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Abstract

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information

Objective

To assess the effect of smoking on postoperative complications following elective primary total hip replacement (THR) or primary total knee replacement (TKR).

Methods

We used data from the national Veterans Affairs Surgical Quality Improvement Program to examine the association of smoking status at surgery with 30-day postoperative complication rates (including surgical site and other infections, pneumonia, stroke, myocardial infarction, mortality, and other complications) in veterans undergoing primary elective THR or TKR. Multilevel multivariable-adjusted logistic regression models, adjusted for age, race/ethnicity, work relative value units, American Society of Anesthesiology classification, and year of surgery, with additional adjustment for wound classification for surgical site infections, were used.

Results

A total of 33,336 patients, 95% men and 80% white with a mean age of 64 years, underwent elective primary THR/TKR between October 2001 and September 2008. Fifty-seven percent never smoked, 19% were prior smokers, and 24% were current smokers. Current smokers undergoing THR/TKR were significantly more likely than never smokers to have surgical site infections (odds ratio [OR] 1.41, 95% CI 1.16–1.72), pneumonia (OR 1.53, 95% CI 1.10–2.14), stroke (OR 2.61, 95% CI 1.26–5.41), and 1-year mortality (OR 1.63, 95% CI 1.31–2.02). Prior smokers were significantly more likely than nonsmokers to have pneumonia, (OR 1.34, 95% CI 1.00–1.80), stroke (OR 2.14, 95% CI 1.12–4.10), and urinary tract infection (OR 1.26, 95% CI 1.02–1.55).

Conclusion

Current smoking at the time of elective THR or TKR is associated with increased postarthroplasty complications, especially surgical site infections and pneumonia. Preoperative smoking cessation programs should be considered in patients undergoing elective THR or TKR.


INTRODUCTION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information

Smoking is a risk factor for peri- and postoperative complications following surgical procedures. Smoking is associated with postoperative pulmonary, cardiac, and wound complications, as well as higher rates of postoperative admission to intensive care and higher mortality (1–10). Approximately 36% of veterans undergoing surgery are current smokers, higher than the smoking rates in all veterans using Veterans Affairs (VA) services (30%) (11) and the general US adult population (23%) (12). Therefore, smoking is an important public health problem in the perioperative period, both in the general US population and in US veterans.

Total hip replacement (THR) and total knee replacement (TKR) are very effective elective surgeries to treat end-stage arthritis. Approximately 750,000 THR and TKR surgeries are performed annually in the US (13), and by 2030 the need is projected to grow by 174% and 673%, respectively (13). THR and TKR are among the most common noncardiac surgical procedures performed in VA facilities (14), the largest health care system in the US providing health care to 5 million veterans. While the complication rates after these elective procedures are low, those that do occur impact patient morbidity significantly (15).

Older age and preexisting cardiac and pulmonary disease are known risk factors for complications (16–18); however, these are largely unmodifiable. In comparison, risk factors, such as smoking, alcoholism, and comorbidity management (diabetes mellitus with optimization of glycosylated hemoglobin, pulmonary disease with optimization of steroid use), are modifiable and may be more amenable to interventions and, thus, are likely to improve outcomes.

A biologic rationale exists for the increased risk of both surgical site infections (SSIs) and pneumonia related to smoking (19–22). On the other hand, clinical studies have provided contradictory evidence regarding smoking and post–joint replacement surgery outcomes, which may in part be explained by the lack of power in these studies. Moller et al studied 232 smokers and 579 never smokers for 1 month following hip or knee arthroplasty (23). In multivariable-adjusted analyses, smoking was associated with cardiopulmonary insufficiency, wound-related complications, total complications, and revision surgery (23). In another multivariable-adjusted analysis in 147 patients (165 hips) who underwent primary elective THR, smokers had a higher hazard rate of 4.5 for revision for aseptic loosening compared to never smokers (24). Although this was not statistically significant (P = 0.066), likely due to an insufficient sample size, it was highly suggestive of a real difference. In another study, Lavernia et al found no differences in rates of complications by smoking status in patients undergoing primary or revision hip/knee replacement (n = 202) (25). Two other studies found no association of smoking with postarthroplasty complications (26, 27), and 1 study found smoking to be protective of painful stiff knee (28). In a large study (n = 3,309), multivariable-adjusted analyses showed that smoking was associated with significantly increased systemic, but not local, complications (29). Therefore, it is unclear from the previous studies (most with small sample sizes) as to whether smoking is associated with an increased risk of post–joint replacement complications, and if so, what the magnitude is of the increased risk. Another major limitation of all previous studies was the lack of validation of the complications.

We need studies with adequate sample sizes and validated outcome assessment to understand whether smoking status is associated with increased local and systemic complication rates after elective THR or TKR. As opposed to other surgical procedures, most of which are nonelective, most THRs and TKRs are elective surgeries. The elective nature of these procedures in conjunction with smoking-associated morbidity can make a compelling case for implementation of a preoperative smoking cessation intervention program that may reduce the risk of peri- and postoperative complications.

In this study, our objective was to assess the risk of complications associated with smoking in a large sample of patients with prospectively collected validated data. We used data from the national VA Surgical Quality Improvement Program (VASQIP) to examine the rate of 30-day complications in veterans undergoing primary elective THR or TKR and the association of smoking status with important postoperative complications.

Significance & Innovations

  • Current smoking at the time of elective total hip replacement (THR)/total knee replacement (TKR) is associated with an increased risk of pneumonia and surgical site infections.

  • Preoperative smoking cessation programs should be considered in patients undergoing elective THR/TKR.

  • Current smoking was also associated with a higher risk of 1-year mortality in patients undergoing elective THR/TKR.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information

VASQIP.

We used data from VASQIP, a system-wide national initiative instituted in 1994 to improve the quality of surgical care through prospective collection and reporting of comparative risk-adjusted postoperative outcomes of major surgeries requiring general, spinal, or epidural anesthesia (30). The abstracted data are >99% complete, with >96% interobserver agreement (31). The study was approved by the Institutional Review Board of each coauthor at the VA Medical Centers at Birmingham, Alabama, Bedford, Massachusetts, Boston, Massachusetts, and Seattle, Washington, and the University of Colorado, and by the Surgical Quality Data Use Group of VA Patient Care Services in the VA Central Office, Washington, DC (a requirement by VASQIP for all studies).

