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Ann Thorac Surg 2002;73:922-926
© 2002 The Society of Thoracic Surgeons

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Original article: general thoracic

Pulmonary complications after esophagectomy

^a Department of Medicine, Medical University of South Carolina, Charleston, South Carolina, USA
^b Department of Biometry and Epidemiology, Medical University of South Carolina, Charleston, South Carolina, USA
^c Department of Surgery, Medical University of South Carolina, Charleston, South Carolina, USA

Accepted for publication November 20, 2001.

* Address reprint requests to Dr Flume, Medical University of South Carolina, 812-CSB, 96 Jonathan Lucas St, Charleston, SC 29425 USA
e-mail: flumepa{at}musc.edu

	Abstract

Top Abstract Introduction Material and methods Results Comment Appendix. Variables collected... References

 
Background. Pulmonary complications are common in patients who have undergone esophagectomy. There are no good predictive variables for these complications. In addition, the role that preoperative treatment with chemotherapy and radiation may play in postoperative complications remains unclear.

Methods. We performed a retrospective review of all patients who underwent esophagectomy by a single surgeon at our institution over a 6-year period. Data were analyzed for a correlation between patient risk factors and pulmonary complications, including mortality, prolonged mechanical ventilation, and hospital length of stay.

Results. Complete data were available on 61 patients. Nearly all patients had some pulmonary abnormality (eg, pleural effusion), although most of these were clinically insignificant. Pneumonia was the most common clinically important complication, and 19.7% of patients required prolonged ventilatory support. Significant risk factors identified included impaired pulmonary function, especially for patients with forced expiratory volume in 1 second (FEV₁) less than 65% of predicted, preoperative chemoradiotherapy, and age.

Conclusions. Impaired lung function is a significant risk factor for pulmonary complications after esophagectomy. Patients with FEV₁ less than 65% of predicted appear to be at greatest risk. There also seems to be an associated risk of preoperative chemoradiotherapy for pulmonary complications after esophagectomy.

	Introduction

Top Abstract Introduction Material and methods Results Comment Appendix. Variables collected... References

 
Carcinoma of the esophagus continues to carry a poor long-term prognosis. Worldwide, esophageal cancer is the sixth most common cause of cancer-related death. Curative resection remains the cornerstone of therapy [1]. Despite advances in anesthesia, operative techniques, and postoperative management, perioperative mortality rates continue to range from 3% to 10% [2, 3]. Postoperative pulmonary complications occur frequently, in approximately 30% of cases, and include pleural effusions, atelectasis, chylothorax, pneumonia, respiratory failure, and pulmonary embolism [4–17]. Furthermore, pulmonary complications have been associated with postoperative mortality [3, 8, 13, 14, 18].

Several authors have attempted to predict postoperative complications and mortality based on preoperative and operative factors [3, 4, 6–8, 10–13, 16, 19–23]. Despite many retrospective reviews, conclusions regarding which patients may be at undue risk for pulmonary complications are difficult to infer. This may be because of variations in surgical techniques and surgical skills among those performing resection in each of these studies. In addition, many patients are now receiving preoperative adjuvant therapy such as combined chemotherapy and radiotherapy (chemoradiotherapy) as a means of improving survival. The effect of preoperative chemoradiotherapy on postoperative pulmonary complications remains unclear.

The purpose of this study was to quantify postoperative pulmonary complications and to evaluate the influences of various preoperative and perioperative factors on clinical outcomes in esophagectomy patients. Of particular interest was the effect of preoperative adjuvant therapy on clinical outcomes.

	Material and methods

Top Abstract Introduction Material and methods Results Comment Appendix. Variables collected... References

 
We performed a retrospective review of patients who had an esophagectomy for esophageal cancer performed at one center by a single cardiothoracic surgeon (C.E.R.) from January 1994 to October 2000. Data were extracted from hospital and clinic records as well as from the clinical outcomes department and cancer registry of our institution. A total of 17 preoperative variables (see Appendix) were recorded and classified as patient, disease, or treatment factors. Seven postoperative pulmonary complications (see Appendix) including pneumonia, chylothorax, and adult respiratory distress syndrome were recorded for the duration of the postoperative hospital stay. Pneumonia was defined as febrile illness with the presence of new pulmonary infiltrates. Chylothorax was defined as a pleural effusion with documentation of chylomicrons on lipoprotein electrophoresis or a triglyceride level greater than 110 mg/dL. Patients were considered to have acute respiratory distress syndrome (ARDS) if they had a PO₂:FIO₂ ratio less than 250 for more than 24 hours with pulmonary infiltrates, without clinical suspicion of volume overload. Four clinical outcomes (ie, ventilator hours, intensive care unit [ICU] and hospital lengths of stay, and mortality) were recorded. Mortality was defined as death occurring during hospitalization after esophagectomy, regardless of length of stay (LOS).

