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Original Research: Pulmonary Procedures |

Patient Safety and Comparative Effectiveness of Anesthetic Technique in Open Lung ResectionsPatient Safety and Anesthesia Type in Lung Surgery FREE TO VIEW

Umut Özbek, PhD; Jashvant Poeran, MD, PhD; Madhu Mazumdar, PhD; Stavros G. Memtsoudis, MD, PhD, FCCP
Author and Funding Information

From the Institute for Healthcare Delivery Science, Department of Population Health Science & Policy (Drs Özbek, Poeran, and Mazumdar), Tisch Cancer Institute (Drs Özbek and Mazumdar), and Department of Medicine (Dr Poeran), Icahn School of Medicine at Mount Sinai, New York, NY; Department of Healthcare Policy and Research (Dr Memtsoudis), Weill Cornell Medical College, and Department of Anesthesiology (Dr Memtsoudis), Hospital for Special Surgery, New York, NY; and Department of Anesthesiology, Perioperative Medicine and Intensive Care Medicine (Dr Memtsoudis), Paracelsus Medical University, Salzburg, Austria.

CORRESPONDENCE TO: Stavros G. Memtsoudis, MD, PhD, FCCP, Department of Anesthesiology, Hospital for Special Surgery, 535 E 70th St, New York, NY 10021; e-mail: memtsoudiss@hss.edu


FUNDING/SUPPORT: Drs Özbek and Mazumdar were partially supported by Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(3):722-730. doi:10.1378/chest.14-3040
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Published online

BACKGROUND:  Despite literature suggesting benefits of using regional anesthesia, the impact of neuraxial anesthesia on perioperative outcomes in patients undergoing lung surgery remains unstudied. We studied the effect of combined neuraxial/general anesthesia (vs general anesthesia) on perioperative outcome in a large national sample of patients who underwent open lung resection.

METHODS:  We extracted data from the Premier Perspective database on patients who underwent open lung resection. The main effect of interest was anesthesia type: general and combined neuraxial/general anesthesia. Patient and health-care variables, complications, and resource use were compared between groups. Multivariable analyses assessed the independent impact of choice of anesthetic technique on outcomes.

RESULTS:  For 18,943 patients, anesthesia type was known: 79% (n = 14,912) were administered general anesthesia, and 21% (n = 4,031) received neuraxial/general anesthesia. Comparing general vs neuraxial/general anesthesia, unadjusted incidences for the latter were lower for acute myocardial infarction (1.09% vs 0.67%, P = .018), pulmonary complications (20.96% vs 18.98%, P = .006), blood transfusion (14.15% vs 9.80%, P < .0001), and mechanical ventilation (11.60% vs 8.81%, P < .0001). Neuraxial/general anesthesia was associated with lower adjusted odds of blood transfusion (OR, 0.82; 95% CI, 0.69-0.98) and mechanical ventilation (OR, 0.81; 95% CI , 0.67-0.98), while higher odds were seen for DVT (OR, 1.50; 95% CI, 1.01-2.23) and pulmonary embolism (OR, 1.56; 95% CI, 1.02-2.38).

CONCLUSIONS:  This study illustrates the association between adding neuraxial to general anesthesia in open lung resections among patients with cancer and perioperative outcomes. Neuraxial anesthesia use was associated with decreased risk for blood transfusion but increased thromboembolic risks. Additional studies are needed to elucidate mechanisms by which neuraxial anesthesia may affect these outcomes.

Approximately 400,000 Americans suffer from lung cancer, the leading cause of cancer death in the United States.1,2 To date, surgical resection represents the main curative approach and is performed approximately 40,000 times per year in the United States alone.35 Despite improvements in surgical techniques and medical management, morbidity and mortality remain relatively high.6 In this context, many practitioners consider the use of neuraxial anesthetic techniques in an attempt to reduce complication rates.7,8

Current evidence is derived from small, single-institution studies suggesting better clinical outcomes with the use of neuraxial anesthesia (combined with general anesthesia), including less intraoperative bleeding, better control of postoperative pain, early mobilization, and oral intake tolerance.7,913 However, large-scale data on anesthesia practices and outcomes, in particular for the United States, are lacking.

Such data are important, given that much of the estimated $12.1 billion per year spent on lung cancer treatment in the United States14 is related to the high use of resources (ie, critical care services, mechanical ventilation, prolonged hospital stay) and potentially high rates of perioperative complications.

In view of the available evidence suggesting benefits of neuraxial anesthesia in this and other patient populations,15 we aimed to (1) determine the extent of the use of neuraxial anesthesia among patients undergoing open resection surgery for lung cancer, and (2) quantify the impact of anesthetic technique on patient perioperative outcomes and resource utilization. We used data from a large, claims-based national database and hypothesized that the addition of neuraxial anesthesia to general anesthesia would positively affect various perioperative outcomes.