Patient population.

We studied a national cohort of unique veterans who underwent elective primary THR (Current Procedural Terminology [CPT] code 27130) or elective primary TKR (CPT code 27447) between fiscal years 2002 and 2008, and were a part of VASQIP. Similar to previous studies (32–35), we excluded patients who had preexisting fracture, infection, or cancer as the underlying diagnoses for THR or TKR, or those undergoing revision THR or TKR identified with the following International Classification of Diseases, Ninth Revision codes: 820 (hip fracture); 821, 822, 823, and 829 (knee, patella, tibia/fibula fracture); 733.1, pathologic fracture (excluding 733.14 for TKR); 711, arthropathy associated with infections; and 170 and 170.9 (malignant neoplasms of bone and articular cartilage). We only took 1 operation (the first operation) for each patient who had multiple operations to allow independence of observations for analysis purposes, since common methods assume independence of observations.

Predictor definition.

Smoking status and amount of tobacco use were assessed as 2 separate variables. Patient medical records were used to determine if patients had smoked cigarettes in the year prior to admission (yes/no) and to calculate pack years (the number of packs smoked per day multiplied by the number of years the patient smoked). We divided smokers into current smokers, prior smokers, and never smokers. Never smokers were patients who had no smoking in the prior year and 0 (or missing) pack years. Prior smokers were those who had >0 pack years, but were noted not to have smoked in the year prior to admission. Current smokers were those who responded “yes” to smoking in the year prior to admission and had pack years not equal to 0. We excluded patients who had a “yes” for current smoker, but who had pack years of 0 (an inconsistency). We classified patients who had a “no” for current smoker and a “missing” for pack years as a never smoker as a more conservative approach to the analysis.

Covariates.

We adjusted the multivariable models for age, race, American Society of Anesthesiology (ASA) physical status, work relative value units (RVUs), and the year of surgery. Wound class was additionally included as an adjustment factor for the outcome of SSI. Race was categorized as: white, Hispanic; white, not of Hispanic origin; black; and other/unknown. ASA, a validated predictor of perioperative mortality and immediate postoperative morbidity (36, 37), was classified as follows: ASA class 1 = a normal healthy patient, ASA class 2 = a patient with mild systemic disease, ASA class 3 = a patient with severe systemic disease, ASA class 4 = a patient with severe systemic disease that is a constant threat to life, and ASA class 5 = a moribund patient (36). ASA classes 4 and 5 were combined due to a very small number in class 5. The principal technique for anesthesia was categorized as general, epidural, spinal, local, monitored, missing, or other. Work Relative Value System (RVU), based on the Medicare Resource-Based Relative Value System, reflects the surgical complexity of CPT-coded procedures in terms of intensity of effort and complexity of operation. The highest possible work RVU, based on all available CPT code fields for each patient, was used. Wound classification, designated by the primary surgeon, was categorized as clean, clean/contaminated, contaminated, or infected, as follows: 1) clean: an uninfected operative wound in which no inflammation is encountered and the respiratory, alimentary, genital, or uninfected urinary tract is not entered; 2) clean/contaminated: an operative wound in which the respiratory, alimentary, genital, or urinary tracts are entered under controlled conditions and without unusual contamination (i.e., no evidence of infection or major break in technique); 3) contaminated: open, fresh, accidental wounds or operations with major breaks in sterile technique (e.g., open cardiac massage) or gross spillage from the gastrointestinal tract, and incisions in which acute, nonpurulent inflammation is encountered; and 4) dirty/infected: old traumatic wounds with retained devitalized tissue and those that involve existing clinical infection or perforated viscera.

Outcomes.

All outcomes of interest were assessed 30 days after THR or TKR. The VASQIP can merge its data with data from the VA vitals database that contains long-term mortality, so we also had 90-day and 1-year mortality but not complications for the patients. All outcomes have standard definitions in VASQIP and are extracted and validated for each patient by an independent nurse abstractor at each VA site for the 30-day period after the surgery (see Supplementary Appendix A, available in the online version of this article at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2151-4658). Specifically, the outcomes were: 1) SSI, 2) venous thromboembolism, 3) stroke/cerebrovascular accident (CVA), 4) myocardial infarction (MI), 5) renal failure, 6) urinary tract infection (UTI), 7) pneumonia, 8) failure to wean, 9) reintubation, and 10) 30-day, 90-day, and 1-year mortality.

In addition to examining individual complications, we defined composite complication outcomes. Vascular complication was defined as an occurrence of MI and/or stroke/CVA. Pulmonary complication was defined as an occurrence of pneumonia, failure to wean, and/or reintubation. Overall composite outcome was an occurrence of SSI, vascular, and/or pulmonary complication.

Statistical analyses.

Summary statistics were calculated for clinical and demographic characteristics. We compared characteristics of patients who underwent THR or TKR to those who underwent other nonemergency nonorthopedic surgical procedures using analysis of variance for continuous variables or Pearson's chi-square test of association for categorical variables. Key clinical characteristics were then compared between current smokers, prior smokers, and never smokers using the same techniques. The unadjusted prevalence of each outcome by smoking status was compared using Pearson's chi-square test of association.

Multilevel multivariable-adjusted logistic regression analyses included smoking as the predictor of interest and adjusted for age, race/ethnicity, work RVU, ASA classification, and year. Regression analysis for SSI was additionally adjusted for wound classification. In addition to patient-level characteristics, the hospital level (clustering of patients within hospitals) was accounted for with a random effect for hospital. We present the odds ratio (OR) and 95% confidence interval (95% CI). A 95% CI not overlapping 1 indicates statistical significance. The overall composite outcome association was compared between THR/TKR versus other orthopedic surgeries as defined by “orthopedic” surgeon specialty versus other surgical procedures to estimate any differences in ORs.

To assess association of pack years with key outcomes, we categorized pack years into 1–23, 24–39, 40–59, and ≥60 pack years for prior and current smokers (never smokers = 0 pack years). This was based on the quartiles of the distribution of pack years. Current smokers missing pack years were excluded from this analysis (n = 2,114 [26% of current smokers]). The association of pack years of smoking with SSI, vascular complication, pulmonary complication, composite outcome, and 30-day and 1-year mortality was investigated.