Values are reported as the mean ± standard deviation. Analysis of variance was used to determine the effect of preoperative treatment and surgical techniques on outcome variables. Correlation coefficients for each treatment variable were calculated for the two main outcome variables, namely, ventilation hours and hospital length of stay. From this information we were able to determine which variables were most significantly correlated with outcome variables. Odds ratios and confidence intervals were calculated with logistic regression. Additional comparisons of outcomes based on categorical distribution of pulmonary function were made using nonparametric methods (Wilcoxon rank sum test). A p value of less than 0.05 was chosen as indicating a difference unlikely to be due to chance. All statistical analyses were performed with the Statistical Analysis Systems package, version 8 (SAS Inc, Cary, NC).

	Results

Top Abstract Introduction Material and methods Results Comment Appendix. Variables collected... References

 
Of the 96 patients identified for study, hospital charts documenting perioperative hospitalization were available for 81. Preoperative data were nearly complete for 61 patients and the analysis was confined to this dataset. Data regarding patient demographics as well as cancer type and stage are shown in Table 1. Three surgical approaches were used in this population; however, transhiatal esophagectomy was considered the preferred route for resection of esophageal cancer for patients who were believed to be at increased risk for pulmonary complications. Preoperative adjuvant therapy was given to patients with T3 or N1 disease with the decision of chemotherapy versus chemoradiotherapy made on an individual case basis.

Clinical outcomes included ventilator hours (mean 91.8 ± 226.2 hours, median 12 hours), ICU days (mean 6.1 ± 11.1 days, median 2 days), and hospital days (mean 17.7 ± 12.5 days, median 13 days). Those patients requiring prolonged mechanical ventilation (> 48 hours) were also the only patients with prolonged ICU length of stays (> 6 days). Thus, statistical analyses are reported to evaluate factors influencing duration of mechanical ventilation and hospital length of stay only.

Patients who had been treated preoperatively with chemoradiotherapy (n = 20; mean 187.3 ± 314.2 hours, median 13.5 hours) had a longer duration (p = 0.05) of mechanical ventilation than did patients who received preoperative chemotherapy (n = 15; mean 10.7 hours, median 9 hours). There was no difference in hospital LOS among patients who received no preoperative treatment, those who underwent chemotherapy alone, and those had chemoradiotherapy.

Preoperative factors that significantly correlated with duration of mechanical ventilation include preoperative chemoradiotherapy (r = 0.30; p = 0.02), forced vital capacity (FVC) (r = -0.43; p < 0.01), and forced expiratory volume in 1 second (FEV₁) (r = -0.34; p = 0.02). Age (r = 0.31; p = 0.02), FVC (r = -0.48; p < 0.01), FEV₁ (r = -0.38; p < 0.01), and preoperative chemoradiotherapy (r = 0.26; p = 0.04) correlated with a prolonged hospital LOS.

We compared outcomes (duration of mechanical ventilation and hospital LOS) between groups based on severity of lung disease. We separated our patients into categories of normal (FEV₁ 80% predicted), mildly impaired (FEV₁ 65% to 79% predicted), and more severely impaired (FEV₁ < 65% predicted). Median and mean values of ventilator hours and LOS for each group are shown in Table 2. The patients with more severe impairment had longer duration of mechanical ventilation (p < 0.01) and a longer hospital LOS (p < 0.001). Those patients with an FEV₁ less than 65% predicted were at a significantly increased risk for requiring mechanical ventilation more than 48 hours (odds ratio = 7.5; 95% confidence interval 1.24 to 45.4), even after controlling for age and type of preoperative treatment. Patients who were treated with chemoradiotherapy or who had an FEV₁ 65% to 80% predicted were also at increased risk for prolonged mechanical ventilation and an increased risk for death, but these risks did not meet statistical significance.

	Comment

Top Abstract Introduction Material and methods Results Comment Appendix. Variables collected... References

 
We found a high rate of pulmonary complications associated with esophageal resection for esophageal cancer. Atelectasis and pleural effusion were the most common pulmonary complication, occurring in 87% of patients, but were of little clinical importance. Pneumonia was the most common clinically important pulmonary complication, occurring in nearly one third of our study population, which is slightly higher than what has been previously reported (15% to 25%) [2, 9, 13, 16]. The overall mortality rate in our series was 8.6%, consistent with other series [3, 9, 16, 18]. Mortality rates as low as 1.2% have been reported [10]; however, factors such as patient selection and the willingness of the surgeon to undertake high-risk cases may influence these outcomes.

We reviewed a number of preoperative clinical variables to determine whether they contributed to postoperative pulmonary complications as well as other clinical outcomes (notably, mortality, duration of mechanical ventilation, and length of stays in the ICU and the hospital). In general, measures of pulmonary function (FVC and FEV₁ as a percentage of predicted), preoperative chemoradiotherapy, and age were the only factors associated with prolonged mechanical ventilation or a prolonged hospital LOS.

