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Approximately 20% of patients undergoing lung volume reduction surgery (LVRS) exhibit no functional improvement postoperatively. Therefore, we examined whether variables characterizing ventilatory mechanics before LVRS could serve as predictors for outcome. In 32 patients undergoing LVRS, lung function, dyspnea score, and ventilatory mechanics were assessed preoperatively and 3 mo after LVRS. Ventilatory mechanics were characterized by total resistive work of breathing (WOB), mean airway resistance (Rawm), and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn). Calculations of WOB, Rawm, and PEEPi,dyn were made from measurements of airflow, volume, and esophageal pressure. Preoperative PEEPi,dyn correlated well with the increase in forced expiratory volume percent predicted (r = 0.75; P < 0.0001) and the decrease in dyspnea score (r = -0.74; P < 0.0001) after LVRS. Rawm and WOB showed inferior correlation compared with PEEPi,dyn. The examination of distinct threshold values for WOB, Rawm, and PEEPi,dyn with respect to predicting improvement resulted in a sensitivity of 93% and specificity of 88% for a cutoff point of preoperative PEEPi,dyn 5 cm H2O. Preoperative PEEPi,dyn correlated well with improvement in forced expiratory volume and dyspnea score after LVRS. Thus, preoperative assessment of PEEPi,dyn could improve risk to benefit stratification before LVRS. Implications: We examined the preoperative ventilatory mechanics of patients with emphysema undergoing lung volume reduction surgery with respect to their value in predicting outcome. Preoperative intrinsic positive end-expiratory pressure correlated well with the increase in forced expiratory volume in 1 s after surgery. Thus, this variable seems promising for improved patient selection.
Lung volume reduction surgery (LVRS) is a new and promising treatment for severe emphysema (13). However, approximately 20% of patients do not show objective and subjective improvement after LVRS (2). Accordingly, it is important to develop variables that can identify patients who will or will not exhibit significant improvement with surgery. This seems especially important because LVRS is associated with a mortality of approximately 4% (2,3). There is still a lack of objective preoperative variables predicting postoperative outcome. Therefore, definition and validation of reliable variables for improved preoperative risk to benefit assessment and, consequently, improved patient selection, remains an important objective. Ventilatory mechanics are severely impaired in patients suffering from emphysema (4,5), and LVRS leads to a significant improvement in many patients (68). Variables characterizing ventilatory mechanics, such as mean airway resistance (Rawm), total resistive work of breathing (WOB), and dynamic intrinsic positive end-expiratory pressure (PEEPi,dyn) relate to pathophysiological changes in patients suffering from emphysema (9). Therefore, these variables are likely to serve as functional predictors for outcome. To define objective variables predicting outcome after LVRS, we assessed the utility of WOB, Rawm, and PEEPi,dyn, which were measured in 32 consecutive patients undergoing LVRS at our institution. Variables characterizing outcome were: (a) forced expiratory volume in 1 s (FEV1) 3 mo postoperatively and (b) dyspnea score 3 mo after LVRS. FEV1 was chosen to represent outcome because it correlates well with mortality in patients with end-stage emphysema (10). Dyspnea score was chosen to describe outcome because severe dyspnea leads to exercise limitation and impaired quality of life (11,12) and is therefore an important variable from the patient's point of view.
Thirty-two consecutive patients undergoing LVRS (Table 1) were examined. The study was approved by the local review board, and all patients gave written, informed consent before LVRS. Significant functional limitations despite dedicated medical therapy were the basis for patient selection. Preoperative assessment included patient history, physical examination, standard pulmonary function testing, whole body plethysmography, arterial blood gas analysis, high-resolution computer tomography, quantitative nuclear lung perfusion/ventilation scan, and catheterization of the right heart. Severe general disease, ventilation/perfusion mismatch, and a mean pulmonary artery pressure >40 mm Hg at rest were regarded as exclusion criteria for LVRS. In addition, patients with bullous emphysema, i.e., air-filled space larger than one third of the hemithorax, were excluded from the study. The first 15 patients undergoing LVRS at our institution were also excluded from the study because it is likely that their results were influenced by the learning curves of the physicians. Of the 32 patients, 28 were treated topically and/or systemically with glucocorticoids. Baseline patient data are shown in Table 1.