Since the majority of complications were similar in THR versus TKR, we performed most comparisons with a combined cohort. Sensitivity analyses were performed by additionally adjusting the analyses for the type of anesthesia. A P value less than 0.05 was used to identify statistical significance. Due to the large sample size, small differences in values may be noted as statistically significant; clinical significance should be assessed by the magnitude of estimates in addition to P values. All analyses were generated using SAS software, version 9.2.

RESULTS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information

Clinical characteristics.

The demographic and clinical characteristics of the cohort of veterans who underwent THR or TKR are shown in Table 1. A total of 33,336 patients provided data: 19,031 were never smokers, 6,305 were prior smokers, and 8,000 were current smokers. The mean age of patients who underwent primary THR or TKR was 64 years, 95% were men (typical of VA population), and 80% were white, not of Hispanic origin. Among THR/TKR patients, 57% were never smokers, 19% were prior smokers, and 24% were current smokers. A higher proportion of those undergoing THR (31%) than TKR (20%) were current smokers. THR/TKR patients had a smaller percentage of current smokers and lower mean pack years compared to the nonorthopedic surgery patients. They also underwent more epidural and spinal anesthesia. Since most estimates for THR and TKR were similar, we combined them into a single category for analyses. Comparison to other nonorthopedic surgical procedures in the VA system is also shown (Table 1).

Table 1. Patient characteristics by surgical cohorts*
 THR (n = 11,785)TKR (n = 21,551)THR or TKR (n = 33,336)Nonorthopedic surgical procedures (n = 293,071)
  • *

    P < 0.0001 comparing total hip replacement (THR), total knee replacement (TKR), and other surgical procedures for each characteristic. Continuous characteristics were compared using analysis of variance; categorical characteristics were compared with Pearson's chi-square test of association. RVU = relative value unit; ASA = American Society of Anesthesiology.

  • Reported percentages are out of those with white Hispanic, white non-Hispanic, or black race/ethnicity. Other/unknown races/ethnicities were excluded: THR, n = 2,085 (17.7%); TKR, n = 3,691 (17.1%); THR/TKR, n = 5,776 (17.3%); and nonorthopedic surgical procedures, n = 55,920 (19.1%).

Age, mean ± SD years62.1 ± 11.164.9 ± 10.163.9 ± 10.662.8 ± 12.2
Pack years, mean ± SD23.8 ± 30.321.1 ± 30.522.1 ± 30.531.1 ± 35.7
Work RVU, mean ± SD20.5 ± 0.721.9 ± 0.721.5 ± 1.014.3 ± 7.8
Male sex, no. (%)11,251 (95.5)20,500 (95.1)31,751 (95.2)282,392 (96.4)
Race/ethnicity, no. (%)    
 White, Hispanic260 (2.7)817 (4.6)1,077 (3.9)11,583 (4.9)
 White, not of Hispanic origin7,459 (76.9)14,521 (81.3)21,980 (79.8)187,342 (79.0)
 Black1,981 (20.4)2,522 (14.1)4,503 (16.3)38,226 (16.1)
ASA class, no. (%)    
 Healthy patient141 (1.2)187 (0.9)328 (1.0)6,501 (2.2)
 Mild systemic disease4,200 (35.6)7,287 (33.8)11,487 (34.5)88,907 (30.3)
 Severe systemic disease7,090 (60.2)13,564 (62.9)20,654 (62.0)174,689 (59.6)
 Constant threat to life354 (3.0)513 (2.4)867 (2.6)22,949 (7.8)
Principal anesthesia technique, no. (%)    
 General9,743 (82.7)14,092 (65.4)23,835 (71.5)238,674 (81.4)
 Epidural295 (2.5)1,144 (5.3)1,439 (4.3)2,045 (0.7)
 Spinal1,700 (14.4)6,038 (28.0)7,738 (23.2)34,664 (11.8)
 Local1 (0.0)1 (0.0)2 (0.0)989 (0.3)
 Monitored11 (0.1)67 (0.3)78 (0.2)14,461 (4.9)
 Missing0 (0)0 (0)0 (0)4 (0.0)
 Other35 (0.3)209 (1.0)244 (0.7)2,234 (0.8)
Smoking status, no. (%)    
 Never smoker6,086 (51.6)12,945 (60.1)19,031 (57.1)131,374 (44.8)
 Prior smoker2,084 (17.7)4,221 (19.6)6,305 (18.9)55,754 (19.0)
 Current smoker3,615 (30.7)4,385 (20.3)8,000 (24.0)105,943 (36.1)

Prior smokers were significantly older, had a worse ASA physical class, and had a higher proportion of non-Hispanic whites compared to current smokers (Table 2). Work RVU and sex were statistically significantly different with this large sample size, but these small differences are likely not clinically significant. The mean number of pack years for prior smokers was only slightly less than that for current smokers, indicating that this group has a similar history of smoking exposure.

Table 2. Characteristics by smoking status in patients who underwent total hip replacement or total knee replacement*
 Never smoker (n = 19,031 [57%])Prior smoker (n = 6,305 [19%])Current smoker (n = 8,000 [24%])
  • *

    P < 0.0001 comparing never, prior, and current smokers for each characteristic. Continuous characteristics were compared using analysis of variance; categorical characteristics were compared with Pearson's chi-square test of association. NA = not applicable; RVU = relative value unit; ASA = American Society of Anesthesiology.

  • Reported percentages are out of those with white Hispanic, white non-Hispanic, or black race/ethnicity. Other/unknown races/ethnicities were excluded: never smoker, n = 3,347 (17.6%); prior smoker, n = 1,079 (17.1%); and current smoker, n = 1,350 (16.9%).

