ICJR REWIND: Are Smoking Cessation Programs Effective for Total Joint Arthroplasty Patients?
The authors examine the literature on the effects of smoking on primary and revision hip and knee replacement and discuss research on the potential health and cost benefits of implementing a smoking cessation program, in an article originally published on November 29, 2018.
Charity Jacobs, MD; Fernando Nussenbaum, MD; Jonathan Vigdorchik, MD; and Ran Schwarzkopf, MD
According to the most recent data available, approximately 600,000 primary total knee arthroplasty (TKA) procedures and 310,000 primary total hip arthroplasty (THA) procedures are performed yearly in the US, and that number continues to grow. 
With the rise in primary knee and hip replacements, there has been a concomitant increase in revision procedures, which have higher rates of complications  and greater costs to patients, hospitals, and healthcare system.  In addition, the advent of bundled payment models for joint replacement surgery has changed the thought process on patient selection for many surgeons. More focus is now being placed on addressing modifiable risk factors that may increase the risk of total joint arthroplasty failure.  One such risk factor is smoking.
Smoking’s Mechanism of Action
The US Surgeon General first warned the public about the deleterious effects of smoking in the 1960s, describing its association with lung cancer. Since then, researchers have described many other harmful consequences of smoking. It is estimated that 20% of Americans currently smoke, a large decrease from nearly 50% in the 1960s. Smoking cigarettes has 2 phases: [6,7]
- During the volatile phase, nearly 500 chemicals are released.
- During the particulate phase, nearly 3500 additional chemicals are encountered in the body.
The nicotine released from cigarettes has many known physiologic effects, including inducing cell death, inducing vascular disturbances, and stimulating the sympathetic nervous system, all of which can be detrimental to the post-surgical healing process. [8,9] Reduced blood supply and tissue hypoxia associated with nicotine and carbon monoxide from smoking has been shown to reduce bone metabolic activity and is thought to cause decreased ingrowth into implants and the cement interface. [10,11]
Cigarette smoking has long been associated with wound healing issues, and several mechanisms are thought to be behind these complications. Nicotine increases catecholamines, which induces chalone formation and inhibits the healing process and epithelialization.  Cigarette smoke has been shown to alter mesenchymal cells, fibroblasts, and growth factors, all of which are vital to formation of granulation tissue. The alteration of these factors is thought to slow the wound healing process.  Smoking also creates free radicals that cause cellular damage and apoptosis. 
A randomized controlled trial in Sweden examined the effect of smoking on wound healing, using healthy patients with experimental incisions just lateral to the sacrum. The researchers found higher infection rates in smokers. Furthermore, with 4 weeks of abstinence from smoking, the infection rate dropped to the same level as in subjects who never smoked. 
Smoking’s Effect on Primary TKA and THA
Kee et al  retrospectively analyzed 128 revision total joint arthroplasties that occurred within 2 years of the index procedure, focusing on modifiable risk factors – including smoking – that were present at the time of the primary procedure. In TKA patients, the only risk factor associated with revision was smoking, and it was specifically associated with deep infection.  The researchers did not find any correlation between smoking and the need for revision THA, although other studies have shown an association between smoking and complications of primary THA.
Crowe et al  examined outcomes of nearly 4000 consecutive primary TKAs completed at their institution over a 3-year period to identify preoperative risk factors associated with periprosthetic joint infections (PJI). They found several risk factors that increased the odds of PJI, including current smoking status (OR 3.07). Smoking plus a BMI over 30 had an additive affect (OR 8.37). 
A retrospective review by Kapadia et al  compared outcomes in 110 THA patients who smoked and 220 patients who had never smoked at a mean follow-up of 57 months (range, 24 to 72 months). There was no difference in Harris Hip Scores between the 2 groups. Smokers had 9 revisions (8%) and non-smokers had 2 revisions (1%). Revisions were due to pain (3), instability (1), and deep infection (5). In addition, smokers had 5 medical complications, while non-smokers had none. There were no radiographic differences between the groups when no revision was required. 
Kapadia et al  did not find pack years of smoking to be statistically significant. However, a study by Duchman et al  noted an increased risk of complications associated with pack years. In addition, a retrospective study of more than 3300 patients undergoing primary THA by Sadr Azodi et al  found that a 40-plus year pack history was associated with increased systemic postoperative complications, including deep vein thrombosis, cerebrovascular accident, myocardial infarction, postoperative anemia, gastrointestinal bleeding, pneumonia, and death.
Singh et al  used data from 33,000 patients in the National Veterans Affairs Surgical Quality Improvement Program to examine the association between smoking and complications following total joint arthroplasty. They found that current smokers were significantly more likely than non-smokers to have surgical site infections (OR 1.41), pneumonia (OR 1.53), stroke (OR 2.61), and 1-year mortality (OR 1.63). In addition, prior smokers were more likely than never smokers to have pneumonia (OR 1.34), stroke (OR 2.14), and urinary tract infection (OR 1.26). 