Data Source

Data collected between 2006 and 2013 were obtained from Premier Perspective Inc, which is an administrative database containing information on all discharges from approximately 20% to 25% of hospitals located in the United States.16 This project was exempt from requirements for consent by our institutional review board (project HS No. 14-00647), as the data are compliant with the Health Insurance Portability and Accountability Act.

Study Sample

All patient records with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) procedure code for open lung resection performed between 2006 and 2013 were identified using codes for segmentectomy (32.39), lobectomy (32.49), and pneumonectomy (32.59). To keep the sample as homogenous as possible, we chose to study only open lung resections. This sample was further restricted to entries with ICD-9-CM codes for malignant neoplasm of main bronchus (162.2), malignant neoplasm of upper lobe bronchus or lung (162.3), malignant neoplasm of middle lobe bronchus or lung (162.4), malignant neoplasm of lower lobe bronchus or lung (162.5), malignant neoplasm of other parts of bronchus or lung (162.8), and malignant neoplasm of bronchus and lung unspecified (162.9). Elective, urgent, and emergent admissions were included. Using billing data as previously described,17 we separated entries into groups of patients, who underwent their procedure under general or combined neuraxial/general anesthesia. Those without indication of type of anesthesia were categorized as missing. To ensure that this step would not skew results, a sensitivity analysis was performed by including and by excluding patients with missing entry for all analyses.

Demographic Variables

We compared the characteristics of patients with lung cancer undergoing lung resection under the different types of anesthesia (general and neuraxial/general). Patient-related characteristics included age, sex, race (white, black, Hispanic, other), admission type (emergent, elective, urgent, and others), and insurance type (commercial, Medicaid, Medicare, uninsured). Health care-related characteristics included hospital size (< 299, 300-499, > 500 beds), geographic location (rural, urban), and teaching status (teaching, nonteaching). Comorbidity prevalence and overall comorbidity burden was assessed using the method described by Deyo et al.18 In addition, the extent of surgery (pneumonectomy, lobectomy, or segmentectomy) was taken into account.

Outcome Variables

Outcome variables were almost all identified by ICD-9-CM codes (e-Table 1) and incidence (or median) was shown by anesthesia group. Complications included acute renal failure, DVT, GI complications, cardiac complications (including conduction disorders, functional disturbances, ventricular fibrillation and flutter, atrial fibrillation and flutter, cardiac arrest, cardiac insufficiency, cardiorespiratory failure, and heart failure resulting from the procedure), acute myocardial infarction, cerebrovascular events, pulmonary complications overall, pulmonary embolism, pneumonia, mortality, and wound complications. Need for blood transfusion, admission to an ICU, need for mechanical ventilation, length of hospital stay, and cost of hospitalization were classified as resource utilization variables.

Statistical Analysis

Patient demographics, health care- and procedure-related variables, and comorbidities were assessed and compared by anesthesia type. Categorical variables were compared using χ2 tests. Due to their skewed distribution, the difference between groups in continuous variables was tested using the Mann-Whitney U test. We used multilevel logistic regression modeling to assess the association between anesthesia types on outcomes. Correlation of patients within each hospital was accounted for by including a random intercept in the models. To meet the minimum recommended sample size cluster, only hospitals having ≥ 30 patients were included.19 Models were adjusted using all variables that were clinically important and found significant in the univariable analysis (P ≤ .15). The Deyo-Charlson Comorbidity Index was used to adjust for comorbidity status. ORs, 95% CIs, and P values are reported and are to be used together as a measure of overall significance. All analyses were performed in SAS version 9.3 statistical software (SAS Institute Inc); the GLIMMIX procedure was used for multilevel regression analyses.

We identified 21,756 patients with lung cancer who underwent open lung resections at 353 hospitals between 2006 and 2013. Among those, 90% (n = 19,611) were elective admissions, 6% (n = 1,294) were urgent, and 4% (n = 851) were emergent admissions. For 87% (n = 18,943) of those admissions, an entry for the type of anesthesia was available: 79% (n = 14,912) were performed under general anesthesia, and 21% (n = 4,031) were performed under combined neuraxial/general anesthesia. Table 1 shows the patient and health care-related variables by anesthesia type. There were no significant differences in age, sex, or insurance type. Most notably, patient race (P ≤ .0001) and hospital characteristics (size [P ≤ .0001], location [P ≤ .0001], and teaching status [P = .008]) were significantly associated with anesthesia type, with Medicare covering > 50% of patients across both anesthesia types and the majority of operations performed at urban hospitals. Furthermore, overall comorbidity burden did not differ between groups (P = .076) (Table 2).