Age, mean ± SD years65.6 ± 10.566.6 ± 9.557.9 ± 8.9
Pack years, mean ± SDNA39.8 ± 32.343.7 ± 28.5
 1–23 pack years, no. (%) 2,286 (36.3)1,333 (16.7)
 24–39 pack years, no. (%) 1,317 (20.9)1,445 (18.1)
 40–59 pack years, no. (%) 1,268 (20.1)1,734 (21.7)
 ≥60 pack years, no. (%) 1,434 (22.7)1,374 (17.2)
 Missing, no. (%)  2,114 (26.4)
Work RVU, mean ± SD21.5 ± 1.021.4 ± 0.921.3 ± 1.0
Male sex, no. (%)18,018 (94.7)6,109 (96.9)7,624 (95.3)
Race/ethnicity, no. (%)   
 White, Hispanic724 (4.6)164 (3.1)189 (2.8)
 White, not of Hispanic origin12,688 (80.9)4,428 (84.7)4,864 (73.1)
 Black2,272 (14.5)634 (12.1)1,597 (24.0)
ASA class, no. (%)   
 Healthy patient233 (1.2)46 (0.7)49 (0.6)
 Mild systemic disease6,814 (35.8)1,713 (27.2)2,960 (37.0)
 Severe systemic disease11,525 (60.6)4,296 (68.1)4,833 (60.4)
 Constant threat to life459 (2.4)250 (4.0)158 (2.0)
Principal anesthesia technique, no. (%)   
 General13,368 (70.2)4,342 (68.9)6,125 (76.6)
 Epidural797 (4.2)359 (5.7)283 (3.5)
 Spinal4,649 (24.4)1,553 (24.6)1,536 (19.2)
 Local1 (0.0)0 (0.0)1 (0.0)
 Monitored61 (0.3)6 (0.1)11 (0.1)
 Other155 (0.8)45 (0.7)44 (0.6)

Preoperative smoking status and postoperative complications.

Unadjusted prevalence of 30-day postoperative complications is shown in Table 3. SSI and UTI were the most common 30-day postoperative complications. For all of the unadjusted outcomes, except for SSI, the rate was higher in the prior smokers compared to the never or current smokers. Prior smokers tended to be sicker than the other groups, thus creating the need for risk adjustment of the outcome comparisons.

Table 3. Unadjusted prevalence of postoperative complications by smoking status
 Never smoker (n = 19,031), no. (%)Prior smoker (n = 6,305), no. (%)Current smoker (n = 8,000), no. (%)P*
  • *

    Pearson's chi-square test of association.

  • Missing data for 69 patients; data were available for: never smoker, n = 18,983; prior smoker, n = 6,294; and current smoker, n = 7,990.

Surgical site infection303 (1.6)107 (1.7)191 (2.4)< 0.001
Venous thromboembolism256 (1.3)105 (1.7)68 (0.9)< 0.001
Stroke/cerebrovascular accident23 (0.1)17 (0.3)14 (0.2)0.037
Myocardial infarction60 (0.3)25 (0.4)13 (0.2)0.026
Renal failure133 (0.7)52 (0.8)34 (0.4)0.007
Urinary tract infection350 (1.8)156 (2.5)79 (1.0)< 0.001
Pneumonia149 (0.8)73 (1.2)56 (0.7)0.006
Failure to wean45 (0.2)21 (0.3)15 (0.2)0.206
Reintubation95 (0.5)41 (0.7)31 (0.4)0.087
Mortality    
 30-day mortality99 (0.5)41 (0.7)19 (0.2)< 0.001
 90-day mortality158 (0.8)63 (1.0)48 (0.6)0.025
 1-year mortality334 (1.8)158 (2.5)145 (1.8)< 0.001
Composite outcomes    
 Vascular complication81 (0.4)42 (0.7)27 (0.3)0.011
 Pulmonary complication217 (1.1)104 (1.6)80 (1.0)< 0.001
 Overall composite outcome575 (3.0)236 (3.7)288 (3.6)0.005

Multivariable-adjusted complication rates differed by smoking status (Table 4 and Supplementary Appendix B, available in the online version of this article at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2151-4658). Current smokers, but not prior smokers, had significantly higher odds of SSI and 1-year mortality compared to never smokers. The odds of pneumonia and stroke/CVA were significantly higher in both current smokers and prior smokers compared to never smokers. Prior smokers, but not current smokers, had significantly higher odds of UTI compared with never smokers. The odds of venous thromboembolism, MI, renal failure, failure to wean, and reintubation did not differ significantly by smoking status. Pulmonary complications, but not vascular complications (MI or stroke/CVA), were significantly higher in both current and prior smokers compared to never smokers. The overall composite outcome (pulmonary, vascular, or SSI complications) occurred significantly more in current smokers, but not prior smokers, compared to never smokers. The multivariable-adjusted OR of 1.45 (95% CI 1.24–1.69) for composite outcome (SSI, pulmonary, or vascular complication) in current smokers was numerically higher in the THR/TKR cohort as compared to other orthopedic procedures (OR 1.39, 95% CI 1.24–1.55) and other nonorthopedic surgical procedures (OR 1.29, 95% CI 1.24–1.34). Additionally controlling for anesthesia technique in the models had virtually no effect on the adjusted ORs (data not shown).

Table 4. Multilevel multivariable-adjusted odds ratios (95% confidence intervals) of postoperative complications by smoking status*
 Never smokerPrior smokerCurrent smoker
  • *

    Multilevel multivariable-adjusted logistic regression models with a random effect for hospital were adjusted for age, race/ethnicity, work relative value unit, American Society of Anesthesiology classification, and year. Model of surgical site infection was additionally adjusted for wound classification.

  • Significant at P < 0.05.

  • Missing data for 69 patients; data were available for: never smoker, n = 18,983; prior smoker, n = 6,294; and current smoker, n = 7,990.

Surgical site infection1.001.01 (0.80–1.28)1.41 (1.16–1.72)
Venous thromboembolism1.001.18 (0.93–1.51)0.75 (0.56–1.00)
Stroke/cerebrovascular accident1.002.14 (1.12–4.10)2.61 (1.26–5.41)
Myocardial infarction1.001.15 (0.71–1.86)0.87 (0.46–1.65)
Renal failure1.001.07 (0.76–1.50)0.80 (0.54–1.20)
Urinary tract infection1.001.26 (1.02–1.55)0.75 (0.58–0.98)
Pneumonia1.001.34 (1.00–1.80)1.53 (1.10–2.14)
Failure to wean1.001.31 (0.76–2.25)1.38 (0.74–2.60)
Reintubation1.001.16 (0.79–1.71)1.34 (0.86–2.08)
Mortality   
 30-day mortality1.001.09 (0.75–1.59)0.90 (0.53–1.51)
 90-day mortality1.001.01 (0.75–1.37)1.31 (0.92–1.86)
 1-year mortality1.001.15 (0.94–1.41)1.63 (1.31–2.02)
Composite outcomes   
 Vascular complication1.001.43 (0.97–2.11)1.38 (0.86–2.20)
 Pulmonary complication1.001.30 (1.02–1.66)1.51 (1.14–2.00)
 Overall composite outcome1.001.14 (0.96–1.34)1.45 (1.24–1.69)

Pack years and postoperative complications.

