates well with true FEV1% measured several months after surgery [5]. But scanty information can be found regarding ppoFEV1% correlation with true FEV1% in the immediate days after surgery, when most cardio-respiratory complications are developed.

The objectives of this prospective multicentric investigation were to describe the evolution of FEV1 in a series of lobectomy patients before hospital discharge, and to identify factors associated with the variation of postoperative residual FEV1, with the ratio between the actual and the predicted postoperative FEV1 measured during the first 6 postoperative days.

	2. Methods

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
2.1 Studied population
Clinical data of 162 consecutive patients who underwent pulmonary lobectomy between November 2004 and September 2005 in our units have been prospectively collected. For this report we have excluded patients with chest wall or diaphragm tumoural involvement (three cases), patients needing early reoperation (one case) and cases experiencing postoperative cardio-respiratory morbidity (33 cases). Therefore, a total of 125 patients constituted the dataset for this study. We elected to exclude complicated patients since the occurrence of complications at different times after operation could have biased the analysis of the natural course of postoperative FEV1.

2.2 Selection criteria and clinical management
Selection criteria for operation were homogeneous for all cases and consisted in the absence of major co-morbidity refractory to medical therapy, PO₂ at rest over 50 mmHg, PCO₂ under 46 mmHg, ppoFEV1% over 30% of the normal value, and a satisfactory cardio-respiratory reserve (height reached at stair climbing test higher than 12 m or VO₂max above 10 ml/(kg min). Calculation of the ppoFEV1% was based on the number of non-obstructed pulmonary segments to be resected [4]. Patients were requested to quit smoking 3 weeks before surgery. Surgical approach was muscle-sparing or video-assisted small axillary thoracotomy in all cases. After a few hours in the recovery room, patients were transferred to dedicated cardio-thoracic wards where chest physiotherapy was started. Postoperative analgesia was achieved by epidural bupivacaine and opiates plus oral dexketoprophene, or continuous infusion of a combination of tramadol and ketorolac for the first 3 days after operation, and was titrated to achieve a visual pain score below 30–40 in a scale from 0 to 100 mm.

Chest tubes remained in place until no air leak and a daily effusion of less than 300 ml were evident.

2.3 Analysed variables
Data were prospectively entered in a, periodically audited, electronic database, which was specifically designed for this analysis. The principle investigators of this study (G.V., A.B., G.R.) were primarily responsible for the accuracy and completeness of the data entered in the database. All variables used in the study were complete. For the purpose of this analysis the following clinical variables were recorded: age, preoperative forced expiratory value in 1 s (FEV1), predicted postoperative FEV1 (ppoFEV1), presence of chronic obstructive pulmonary disease (COPD) according to GOLD criteria (FEV1 < 80% and FEV1/FVC ratio < 0.7), the surgical approach (VATS or muscle-sparing thoracotomy), the side (right or left) and site (upper or lower) of resection, the type of analgesia (epidural or intravenous), daily visual analogue pain score (VAS). 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 GOLD recommendations. FEV1 recordings were performed three times by means of a calibrated portable spirometer (SpiroPro E. Jaeger GmbH), with the patient seated or standing up, and the best value was selected. FEV1 was expressed as percentage of predicted value for age, gender and height, according to the European Community for Steel and Coal prediction equations [6]. PpoFEV1 was calculated by taking into account the number of the functioning segments removed during operation and estimated by means of bronchoscopy or CT scan.

The daily ratios of postoperative FEV1% to ppoFEV1% (FEV1 ratio) were calculated for each patient, according to the formula: FEV1 ratio = (actual postoperative FEV1 x 100)/ppoFEV1.

Prior to spirometry, thoracotomy pain was measured by an analogical visual scale (0–100 mm) and subjective score was registered.

2.4 Statistical analysis
Random effects time-series cross-sectional regression analyses were performed to identify factors associated with variation of postoperative residual function (100 – (preoperative FEV1 – postoperative FEV1/preoperative FEV1 x 100)), and of FEV1 ratio ((actual postoperative FEV1 x 100)/ppoFEV1). For these analyses, the dependent variables (postoperative residual function and FEV1 ratio) and the pain score were analysed as panel longitudinal data.

Variables initially used in the analyses were the following: age, preoperative FEV1%, COPD (according to GOLD criteria), epidural analgesia, surgical approach (muscle-sparing thoracotomy vs VATS), site of resection (upper vs lower), side of resection (right vs left), pain score (in panel longitudinal format) from postoperative day 1 to postoperative day 6.

There are two kinds of information in cross-sectional time-series data: the cross-sectional information reflected in the differences between subjects, and the time-series or within-subject information reflected in the changes within subjects over time. Panel data regression techniques allow you to take advantage of these different types of information. Although it is possible to use ordinary multiple regression techniques on panel data, they may not be optimal. The estimates of coefficients derived from regression may be subject to omitted variable bias—a problem that arises when there is some unknown variable or variables that cannot be controlled, for that affect the dependent variable. With panel data, it is possible to control for some types of omitted variables even without observing them, by observing changes in the dependent variable over time. This controls either for omitted variables that differ between cases but are constant over time, or for omitted variables that vary over time but are constant between cases. The analysis was performed under the XTreg command on Stata 8.2 software (Stata Corp., College Station, TX, USA).

The regression analyses were subsequently validated by bootstrap procedure. In the bootstrap analysis, 1000 samples of 125 patients (the same as the original dataset) were drawn with replacement from the original database. In each of these 1000 samples, time-series cross-sectional analyses were performed and the stability of the final stepwise model was 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 was judged to be stable [7,8].

All statistical analyses were performed on the statistical software Stata 8.2 (Stata Corp.).