Pulmonary function has long been known to be associated with pulmonary complications after esophagectomy. Fan and colleagues [6] suggested that a preoperative peak expiratory flow rate (PEFR) of less than 65% predicted correlated well with the incidence of pulmonary complications. However, PEFR had less predictive value than other variables including age, albumin level, and arterial oxygen tension. Nagawa and coworkers [12] reported a significant difference in vital capacity between patients who developed pulmonary complications and those who did not. However, the mean vital capacity of patients who developed pulmonary complications was still 91.8% of predicted, which is normal. Our analysis demonstrates a negative correlation between pulmonary function (both FVC and FEV₁) and clinical outcomes; that is, worse lung function predicts longer duration of mechanical ventilation and hospital LOS. A specific degree of pulmonary impairment that would predict undue risk is not derived from our analysis; however, those patients with an FEV₁ less than 65% predicted had considerably and significantly longer durations of mechanical ventilation and a prolonged LOS. It should be noted that a bias is present in such an analysis, in that patients with very severe pulmonary impairment are unlikely to have been offered an operation because of presumed greater risk of complications, meaning that the population is generally selected for those with better lung function.

The finding of an association between preoperative chemoradiotherapy and pulmonary complications (ie, duration of mechanical ventilation) could have implications with regard to adjuvant therapy for resectable esophageal cancer. The purpose of adjuvant chemoradiotherapy is to improve survival, although there are conflicting results as to whether it offers a survival advantage in patients with adenocarcinoma [2, 24–30]. Our study was not designed to determine a survival benefit of adjuvant chemoradiotherapy but to see whether such treatment causes increased morbidity; if it does, we will need to take this into consideration in determining its risk-benefit ratio. Some authors have reported complications that may have been attributable to preoperative chemoradiotherapy [31], whereas others report that it was well tolerated [2, 24, 25]. Only Swisher and colleagues [25] used multivariate analysis to look at any correlation of preoperative adjuvant therapy and associated morbidity; however, no association was found.

In contrast to previous studies, we found no significant correlation between nutritional status and duration of mechanical ventilation or LOS. There was an association with albumin and mortality, although the numbers are small. The minimal influence of serum albumin on outcomes may be due to the relatively well-preserved nutritional status of our patients. Only 2 of our patients had serum albumin levels less than 3.0 mg/dL.

Although our study may be limited by the small numbers of patients, there are certain features that separate it from other analyses of pulmonary complications after esophagectomy. Our series occurred over a relatively short period (6 years) so that there would be few effects due to changes in anesthesia or surgical approach. Although more than one surgical approach was used in our series, there was no significant difference in outcomes. Our series was performed by 1 surgeon, which should reduce the variability due to the operator. Only one other study may have had only 1 attending surgeon perform all esophagectomies and manage all patients postoperatively; these data were collected for more than 40 years [5]. Matthews and colleagues [32] found that there is a highly significant difference in operative mortality rate for surgeons based on the number of resections performed annually. By having a single surgeon perform all of the procedures in the study, we hoped to control for poorly quantifiable variables, which may influence outcome such as surgical experience and preferences of the individual surgeon. Our surgeon had performed 15 to 20 esophagectomies per year consistently for 10 years before the start of this series, so it is doubtful that a "learning curve" could be implied.

In conclusion, we report a high frequency of pulmonary complications after esophagectomy. Although most were not clinically important, there was an associated mortality and morbidity. Impaired pulmonary function was associated with prolonged mechanical ventilation and prolonged hospital LOS, particularly in those patients with FEV₁ less than 65% predicted. Furthermore, there may be an association with preoperative chemoradiotherapy and increased morbidity, a finding that should be investigated further.

	Appendix. Variables collected and used in analysis

Top Abstract Introduction Material and methods Results Comment Appendix. Variables collected... References

 

Preoperative/Intraoperative Variables Estimated blood loss Age Blood transfusion Comorbidities Forced vital capacity (FVC) as a percentage of predicted Postoperative Pulmonary Complications Forced expiratory volume in 1 second (FEV1) as a percent of predicted Pneumonia Arterial carbon dioxide tension (PCO2) Atelectasis/effusions Arterial oxygen tension (PO2) Pleural effusion requiring placement of additional chest tubes Alveolar-arterial oxygen gradient Chylothorax Body mass index Adult respiratory distress syndrome Preoperative albumin level Respiratory failure requiring mechanical ventilation Tumor histology Pulmonary embolism Clinical tumor stage Preoperative (adjuvant) treatment (chemotherapy, chemoradiotherapy, or no treatment) Clinical Outcomes Surgical technique (transhiatal, three-field cervical esophagostomy, or abdominal laparotomy/right thoracotomy [Ivor-Lewis approach]) Ventilator hours Total anesthesia time Intensive care unit length of stay Perioperative fluid repletion including both crystalloid and colloid replacement Hospital length of stay Mortality

	References

Top Abstract Introduction Material and methods Results Comment Appendix. Variables collected... 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): Carolyn E. Reed Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Avendano, C. E. Articles by Reed, C. E. Search for Related Content PubMed PubMed Citation Articles by Avendano, C. E. Articles by Reed, C. E.