j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 3 0 3 e3 1 0
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Prediction of postoperative dyspnea and chronic respiratory failure Junichi Murakami, MD,a Kazuhiro Ueda, MD,a,* Fumiho Sano, MD,a Masataro Hayashi, MD,a Nobuyuki Tanaka, MD,b and Kimikazu Hamano, MDa a
Division of Chest Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan b Division of Radiology, Department of Radiopathology and Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
article info
abstract
Article history:
Background: Even among patients considered to be functionally eligible for major lung
Received 23 October 2014
resection, some experience postoperative dyspnea. Based on our previous study with
Received in revised form
quantitative computed tomography (CT), we hypothesized that postoperative dyspnea is
6 January 2015
associated with the collapse of the remaining lung, and thus, prediction of the post-
Accepted 9 January 2015
operative lung volume may contribute to risk assessment for postoperative dyspnea.
Available online 14 January 2015
Methods: We measured the emphysematous lung volume and functional lung volume (FLV) separately on whole lung CT using an image analysis software in 290 patients undergoing
Keywords:
major lung resection for cancer between January 2006 and December 2012. The post-
Dyspnea
operative FLV was predicted by a stepwise multiple regression analysis.
Respiratory failure
Results: Fourteen patients complained of postoperative dyspnea (complicated group), five of
Pulmonary resection
them presented with chronic respiratory failure. The postoperatively measured FLV was
Computed tomography
significantly lower in the complicated group than in the control group (P < 0.01). The postoperative FLV could be calculated using preoperative variables, including the forced vital capacity, number of resected segments, FLV, and emphysematous lung volume. The predicted postoperative FLV was significantly lower in the complicated group than in the control group (P < 0.01, area under the curve ¼ 0.78; sensitivity 86%; specificity 73%). The predicted postoperative FLV was also useful in distinguishing complicated patients from matched-control patients who had similar preoperative pulmonary function (P ¼ 0.02). Conclusions: Postoperative dyspnea is likely accompanied by a collapse of the remaining lung. Quantitative assessment of the lung morphology on preoperative CT is useful to screen for patients at risk of postoperative dyspnea. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Postoperative intractable dyspnea can sometimes develop in patients who undergo major lung resection for cancer,
although the patients had been regarded to be functionally operable based on the routine preoperative examinations. However, postoperative dyspnea is rarely a focus of preoperative risk assessment because this symptom does not directly
* Corresponding author. Division of Chest Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755 8505, Japan. Tel.: þ81 836 22 2259; fax: þ81 836 22 2423. E-mail address: [email protected] (K. Ueda). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.01.018
304
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 3 0 3 e3 1 0
lead to death, and that the patients can continue their daily lives without hospitalization. Nevertheless, the patients are seriously affected by such dyspnea, which leads to significant deterioration of their quality of life and decreased survival [1e3]. Little has been known regarding the risk factors for postoperative dyspnea, particularly if the patients have normal or mildly impaired pulmonary function. Although preoperative measurement of the diffusing capacity of the lung for carbon monoxide (DLCO), the maximum oxygen consumption (VO2max), and a ventilation and/or perfusion mismatch can be helpful to predict postoperative dyspnea, these parameters are not routinely obtained in patients without significant pulmonary dysfunction unless the patients already have respiratory symptoms, such as dyspnea [4]. Therefore, it may be desirable to develop a novel parameter to screen for postoperative dyspnea based on routine clinical work, without the need for additional modalities. Chest computed tomography (CT) scanning is routinely performed in patients scheduled to undergo lung resection for lung cancer. An evaluation of chest CT-derived radiologic parameters using a user-friendly software program enables the measurement of the regional lung density and volume without requiring significant time, labor, or costs (quantitative CT). Quantitative CT is particularly advantageous for measuring the lung volumes of abnormally low attenuation, representing emphysema, as well as the measurement of the lung volumes of normal attenuation, and representing the normal lung structure [5e8]. We previously found that the use of quantitative CT, in combination with spirometry and a blood gas analysis, contributed to improving the accuracy of predicting postoperative cardiopulmonary complications, such as ventilatory inefficiency, pneumonia, lobar atelectasis, atrial fibrillation, and prolonged air leaks [9]. Quantitative CT is also useful to determine the functional loss induced by major lung resection. According to our previous study on both preoperative and postoperative CT, the quantitative CT-based reduction in the lung volume of the normal structure induced by major lung resection was, to at least some degree, linked to the spirometry-based functional loss [10,11]. The postoperative collapse of the remaining lung may adversely affect the postoperative pulmonary function [11e13]. However, little has been studied on the relationship between the development of postoperative dyspnea and the quantitative CT-based parameters. In the present study, we hypothesized that postoperative dyspnea is associated with the remarkable reduction in the CT-based lung volume of normal-attenuation areas, and thus, estimation of the CT-based lung volume after major lung resection is helpful in the preoperative assessment of the risk of postoperative dyspnea and chronic respiratory failure.