Table Graphic Jump Location
TABLE 1 ]  Patient and Health Care-Related Characteristics by Anesthesia Type
a 

P value is to test the null hypothesis of no incidence difference between general and neuraxial/general (χ2 test).

Table Graphic Jump Location
TABLE 2 ]  Preexisting Comorbidities by Anesthesia Type
a 

P value is to test the null hypothesis of no prevalence difference between general and neuraxial/general (χ2 test for categorical variables, Mann-Whitney U test for continuous variables).

b 

Continuous variable median and lower and upper quartiles instead of No. and %, respectively.

Table 3 depicts outcomes by anesthesia type. Most notably, when comparing general vs neuraxial/general anesthesia, the latter appeared more favorable for incidences of acute myocardial infarction (1.09% vs 0.67%, P = .018), pulmonary complications (20.96% vs 18.98%, P = .006), blood transfusion (14.15% vs 9.80%, P < .0001), and mechanical ventilation (11.60% vs 8.81%, P < .0001). On the other hand, using the same comparison, we observed significantly higher incidence rates of DVT (0.83% vs 1.17%, P = .041), and pulmonary embolism (0.67% vs 0.99%, P = .034) in the neuraxial/general anesthesia group. There were no statistically significant differences in length of stay or cost of hospitalization between anesthesia groups.

Table Graphic Jump Location
TABLE 3 ]  Outcomes by Anesthesia Type
a 

P value is to test the null hypothesis of no incidence difference between general and neuraxial/general (χ2 test for categorical variables, Mann-Whitney U test for continuous variables).

b 

Conduction disorders, functional disturbances, ventricular fibrillation and flutter, atrial fibrillation and flutter, cardiac arrest, cardiac insufficiency, cardiorespiratory failure, and heart failure resulting from procedure.

c 

Data given as continuous variable median and lower and upper quartiles.

When we controlled for the covariates age, sex, race, geographic location, size of the hospital, comorbidity burden, extent of surgery, and admission type, with hospitals as random intercept in the models, combined neuraxial/general anesthesia (compared with general anesthesia) was associated with lower odds for blood product transfusion (OR, 0.82; 95% CI, 0.69-0.98; P = .027) and mechanical ventilation (OR, 0.81; 95% CI, 0.67-0.98; P = .029), while higher odds were observed for DVT (OR, 1.50; 95% CI, 1.01-2.23; P = .043), cerebrovascular events (OR, 1.59; 95% CI, 1.04-2.44; P = .035), and pulmonary embolism (OR, 1.56; 95% CI, 1.02-2.38; P = .043) (Table 4). There were no statistically significant associations with the anesthesia type for the other outcomes.

Table Graphic Jump Location
TABLE 4 ]  Results From the Multivariable Regression Analysis
a 

This table displays the results of the multivariable regression analysis for various complications and outcomes comparing combined neuraxial/general vs general (reference) anesthesia for patients receiving lung resection. For each outcome, logistic regression was used to evaluate its association with the type of anesthesia while controlling for age, sex, race (white, black, Hispanic, other), geographic location (urban or rural), hospital size, comorbidity burden, extent of surgery (pneumonectomy, lobectomy, or segmentectomy), admission type (elective, urgent, or emergent), and pulmonary complications.

b 

Conduction disorders, functional disturbances, ventricular fibrillation and flutter, atrial fibrillation and flutter, cardiac arrest, cardiac insufficiency, cardiorespiratory failure, and heart failure resulting from procedure.

c 

Other pulmonary complications were not controlled for.

In this study of 21,756 hospitalized patients with lung cancer who underwent open lung resection surgery, we found that neuraxial anesthesia was used in approximately one-fifth of patients. The use of neuraxial techniques was associated with reduced risk for blood transfusions and mechanical ventilation, while odds were increased for thromboembolic and cerebrovascular events. The use of neuraxial in addition to general anesthesia failed to show an impact on other outcomes, including mortality and other resources.

Large randomized trials addressing optimal anesthesia in perioperative practice have not seemed feasible, given the costs and the number of patients needed to study the relatively low incidence of outcomes. Although some propose combined neuraxial and general anesthesia to be preferred over just general anesthesia in lung resections, these claims are based on results from relatively small and single-institution trials involving non-US patients.7,913 Moreover, data are lacking on perioperative outcomes (eg, complication rates or mortality). Thus, available data on the proposed benefits of neuraxial anesthesia are burdened with significant limitations associated with small sample sizes and general applicability of results representing current practice.2024 Moreover, data are specially limited for patients undergoing noncardiac thoracic surgery, such as lung resections. There is another significant knowledge gap with respect to perioperative outcomes for subpopulations, which is becoming increasingly important in this age of patient-tailored medicine.