A prospective cohort study from Mayo Clinic  investigated outcomes of 8000 current smokers, former smokers, and never smokers who underwent TKA and THA over a 4-year period. Smokers tended to be younger (under age 60), male, and less likely to be obese. Current smokers had increased hazard ratios for deep infection (2.37) and implant revisions (1.78) compared with non-smokers. There were no differences in periprosthetic fractures or superficial infections. 
A systemic review completed in 2011 included 21 articles that discussed primary total joint arthroplasty and smoking. The study authors found that current and former smokers had a statistically significant increase in all complications (current smokers, OR 1.24; former smokers, OR 1.21) and death (current smokers, OR 1.63; former smokers, OR 1.69).  A second systemic review completed in 2017 included all articles published between 1998 and 2016 that discussed PJI in primary total joint arthroplasty. The study authors found that overall, smoking was one of the highest risk factors for PJI (OR = 12.76, 95% CI: 2.47-66.16; P=0.0017). 
Smoking’s Effect on Revision TKA and THA
In a retrospective chart review of the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database, Bedard et al  identified 8766 patients who underwent revision TKA between 2006 and 2014. They found that smokers (11.6% of the patients in the study) had an increased risk of wound complications (3.8% for smokers vs 1.8% for non-smokers; P<0.0001), 30-day reoperation rates (5% for smokers vs 3.8 % non-smokers; P<0.001), and PJI (2.5% for smokers vs 1% non-smokers; P<0.001). 
Bedard et al  also used the NSQIP database to examine wound complications, 30-day return to the operating room, and PJI in 8237 revision THAs performed between 2006 and 2014. As with the review of data on revision TKAs, the researcher reported higher rates of all 3 complications in smokers compared with non-smokers: 4.1% vs 3.0% (P=0.04) for wound complications, 3.2% vs 1.9% (P=0.003) for PJIs, and 6.8% vs 4.8% (P=0.003) for reoperation. .
McGee el al  evaluated readmissions following revision THA for non-infection causes among patients in their practice. Over a 10-year period, they had 85 revisions in 61 patients. The only risk factor they found for readmission was coronary artery disease. They did not find an association with smoking; however, this finding may have been confounded by removing infection as an indication for revision. 
The initial visit for TKA or THA patients offers the physician an opportunity to discuss smoking cessation. [27,28] The motivation to pursue joint replacement may incentivize patients to pursue smoking cessation as well.  To understand how orthopaedic surgeons manage patients’ nicotine use in their practice, Lilley et al  distributed a survey on the topic at the 2012 Annual Meeting of the American Academy of Orthopaedic Surgeons. They received back 211 of 300 surveys. Although 98% of respondents said they counsel their patients about smoking, fewer than 50% reported spending more than 5 minutes on the topic. Only 20% of survey respondents frequently or always use smoking cessation programs, 6% frequently or always test for nicotine by products, and 29% write orders to prevent smoking during the inpatient stay. 
A 2014 Cochrane review evaluated randomized controlled trials to determine the effect of preoperative interventions on smoking cessation. Intensive interventions were pooled separately from brief interactions, with intensive interventions (RR 10.76; 95% CI 4.55 to 25.46; 2 trials with 210 participants) found to have larger and longer lasting effect size then brief interventions (RR 1.30; 95% CI 1.16 to 1.46; 7 trials with 1141 participants). . “Intensive” interventions began 4 to 8 weeks preoperatively and included nicotine replacement therapy.
The Cochrane review included studies with non-orthopaedic patients. Findings from studies of smoking cessation programs in orthopaedic patients are summarized below.
In a randomized trial, Møller et al  provided standard care to 52 patients and standard care plus weekly counseling sessions and free nicotine replacement therapy to 56 patients 6 to 8 weeks before hip or knee replacement surgery. The goal was for patients in the intervention group to either stop smoking or reduce their tobacco consumption by 50%. Thirty-six patients (64%) in the intervention group and 4 patients (7%) in the control group stopped smoking.
There were no wound complications among patients who stopped smoking (P=0.0004), while 7 patients (27%; P=0.98) who reduced their cigarette use and 12 patients (26%) who continued to smoke experienced wound complications. Overall complications were also reduced: 4 complications (10%; P=0.001) among patients who stopped smoking, 12 (46%, P=0.89) in patients who reduced cigarette use, and 20 (44%) in smokers. 
Villebro et al  followed the patients in the Møller et al study  to determine 1-year outcomes. Thirteen (22%) of the intervention patients and 2 (3%) of the control patients continued to abstain from smoking 1 year after the intervention. Male gender, low nicotine dependency, non-smoking partner, and preoperative smoking intervention were the most important predictive factors for smoking abstinence 1 year after the intervention. 
Lindstrom et al  performed a randomized trial to determine if postoperative complications could be reduced by smoking cessation as little as 1 week preoperatively. Fifty-four patients received standard care and 48 patients received weekly counseling sessions and free nicotine replacement therapy, with the goal of complete smoking cessation from 4 weeks preoperatively to 4 weeks postoperatively. An exhaled carbon monoxide test was used to assess compliance.