2.
Patients and methods
2.1.
Patients
We retrospectively reviewed our prospective database of 350 patients who underwent anatomic resection for primary lung cancer between January 2006 and December 2012. Thirteen
patients who underwent resection of two lobes or more were excluded because these patients are known to have an increased risk of postoperative dyspnea. Three patients with limited physical activity (Eastern Cooperative Oncology Group-performance status [14] grade 2 or more) or who complained of moderate dyspnea (unable to keep up with healthy controls but able to walk about a mile or more at their own speed) [15] preoperatively were also excluded because these conditions may prevent the accurate identification of dyspnea. Because this study focused on the patient’s complaints during the first postoperative year, patients who died within the first postoperative year (n ¼ 6), patients who had recurrent disease identified during the first postoperative year (n ¼ 23), or patients who dropped out from the follow-up (n ¼ 15) were excluded. Finally, 290 cases were included in this study. This study was approved by our institutional review board. The patient data obtained before surgery included the age, sex, height, smoking habits, Eastern Cooperative Oncology Groupperformance status, FletchereHugheJones grading for dyspnea [15], spirometric variables, surgical procedures, and quantitative CT-derived parameters, as described later. The smoking data included the pack-years smoked (smoking index; average number of packages of cigarettes smoked per day multiplied by the number of years the individual smoked). There were 173 males and 117 females, with a mean age of 69.8 9.9 y. Fourteen patients complained of grade 2 dyspnea (inability to keep up with healthy persons of equivalent age on hills or stairs) preoperatively, and 31 patients were restricted with respect to physically strenuous activity (performance status grade 1). A total of 231 patients underwent lobectomy, and 59 patients underwent segmentectomy (the mean number of segments resected was 3.5).
2.2.
Operation
Operability was determined based on the existing guidelines for pulmonary resection [4]. The operation was basically performed via two ports and one window (2e8 cm), without rib spreading. During lobectomy, we used an endoscopic stapler (Ethicon, Cincinnati, OH) to divide fused fissures and to excise the bronchus. During the anatomic segmentectomy, we used electrocautery to dissect the intersegmental plane. We did not perform pleural tenting to obliterate the residual pleural space after an upper lobectomy.
2.3.
Postoperative dyspnea
Patients were routinely followed up at our outpatient clinic with chest CT scans and peripheral blood examinations performed at 3, 6, and 12 mo postoperatively. During the postoperative follow-up, 14 (5%) patients complained of newly developed dyspnea affecting their daily lives, which caused deterioration of their quality of life. In addition, the symptom was resistant to bronchodilators, such as muscarinic antagonists and/or b2-agonists, and persisted for at least 6 mo. Echocardiography was used routinely in these patients to rule out cardiac failure as a cause of the dyspnea, the left ventricular ejection fraction was more than 50% in all these patients. Chest CT was also performed to rule out structural lung diseases that cause dyspnea.