	3. Results

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 
Age of the patients ranged from 18 to 83 years (50 percentile 68.46), and 93 were male. Diagnosis was pulmonary malignancy in all but five cases. Hospital stay ranged 3–15 days (median 6 days). Table 1 summarises the characteristics of the patients in this study. Table 2 shows the ppoFEV1 value and the evolution of postoperative FEV1% and pain score at days 1–6. FEV1% was lower at first postoperative day and increased gradually up to day 6 but mean values never reached ppoFEV1%. Pain scores decreased from day 1 to day 6. Fig. 1 summarises the median values of preoperative FEV1%, ppoFEV1% and measured FEV1 from postoperative days 1–6. Table 3 shows the results of the time-series cross-sectional regression analysis to identify factors associated with postoperative residual function. Preoperative FEV1 (p < 0.0001) and postoperative pain score (p < 0.0001) resulted independently and reliably inversely associated with postoperative residual FEV1.

View larger version (12K): [in this window] [in a new window]   Fig. 1. Comparison of preoperative FEV1%, ppoFEV1% and measured postoperative FEV1% on postoperative days 1–6.

	4. Discussion

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

Predicted postoperative FEV1 is one of the most commonly used predictors of postoperative mortality and morbidity after lung resection. It is widely applied for selection of surgical candidates [12,13] and for audit purposes [3] in risk model construction. There are several papers [2,4,5] reporting high correlation between calculated postoperative FEV1 (based on the number of resected pulmonary segments) and residual pulmonary function as assessed 3–6 months after operation. However, most of the major cardio-pulmonary complications would occur in the immediate days after operation. Changes in the expiratory volumes during this period have rarely been reported; therefore, for the mere purpose of risk stratification, an attempt should be made to predict FEV1 in the early postoperative period.

According to Bastin et al. [14] FEV1 measured in the immediate period after lobectomy is severely decreased on first postoperative day and increases gradually further on. Furrer et al. [15] have conducted an investigation measuring FVC and FEV1 in 15 lung resection cases. They have found that the ratio of postoperative FEV1 to ppoFEV1 is around 0.60 on day 1, returning to around 0.90 at discharge and it is nor related to the type of analgesia or surgical approach. Although half of their patients had no major resections, their data are similar to ours and can be in consonance with those reported by Hallfeldt et al. [16] on the negative influence of the simple lung manipulation on postoperative pulmonary volumes. In addition to the removal of lung tissue, other factors may account for the disproportionate loss in respiratory function observed early after lung resection: impairment in chest wall compliance, accumulated bronchial secretion, bronchial hyper-reactivity, microatelectasis, increased lung water, diaphragm dysfunction and reduced surfactant activity [17].

We have shown that postoperative FEV1% in the immediate days after lobectomy is approximately 30% lower than ppoFEV1% and this fact could seriously affect the clinical reliability of ppoFEV1 when used for selecting surgical candidates.

To assess which factors were associated with the variation of postoperative residual FEV1, with the ratio between the actual and the predicted postoperative FEV1 measured during the first 6 postoperative days, we used time-series cross-sectional regression analyses. Along with providing information on both the differences between subjects and within-subject over time, and making it possible to control for omitted variables by observing changes in the dependent variable over time, this type of analysis allows for unbalanced panels (variable number of time-series observations per cross-sectional unit) obviating possible selection bias due to missing values.

We found that the residual FEV1 was greater in patients with lower values of preoperative FEV1, and in those with lower postoperative pain score.

Similarly, the postoperative FEV1 ratio was inversely associated with preoperative FEV1 and with postoperative pain score, and positively associated with epidural analgesia.

Patients with lower values of preoperative FEV1 had a lower reduction in postoperative function. In addition, their measured FEV1 was closer to the predicted one in the immediate postoperative period. Our results, focused on an earlier postoperative functional assessment, confirm previous investigations that found a minimal loss or even improvement several months after lobectomy in patients with airflow limitation and lung cancer [18–23]. It appears that the mechanical improvement and the relief of airflow obstruction observed in COPD patients play a significant role already in the very early days after operation. This effect can be the reason why ppoFEV1 has not been found a valuable predictor of complications in these patients [24].

As the focus of the present analysis was not to provide corrective predictive equations but to identify factors associated with postoperative function, we chose to include among the variables the postoperative pain score, which may be a potentially modifiable factor affecting forced expiratory efforts.

Indeed, pain score was a factor associated with the postoperative FEV1 variation [25]. Lower pain scores were associated with higher residual values of FEV1 and with FEV1 values closer to ppoFEV1 (higher FEV1 ratio). This warrants the use of every possible prophylactic measures (minimally invasive accesses, intercostals nerve sparing, epidural analgesia, etc.) for minimising the thoracotomy chest pain during the immediate postoperative days. In particular, the use of epidural analgesia was independently associated with higher FEV1 ratios. These data have to be considered with caution since this is not a randomised study.

In conclusion, we demonstrated that current methods of prediction of postoperative FEV1 greatly underestimated the real functional loss in the immediate postoperative period. Therefore, for the purpose of a more accurate risk stratification we need to correct the traditional prediction of postoperative FEV1. Future analyses are warranted in order to identify variables to be factored into corrective predictive equations.

	References

Top Abstract 1. Introduction 2. Methods 3. Results 4. Discussion References

 

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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): Gonzalo Varela Alessandro Brunelli Gaetano Rocco Marcelo F. Jiménez Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Varela, G. Articles by Gatani, T. Search for Related Content PubMed PubMed Citation Articles by Varela, G. Articles by Gatani, T. Related Collections Lung - other