Multivariable-adjusted odds of SSI, vascular complications, pulmonary complications, the overall composite outcomes, and mortality with pack years are shown in Table 5 and Supplementary Appendix C (available in the online version of this article at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)2151-4658). In multilevel multivariable-adjusted analyses, ≥60 pack years in current smokers significantly increased the odds of all outcomes, except 30-day mortality compared to never smokers. Current smokers had significantly increased odds of 1-year mortality compared to never smokers, without a dose gradient. Although not consistently significant, there is an apparent trend among prior smokers for fewer pack years of smoking to be associated with worse outcomes.

Table 5. Multilevel multivariable-adjusted odds ratios (95% confidence intervals) of postoperative complications by pack years smoked*
 Never smoker, 0 pack yearsPrior smoker, pack yearsCurrent smoker, pack years
1–2324–3940–59≥601–2324–3940–59≥60
  • *

    Multilevel multivariable-adjusted logistic regression models with a random effect for hospital were adjusted for age, race/ethnicity, work relative value unit, American Society of Anesthesiology classification, and year. Model of surgical site infection was additionally adjusted for wound classification.

  • Significant at P < 0.05.

Surgical site infection1.001.11 (0.80–1.55)1.05 (0.69–1.62)1.00 (0.63–1.57)0.82 (0.51–1.31)1.28 (0.85–1.92)1.33 (0.91–1.94)1.34 (0.96–1.89)1.76 (1.25–2.47)
Vascular complication1.001.62 (0.92–2.85)1.34 (0.64–2.80)1.49 (0.76–2.91)1.27 (0.63–2.56)1.64 (0.58–4.65)0.71 (0.17–2.95)1.01 (0.40–2.54)2.20 (1.11–4.33)
Pulmonary complication1.001.24 (0.85–1.82)1.67 (1.10–2.52)1.02 (0.63–1.65)1.33 (0.87–2.02)1.22 (0.59–2.53)1.30 (0.67–2.51)0.91 (0.50–1.65)2.29 (1.51–3.46)
Composite outcome1.001.11 (0.87–1.42)1.30 (0.98–1.73)1.05 (0.77–1.44)1.09 (0.81–1.46)1.38 (0.98–1.94)1.34 (0.97–1.85)1.17 (0.88–1.55)1.90 (1.47–2.46)
30-day mortality1.001.71 (1.05–2.81)0.91 (0.41–1.98)0.91 (0.44–1.89)0.65 (0.28–1.50)1.15 (0.35–3.76)0.34 (0.05–2.48)1.50 (0.71–3.15)0.56 (0.18–1.80)
1-year mortality1.001.38 (1.03–1.84)1.13 (0.77–1.65)1.10 (0.77–1.58)0.97 (0.67–1.40)2.18 (1.41–3.38)1.42 (0.87–2.30)1.53 (1.07–2.21)1.85 (1.31–2.61)

DISCUSSION

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information

In this study, we found that preoperative smoking status was a significant predictor of 30-day postoperative complications and mortality at 1 year in patients undergoing elective THR/TKR. Current smokers had significantly higher rates of SSIs, pneumonia, stroke, and 1-year mortality compared to never smokers. Pulmonary and composite complication outcomes were higher in current smokers compared to never smokers. Prior smokers were at a higher risk of stroke, pneumonia, UTI, and composite pulmonary complications compared to never smokers. Heavy/long smoking in current smokers denoted by ≥60 pack years of smoking was associated with SSI, pulmonary complications, vascular complications, the overall composite outcome, and 1-year mortality. The rates of complications in our study are similar to those reported in the past: 1.4% with pneumonia and 0.8% with pulmonary embolus (35). The odds for composite outcome in current smokers undergoing THR/TKR were numerically higher than those undergoing other orthopedic surgeries or nonorthopedic surgical procedures. These findings have significant implications.

First, our study included elective THR/TKR patients only, and our finding of higher morbidity and mortality in current smokers compared to nonsmokers indicates that a preoperative smoking cessation program may be a consideration in these patients undergoing an elective procedure. The smoking-associated risk of complications is quite significant; therefore, approaching these patients for a preoperative smoking cessation intervention seems very reasonable. One may view increased risk in prior smokers and accept that the risk is not entirely modifiable, i.e., even with quitting these patients may still be at a somewhat higher risk; however, the odds of each complication were always higher in current versus prior smokers when compared to never smokers as the reference category. The sustainability of quitting, and the amount of risk reduction with implementation of a preoperative smoking cessation program, remains to be seen. It is possible that even short-term cessation may provide significant protection from immediate smoking-related complications. The preoperative period provides a “window of opportunity” and “a golden moment” for smoking cessation. In addition, patients undergoing elective THR/TKR are usually considered healthier than age- and sex-matched patients undergoing other orthopedic or other surgical procedures (with a large proportion undergoing nonelective procedures in a less optimal setting). A higher OR of composite outcome (pulmonary, vascular, and SSI) in the THR/TKR group, as compared to undergoing other orthopedic or other surgical procedures, is worrisome and identifies THR/TKR cohorts as an ideal target for a preoperative smoking cessation intervention.

We found that current smokers had 41% increased odds of SSI compared to never smokers and no increase in prior smokers. This is an important observation, since SSIs account for 38% of all infections in surgical patients (38) and are associated with longer hospital stay (38), making them one of the most costly postoperative complications (38, 39). Previous studies in thoracic, abdominal, and multiple surgical cohorts found relative risk with smoking ranging from 1.4–6.0 (40–43). Our adjusted OR was 1.41, which is similar to the lower end of the range of risk ratios reported previously (40–43). Previous multivariable-adjusted studies of smoking as a risk factor for postarthroplasty complications (26–29, 44, 45) reported contradictory findings. Three studies reported more systemic complications in smokers (29), higher charges and operative time (44), and higher risk of any complication, wound complication, and intensive care unit (ICU) admission (45) in smokers compared to nonsmokers. However, 2 studies found no association of smoking with postarthroplasty complications (26, 27), and 1 study found smoking to be protective of painful stiff knee (28). In 3 previous studies in arthroplasty populations (adjusting for different confounders and defining smoking exposure differently), 1 study found an association of smoking with surgical site infections (23), while 2 other studies found no such association (25, 29). Our study had a large sample size, controlled for several important confounders, including wound classification, had detailed information on pack years, used standardized definitions, and used prospectively collected validated data. Therefore, we think these estimates provide a fairly accurate risk of SSIs in patients undergoing THR or TKR.