Surgery was performed on both lungs using a video-endoscopic approach. The goal was to remove 20%30% of the volume of each lung, concentrating on the most severely diseased portions of the lung. In patients who displayed a relatively homogeneous morphological distribution of the emphysematous process, portions of all lobes were excised.
Ventilatory mechanics were assessed 510 days before surgery and 3 mo (range 8497 days) after LVRS. Ventilatory mechanics were assessed with the patient in an upright sitting position, and all patients breathed room air. Airflow (
Minute ventilation ( Chest wall compliance was not included in our WOB calculations because the patients breathed spontaneously during the entire measuring period.
PEEPi,dyn was measured, whereby PEEPi,dyn is equal to the absolute change in Pes from the onset of inspiratory effort to the onset of inspiratory The Baseline Dyspnea Index was used to evaluate dyspnea (18). This score was chosen for the evaluation of dyspnea because subjective, individual impairment is questioned, as is the magnitude of task and effort, which is differs among individuals. Dyspnea score was assessed preoperatively and 3 mo after surgery. For adequate comparison of improvement in dyspnea score, the preoperatively determined score was regarded as 100%, and the value determined 3 mo after surgery was compared with this 100% (normalized dyspnea score). Spirometry and whole body plethysmography were performed in all patients preoperatively and 3 mo postoperatively, and the values compared with the reference value given by the European Community for Steel and Coal (19). Statistical analysis was performed by using paired Student's t-tests. Preoperative spirometric values and mechanics were compared with values derived 3 mo after surgery and are expressed as mean ± SEM if not otherwise noted. P < 0.05 was considered the level of significance. For all further calculations, preoperative values of FEV1 percent (%) predicted were regarded as 100%, and FEV1 % predicted 3 mo after surgery was expressed as a percentage of the preoperative value (normalized FEV1 % predicted). This approach was chosen to generate a comparable situation among patients because absolute changes in FEV1 in liters are difficult to interpret when they are not correlated with the age, gender, body weight, and height of a patient. Furthermore, an increase in FEV1 expressed in liters does not express the magnitude of improvement in relation to the preoperative situation.
To evaluate the accuracy of predicting outcome for different threshold values of a specific ventilatory parameter (viz.: PEEPi,dyn, WOB, Rawm), we defined a good result as a gain in normalized FEV1 % predicted of Standard formulas were used to calculate the sensitivity (true positive/[true positives + false negatives]), specificity (true negatives/[true negatives + false positives]), positive predictive value (true positives/[true positives + false positives]), and negative predictive value (true negatives/[true negatives + false negatives]) of each index.
Preoperatively ventilatory mechanics of all 32 patients enrolled in the study could be measured successfully, and none of the single measurements required more than 30 min. No complications associated with the measurements (swallowing of the esophageal balloon) were observed during or after all 62 measurements, which were performed in the course of the study. Of the 32 patients, 30 were extubated within 24 h of surgery; none required reintubation. One patient could not be weaned and underwent successful lung transplantation 15 days after LVRS. The preoperative values for this patient were: 18.9% (0.89 L) FEV1 % predicted, 1.5 cm H2O PEEPi,dyn, 1.78 J/L WOB, and 10.8 cm H2O · L-1 · s-1 Rawm. Another patient remained extubated for 48 h but required mechanical ventilation on the third postoperative day because of the development of bilateral, panlobular pneumonia, resulting in adult respiratory distress syndrome. This patient died on the 10th postoperative day. The preoperative values for this patient were: 26.6% (1.09 L) FEV1 % predicted, 2.8 cm H2O PEEPi,dyn, 1.51 J/L WOB, and 8.7 cm H2O · L-1 · s-1 Rawm. The data presented were derived from the remaining 30 patients. Preoperative FEV1 was 0.75 ± 0.04 L versus 1.18 ± 0.12 L (P < 0.005) 3 mo after LVRS. FEV1 % predicted showed comparable values: 25.4% ± 1.4% preoperatively versus 38.5% ± 4.2% (P < 0.005) 3 mo after LVRS. Of the 30 patients, 14 improved >40% in FEV1 % predicted after LVRS, whereas 2 of the 30 patients had worse FEV1 % predicted after the surgical procedure.