One (2%) control patient and 19 (40%) intervention patients stopped smoking. Twenty-two patients (41%) in the control group and 10 patients (21%) in the intervention group experienced postoperative complications (P=0.03). A per protocol analysis was stratified by duration of smoking cessation: more than 3 weeks preoperatively, 1 to 2 weeks preoperatively, and continued smoking. The results were not statistically significant for wound complications or total complications, although the study authors speculated that the trial may have been underpowered to detect a difference in these groups. 
Cotinine is metabolite of nicotine and can be identified in blood, saliva, or urine. [27,33] The half-life of cotinine is 15 to 40 hours.  The classic serum cut point is 14 ng/mL; however, this number was generated in the 1980s when secondhand smoke was more prevalent.  In 2009, Benowitz et al  proposed new cut points. Their overall cut point for adults was 3.08 ng/mL, but cut points differed by racial/ethnic group: 5.92 ng/mL for non-Hispanic blacks, 4.85 ng/mL for non-Hispanic whites, and 0.84 ng/mL for Mexican Americans.  Cotinine testing is not accurate in patients who are using nicotine replacement therapy. 
Exhaled carbon monoxide has a half-life of 4 to 5 hours and can be used to determine if patients are currently smoking tobacco products. [27,34] Exhaled carbon monoxide only shows if a patient has recently abstained from smoking, but it is not influenced by nicotine replacement therapy. [27,34]
Counseling and Testing
Akhavan et al  reported on a prospective cohort of 30 candidates for elective THA or TKA who were given a 1-page handout about the increase in perioperative complications due to smoking, as well as information on local smoking cessation resources. Patients were allowed to choose their method of smoking cessation. They had to pass an exhaled carbon monoxide test before surgery.
Twenty-one patients (70%) passed this test, with 13 of these patients using the “cold turkey” method of smoking cessation, 5 patients using nicotine replacement therapy, 2 patients using more intensive methods, and 1 patient switching to e-cigarettes. Six-month follow-up was obtained for 14 patients, 9 (64%) of whom continued to abstain from smoking. 
Cost-Effectiveness of Smoking Cessation
Hejblum et al  used a Markov-type model and French hospital costs for 2008 to simulate the hospital course for 1 million total joint arthroplasty patients to compare costs for those who were and those who were not exposed to a smoking cessation program. Patient data were modeled using the study by Møller et al,  with the preoperative intervention for smoking cessation beginning 6 to 8 weeks before surgery.
The cost of the average hospital stay was €6246 for patients in the intervention group and €6559 for the patients in the control group, an overall cost savings of €313 per patient for the intervention group. Once the program cost (€196) was deducted, the savings per patient was €117. The lower cost primarily depended on a reduction in the length of stay in the ICU for the intervention group compared with the control group. Hejblum et al  did not consider factors after patient discharge, such as readmission for wound complications or PJI. Overall, they found a modest cost savings with the implementation of a preoperative smoking cessation program.
Boylan et al  considered the cost effectiveness of a mandatory preoperative smoking cessation intervention over a 90-day episode of care for TKA and THA patients. Their model was based on an intervention that cost less than $219, a success rate of 56%, a reduction in PJI by at least 25% and a $95,410 short-term cost per PJI. Using their model, the average 90-day cost was $32 less for patients in the intervention group. 
Preoperative smoking cessation programs have been shown to be effective at helping patients stop smoking at the time of surgery and to provide a modest cost savings. [27,30-32,35,36] Although current literature shows a decrease in complications for patients who stop smoking more than 4 weeks preoperatively, more research is needed on the outcomes for patients who stop smoking less than 4 weeks preoperatively. [30,31]
Intensive programs that utilize nicotine replacement therapy are thought to be more effective than brief interactions,  but a recent study showed that a brief interaction combined with preoperative exhaled carbon monoxide testing can be effective in reducing smoking rates among patients undergoing THA and TKA. However, data from 2012 show that only 6% of orthopaedic surgeons are routinely testing patients for smoking preoperatively. [27,29] Increased testing may provide greater incentive for patients undergoing TKA and THA to stop smoking before surgery, but further research is needed to generalize the results of this small prospective cohort study. 
Charity Jacobs, MD, and Fernando Nussenbaum, MD, are adult reconstruction fellows from the NYU Langone Orthopedic Hospital/Insall Scott Kelly, Department of Adult Reconstruction, New York, New York. Jonathan Vigdorchik, MD, is an Assistant Professor of Orthopedic Surgery, Associate Fellowship Director in Adult Reconstruction, and Co-Director of Robotics in Orthopedic Surgery at the NYU Langone Orthopedic Hospital, New York, New York. Ran Schwarzkopf, MD, is an Associate Professor of Orthopedic Surgery at the NYU Langone Orthopedic Hospital, New York, New York.
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