The availability of large national databases and advances in methodologic approaches provide opportunities to study perioperative outcomes in the context of different anesthesia practices in the US population. Similar to the current study, we used data from the large national Premier Perspective claims-based database for other published studies.16,25,26 In these studies, we compared perioperative outcome after general, neuraxial, and general/neuraxial anesthesia in (1) all patients undergoing primary joint (hip or knee) arthroplasty and (2) the subgroup of patients suffering from sleep apnea.25,26 These studies showed neuraxial and neuraxial/general anesthesia combined to be preferred over general anesthesia (in terms of patient safety outcomes and resource use) in all arthroplasty patients as well as in the subgroup of patients with sleep apnea, thus providing the first large-scale support, to our knowledge, for the widely used guidelines published by the American Society of Anesthesiologists in 2006 on the perioperative care of patients with sleep apnea.25,27

In this study, using a large nationwide sample, we were able to compare the effect of anesthesia types on perioperative outcomes after open lung resection among patients with cancer. While we were able to identify benefits for the outcomes of reduced need for blood transfusions and mechanical ventilation, patients receiving a neuraxial anesthetic had higher risk for thromboembolic events, including DVT, pulmonary embolism, and cerebrovascular accidents. The reasons for these findings have to remain speculative from our data, but possible explanations exist.

The addition of neuraxial to general anesthesia has been associated with a blunting of the sympathetic system, and, thus, leads to better BP control with subsequent less blood loss and transfusion, as observed in our study.13 A trend toward reduced myocardial ischemic events may equally be explained by such a mechanism. On the other hand, using neuraxial anesthesia may promote hypotension, which may be associated with cerebrovascular ischemic events. The increased risk of thromboembolic events may be linked to the inability to use more potent anticoagulants, especially if epidural catheters remain in place postoperatively, thus putting patients (especially those with cancer), known to be hypercoagulable, at increased risk for thrombotic complications.28 This mechanism might be responsible for the observed thromboembolic risk in our study. To test this hypothesis, we analyzed the use of anticoagulant medications in both groups of interest (e-Table 2) and were able to confirm this assumption: Anticoagulant use was significantly lower for all categories for patients undergoing their procedure under neuraxial/general anesthesia compared with those undergoing their procedure under general anesthesia.

Controversy has persisted among clinicians over the potential impact of the type of anesthesia on perioperative outcomes.2024 General anesthesia provides fast and effective anesthesia, muscle relaxation, and unawareness, but, unfortunately, contributes to unfavorable postoperative symptoms, such as nausea and vomiting, fatigue, and drowsiness.29,30 To provide effective postoperative analgesia, general anesthesia is often combined with neuraxial anesthesia.31

Compared with general anesthesia, neuraxial anesthesia has been associated with beneficial effects on intestinal perfusion, accelerated postoperative recovery of intestinal function, antiischemic effects due to postoperative stress reduction, and reduction of systemic sympathetic activity.9,13,32,33 An increasingly mentioned potential benefit of neuraxial anesthesia is the opioid-sparing effect and reduced neurohumoral stress response; in case of cancer surgery, some studies show reduced tumor recurrence and improved survival in procedures under neuraxial anesthesia.31,34 Possible side effects associated with neuraxial anesthesia comprise intraoperative hypotension, pruritus, urinary retention, respiratory depression, postdural puncture headache, and, most importantly, the risk of permanent neurologic damage, which is rare (0-4 per 10,000 applied spinal anesthetics).35

Our study has several limitations due to the analysis of secondary data from a large administrative database not originally intended for clinical research. First, detailed clinical information may not be available and the impact of that information cannot be assessed on outcome. Second, the database is based on discharges; therefore, it is not possible to detect the effect of repeated measures, such as people registered more than once. Moreover, it is not possible to capture postdischarge outcomes such as the incidence of postthoracotomy pain syndrome, a frequent and debilitating condition. In this context, a Cochrane review showed that the addition of neuraxial anesthesia was associated with improved outcomes at 6 months after surgery.36 Another limitation of our study pertains to the potential for coding bias because of the ICD-9-CM coding system for defining comorbidities, complications, and surgical pathology. However, both groups should have been exposed equally to such bias, thus diminishing its influence on comparative results. The true incidence of complications may not be captured and, indeed, may be underestimated due to the specific ICD-9-CM codes used (e-Table 1). Finally, we found 13% missingness of our effect variable of interest (ie, anesthesia type), using billing data for identification. This proportion of missingness compares well with that reported in the comprehensive National Anesthesia Clinical Outcomes Registry, which has a missing rate of around 18%37 and was designed specifically to capture anesthesia-related information. To investigate how this missingness would affect outcomes, however, we performed a sensitivity analysis and found no differences when including the missing subjects in our analyses.