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 3 0 3 e3 1 0
2.4.
305
Pulmonary function tests
Preoperative spirometric variables were obtained within 1 mo preoperatively and included the forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The % predicted FEV1 is expressed as the percentage of the predicted value for age, gender, and height. Postoperative spirometric variables were also obtained at 6 mo postoperatively in the most recent 150 cases.
2.5.
CT scanning
Helical CT scans were obtained using a four-detector (Somatom Plus4 or Somatom Volume Zoom; Siemens Medical Solutions, Erlangen, Germany) and 64-detector (Somatom Definition or Sensation 64; Siemens) row CT scanners. With the patient in the supine position, we obtained 2-mm high resolution CT images of the entire lungs during a deep inspiratory breath hold. We used a 512 512 matrix, 2-mm collimation, and a scan time of 1.0 s at 120e130 kVp and 220e230 mA. This is a routine practice, and thus, patients were not exposed to additional radiation for the purpose of measuring the radiologic parameters in this study.
2.6.
Image interpretation and data analysis
Three-dimensional volume-rendering lung images were created using a commercially available, user-friendly imaging software (Virtual Place Raijin; AZE, Tokyo, Japan). Threshold limits of 600 to 1024 HU were applied to segment the entire lungs and to exclude soft tissues surrounding the lungs and the large vessels, atelectasis, fibrosis, and tumors within the lung. The volume of a lung that is segmented by certain threshold limits can be readily obtained with the imaging software. We called the volume of the entire lung (600 to 1024 HU) the total lung volume (TLV). The entire lung was divided into two areas, low-attenuation areas (LAAs), representing emphysematous lung tissue (4 was considered to indicate a significant dependent variable. Cumulative postoperative survival rates were calculated using KaplaneMeier’s method. Differences of the survival rates between the groups were determined by a log-rank test. A P value
Available online at www.sciencedirect.com
ScienceDirect journal homepage: www.JournalofSurgicalResearch.com
Prediction of postoperative dyspnea and chronic respiratory failure Junichi Murakami, MD,a Kazuhiro Ueda, MD,a,* Fumiho Sano, MD,a Masataro Hayashi, MD,a Nobuyuki Tanaka, MD,b and Kimikazu Hamano, MDa a
Division of Chest Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan b Division of Radiology, Department of Radiopathology and Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi, Japan
article info
abstract
Article history:
Background: Even among patients considered to be functionally eligible for major lung
Received 23 October 2014
resection, some experience postoperative dyspnea. Based on our previous study with
Received in revised form
quantitative computed tomography (CT), we hypothesized that postoperative dyspnea is
6 January 2015
associated with the collapse of the remaining lung, and thus, prediction of the post-
Accepted 9 January 2015
operative lung volume may contribute to risk assessment for postoperative dyspnea.
Available online 14 January 2015
Methods: We measured the emphysematous lung volume and functional lung volume (FLV) separately on whole lung CT using an image analysis software in 290 patients undergoing
Keywords:
major lung resection for cancer between January 2006 and December 2012. The post-
Dyspnea
operative FLV was predicted by a stepwise multiple regression analysis.
Respiratory failure
Results: Fourteen patients complained of postoperative dyspnea (complicated group), five of
Pulmonary resection
them presented with chronic respiratory failure. The postoperatively measured FLV was
Computed tomography
significantly lower in the complicated group than in the control group (P < 0.01). The postoperative FLV could be calculated using preoperative variables, including the forced vital capacity, number of resected segments, FLV, and emphysematous lung volume. The predicted postoperative FLV was significantly lower in the complicated group than in the control group (P < 0.01, area under the curve ¼ 0.78; sensitivity 86%; specificity 73%). The predicted postoperative FLV was also useful in distinguishing complicated patients from matched-control patients who had similar preoperative pulmonary function (P ¼ 0.02). Conclusions: Postoperative dyspnea is likely accompanied by a collapse of the remaining lung. Quantitative assessment of the lung morphology on preoperative CT is useful to screen for patients at risk of postoperative dyspnea. ª 2015 Elsevier Inc. All rights reserved.