The odds of current smokers experiencing 30-day postoperative pneumonia in our study were significantly higher than the odds for never smokers experiencing 30-day postoperative pneumonia. Prior smokers also had significantly higher odds of 30-day postoperative pneumonia compared with never smokers, although not as high as current smokers. Our study findings confirm similar findings from nonarthroplasty populations (9, 46–49) and extend it to arthroplasty populations. The occurrence of postoperative pneumonia has a significant impact not only on immediate outcomes (failure to wean, reintubation, ICU stay), but also later outcomes, such as readmission. Furthermore, pneumonia is the most costly postoperative complication (39). Decreasing the risk of postoperative smoking–associated pneumonia can significantly decrease morbidity and mortality associated with pneumonia, thus improving outcomes in patients undergoing elective arthroplasty.

A biologic rationale also exists for the increased risk of both SSIs and pneumonia related to smoking. Tobacco smoke stimulates fibroblasts to produce stress response, decreases cell migration, and increases cell adhesion and alterations in cytoskeletal elements, which may lead to buildup of connective tissue in the area of a wound, delaying wound healing (19). Tobacco smoke also causes tissue hypoxia, a major mechanism for delayed wound healing (20). In animal studies, cigarette smoke suppresses respiratory antibacterial host defense (21) and dramatically reduces dendritic cells in the lung tissue and activated CD4 and CD8 T cells (22).

Smoking-attributable risk can be related to the dangers of active smoking or the permanent damage resulting from multiple years of exposure to tobacco, even though the person has quit. For pneumonia, the risk seems to be both, as prior smokers also had an increased risk of pneumonia after adjustment. Therefore, although smoking cessation should be valuable in this population, it will not remove all risk. Prior smokers should undergo more intense monitoring, and increased precautions should be taken to prevent perioperative pneumonia. With previous randomized controlled trial (RCT) evidence supporting the benefits of smoking cessation before elective surgery, our study findings of smoking-associated postoperative risks in current smokers suggest that a preoperative smoking cessation program merits discussion in patients undergoing elective THR or TKR. More specifically, as veterans are sicker than age- and sex-matched nonveterans in the US (50), targeted interventions to reduce risk may be particularly helpful in this high-risk group.

Higher pack years were associated with increased odds of postoperative complications in current smokers and prior smokers compared with never smokers; however, significant increases in the odds of postoperative complications were mainly limited to current smokers with ≥60 pack years. Again, this is an important finding and addition to the literature, and suggests that a preoperative smoking cessation program may prove to be particularly beneficial in long-term/heavy smokers.

RCTs that included arthroplasty and other surgical populations found that smoking cessation was associated with improved postsurgical outcomes, including wound complications and any postoperative complication (51–53). In a systematic review of smoking cessation interventions, with 11 RCTs identified, smoking cessation reduced the overall risk of complications to a pooled risk ratio of 0.56 (95% CI 0.41–0.78, P < 0.001); intensive interventions (weekly individual behavioral counseling 4–8 weeks before surgery with professionally trained smoking cessation counselors) increased smoking cessation rates before and up to 12 months after surgery (54). In another systematic review by the same group, 5 RCTs that assessed the risk of smoking cessation and postoperative complications were identified and an intensive smoking cessation program 4–8 weeks prior to surgery was associated with relative risks of 0.42 (95% CI 0.27–0.65) for any complication and 0.31 (95% CI 0.16–0.62) for wound complications (55).

The odds of mortality at 1 year were higher in current smokers, but not prior smokers, compared to never smokers. This observation confirms a previous observation of increased mortality associated with smoking (56).

Our study has several strengths and limitations. We used state-of-the-art national VASQIP databases, where data are abstracted by trained nurses, using validated outcome definitions. We also had a large sample size. Our study also has several limitations. Findings from this study may not be generalizable to younger patients and women undergoing arthroplasty, since the majority of our participants were older men. Residual confounding is possible; however, we adjusted for multiple important covariates, which were all prospectively collected. Even with such a large sample size we did not have enough events in some categories for comparisons, which may have led to Type II error. Studies with an even larger sample size can surmount this limitation. As a conservative approach, we classified patients who were not current smokers, but had missing pack years as never smokers, although some of them could have been prior smokers. This would bias the hypothesis toward the null, which makes our findings conservative and still valid. Misclassification bias was minimized by excluding patients with a “yes” response for current smoker and 0 pack years. However, this constituted <1% of the entire cohort, signifying that this bias was minimal. We could not adjust for the implant type due to lack of data for types of implants; however, this is unlikely to have confounded the effect by the smoking status.

In summary, current smoking status at the time of elective THR/TKR is associated with increased postarthroplasty complications, especially SSIs and pneumonia. Some associations are primarily driven by pack years in patients with current smoker status. For an elective surgery such as THR/TKR, the preoperative period provides a golden opportunity for quitting. Given the other well-known health benefits of smoking cessation, patients and surgeons should consider discussing smoking cessation at the time of THR/TKR. Studies of different approaches to preoperative smoking cessation are needed to address this important problem and to find the most optimal approach to preoperative smoking cessation.

AUTHOR CONTRIBUTIONS

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information

All authors were involved in drafting the article or revising it critically for important intellectual content, and all authors approved the final version to be published. Mr. Singh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study conception and design. Houston, Bishop, Campagna, Henderson, Hawn.

Acquisition of data. Bishop, Campagna, Henderson, Hawn.

Analysis and interpretation of data. Singh, Houston, Ponce, Maddox, Bishop, Richman, Campagna, Henderson, Hawn.