WOB decreased significantly (P < 0.005) after the surgical procedure (1.65 ± 0.10 vs 0.93 ± 0.08 J/L). Preoperative WOB per liter showed a correlation coefficient of r = 0.56 (P < 0.002) when correlated with normalized FEV1 % predicted 3 mo after LVRS (Fig. 1). The correlation coefficient of linear regression was r = -0.57 (P < 0.002) when correlating preoperative WOB with decrease in normalized dyspnea score (Fig. 1). Thereafter, cutoff points of 1.25, 1.50, 1.75, and 2 J/L were tested with respect to their accuracy in predicting a good surgical result, defined as an increase in FEV1 % predicted
A significant (P < 0.005) decrease in Rawm (17.3 ± 1.7 vs 9.7 ± 1.4 cm H2O · L-1 · s-1) was noted 3 mo after LVRS. Preoperative Rawm showed a correlation coefficient of r = 0.48 (P < 0.01) when correlated with normalized FEV1 % predicted (Fig. 2) and a correlation coefficient of r = -0.38 (P < 0.05) when correlated with the decrease in normalized dyspnea score 3 mo after surgery (Fig. 2). Rawm 10 cm H2O · L-1 · s-1 was better in predicting outcome than Rawm 15 and 20 cm H2O · L-1 · s-1 (Table 2).
Preoperative PEEPi,dyn was 6.3 ± 0.9 cm H2O, which decreased to 1.9 ± 0.3 cm H2O (P < 0.001) 3 mo after surgery. Single-patient data of changes in PEEPi,dyn are displayed in Figure 3. Correlation of preoperative PEEPi,dyn with normalized FEV1 % predicted 3 mo after LVRS showed a correlation coefficient of r = 0.75 (P < 0.0001) (Fig. 4). The correlation of preoperative PEEPi,dyn with normalized dyspnea score 3 mo after surgery resulted in a correlation coefficient of r = -0.74 (P < 0.0001) (Fig. 4). When testing different values of preoperative PEEPi,dyn as possible predictors for outcome, PEEPi,dyn 5 cm H2O showed the best results, predicting outcome accurately in 27 of 30 patients. A threshold value of PEEPi,dyn 5 cm H2O showed a sensitivity of 93%, a specificity of 88%, a positive predictive value of 87%, and a negative predictive value of 93% (Table 2).
Values characterizing breathing pattern, such as E, f, and the duty cycle, were unchanged after LVRS. E was 8.4 ± 0.7 L/min preoperatively versus 9.6 ± 1.0 L/min 3 mo after surgery, and f was 19.7 ± 1.2 breaths/min preoperatively versus 19.9 ± 1.0 breaths/min 3 mo postoperatively. Breathing pattern was assessed together with ventilatory mechanics (WOB, Rawm, PEEPi,dyn).
This study was performed to examine whether preoperative functional variables characterizing ventilatory mechanics could serve as predictors for outcome after LVRS. Three months after surgery, FEV1 was significantly increased; WOB, Rawm, and PEEPi,dyn were significantly decreased. A threshold value for preoperative PEEPi,dyn 5 cm H2O resulted in the best combination of sensitivity (93%) and specificity (88%) of all examined threshold values when a good functional result was defined as an increase in normalized FEV1 % predicted 40%. A variable serving as preoperative predictor for outcome in daily clinical routine must meet several demands. The measurement of the variable must be safe, of considerably short duration, and accurate. In our study, we assessed ventilatory mechanics by using the Bicore CP-100 pulmonary monitor. No adverse events associated with the measurements were observed. Thus, we conclude that the measuring technique is safe. Furthermore, a maximum of 30 min was required for the setup and calibration of the equipment and the measurement. This seems to be reasonably time efficient and, thus, practical in daily clinical routine. Additionally, in a prestudy evaluation, we found the measurements and calculations of the device to be accurate (15).