In conclusion, using a large national sample, we demonstrate that choice of combined neuraxial/general anesthesia over general anesthesia alone has superior effect on the risk of blood transfusion and mechanical ventilation. However, adding neuraxial anesthesia was associated with increased risk of pulmonary embolism and DVT, which may be due to the reduced use of anticoagulant medications for fear of neuraxial hematoma formation. Combined neuraxial/general anesthesia may have benefits over general anesthesia only, but more effective anticoagulation strategies compatible with neuraxial techniques need to be established to avoid thromboembolic events. Based on these findings, further research should be conducted into mechanisms by which neuraxial anesthesia may affect these outcomes.

Author contributions: U. Ö. and J. P. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. U. Ö. served as principal author. U. Ö., J. P., and M. M. designed the study; M. M. and S. G. M. attained the Premier Perspective database; U. Ö. and J. P. analyzed data under guidance of M. M. and S. G. M.; and U. Ö., J. P., M. M., and S. G. M. contributed to the interpretation of the results and reviewed and approved the final manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of sponsors: The sponsor had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: Data were purchased from Premier Inc and, as such, are restricted for this project and cannot be shared because of these restrictions on use of data. Syntax is available from the corresponding author. The authors thank Rehana Rasul, MA, MPH, for database management and creating the analytic datasets.

Additional information: The e-Tables can be found in the Supplemental Materials section of the online article.

ICD-9-CM

International Classification of Diseases, Ninth Revision, Clinical Modification

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Shaw A, Swaminathan M, Phillips-Bute B, et al. Mortality after lung resection: a 15-year analysis of US hospital discharge data. Cancer Ther. 2008;6(2):787-792.
 
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Figures

Tables

Table Graphic Jump Location
TABLE 1 ]  Patient and Health Care-Related Characteristics by Anesthesia Type
a 

P value is to test the null hypothesis of no incidence difference between general and neuraxial/general (χ2 test).

Table Graphic Jump Location
TABLE 2 ]  Preexisting Comorbidities by Anesthesia Type
a 

P value is to test the null hypothesis of no prevalence difference between general and neuraxial/general (χ2 test for categorical variables, Mann-Whitney U test for continuous variables).

b 

Continuous variable median and lower and upper quartiles instead of No. and %, respectively.

Table Graphic Jump Location
TABLE 3 ]  Outcomes by Anesthesia Type
a 

P value is to test the null hypothesis of no incidence difference between general and neuraxial/general (χ2 test for categorical variables, Mann-Whitney U test for continuous variables).

b 

Conduction disorders, functional disturbances, ventricular fibrillation and flutter, atrial fibrillation and flutter, cardiac arrest, cardiac insufficiency, cardiorespiratory failure, and heart failure resulting from procedure.

c 

Data given as continuous variable median and lower and upper quartiles.

Table Graphic Jump Location
TABLE 4 ]  Results From the Multivariable Regression Analysis
a 

This table displays the results of the multivariable regression analysis for various complications and outcomes comparing combined neuraxial/general vs general (reference) anesthesia for patients receiving lung resection. For each outcome, logistic regression was used to evaluate its association with the type of anesthesia while controlling for age, sex, race (white, black, Hispanic, other), geographic location (urban or rural), hospital size, comorbidity burden, extent of surgery (pneumonectomy, lobectomy, or segmentectomy), admission type (elective, urgent, or emergent), and pulmonary complications.

b 

Conduction disorders, functional disturbances, ventricular fibrillation and flutter, atrial fibrillation and flutter, cardiac arrest, cardiac insufficiency, cardiorespiratory failure, and heart failure resulting from procedure.

c 

Other pulmonary complications were not controlled for.

References

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11-30. [CrossRef] [PubMed]
 
National Cancer Institute. Surveillance, Epidemiology, and End Results Program. National Cancer Institute website. http://seer.cancer.gov/. Accessed December 3, 2014.
 
Shaw A, Swaminathan M, Phillips-Bute B, et al. Mortality after lung resection: a 15-year analysis of US hospital discharge data. Cancer Ther. 2008;6(2):787-792.
 
National Comprehensive Cancer Network. Clinical practice guidelines in oncology: non-small cell lung cancer. National Comprehensive Cancer Network website. http://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed September 2014.
 
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