REFERENCES

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information
  • 1
    Scholes RL, Browning L, Sztendur EM, Denehy L. Duration of anaesthesia, type of surgery, respiratory co-morbidity, predicted VO2max and smoking predict postoperative pulmonary complications after upper abdominal surgery: an observational study. Aust J Physiother 2009; 55: 1918.
  • 2
    Delgado-Rodriguez M, Medina-Cuadros M, Martinez-Gallego G, Gomez-Ortega A, Mariscal-Ortiz M, Palma-Perez S, et al. A prospective study of tobacco smoking as a predictor of complications in general surgery. Infect Control Hosp Epidemiol 2003; 24: 3743.
  • 3
    Moores LK. Smoking and postoperative pulmonary complications: an evidence-based review of the recent literature. Clin Chest Med 2000; 21: 13946.
  • 4
    Ridderstolpe L, Gill H, Granfeldt H, Ahlfeldt H, Rutberg H. Superficial and deep sternal wound complications: incidence, risk factors and mortality. Eur J Cardiothorac Surg 2001; 20: 116875.
  • 5
    Hussey LC, Hynan L, Leeper B. Risk factors for sternal wound infection in men versus women. Am J Crit Care 2001; 10: 1126.
  • 6
    Trayner E Jr, Celli BR. Postoperative pulmonary complications. Med Clin North Am 2001; 85: 112939.
  • 7
    Mason DP, Subramanian S, Nowicki ER, Grab JD, Murthy SC, Rice TW, et al. Impact of smoking cessation before resection of lung cancer: a Society of Thoracic Surgeons General Thoracic Surgery Database study. Ann Thorac Surg 2009; 88: 36270.
  • 8
    Schwilk B, Bothner U, Schraag S, Georgieff M. Perioperative respiratory events in smokers and nonsmokers undergoing general anaesthesia. Acta Anaesthesiol Scand 1997; 41: 34855.
  • 9
    Bluman LG, Mosca L, Newman N, Simon DG. Preoperative smoking habits and postoperative pulmonary complications. Chest 1998; 113: 8839.
  • 10
    Frick WG, Seals RR Jr. Smoking and wound healing: a review. Tex Dent J 1994; 111: 213.
  • 11
    Office of Quality and Performance VHA. Health behaviors of veterans in the VHA: tobacco use. 1999 large health survey of VHA enrollees. Washington, DC: Veterans Health Administration; 2001.
  • 12
    Borowsky SJ, Nelson DB, Fortney JC, Hedeen AN, Bradley JL, Chapko MK. VA community-based outpatient clinics: performance measures based on patient perceptions of care. Med Care 2002; 40: 57886.
  • 13
    Kurtz S, Ong K, Lau E, Mowat F, Halpern M. Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. J Bone Joint Surg Am 2007; 89: 7805.
  • 14
    Khuri SF, Daley J, Henderson W, Barbour G, Lowry P, Irvin G, et al. The National Veterans Administration Surgical Risk Study: risk adjustment for the comparative assessment of the quality of surgical care. J Am Coll Surg 1995; 180: 51931.
  • 15
    Warner DO. Preventing postoperative pulmonary complications: the role of the anesthesiologist. Anesthesiology 2000; 92: 146772.
  • 16
    Goldman L, Caldera DL, Nussbaum SR, Southwick FS, Krogstad D, Murray B, et al. Multifactorial index of cardiac risk in noncardiac surgical procedures. N Engl J Med 1977; 297: 84550.
  • 17
    Mangano DT. Perioperative cardiac morbidity. Anesthesiology 1990; 72: 15384.
  • 18
    Mangano DT, Layug EL, Wallace A, Tateo I, for the Multicenter Study of Perioperative Ischemia Research Group. Effect of atenolol on mortality and cardiovascular morbidity after noncardiac surgery. N Engl J Med 1996; 335: 171320.
  • 19
    Wong LS, Martins-Green M. Firsthand cigarette smoke alters fibroblast migration and survival: implications for impaired healing. Wound Repair Regen 2004; 12: 47184.
  • 20
    Ninikoski J. Oxygen and wound healing. Clin Plast Surg 1977; 4: 36174.
  • 21
    Drannik AG, Pouladi MA, Robbins CS, Goncharova SI, Kianpour S, Stampfli MR. Impact of cigarette smoke on clearance and inflammation after Pseudomonas aeruginosa infection. Am J Respir Crit Care Med 2004; 170: 116471.
  • 22
    Robbins CS, Dawe DE, Goncharova SI, Pouladi MA, Drannik AG, Swirski FK, et al. Cigarette smoke decreases pulmonary dendritic cells and impacts antiviral immune responsiveness. Am J Respir Cell Mol Biol 2004; 30: 20211.
  • 23
    Moller AM, Pedersen T, Villebro N, Munksgaard A. Effect of smoking on early complications after elective orthopaedic surgery. J Bone Joint Surg Br 2003; 85: 17881.
  • 24
    Meldrum RD, Wurtz LD, Feinberg JR, Capello WN. Does smoking affect implant survivorship in total hip arthroplasty? A preliminary retrospective case series. Iowa Orthop J 2005; 25: 1724.
  • 25
    Lavernia CJ, Sierra RJ, Gomez-Marin O. Smoking and joint replacement: resource consumption and short-term outcome. Clin Orthop Relat Res 1999; 367: 17280.
  • 26
    Espehaug B, Havelin LI, Engesaeter LB, Langeland N, Vollset SE. Patient-related risk factors for early revision of total hip replacements: a population register-based case-control study of 674 revised hips. Acta Orthop Scand 1997; 68: 20715.
  • 27
    Sadr Azodi O, Adami J, Lindstrom D, Eriksson KO, Wladis A, Bellocco R. High body mass index is associated with increased risk of implant dislocation following primary total hip replacement: 2,106 patients followed for up to 8 years. Acta Orthop 2008; 79: 1417.
  • 28
    Fisher DA, Dierckman B, Watts MR, Davis K. Looks good but feels bad: factors that contribute to poor results after total knee arthroplasty. J Arthroplasty 2007; 22 Suppl: 3942.
  • 29
    Sadr Azodi O, Bellocco R, Eriksson K, Adami J. The impact of tobacco use and body mass index on the length of stay in hospital and the risk of post-operative complications among patients undergoing total hip replacement. J Bone Joint Surg Br 2006; 88: 131620.
  • 30