A good surgical result was defined as an increase in FEV1 % predicted Preoperative WOB did not correlate well with the increase in normalized FEV1 % predicted (Fig. 1) or decrease in normalized dyspnea score 3 mo after LVRS (Fig. 1). Additionally, preoperative WOB was inferior in predicting outcome compared with preoperative PEEPi,dyn (Table 2). WOB is significantly increased in many diseases of the lungs and the thorax and is therefore not specific for emphysema (16). LVRS candidates often suffer additionally from interstitial fibrotic scarring and long-term inflammation of the airways (21), which also leads to increased WOB but cannot be improved by LVRS. We assume that this is why preoperative WOB could not sufficiently predict outcome.
Our results demonstrated good correlation between preoperative PEEPi,dyn and the increase in normalized FEV1 % predicted and normalized dyspnea score 3 mo after surgery. PEEPi,dyn When PEEPi,dyn is measured at comparable breathing pattern (22), which was the case in our patients, its magnitude is determined by (a) the magnitude of expiratory flow limitation and, thus, the magnitude of expiratory airway resistance (23); (b) the magnitude of reduction in elastic recoil of the lungs (23); and (c) the activity of expiratory muscles (24). Rawm has been shown to be significantly reduced after LVRS, probably by decompression of healthy lung tissue after removal of hyperinflated, destroyed tissue (8). Additionally, Scruiba et al. (6) found significantly improved elastic recoil after LVRS, and Benditt et al. (25) showed significant reduction of expiratory muscle activity during rest and exercise after LVRS. PEEPi,dyn is determined by the most important pathophysiological variables characterizing emphysema. All these variables undergo specific changes after LVRS (6,8,25). Thus, it is not surprising that the magnitude of preoperative PEEPi,dyn correlated well with the postoperative improvement in FEV1 (Fig. 4) and dyspnea score (Fig. 4).
When retrospectively evaluating specific threshold values of preoperative PEEPi,dyn as cutoff points for predicting outcome, we found a positive predictive value of 87% and a negative predictive value of 93% for preoperative PEEPi,dyn The correlation of preoperative Rawm with postoperative increase in normalized FEV1 % predicted (Fig. 2) and decrease in dyspnea score was poor. Additionally, preoperative Rawm was inferior compared with preoperative PEEPi,dyn in predicting postoperative improvement (Table 2). Ingenito et al. (26) showed in 29 subjects that inspiratory airway resistance correlated (r = -0.63) with a poor surgical result after LVRS. In contrast, patients presenting for LVRS with high expiratory airway resistance were likely to benefit from surgery. We evaluated the mean of inspiratory airway resistance and expiratory airway resistance in our patients. Therefore, we cannot rule out that pure inspiratory or pure expiratory airway resistance could serve more sufficiently as a predictor of outcome after LVRS than Rawm. However, the correlation coefficient determined for inspiratory airway resistance by Ingenito et al. (26) was r = -0.63, whereas the correlation coefficient for PEEPi,dyn in our study was r = 0.75. Because PEEPi,dyn is partially determined by expiratory flow resistance, our finding of the good predictive value of preoperative PEEPi,dyn is in line with the findings of Ingenito et al. (26).
In summary, our findings indicate that the magnitude of preoperative PEEPi,dyn is a good predictor for postoperative outcome after LVRS. From the observations made in 30 patients undergoing LVRS, we propose using a preoperative PEEPi,dyn
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