1.
Introduction
Postoperative intractable dyspnea can sometimes develop in patients who undergo major lung resection for cancer,
although the patients had been regarded to be functionally operable based on the routine preoperative examinations. However, postoperative dyspnea is rarely a focus of preoperative risk assessment because this symptom does not directly
* Corresponding author. Division of Chest Surgery, Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755 8505, Japan. Tel.: þ81 836 22 2259; fax: þ81 836 22 2423. E-mail address: [email protected] (K. Ueda). 0022-4804/$ e see front matter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jss.2015.01.018
304
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 3 0 3 e3 1 0
lead to death, and that the patients can continue their daily lives without hospitalization. Nevertheless, the patients are seriously affected by such dyspnea, which leads to significant deterioration of their quality of life and decreased survival [1e3]. Little has been known regarding the risk factors for postoperative dyspnea, particularly if the patients have normal or mildly impaired pulmonary function. Although preoperative measurement of the diffusing capacity of the lung for carbon monoxide (DLCO), the maximum oxygen consumption (VO2max), and a ventilation and/or perfusion mismatch can be helpful to predict postoperative dyspnea, these parameters are not routinely obtained in patients without significant pulmonary dysfunction unless the patients already have respiratory symptoms, such as dyspnea [4]. Therefore, it may be desirable to develop a novel parameter to screen for postoperative dyspnea based on routine clinical work, without the need for additional modalities. Chest computed tomography (CT) scanning is routinely performed in patients scheduled to undergo lung resection for lung cancer. An evaluation of chest CT-derived radiologic parameters using a user-friendly software program enables the measurement of the regional lung density and volume without requiring significant time, labor, or costs (quantitative CT). Quantitative CT is particularly advantageous for measuring the lung volumes of abnormally low attenuation, representing emphysema, as well as the measurement of the lung volumes of normal attenuation, and representing the normal lung structure [5e8]. We previously found that the use of quantitative CT, in combination with spirometry and a blood gas analysis, contributed to improving the accuracy of predicting postoperative cardiopulmonary complications, such as ventilatory inefficiency, pneumonia, lobar atelectasis, atrial fibrillation, and prolonged air leaks [9]. Quantitative CT is also useful to determine the functional loss induced by major lung resection. According to our previous study on both preoperative and postoperative CT, the quantitative CT-based reduction in the lung volume of the normal structure induced by major lung resection was, to at least some degree, linked to the spirometry-based functional loss [10,11]. The postoperative collapse of the remaining lung may adversely affect the postoperative pulmonary function [11e13]. However, little has been studied on the relationship between the development of postoperative dyspnea and the quantitative CT-based parameters. In the present study, we hypothesized that postoperative dyspnea is associated with the remarkable reduction in the CT-based lung volume of normal-attenuation areas, and thus, estimation of the CT-based lung volume after major lung resection is helpful in the preoperative assessment of the risk of postoperative dyspnea and chronic respiratory failure.
2.
Patients and methods
2.1.
Patients
We retrospectively reviewed our prospective database of 350 patients who underwent anatomic resection for primary lung cancer between January 2006 and December 2012. Thirteen
patients who underwent resection of two lobes or more were excluded because these patients are known to have an increased risk of postoperative dyspnea. Three patients with limited physical activity (Eastern Cooperative Oncology Group-performance status [14] grade 2 or more) or who complained of moderate dyspnea (unable to keep up with healthy controls but able to walk about a mile or more at their own speed) [15] preoperatively were also excluded because these conditions may prevent the accurate identification of dyspnea. Because this study focused on the patient’s complaints during the first postoperative year, patients who died within the first postoperative year (n ¼ 6), patients who had recurrent disease identified during the first postoperative year (n ¼ 23), or patients who dropped out from the follow-up (n ¼ 15) were excluded. Finally, 290 cases were included in this study. This study was approved by our institutional review board. The patient data obtained before surgery included the age, sex, height, smoking habits, Eastern Cooperative Oncology Groupperformance status, FletchereHugheJones grading for dyspnea [15], spirometric variables, surgical procedures, and quantitative CT-derived parameters, as described later. The smoking data included the pack-years smoked (smoking index; average number of packages of cigarettes smoked per day multiplied by the number of years the individual smoked). There were 173 males and 117 females, with a mean age of 69.8 9.9 y. Fourteen patients complained of grade 2 dyspnea (inability to keep up with healthy persons of equivalent age on hills or stairs) preoperatively, and 31 patients were restricted with respect to physically strenuous activity (performance status grade 1). A total of 231 patients underwent lobectomy, and 59 patients underwent segmentectomy (the mean number of segments resected was 3.5).