    Daley J, Khuri SF, Henderson W, Hur K, Gibbs JO, Barbour G, et al. Risk adjustment of the postoperative morbidity rate for the comparative assessment of the quality of surgical care: results of the National Veterans Affairs Surgical Risk Study. J Am Coll Surg 1997; 185: 32840.
  • 31
    Davis CL, Pierce JR, Henderson W, Spencer CD, Tyler C, Langberg R, et al. Assessment of the reliability of data collected for the Department of Veterans Affairs national surgical quality improvement program. J Am Coll Surg 2007; 204: 55060.
  • 32
    Katz JN, Losina E, Barrett J, Phillips CB, Mahomed NN, Lew RA, et al. Association between hospital and surgeon procedure volume and outcomes of total hip replacement in the United States Medicare population. J Bone Joint Surg Am 2001; 83-A: 16229.
  • 33
    Mahomed NN, Barrett JA, Katz JN, Phillips CB, Losina E, Lew RA, et al. Rates and outcomes of primary and revision total hip replacement in the United States Medicare population. J Bone Joint Surg Am 2003; 85-A: 2732.
  • 34
    Ong KL, Kurtz SM, Lau E, Bozic KJ, Berry DJ, Parvizi J. Prosthetic joint infection risk after total hip arthroplasty in the Medicare population. J Arthroplasty 2009; 24 Suppl: 1059.
  • 35
    Katz JN, Barrett J, Mahomed NN, Baron JA, Wright RJ, Losina E. Association between hospital and surgeon procedure volume and the outcomes of total knee replacement. J Bone Joint Surg Am 2004; 86-A: 190916.
  • 36
    Dripps RD, Lamont A, Eckenhoff JE. The role of anesthesia in surgical mortality. JAMA 1961; 178: 2616.
  • 37
    Weaver F, Hynes D, Hopkinson W, Wixson R, Khuri S, Daley J, et al. Preoperative risks and outcomes of hip and knee arthroplasty in the Veterans Health Administration. J Arthroplasty 2003; 18: 693708.
  • 38
    Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR, for the Hospital Infection Control Practices Advisory Committee. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol 1999; 20: 25078.
  • 39
    Dimick JB, Chen SL, Taheri PA, Henderson WG, Khuri SF, Campbell DA Jr. Hospital costs associated with surgical complications: a report from the private-sector National Surgical Quality Improvement Program. J Am Coll Surg 2004; 199: 5317.
  • 40
    Finan KR, Vick CC, Kiefe CI, Neumayer L, Hawn MT. Predictors of wound infection in ventral hernia repair. Am J Surg 2005; 190: 67681.
  • 41
    Myles PS, Iacono GA, Hunt JO, Fletcher H, Morris J, McIlroy D, et al. Risk of respiratory complications and wound infection in patients undergoing ambulatory surgery: smokers versus nonsmokers. Anesthesiology 2002; 97: 8427.
  • 42
    Manassa EH, Hertl CH, Olbrisch RR. Wound healing problems in smokers and nonsmokers after 132 abdominoplasties. Plast Reconstr Surg 2003; 111: 20827.
  • 43
    Olsen MA, Lock-Buckley P, Hopkins D, Polish LB, Sundt TM, Fraser VJ. The risk factors for deep and superficial chest surgical-site infections after coronary artery bypass graft surgery are different. J Thorac Cardiovasc Surg 2002; 124: 13645.
  • 44
    Lavernia CJ, Sierra RJ, Gomez-Marin O. Smoking and joint replacement: resource consumption and short-term outcome. Clin Orthop Relat Res 1999; 367: 17280.
  • 45
    Moller AM, Pedersen T, Villebro N, Munksgaard A. Effect of smoking on early complications after elective orthopaedic surgery. J Bone Joint Surg Br 2003; 85: 17881.
  • 46
    Fisher DA. Evaluation of the painful total hip arthroplasty. Semin Arthroplasty 1992; 3: 22938.
  • 47
    Kinugasa S, Tachibana M, Yoshimura H, Ueda S, Fujii T, Dhar DK, et al. Postoperative pulmonary complications are associated with worse short- and long-term outcomes after extended esophagectomy. J Surg Oncol 2004; 88: 717.
  • 48
    Barrera R, Shi W, Amar D, Thaler HT, Gabovich N, Bains MS, et al. Smoking and timing of cessation: impact on pulmonary complications after thoracotomy. Chest 2005; 127: 197783.
  • 49
    Brooks-Brunn JA. Predictors of postoperative pulmonary complications following abdominal surgery. Chest 1997; 111: 56471.
  • 50
    Agha Z, Lofgren RP, VanRuiswyk JV, Layde PM. Are patients at Veterans Affairs medical centers sicker? A comparative analysis of health status and medical resource use. Arch Intern Med 2000; 160: 32527.
  • 51
    Davis FM, Laurenson VG, Gillespie WJ, Wells JE, Foate J, Newman E. Deep vein thrombosis after total hip replacement: a comparison between spinal and general anaesthesia. J Bone Joint Surg Br 1989; 71: 1815.
  • 52
    Lindstrom D, Sadr Azodi O, Wladis A, Tonnesen H, Linder S, Nasell H, et al. Effects of a perioperative smoking cessation intervention on postoperative complications: a randomized trial. Ann Surg 2008; 248: 73945.
  • 53
    Moller AM, Villebro N, Pedersen T, Tonnesen H. Effect of preoperative smoking intervention on postoperative complications: a randomised clinical trial. Lancet 2002; 359: 1147.
  • 54
    Thomsen T, Tonnesen H, Moller AM. Effect of preoperative smoking cessation interventions on postoperative complications and smoking cessation. Br J Surg 2009; 96: 45161.
  • 55
    Thomsen T, Villebro N, Moller AM. Interventions for preoperative smoking cessation. Cochrane Database Syst Rev 2010; 7: CD002294.
  • 56
    Hasdai D, Garratt KN, Grill DE, Lerman A, Holmes DR Jr. Effect of smoking status on the long-term outcome after successful percutaneous coronary revascularization. N Engl J Med 1997; 336: 75561.

Supporting Information

  1. Top of page
  2. Abstract
  3. INTRODUCTION
  4. MATERIALS AND METHODS
  5. RESULTS
  6. DISCUSSION
  7. AUTHOR CONTRIBUTIONS
  8. REFERENCES
  9. Supporting Information

Additional Supporting Information may be found in the online version of this article.

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