2.2.
Operation
Operability was determined based on the existing guidelines for pulmonary resection [4]. The operation was basically performed via two ports and one window (2e8 cm), without rib spreading. During lobectomy, we used an endoscopic stapler (Ethicon, Cincinnati, OH) to divide fused fissures and to excise the bronchus. During the anatomic segmentectomy, we used electrocautery to dissect the intersegmental plane. We did not perform pleural tenting to obliterate the residual pleural space after an upper lobectomy.
2.3.
Postoperative dyspnea
Patients were routinely followed up at our outpatient clinic with chest CT scans and peripheral blood examinations performed at 3, 6, and 12 mo postoperatively. During the postoperative follow-up, 14 (5%) patients complained of newly developed dyspnea affecting their daily lives, which caused deterioration of their quality of life. In addition, the symptom was resistant to bronchodilators, such as muscarinic antagonists and/or b2-agonists, and persisted for at least 6 mo. Echocardiography was used routinely in these patients to rule out cardiac failure as a cause of the dyspnea, the left ventricular ejection fraction was more than 50% in all these patients. Chest CT was also performed to rule out structural lung diseases that cause dyspnea.
j o u r n a l o f s u r g i c a l r e s e a r c h 1 9 5 ( 2 0 1 5 ) 3 0 3 e3 1 0
2.4.
305
Pulmonary function tests
Preoperative spirometric variables were obtained within 1 mo preoperatively and included the forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). The % predicted FEV1 is expressed as the percentage of the predicted value for age, gender, and height. Postoperative spirometric variables were also obtained at 6 mo postoperatively in the most recent 150 cases.
2.5.
CT scanning
Helical CT scans were obtained using a four-detector (Somatom Plus4 or Somatom Volume Zoom; Siemens Medical Solutions, Erlangen, Germany) and 64-detector (Somatom Definition or Sensation 64; Siemens) row CT scanners. With the patient in the supine position, we obtained 2-mm high resolution CT images of the entire lungs during a deep inspiratory breath hold. We used a 512 512 matrix, 2-mm collimation, and a scan time of 1.0 s at 120e130 kVp and 220e230 mA. This is a routine practice, and thus, patients were not exposed to additional radiation for the purpose of measuring the radiologic parameters in this study.
2.6.
Image interpretation and data analysis
Three-dimensional volume-rendering lung images were created using a commercially available, user-friendly imaging software (Virtual Place Raijin; AZE, Tokyo, Japan). Threshold limits of 600 to 1024 HU were applied to segment the entire lungs and to exclude soft tissues surrounding the lungs and the large vessels, atelectasis, fibrosis, and tumors within the lung. The volume of a lung that is segmented by certain threshold limits can be readily obtained with the imaging software. We called the volume of the entire lung (600 to 1024 HU) the total lung volume (TLV). The entire lung was divided into two areas, low-attenuation areas (LAAs), representing emphysematous lung tissue (4 was considered to indicate a significant dependent variable. Cumulative postoperative survival rates were calculated using KaplaneMeier’s method. Differences of the survival rates between the groups were determined by a log-rank test. A P value
